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A Safety and Immune Response Study of 2 Experimental HIV Vaccines

Sponsor
National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
Overall Status
Completed
CT.gov ID
NCT02404311
Collaborator
HIV Vaccine Trials Network (Other), Bill and Melinda Gates Foundation (Other), Medical Research Council (Other), Sanofi Pasteur, a Sanofi Company (Industry), GlaxoSmithKline (Industry)
252
Enrollment
5
Locations
5
Arms
42.1
Actual Duration (Months)
50.4
Patients Per Site
1.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The HIV Vaccine Trials Network (HVTN) is doing a study to test a new HIV vaccine combination. HIV is the virus that causes AIDS.

252 people are taking part in this study at multiple sites. The US National Institutes of Health (NIH) is paying for the study.

The investigators are doing this study to answer several questions.

  • Are the study vaccines safe to give to people?

  • Are people able to take the study vaccines without becoming too uncomfortable?

  • How do people's immune systems respond to the study vaccines? (Your immune system protects you from disease.)

Condition or Disease Intervention/Treatment Phase
  • Biological: ALVAC-HIV
  • Biological: Bivalent Subtype C gp120/MF59®
  • Biological: ALVAC-HIV (vCP2438) Placebo
  • Biological: Bivalent gp120/MF59® Placebo
 Phase 1/Phase 2

Detailed Description

The HIV Vaccine Trials Network (HVTN) is doing a study to test a new HIV vaccine combination. HIV is the virus that causes AIDS. The investigators are doing this study to answer several questions:

  • Are the study vaccines safe to give to people?

  • Are people able to take the study vaccines without becoming too uncomfortable?

  • How do people's immune systems respond to the study vaccines? (Your immune system protects you from disease.)

The study uses 2 different vaccines: ALVAC-HIV (vCP2438) and bivalent gp120/MF59. These are experimental HIV vaccines -- the investigators do not know whether the vaccines will be safe to use in people, or whether they will work to prevent HIV infection. These vaccines are used only in research studies.

The ALVAC vaccine is made out of canarypox virus, which infects birds but cannot grow in human cells. This virus has small bits of man-made DNA inserted into it. DNA is a natural substance found in all living things, including people and some viruses. The canarypox virus helps get the DNA into the body's cells. The DNA then tells those cells to make small amounts of proteins that look like some of the ones found in HIV.

A study in South Africa, HVTN 097, gave a similar ALVAC vaccine to about 80 participants. So far, no one has had serious health problems.

The Protein vaccine has man-made pieces of a protein found on the outside of HIV. These protein pieces are mixed with an adjuvant called MF59. An adjuvant is something added to the vaccine to help the immune system respond better. MF59 has been included with other vaccines that have been given to over 50,000 people in clinical trials without causing any serious health problems.

This combination of study vaccines has not been given to people before. However, similar ALVAC and protein vaccines have been given to more than 10,000 people in clinical trials without causing any serious health problems. Also, over 300 people have received a similar combination of ALVAC and protein vaccines with the MF59 adjuvant in clinical trials without having any serious health problems.

The study is in 2 parts, Part A and Part B. Part B continues the study in order to learn how well boosting the study vaccines improves immune responses. 252 people took part in Part A of this study at multiple sites. Those who continue to meet eligibility requirements are invited to continue in Part B.

The US National Institutes of Health (NIH) is paying for the study. For people who continue to Part B, the study requires about 23 clinic visits in 4 years.

Study Design

Study Type:
Interventional
Actual Enrollment :
252 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Prevention
Official Title:
A Phase 1-2 Randomized, Double-blind, Placebo-controlled Clinical Trial of Clade C ALVAC-HIV (vCP2438) and Bivalent Subtype C gp120/MF59® in HIV-uninfected Adults at Low Risk of HIV Infection
Actual Study Start Date :
Feb 2, 2015
Actual Primary Completion Date :
Aug 7, 2018
Actual Study Completion Date :
Aug 7, 2018

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Part A, Group 1: Vaccine

ALVAC-HIV at months 0 and 1, and ALVAC-HIV + bivalent subtype C gp120/MF59 at months 3, 6, and 12

Biological: ALVAC-HIV
a lyophilized vaccine for injection at a viral titer ≥ 1 × 10E6 cell culture infectious dose (CCID)50 and < 1 × 10E8 CCID50 (nominal dose of 10E7 CCID50) and is reconstituted with 1mL of sterile sodium chloride solution (NaCl 0.4%) for intramuscular (IM) injection as a single dose.

Biological: Bivalent Subtype C gp120/MF59®
2 recombinant monomeric proteins, each at a dose of 100 mcg, mixed with MF59® adjuvant (an oil-in-water emulsion) delivered as a 0.5 mL IM injection
Placebo Comparator: Part A, Group 2: Placebo

Placebo for ALVAC-HIV at months 0 and 1, and placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at months 3, 6, and 12

Biological: ALVAC-HIV (vCP2438) Placebo
a sterile, lyophilized product that consists of a mixture of virus stabilizer, and freeze drying medium and is reconstituted with 1mL of sterile sodium chloride solution (NaCl 0.4%) for injection as a single dose IM

Biological: Bivalent gp120/MF59® Placebo
Sodium chloride for injection, 0,9% delivered as a 0.5 mL IM injection
Active Comparator: Part B, Group 1a: Vaccine

Participants originally in Part A Group 1 (Vaccine) receive ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30

Biological: ALVAC-HIV
a lyophilized vaccine for injection at a viral titer ≥ 1 × 10E6 cell culture infectious dose (CCID)50 and < 1 × 10E8 CCID50 (nominal dose of 10E7 CCID50) and is reconstituted with 1mL of sterile sodium chloride solution (NaCl 0.4%) for intramuscular (IM) injection as a single dose.

Biological: Bivalent Subtype C gp120/MF59®
2 recombinant monomeric proteins, each at a dose of 100 mcg, mixed with MF59® adjuvant (an oil-in-water emulsion) delivered as a 0.5 mL IM injection
Active Comparator: Part B, Group 1b: Vaccine + Placebo

Participants originally in Part A Group 1 (Vaccine) receive placebo for ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30

Biological: Bivalent Subtype C gp120/MF59®
2 recombinant monomeric proteins, each at a dose of 100 mcg, mixed with MF59® adjuvant (an oil-in-water emulsion) delivered as a 0.5 mL IM injection

Biological: ALVAC-HIV (vCP2438) Placebo
a sterile, lyophilized product that consists of a mixture of virus stabilizer, and freeze drying medium and is reconstituted with 1mL of sterile sodium chloride solution (NaCl 0.4%) for injection as a single dose IM
Placebo Comparator: Part B, Group 2: Placebo

Participants originally in Part A Group 2 (Placebo) receive placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at month 30

Biological: ALVAC-HIV (vCP2438) Placebo
a sterile, lyophilized product that consists of a mixture of virus stabilizer, and freeze drying medium and is reconstituted with 1mL of sterile sodium chloride solution (NaCl 0.4%) for injection as a single dose IM

Biological: Bivalent gp120/MF59® Placebo
Sodium chloride for injection, 0,9% delivered as a 0.5 mL IM injection

Outcome Measures

Primary Outcome Measures

  1. Part A: Number of Participants Reporting Local Reactogenicity Signs and Symptoms During the Primary Vaccine Regimen [Measured through 3 days after participants' last vaccination at Month 0,1,3, and 6]

    Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [March 2017] The maximum grade observed for each symptom over the time frame is presented.

  2. Part A: Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms During the Primary Vaccine Regimen [Measured through 3 days after each vaccination at Month 0, 1, 3, and 6]

    Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [March 2017]

  3. Part A: Number of Participants With Early Study Termination Associated With an AE or Reactogenicity [Measured through Month 18]

    From the study termination form, early termination reasons associated with an AE or reactogenicity are tabulated by treatment arm

  4. Part A: Number of Participants With Study Product Discontinuation Associated With an AE or Reactogenicity [Measured through the Month 12 vaccination]

    From the study product discontinuation form, study product administration reasons are tabulated by treatment arm

  5. Part A: Chemistry and Hematology Laboratory Results With Grade 1 or Higher [Measured during screening for part A, and 2 weeks after each vaccination at Month 0, 1, 3, 6, and 12]

    Laboratory results are summarized by analyte and timepoint. Analytes and timepoint combinations with no grade 1 or higher results are not shown.

  6. Part A Chemistry Laboratory Measures: Alkaline Phosphatase, AST, and ALT [Time Frame: Measured during screening for part A, and 2 weeks after each vaccination at Month 0, 1, 3, 6, and 12]

    For each chemistry laboratory measure, summary statistics were presented by analyte and treatment group for the overall population.

  7. Part A Chemistry Laboratory Measures: Hemoglobin, Creatinine [Time Frame: Measured during screening for part A, and 2 weeks after each vaccination at Month 0, 1, 3, 6, and 12]

    For each chemistry laboratory measure, summary statistics were presented by analyte and treatment group for the overall population.

  8. Part A Hematology Laboratory Measures: WBC, Platelets, Lymphocytes, Neutrophils [Measured during screening for part A, and 2 weeks after each vaccination at Month 0, 1, 3, 6, and 12]

    For each chemistry laboratory measure, summary statistics were presented by analyte and treatment group for the overall population.

  9. Part A: Occurrence of IgG Ab Binding to gp120 Env Proteins Contained in the Vaccine (ZM96, TV1.C, 1086.C) After the Primary Vaccine Regimen, Measured by HIV-1 Multiplex Antibody Assay [Measured at Month 6.5]

    Serum HIV-1-specific IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. Samples from post-enrollment visits have positive responses if they meet three conditions: (1) net MFI greater than or equal to an antigen-specific response threshold (defined as the maximum of 100 and the 95th percentile of pre-vaccination net MFI), (2) net MFI values are greater than 3 times pre-vaccination net MFI, and (3) experimental antigen MFI values are greater than 3 times pre-vaccination MFI. Data are excluded if the blood draw date was outside the allowable window, a participant was HIV-infected, or the reference antigen exceeds 5000 MFI.

  10. Part A: Level of IgG Ab Binding to gp120 Env Proteins Contained in the Vaccine (ZM96, TV1.C, 1086.C) After the Primary Vaccine Regimen, Measured by HIV-1 Multiplex Antibody Assay [Measured at Month 6.5]

    Serum HIV-1-specific IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. The measure unit fluorescence units are relative to assay background, not relative to the placebo arm. Background is used here rather than negative control stimulation, since the antigens are used as bead coating rather than stimulation.

  11. Part A: Occurrence of IgG Binding Antibodies to 3 V1V2-scaffolded Env Proteins After the Primary Vaccine Regimen [Measured at Month 6.5]

    Measured by HIV-1 multiplex Ab assay: refer to earlier description for assay methods and analysis variable derivation. The number and percentage of participants with positive responses are summarized by antigen.

  12. Part A: Level of IgG Binding Antibodies to 3 V1V2-scaffolded Env Proteins After the Primary Vaccine Regimen [Measured at Month 6.5]

    Serum HIV-1-specific IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. The measure unit fluorescence units are relative to assay background, not relative to the placebo arm. Background is used here rather than negative control stimulation, since the antigens are used as bead coating rather than stimulation.

  13. Part A: Occurrence of CD4+ T Cell Responses to the HIV Proteins Included in the Vaccine After the Primary Vaccine Regimen. Measured by Flow Cytometry. [Measured at Month 6.5]

    PBMC samples are stimulated with synthetic peptide pools or left unstimulated as a negative control. For each sample, T-cell subset, and peptide pool, response magnitude is % cells expressing markers after peptide stimulation minus % cells expressing markers after no stimulation. A contingency table is constructed to assess response: stimulation (peptide/none) vs. marker expression (yes/no). A one-sided Fisher's exact test is applied, testing if the number of cells positive for the marker is equal in the stimulated vs. unstimulated cells. A discrete Bonferroni adjustment is made over the peptide pools. Response is positive if p<=0.00001. Data are excluded if the blood draw date was outside the visit window, the participant was HIV-infected, PBMC viability or T-cell count were low, or negative control was high.

  14. Part A: Level of CD4+ T Cell Responses to the HIV Proteins Included in the Vaccine After the Primary Vaccine Regimen. [Measured at Month 6.5]

    Measured by flow cytometry ICS assay: refer to earlier description for assay methods and analysis variable derivation. Percentage of T-cells expressing cytokines are summarized for positive responders only.

  15. Part B: Number of Participants Reporting Local Reactogenicity Signs and Symptoms in the Extension Study [Measured through 3 days after the Month 30 vaccination]

    Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [March 2017]. For each participant, the maximum grade observed for each symptom over the time frame is presented.

  16. Part B: Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms in the Extension Study [Measured through 3 days after the Month 30 vaccination]

    Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [March 2017]. For each participant, the maximum grade observed for each symptom over the time frame is presented.

  17. Part B: Number of Participants With Early Study Termination Associated With an AE or Reactogenicity [Measured through Month 36]

    From the study termination form, early termination reasons associated with an AE are tabulated by treatment arm

  18. Part B: Chemistry and Hematology Laboratory Results of Grade 1 or Higher [Time Frame: Measured during screening for part B, and 2 weeks after vaccination at Month 30]

    Laboratory results are summarized by analyte and timepoint. Analytes and timepoint combinations with no grade 1 or higher results are not shown.

  19. Part B Chemistry Laboratory Measures: Alkaline Phosphatase, AST, and ALT [Measured during screening for part B, and 2 weeks after vaccination at Month 30]

    For each chemistry laboratory measure, summary statistics were presented by analyte and treatment group for the overall population.

  20. Part B Chemistry Laboratory Measures: Hemoglobin, Creatinine [Measured during screening for part B, and 2 weeks after vaccination at Month 30]

    For each chemistry laboratory measure, summary statistics were presented by analyte and treatment group for the overall population.

  21. Part B Chemistry Laboratory Measures: WBC, Platelets, Lymphocytes, Neutrophils [Measured during screening for part B, and 2 weeks after vaccination at Month 30]

    For each chemistry laboratory measure, summary statistics were presented by analyte and treatment group for the overall population.

  22. Part B: Occurrence of IgG Binding Antibodies to 3 V1V2-scaffolded Env Proteins in the Extension Study [Measured at Month 30.5]

    Measured by HIV-1 multiplex Ab assay: refer to earlier description for assay methods and analysis variable derivation. The number and percentage of participants with positive responses are summarized by antigen.

  23. Part B: Level of IgG Binding Antibodies to 3 V1V2-scaffolded Env Proteins in the Extension Study [Measured at Month 30.5]

    Serum HIV-1-specific IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. The measure unit fluorescence units are relative to assay background, not relative to the placebo arm. Background is used here rather than negative control stimulation, since the antigens are used as bead coating rather than stimulation.

  24. Part B: Occurrence of IgG Ab Binding to gp120 Env Proteins Contained in the Vaccine (ZM96, TV1.C, 1086.C) in the Extension Study [Measured at Month 30.5]

    Measured by HIV-1 multiplex Ab assay: refer to earlier description for assay methods and analysis variable derivation. The number and percentage of participants with positive responses are summarized by antigen.

  25. Part B: Level of IgG Ab Binding to gp120 Env Proteins Contained in the Vaccine (ZM96, TV1.C, 1086.C) in the Extension Study [Measured at Month 30.5]

    Serum HIV-1-specific IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. The measure unit fluorescence units are relative to assay background, not relative to the placebo arm. Background is used here rather than negative control stimulation, since the antigens are used as bead coating rather than stimulation.

  26. Part B: Occurrence of CD4+ T Cell Responses to the HIV Proteins Included in the Vaccine in the Extension Study [Measured at Month 30.5]

    Measured by flow cytometry ICS assay: refer to earlier description for assay methods and analysis variable derivation. The number and percentage of participants with positive responses are summarized by peptide pool.

  27. Part B: Level of CD4+ T Cell Responses to the HIV Proteins Included in the Vaccine in the Extension Study [Measured at Month 30.5]

    Measured by flow cytometry ICS assay: refer to earlier description for assay methods and analysis variable derivation. Percentage of T-cells expressing cytokines are summarized for positive responders only.

Secondary Outcome Measures

  1. Part A: Frequency of Severe Local Reactogenicity Signs and Symptoms, Through the Fifth Vaccination [Measured through 3 days after each vaccination at Month 0, 1, 3, 6, and 12]

    Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [March 2017]. The maximum grade observed for each symptom over the time frame is presented.

  2. Part A: Frequency of Severe Systemic Reactogenicity Signs and Symptoms, Through the Fifth Vaccination [Measured through 3 days after each vaccination at Month 0, 1, 3, 6, and 12]

    Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [March 2017]. The maximum grade observed for each symptom over the time frame is presented.

  3. Part A: Compare the Occurrence of IgG Ab Binding to gp120 Env Proteins Contained in the Vaccine (ZM96, TV1.C, 1086.C) After the Fourth Versus the Fifth Vaccination [Measured at Month 6.5 and 12.5]

    Serum HIV-1-specific IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. Samples from post-enrollment visits have positive responses if they meet three conditions: (1) net MFI greater than or equal to an antigen-specific response threshold (defined as the maximum of 100 and the 95th percentile of pre-vaccination net MFI), (2) net MFI values are greater than 3 times pre-vaccination net MFI, and (3) experimental antigen MFI values are greater than 3 times pre-vaccination MFI. Data are excluded if the blood draw date was outside the allowable window, a participant was HIV-infected, or the reference antigen exceeds 5000 MFI.

  4. Part A: Compare the Level of IgG Ab Binding to gp120 Env Proteins Contained in the Vaccine (ZM96, TV1.C, 1086.C) After the Fourth Versus the Fifth Vaccination [Measured at Month 6.5 and 12.5]

    Serum HIV-1-specific IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. The measure unit fluorescence units are relative to assay background, not relative to the placebo arm. Background is used here rather than negative control stimulation, since the antigens are used as bead coating rather than stimulation. Comparisons were performed among positive responders only (positivity criteria is described in Outcome 30).

  5. Part A: Compare the Occurrence of IgG Binding Antibodies to 3 V1V2-scaffolded Env Proteins After the Fourth Versus the Fifth Vaccination [Measured at Month 6.5 and 12.5]

    Serum HIV-1-specific IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. Samples from post-enrollment visits have positive responses if they meet three conditions: (1) net MFI greater than or equal to an antigen-specific response threshold (defined as the maximum of 100 and the 95th percentile of pre-vaccination net MFI), (2) net MFI values are greater than 3 times pre-vaccination net MFI, and (3) experimental antigen MFI values are greater than 3 times pre-vaccination MFI. Data are excluded if the blood draw date was outside the allowable window, a participant was HIV-infected, or the reference antigen exceeds 5000 MFI.

  6. Part A: Compare the Level of IgG Binding Antibodies to 3 V1V2-scaffolded Env Proteins After the Fourth Versus the Fifth Vaccination [Measured at Month 6.5 and 12.5]

    Serum HIV-1-specific IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. The measure unit fluorescence units are relative to assay background, not relative to the placebo arm. Background is used here rather than negative control stimulation, since the antigens are used as bead coating rather than stimulation. Comparisons were performed among positive responders only (positivity criteria is described in Outcome 32).

  7. Part A: Compare the Occurrence of CD4+ T Cell Responses to the HIV Proteins Included in the Vaccine After the Fourth Versus the Fifth Vaccinations [Measured at Month 6.5 and 12.5]

    PBMC samples are stimulated with synthetic peptide pools or left unstimulated as a negative control. For each sample, T-cell subset, and peptide pool, response magnitude is % cells expressing markers after peptide stimulation minus % cells expressing markers after no stimulation. A contingency table is constructed to assess response: stimulation (peptide/none) vs. marker expression (yes/no). A one-sided Fisher's exact test is applied, testing if the number of cells positive for the marker is equal in the stimulated vs. unstimulated cells. A discrete Bonferroni adjustment is made over the peptide pools. Response is positive if p<=0.00001. Data are excluded if the blood draw date was outside the visit window, the participant was HIV-infected, PBMC viability or T-cell count were low, or negative control was high.

  8. Part A: Compare the Level of CD4+ T Cell Responses to the HIV Proteins Included in the Vaccine After the Fourth Versus the Fifth Vaccinations [Measured at Month 6.5 and 12.5]

    PBMC samples are stimulated with synthetic peptide pools or left unstimulated as a negative control. For each sample, T-cell subset, and peptide pool, response magnitude is % cells expressing markers after peptide stimulation minus % cells expressing markers after no stimulation. A contingency table is constructed to assess response: stimulation (peptide/none) vs. marker expression (yes/no). A one-sided Fisher's exact test is applied, testing if the number of cells positive for the marker is equal in the stimulated vs. unstimulated cells. A discrete Bonferroni adjustment is made over the peptide pools. Response is positive if p<=0.00001. Data are excluded if the blood draw date was outside the visit window, the participant was HIV-infected, PBMC viability or T-cell count were low, or negative control was high. Comparisons were performed among positive responders only.

  9. Part B: Occurrence of IgG Ab Binding to gp120 Env Proteins Contained in the Vaccine (ZM96, TV1.C, 1086.C) in the Extension Study, at 6 Months After the Month 30 Vaccination [Measured at Month 30 and 36]

    Serum HIV-1-specific IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. Samples from post-enrollment visits have positive responses if they meet three conditions: (1) net MFI greater than or equal to an antigen-specific response threshold (defined as the maximum of 100 and the 95th percentile of pre-vaccination net MFI), (2) net MFI values are greater than 3 times pre-vaccination net MFI, and (3) experimental antigen MFI values are greater than 3 times pre-vaccination MFI. Data are excluded if the blood draw date was outside the allowable window, a participant was HIV-infected, or the reference antigen exceeds 5000 MFI.

  10. Part B: Level of IgG Ab Binding to gp120 Env Proteins Contained in the Vaccine (ZM96, TV1.C, 1086.C) in the Extension Study, at 6 Months After the Month 30 Vaccination [Measured at Month 30 and 36]

    Serum HIV-1-specific IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. The measure unit fluorescence units are relative to assay background, not relative to the placebo arm. Background is used here rather than negative control stimulation, since the antigens are used as bead coating rather than stimulation.

  11. Part B: Occurrence of IgG Binding Antibodies to 3 V1V2-scaffolded Env Proteins in the Extension Study, at 6 Months After the Month 30 Vaccination [Measured at Month 30 and 36]

    Serum HIV-1-specific IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. Samples from post-enrollment visits have positive responses if they meet three conditions: (1) net MFI greater than or equal to an antigen-specific response threshold (defined as the maximum of 100 and the 95th percentile of pre-vaccination net MFI), (2) net MFI values are greater than 3 times pre-vaccination net MFI, and (3) experimental antigen MFI values are greater than 3 times pre-vaccination MFI. Data are excluded if the blood draw date was outside the allowable window, a participant was HIV-infected, or the reference antigen exceeds 5000 MFI.

  12. Part B: Level of IgG Binding Antibodies to 3 V1V2-scaffolded Env Proteins in the Extension Study, at 6 Months After the Month 30 Vaccination [Measured at Month 30 and 36]

    Serum HIV-1-specific IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. The measure unit fluorescence units are relative to assay background, not relative to the placebo arm. Background is used here rather than negative control stimulation, since the antigens are used as bead coating rather than stimulation.

  13. Part B: Occurrence of CD4+ T Cell Responses to the HIV Proteins Included in the Vaccine in the Extension Study, at 6 Months After the Month 30 Vaccination [Measured at Month 30 and 36]

    PBMC samples are stimulated with synthetic peptide pools or left unstimulated as a negative control. For each sample, T-cell subset, and peptide pool, response magnitude is % cells expressing markers after peptide stimulation minus % cells expressing markers after no stimulation. A contingency table is constructed to assess response: stimulation (peptide/none) vs. marker expression (yes/no). A one-sided Fisher's exact test is applied, testing if the number of cells positive for the marker is equal in the stimulated vs. unstimulated cells. A discrete Bonferroni adjustment is made over the peptide pools. Response is positive if p<=0.00001. Data are excluded if the blood draw date was outside the visit window, the participant was HIV-infected, PBMC viability or T-cell count were low, or negative control was high.

  14. Part B: Level of CD4+ T Cell Responses to the HIV Proteins Included in the Vaccine in the Extension Study, at 6 Months After the Month 30 Vaccination [Measured at Month 30 and 36]

    PBMC samples are stimulated with synthetic peptide pools or left unstimulated as a negative control. For each sample, T-cell subset, and peptide pool, response magnitude is % cells expressing markers after peptide stimulation minus % cells expressing markers after no stimulation. A contingency table is constructed to assess response: stimulation (peptide/none) vs. marker expression (yes/no). A one-sided Fisher's exact test is applied, testing if the number of cells positive for the marker is equal in the stimulated vs. unstimulated cells. A discrete Bonferroni adjustment is made over the peptide pools. Response is positive if p<=0.00001. Data are excluded if the blood draw date was outside the visit window, the participant was HIV-infected, PBMC viability or T-cell count were low, or negative control was high.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 40 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:

  • Age of 18 to 40 years

  • Access to a participating HVTN CRS and willingness to be followed for the planned duration of the study

  • Ability and willingness to provide informed consent

  • Assessment of understanding: volunteer demonstrates understanding of this study; completes a questionnaire prior to first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly

  • Agrees not to enroll in another study of an investigational research agent

  • Good general health as shown by medical history, physical exam, and screening laboratory tests

  • Willingness to receive HIV test results

  • Willingness to discuss HIV infection risks and amenable to HIV risk reduction counseling

  • Assessed by the clinic staff as being at "low risk" for HIV infection (per Low Risk Guidelines for South African sites) and committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit

  • Hemoglobin ≥ 11.0 g/dL for volunteers who were born female, ≥ 13.0 g/dL for volunteers who were born male

  • WBC = 3,300 to 12,000 cells/mm3

  • Total lymphocyte count ≥ 800 cells/mm3

  • Remaining differential either within institutional normal range or with site physician approval

  • Platelets = 125,000 to 550,000/mm3

  • Chemistry panel: ALT, AST, and ALP < 1.25 times the institutional upper limit of normal; creatinine ≤ institutional upper limit of normal.

  • Negative HIV-1 and -2 blood test: Sites may use locally available assays that have been approved by HVTN Laboratory Operations.

  • Negative Hepatitis B surface antigen (HBsAg)

  • Negative anti-Hepatitis C virus antibodies (anti-HCV), or negative HCV polymerase chain reaction (PCR) if the anti-HCV is positive

  • Normal urine:

  • Negative urine glucose, and

  • Negative or trace urine protein, and

  • Negative or trace urine hemoglobin (if trace hemoglobin is present on dipstick, a microscopic urinalysis with red blood cells levels within institutional normal range).

  • Volunteers who were born female: negative urine beta human chorionic gonadotropin (β-HCG) pregnancy test performed prior to vaccination on the day of initial vaccination or negative serum beta human chorionic gonadotropin (β-HCG) pregnancy test within 24 hours prior to initial vaccination. Persons who are NOT of reproductive potential due to having undergone total hysterectomy with bilateral oophorectomy (verified by medical records), are not required to undergo pregnancy testing.

  • Reproductive status: A volunteer who was born female must:

  • Agree to consistently use effective contraception for sexual activity that could lead to pregnancy from at least 21 days prior to enrollment through the last required protocol clinic visit. Effective contraception for participants in South

Africa is defined as using 2 methods, including the following:

  • Condoms (male or female), or

  • Diaphragm or cervical cap,

PLUS 1 of the following methods:

  • Intrauterine device (IUD),

  • Hormonal contraception (in accordance with Republic of South Africa: National Contraception Clinical Guidelines),

  • Successful vasectomy in the male partner (considered successful if a volunteer reports that a male partner has [1] documentation of azoospermia by microscopy, or [2] a vasectomy more than 2 years ago with no resultant pregnancy despite sexual activity postvasectomy); or

  • Any other contraceptive method approved by the HVTN 100 PSRT

  • Or not be of reproductive potential, such as having reached menopause (no menses for 1 year) or having undergone hysterectomy, bilateral oophorectomy, or tubal ligation;

  • Or be sexually abstinent.

  • Volunteers who were born female must also agree not to seek pregnancy through alternative methods, such as artificial insemination or in vitro fertilization until after the last required protocol clinic visit

Exclusion Criteria:

  • Blood products received within 120 days before first vaccination

  • Investigational research agents received within 30 days before first vaccination

  • Body mass index (BMI) ≥ 40; or BMI ≥ 35 with 2 or more of the following: systolic blood pressure > 140 mm Hg, diastolic blood pressure > 90 mm Hg, current smoker, known hyperlipidemia

  • Intent to participate in another study of an investigational research agent or any study that includes HIV testing during the planned duration of the HVTN 100 study

  • Pregnant, breastfeeding, or lactating

  • HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received control/placebo in an HIV vaccine trial, the HVTN 100 PSRT will determine eligibility on a case-by-case basis.

  • Non-HIV experimental vaccine(s) received within the last 5 years in a prior vaccine trial. Exceptions may be made for vaccines that have subsequently undergone licensure by the South Africa Medicines Control Council (MCC). For volunteers who have received control/placebo in an experimental vaccine trial, the HVTN 100 PSRT will determine eligibility on a case-by-case basis. For volunteers who have received an experimental vaccine(s) greater than 5 years ago, eligibility for enrollment will be determined by the HVTN 100 PSRT on a case-by-case basis.

  • Live attenuated vaccines other than influenza vaccine received within 30 days before first vaccination or scheduled within 14 days after injection (eg, measles, mumps, and rubella [MMR]; oral polio vaccine [OPV]; varicella; yellow fever)

  • Influenza vaccine or any vaccines that are not live attenuated vaccines and were received within 14 days prior to first vaccination (eg, tetanus, pneumococcal, Hepatitis A or B)

  • Allergy treatment with antigen injections within 30 days before first vaccination or that are scheduled within 14 days after first vaccination

  • Immunosuppressive medications received within 168 days before first vaccination. (Not excluded from participation: [1] corticosteroid nasal spray; [2] inhaled corticosteroids; [3] topical corticosteroids for mild, uncomplicated dermatitis; or [4] a single course of oral/parenteral corticosteroids at doses < 2 mg/kg/day and length of therapy < 11 days with completion at least 30 days prior to enrollment.)

  • Serious adverse reactions to vaccines or to vaccine components such as eggs, egg products, or neomycin, including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain. (Not excluded from participation: a volunteer who had a nonanaphylactic adverse reaction to pertussis vaccine as a child.)

  • Immunoglobulin received within 60 days before first vaccination

  • Autoimmune disease

  • Immunodeficiency

  • Untreated or incompletely treated syphilis infection

  • Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health. A clinically significant condition or process includes but is not limited to:

  • A process that would affect the immune response,

  • A process that would require medication that affects the immune response,

  • Any contraindication to repeated injections or blood draws,

  • A condition that requires active medical intervention or monitoring to avert grave danger to the volunteer's health or well-being during the study period,

  • A condition or process for which signs or symptoms could be confused with reactions to vaccine, or

  • Any condition specifically listed among the exclusion criteria below.

  • Any medical, psychiatric, occupational, or other condition that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence, assessment of safety or reactogenicity, or a volunteer's ability to give informed consent

  • Psychiatric condition that precludes compliance with the protocol. Specifically excluded are persons with psychoses within the past 3 years, ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years.

  • Current anti-tuberculosis (TB) prophylaxis or therapy

  • Asthma other than mild or moderate, well-controlled asthma. (Symptoms of asthma severity as defined in the most recent National Asthma Education and Prevention

Program (NAEPP) Expert Panel report). Exclude a volunteer who:

  • Uses a short-acting rescue inhaler (typically a beta 2 agonist) daily, or

  • Uses high dose inhaled corticosteroids, or

  • In the past year has either of the following:

  • Greater than 1 exacerbation of symptoms treated with oral/parenteral corticosteroids;

  • Needed emergency care, urgent care, hospitalization, or intubation for asthma.

  • Diabetes mellitus type 1 or type 2, including cases controlled with diet alone. (Not excluded: history of isolated gestational diabetes.)

  • Thyroidectomy, or thyroid disease requiring medication during the last 12 months

  • Hypertension:

  • If a person has been found to have elevated blood pressure or hypertension during screening or previously, exclude for blood pressure that is not well controlled. Well-controlled blood pressure is defined as consistently ≤ 140 mm Hg systolic and ≤ 90 mm Hg diastolic, with or without medication, with only isolated, brief instances of higher readings, which must be ≤ 150 mm Hg systolic and ≤ 100 mm Hg diastolic. For these volunteers, blood pressure must be ≤ 140 mm Hg systolic and ≤ 90 mm Hg diastolic at enrollment.

  • If a person has NOT been found to have elevated blood pressure or hypertension during screening or previously, exclude for systolic blood pressure ≥ 150 mm Hg at enrollment or diastolic blood pressure ≥ 100 mm Hg at enrollment.

  • Bleeding disorder diagnosed by a doctor (eg, factor deficiency, coagulopathy, or platelet disorder requiring special precautions)

  • Malignancy (Not excluded: Volunteer who has had malignancy excised surgically and who, in the investigator's estimation, has a reasonable assurance of sustained cure or who is unlikely to experience recurrence of malignancy during the period of the study)

  • Seizure disorder: History of seizure(s) within past three years. Also exclude if volunteer has used medications in order to prevent or treat seizure(s) at any time within the past 3 years.

  • Asplenia: any condition resulting in the absence of a functional spleen

  • History of hereditary angioedema, acquired angioedema, or idiopathic angioedema.

Contacts and Locations

Locations

Site City State Country Postal Code
1 CAPRISA eThekwini CRS Durban KwaZulu-Natal South Africa 4001
2 Isipingo CRS Durban KwaZulu-Natal South Africa 4133
3 Emavundleni Desmond Tutu HIV Centre CRS Cape Town Western Cape South Africa 7750
4 Aurum Institute for Health Research Klerksdorp South Africa 2570
5 Perinatal HIV Research Unit Soweto South Africa 2013

Sponsors and Collaborators

  • National Institute of Allergy and Infectious Diseases (NIAID)
  • HIV Vaccine Trials Network
  • Bill and Melinda Gates Foundation
  • Medical Research Council
  • Sanofi Pasteur, a Sanofi Company
  • GlaxoSmithKline

Investigators

  • Study Chair: Linda-Gail Bekker, MBChB, DTMH, DCH, FCP(SA), PhD, HIV Vaccine Trials Network

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT02404311
Other Study ID Numbers:
  • HVTN 100
First Posted:
Mar 31, 2015
Last Update Posted:
Nov 5, 2021
Last Verified:
Jul 1, 2020
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
Yes
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID)
HIV
AIDS
Vaccine
Additional relevant MeSH terms:
Infections
HIV Infections
Acquired Immunodeficiency Syndrome
MF59 oil emulsion

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail Participants who received all vaccinations in Part A and completed Part A as scheduled were eligible for the Part B extension study. N=63 vaccination recipients in Part A (Group 1) were re-randomized to Part B Group 1a or 1b with a 1:1 ratio, while N=7 placebo recipients from Part A (Group 2) re-enrolled to receive placebo injections in Part B.
Arm/Group Title Part A, Group 1: Vaccine Part A, Group 2: Placebo Part B, Group 1a: Vaccine Part B, Group 1b: Vaccine + Placebo Part B, Group 2: Placebo
Arm/Group Description Participants receive ALVAC-HIV (vCP2438) injections at months 0 and 1, and ALVAC-HIV (vCP2438) + bivalent subtype C gp120/MF59® injections at months 3, 6, and 12. Participants receive placebo for ALVAC-HIV (vCP2438) at months 0 and 1, and placebo for ALVAC-HIV (vCP2438) + placebo for bivalent subtype C gp120/MF59® injections at months 3, 6, and 12. Participants originally in Part A Group 1 receive ALVAC-HIV (vCP2438) + bivalent subtype C gp120/MF59® (vCP2438) injections at month 30. Participants originally in Part A Group 1 receive placebo for ALVAC-HIV (vCP2438) + active bivalent subtype C gp120/MF59® at month 30. Participants originally in Part A Group 2 (Placebo) receive placebo for ALVAC-HIV (vCP2438) + placebo for bivalent subtype C gp120/MF59® at month 30.
Period Title: Part A: Month 0-18
STARTED 210 42 0 0 0
Per Protocol 185 37 0 0 0
Month 6.5 Immunogenicity Timepoint 194 37 0 0 0
Month 12.5 Immunogenicity Timepoint 186 33 0 0 0
COMPLETED 184 36 0 0 0
NOT COMPLETED 26 6 0 0 0
Period Title: Part A: Month 0-18
STARTED 0 0 32 31 7
Month 30.5 Immunogenicity Timepoint 0 0 28 30 6
COMPLETED 0 0 32 31 7
NOT COMPLETED 0 0 0 0 0

Baseline Characteristics

Arm/Group Title Part A Only: Group 1 (Vaccine) Part A Only: Group 2 (Placebo) Part A, Group 1 (Vaccine) + Part B, Group 1a (Vaccine) Part A, Group 1 (Vaccine) + Part B, Group 1b: Vaccine/Placeb Part A, Group 2 (Placebo) + Part B, Group 2 (Placebo) Total
Arm/Group Description Participants did not go on to Part B. In Part A, participants received ALVAC-HIV at months 0 and 1, and ALVAC-HIV + bivalent subtype C gp120/MF59 at months 3, 6, and 12 Participants did not go on to Part B. In Part A, participants received Placebo for ALVAC-HIV at months 0 and 1, and placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at months 3, 6, and 12 Participants completed Part A in Group 1 (Vaccine), joined Part B and were randomized to Group 1a (Vaccine): ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants completed Part A in Group 1 (Vaccine), joined Part B and were randomized to Group 1b (Vaccine/Placebo ): placebo for ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants completed Part A in Group 2 (Placebo), joined Part B and received placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at month 30 Total of all reporting groups
Overall Participants 147 35 32 31 7 252
Age (years) [Median (Full Range) ]
Median (Full Range) [years]
23
23
25
23
24
23
Age, Customized (Count of Participants)
Less than 18 years
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
18 - 20 years
38
25.9%
7
20%
7
21.9%
3
9.7%
1
14.3%
56
22.2%
21 - 30 years
95
64.6%
24
68.6%
17
53.1%
26
83.9%
5
71.4%
167
66.3%
31 - 40 years
14
9.5%
4
11.4%
8
25%
2
6.5%
1
14.3%
29
11.5%
41 - 50 years
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Above 50 years
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Unknown or Not Reported
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Sex: Female, Male (Count of Participants)
Female
64
43.5%
18
51.4%
12
37.5%
12
38.7%
3
42.9%
109
43.3%
Male
83
56.5%
17
48.6%
20
62.5%
19
61.3%
4
57.1%
143
56.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Not Hispanic or Latino
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Unknown or Not Reported
147
100%
35
100%
32
100%
31
100%
7
100%
252
100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Asian
1
0.7%
0
0%
0
0%
0
0%
0
0%
1
0.4%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Black or African American
143
97.3%
34
97.1%
31
96.9%
31
100%
7
100%
246
97.6%
White
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
More than one race
3
2%
1
2.9%
1
3.1%
0
0%
0
0%
5
2%
Unknown or Not Reported
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Region of Enrollment (Count of Participants)
South Africa
147
100%
35
100%
32
100%
31
100%
7
100%
252
100%

Outcome Measures

1. Primary Outcome
Title Part A: Number of Participants Reporting Local Reactogenicity Signs and Symptoms During the Primary Vaccine Regimen
Description Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [March 2017] The maximum grade observed for each symptom over the time frame is presented.
Time Frame Measured through 3 days after participants' last vaccination at Month 0,1,3, and 6

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Part A, Group 1: Vaccine Part A, Group 2: Placebo
Arm/Group Description ALVAC-HIV at months 0 and 1, and ALVAC-HIV + bivalent subtype C gp120/MF59 at months 3, 6, and 12 Placebo for ALVAC-HIV at months 0 and 1, and placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at months 3, 6, and 12
Measure Participants 210 42
None
42
28.6%
26
74.3%
Mild
126
85.7%
16
45.7%
Moderate
40
27.2%
0
0%
Severe
2
1.4%
0
0%
Life Threatening
0
0%
0
0%
None
69
46.9%
34
97.1%
Mild
114
77.6%
8
22.9%
Moderate
26
17.7%
0
0%
Severe
1
0.7%
0
0%
Life Threatening
0
0%
0
0%
None
35
23.8%
26
74.3%
Mild
131
89.1%
16
45.7%
Moderate
42
28.6%
0
0%
Severe
2
1.4%
0
0%
Life Threatening
0
0%
0
0%
None
201
136.7%
42
120%
Mild
6
4.1%
0
0%
Moderate
2
1.4%
0
0%
Severe
1
0.7%
0
0%
Life Threatening
0
0%
0
0%
None
187
127.2%
42
120%
Mild
13
8.8%
0
0%
Moderate
9
6.1%
0
0%
Severe
1
0.7%
0
0%
Life Threatening
0
0%
0
0%
None
185
125.9%
42
120%
Mild
14
9.5%
0
0%
Moderate
10
6.8%
0
0%
Severe
1
0.7%
0
0%
Life Threatening
0
0%
0
0%
2. Primary Outcome
Title Part A: Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms During the Primary Vaccine Regimen
Description Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [March 2017]
Time Frame Measured through 3 days after each vaccination at Month 0, 1, 3, and 6

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Part A, Group 1: Vaccine Part A, Group 2: Placebo
Arm/Group Description ALVAC-HIV at months 0 and 1, and ALVAC-HIV + bivalent subtype C gp120/MF59 at months 3, 6, and 12 Placebo for ALVAC-HIV at months 0 and 1, and placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at months 3, 6, and 12
Measure Participants 210 42
None
125
85%
28
80%
Mild
76
51.7%
13
37.1%
Moderate
9
6.1%
1
2.9%
Severe
0
0%
0
0%
Potentially Life-threatening
0
0%
0
0%
None
132
89.8%
34
97.1%
Mild
60
40.8%
7
20%
Moderate
18
12.2%
1
2.9%
Severe
0
0%
0
0%
Potentially Life-threatening
0
0%
0
0%
None
139
94.6%
21
60%
Mild
56
38.1%
15
42.9%
Moderate
15
10.2%
6
17.1%
Severe
0
0%
0
0%
Potentially Life-threatening
0
0%
0
0%
None
179
121.8%
39
111.4%
Mild
29
19.7%
3
8.6%
Moderate
2
1.4%
0
0%
Severe
0
0%
0
0%
Potentially Life-threatening
0
0%
0
0%
None
200
136.1%
41
117.1%
Mild
9
6.1%
1
2.9%
Moderate
1
0.7%
0
0%
Severe
0
0%
0
0%
Potentially Life-threatening
0
0%
0
0%
None
195
132.7%
40
114.3%
Mild
14
9.5%
2
5.7%
Moderate
1
0.7%
0
0%
Severe
0
0%
0
0%
Potentially Life-threatening
0
0%
0
0%
None
151
102.7%
33
94.3%
Mild
53
36.1%
8
22.9%
Moderate
4
2.7%
1
2.9%
Severe
2
1.4%
0
0%
Potentially Life-threatening
0
0%
0
0%
None
68
46.3%
16
45.7%
Mild
109
74.1%
18
51.4%
Moderate
31
21.1%
8
22.9%
Severe
2
1.4%
0
0%
Potentially Life-threatening
0
0%
0
0%
None
195
132.7%
41
117.1%
Mild
8
5.4%
0
0%
Moderate
7
4.8%
1
2.9%
Severe
0
0%
0
0%
Potentially Life-threatening
0
0%
0
0%
3. Primary Outcome
Title Part A: Number of Participants With Early Study Termination Associated With an AE or Reactogenicity
Description From the study termination form, early termination reasons associated with an AE or reactogenicity are tabulated by treatment arm
Time Frame Measured through Month 18

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Part A, Group 1: Vaccine Part A, Group 2: Placebo
Arm/Group Description ALVAC-HIV at months 0 and 1, and ALVAC-HIV + bivalent subtype C gp120/MF59 at months 3, 6, and 12 Placebo for ALVAC-HIV at months 0 and 1, and placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at months 3, 6, and 12
Measure Participants 210 42
Termination due to AE/Reactogenicity
4
2.7%
2
5.7%
Other Reasons
206
140.1%
40
114.3%
4. Primary Outcome
Title Part A: Number of Participants With Study Product Discontinuation Associated With an AE or Reactogenicity
Description From the study product discontinuation form, study product administration reasons are tabulated by treatment arm
Time Frame Measured through the Month 12 vaccination

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Part A, Group 1: Vaccine Part A, Group 2: Placebo
Arm/Group Description ALVAC-HIV at months 0 and 1, and ALVAC-HIV + bivalent subtype C gp120/MF59 at months 3, 6, and 12 Placebo for ALVAC-HIV at months 0 and 1, and placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at months 3, 6, and 12
Measure Participants 210 42
Clinical Event
1
0.7%
0
0%
Reactogenicity
1
0.7%
0
0%
Other Reasons
19
12.9%
3
8.6%
No Discontinuation
189
128.6%
39
111.4%
5. Primary Outcome
Title Part A: Chemistry and Hematology Laboratory Results With Grade 1 or Higher
Description Laboratory results are summarized by analyte and timepoint. Analytes and timepoint combinations with no grade 1 or higher results are not shown.
Time Frame Measured during screening for part A, and 2 weeks after each vaccination at Month 0, 1, 3, 6, and 12

Outcome Measure Data

Analysis Population Description
The "overall number of participants analyzed" represents participants enrolled and eligible for laboratory assessment. Participants do not have laboratory assessments if they attended the visit but laboratory specimens were not collected, or they missed the scheduled visit, or they terminated participation in the study prior to the scheduled visit.
Arm/Group Title Part A, Group 1: Vaccine Part A, Group 2: Placebo
Arm/Group Description ALVAC-HIV at months 0 and 1, and ALVAC-HIV + bivalent subtype C gp120/MF59 at months 3, 6, and 12 Placebo for ALVAC-HIV at months 0 and 1, and placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at months 3, 6, and 12
Measure Participants 210 42
WBC (1000/cubic mm)-Screening
0
0%
0
0%
WBC (1000/cubic mm)-Day 14
0
0%
0
0%
WBC (1000/cubic mm)-Day 42
0
0%
0
0%
WBC (1000/cubic mm)-Day 98
0
0%
0
0%
WBC (1000/cubic mm)-Day 182
0
0%
0
0%
WBC (1000/cubic mm)-Day 378
0
0%
0
0%
Neutrophils (1000/cubic mm)-Screening
0
0%
0
0%
Neutrophils (1000/cubic mm)-Day 14
0
0%
0
0%
Neutrophils (1000/cubic mm)-Day 42
0
0%
0
0%
Neutrophils (1000/cubic mm)-Day 98
0
0%
0
0%
Neutrophils (1000/cubic mm)-Day 182
0
0%
0
0%
Neutrophils (1000/cubic mm)-Day 378
0
0%
0
0%
Hemoglobin (g/dL)-Screening
0
0%
0
0%
Hemoglobin (g/dL)-Day 14
0
0%
0
0%
Hemoglobin (g/dL)-Day 42
0
0%
0
0%
Hemoglobin (g/dL)-Day 98
0
0%
0
0%
Hemoglobin (g/dL)-Day 182
0
0%
0
0%
Hemoglobin (g/dL)-Day 378
1
0.7%
0
0%
Lymphocytes (1000/cubic mm)-Screening
0
0%
0
0%
Lymphocytes (1000/cubic mm)-Day 14
0
0%
0
0%
Lymphocytes (1000/cubic mm)-Day 42
0
0%
0
0%
Lymphocytes (1000/cubic mm)-Day 98
0
0%
0
0%
Lymphocytes (1000/cubic mm)-Day 182
0
0%
0
0%
Lymphocytes (1000/cubic mm)-Day 378
0
0%
0
0%
Platelets (1000/cubic mm)-Screening
0
0%
0
0%
Platelets (1000/cubic mm)-Day 14
0
0%
0
0%
Platelets (1000/cubic mm)-Day 42
0
0%
0
0%
Platelets (1000/cubic mm)-Day 98
0
0%
0
0%
Platelets (1000/cubic mm)-Day 182
0
0%
0
0%
Platelets (1000/cubic mm)-Day 378
0
0%
0
0%
ALT (SGPT) (U/L)-Screening
0
0%
0
0%
ALT (SGPT) (U/L)-Day 14
0
0%
0
0%
ALT (SGPT) (U/L)-Day 42
1
0.7%
0
0%
ALT (SGPT) (U/L)-Day 98
1
0.7%
0
0%
ALT (SGPT) (U/L)-Day 182
0
0%
0
0%
ALT (SGPT) (U/L)-Day 378
1
0.7%
0
0%
AST (U/L)-Screening
0
0%
0
0%
AST (U/L)-Day 14
0
0%
0
0%
AST (U/L)-Day 42
2
1.4%
0
0%
AST (U/L)-Day 98
0
0%
0
0%
AST (U/L)-Day 182
0
0%
0
0%
AST (U/L)-Day 378
1
0.7%
0
0%
Alkaline Phosphatase (U/L)-Screening
0
0%
0
0%
Alkaline Phosphatase (U/L)-Day 14
0
0%
0
0%
Alkaline Phosphatase (U/L)-Day 42
0
0%
0
0%
Alkaline Phosphatase (U/L)-Day 98
0
0%
0
0%
Alkaline Phosphatase (U/L)-Day 182
0
0%
0
0%
Alkaline Phosphatase (U/L)-Day 378
0
0%
0
0%
Creatinine (g/dL)-Screening
0
0%
0
0%
Creatinine (g/dL)-Day 14
0
0%
0
0%
Creatinine (g/dL)-Day 42
1
0.7%
0
0%
Creatinine (g/dL)-Day 98
0
0%
0
0%
Creatinine (g/dL)-Day 182
0
0%
0
0%
Creatinine (g/dL)-Day 378
3
2%
0
0%
6. Primary Outcome
Title Part A Chemistry Laboratory Measures: Alkaline Phosphatase, AST, and ALT
Description For each chemistry laboratory measure, summary statistics were presented by analyte and treatment group for the overall population.
Time Frame Time Frame: Measured during screening for part A, and 2 weeks after each vaccination at Month 0, 1, 3, 6, and 12

Outcome Measure Data

Analysis Population Description
The "overall number of participants analyzed" represents participants enrolled and eligible for laboratory assessment. Participants do not have laboratory assessments if they attended the visit but laboratory specimens were not collected, or they missed the scheduled visit, or they terminated participation in the study prior to the scheduled visit.
Arm/Group Title Part A, Group 1: Vaccine Part A, Group 2: Placebo
Arm/Group Description ALVAC-HIV at months 0 and 1, and ALVAC-HIV + bivalent subtype C gp120/MF59 at months 3, 6, and 12 Placebo for ALVAC-HIV at months 0 and 1, and placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at months 3, 6, and 12
Measure Participants 210 42
ALT (SGPT) (U/L)-Screening
17
19
ALT (SGPT) (U/L)-Day 14
17
19
ALT (SGPT) (U/L)-Day 42
19
21
ALT (SGPT) (U/L)-Day 98
18.5
18
ALT (SGPT) (U/L)-Day 182
19
19
ALT (SGPT) (U/L)-Day 378
20
21
AST (U/L)-Screening
22
22
AST (U/L)-Day 14
22
21
AST (U/L)-Day 42
23
23
AST (U/L)-Day 98
23
23
AST (U/L)-Day 182
24
25
AST (U/L)-Day 378
24
22.5
Alkaline Phosphatase (U/L)-Screening
71.5
72.5
Alkaline Phosphatase (U/L)-Day 14
69
71
Alkaline Phosphatase (U/L)-Day 42
70
71
Alkaline Phosphatase (U/L)-Day 98
73
74
Alkaline Phosphatase (U/L)-Day 182
69
70
Alkaline Phosphatase (U/L)-Day 378
72
74.5
7. Primary Outcome
Title Part A Chemistry Laboratory Measures: Hemoglobin, Creatinine
Description For each chemistry laboratory measure, summary statistics were presented by analyte and treatment group for the overall population.
Time Frame Time Frame: Measured during screening for part A, and 2 weeks after each vaccination at Month 0, 1, 3, 6, and 12

Outcome Measure Data

Analysis Population Description
The "overall number of participants analyzed" represents participants enrolled and eligible for laboratory assessment. Participants do not have laboratory assessments if they attended the visit but laboratory specimens were not collected, or they missed the scheduled visit, or they terminated participation in the study prior to the scheduled visit.
Arm/Group Title Part A, Group 1: Vaccine Part A, Group 2: Placebo
Arm/Group Description ALVAC-HIV at months 0 and 1, and ALVAC-HIV + bivalent subtype C gp120/MF59 at months 3, 6, and 12 Placebo for ALVAC-HIV at months 0 and 1, and placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at months 3, 6, and 12
Measure Participants 210 42
Hemoglobin (g/dL)-Screening
14.7
14.4
Hemoglobin (g/dL)-Day 14
14.1
13.4
Hemoglobin (g/dL)-Day 42
14.4
13.75
Hemoglobin (g/dL)-Day 98
14.3
13.5
Hemoglobin (g/dL)-Day 182
14.1
13.9
Hemoglobin (g/dL)-Day 378
13.9
13.4
Creatinine (g/dL)-Screening
0.0007
0.0007
Creatinine (g/dL)-Day 14
0.00077
0.0007
Creatinine (g/dL)-Day 42
0.0007
0.0007
Creatinine (g/dL)-Day 98
0.00073
0.00077
Creatinine (g/dL)-Day 182
0.0008
0.0007
Creatinine (g/dL)-Day 378
0.0008
0.0007
8. Primary Outcome
Title Part A Hematology Laboratory Measures: WBC, Platelets, Lymphocytes, Neutrophils
Description For each chemistry laboratory measure, summary statistics were presented by analyte and treatment group for the overall population.
Time Frame Measured during screening for part A, and 2 weeks after each vaccination at Month 0, 1, 3, 6, and 12

Outcome Measure Data

Analysis Population Description
The "overall number of participants analyzed" represents participants enrolled and eligible for laboratory assessment. Participants do not have laboratory assessments if they attended the visit but laboratory specimens were not collected, or they missed the scheduled visit, or they terminated participation in the study prior to the scheduled visit.
Arm/Group Title Part A, Group 1: Vaccine Part A, Group 2: Placebo
Arm/Group Description ALVAC-HIV at months 0 and 1, and ALVAC-HIV + bivalent subtype C gp120/MF59 at months 3, 6, and 12 Placebo for ALVAC-HIV at months 0 and 1, and placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at months 3, 6, and 12
Measure Participants 210 42
WBC (1000/cubic mm)-Screening
6.135
6.3
WBC (1000/cubic mm)-Day 14
6
5.9
WBC (1000/cubic mm)-Day 42
5.87
5.425
WBC (1000/cubic mm)-Day 98
6.055
5.9
WBC (1000/cubic mm)-Day 182
5.67
5.63
WBC (1000/cubic mm)-Day 378
5.69
5.815
Neutrophils (1000/cubic mm)-Screening
3.23
3.265
Neutrophils (1000/cubic mm)-Day 14
3.18
3.08
Neutrophils (1000/cubic mm)-Day 42
3.057
2.9015
Neutrophils (1000/cubic mm)-Day 98
3.284
3.25
Neutrophils (1000/cubic mm)-Day 182
2.927
2.629
Neutrophils (1000/cubic mm)-Day 378
3.08
3.089
Lymphocytes (1000/cubic mm)-Screening
2.182
2.299
Lymphocytes (1000/cubic mm)-Day 14
2.102
2.064
Lymphocytes (1000/cubic mm)-Day 42
2.0545
2.031
Lymphocytes (1000/cubic mm)-Day 98
1.9435
2.02
Lymphocytes (1000/cubic mm)-Day 182
2.004
1.96
Lymphocytes (1000/cubic mm)-Day 378
2
1.975
Platelets (1000/cubic mm)-Screening
250.5
275
Platelets (1000/cubic mm)-Day 14
265
272
Platelets (1000/cubic mm)-Day 42
267
270
Platelets (1000/cubic mm)-Day 98
267
276
Platelets (1000/cubic mm)-Day 182
259.5
267
Platelets (1000/cubic mm)-Day 378
273
264.5
9. Primary Outcome
Title Part A: Occurrence of IgG Ab Binding to gp120 Env Proteins Contained in the Vaccine (ZM96, TV1.C, 1086.C) After the Primary Vaccine Regimen, Measured by HIV-1 Multiplex Antibody Assay
Description Serum HIV-1-specific IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. Samples from post-enrollment visits have positive responses if they meet three conditions: (1) net MFI greater than or equal to an antigen-specific response threshold (defined as the maximum of 100 and the 95th percentile of pre-vaccination net MFI), (2) net MFI values are greater than 3 times pre-vaccination net MFI, and (3) experimental antigen MFI values are greater than 3 times pre-vaccination MFI. Data are excluded if the blood draw date was outside the allowable window, a participant was HIV-infected, or the reference antigen exceeds 5000 MFI.
Time Frame Measured at Month 6.5

Outcome Measure Data

Analysis Population Description
"Overall Number of Participants Analyzed" includes those with samples collected at the month 6.5 immunogenicity timepoint, who were HIV-uninfected and received the first 4 vaccinations. "Number Analyzed" shows the number of participants with available data after filtering for assay-specific quality control criteria.
Arm/Group Title Part A, Group 1: Vaccine Part A, Group 2: Placebo
Arm/Group Description ALVAC-HIV at months 0 and 1, and ALVAC-HIV + bivalent subtype C gp120/MF59 at months 3, 6, and 12 Placebo for ALVAC-HIV at months 0 and 1, and placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at months 3, 6, and 12
Measure Participants 185 37
1086C_D7gp120.avi/293F
185
125.9%
0
0%
96ZM651.D11gp120.avi
185
125.9%
0
0%
TV1c8_D11gp120.avi/293F
185
125.9%
0
0%
10. Primary Outcome
Title Part A: Level of IgG Ab Binding to gp120 Env Proteins Contained in the Vaccine (ZM96, TV1.C, 1086.C) After the Primary Vaccine Regimen, Measured by HIV-1 Multiplex Antibody Assay
Description Serum HIV-1-specific IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. The measure unit fluorescence units are relative to assay background, not relative to the placebo arm. Background is used here rather than negative control stimulation, since the antigens are used as bead coating rather than stimulation.
Time Frame Measured at Month 6.5

Outcome Measure Data

Analysis Population Description
"Overall Number of Participants Analyzed" includes those with samples collected at the month 6.5 immunogenicity timepoint, who were HIV-uninfected and received the first 4 vaccinations. "Number Analyzed" shows the number of participants with available data after filtering for assay-specific quality control criteria.
Arm/Group Title Part A, Group 1: Vaccine Part A, Group 2: Placebo
Arm/Group Description ALVAC-HIV at months 0 and 1, and ALVAC-HIV + bivalent subtype C gp120/MF59 at months 3, 6, and 12 Placebo for ALVAC-HIV at months 0 and 1, and placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at months 3, 6, and 12
Measure Participants 185 37
1086C_D7gp120.avi/293F
28359.5
1
96ZM651.D11gp120.avi
2650
1
TV1c8_D11gp120.avi/293F
12883.5
1
11. Primary Outcome
Title Part A: Occurrence of IgG Binding Antibodies to 3 V1V2-scaffolded Env Proteins After the Primary Vaccine Regimen
Description Measured by HIV-1 multiplex Ab assay: refer to earlier description for assay methods and analysis variable derivation. The number and percentage of participants with positive responses are summarized by antigen.
Time Frame Measured at Month 6.5

Outcome Measure Data

Analysis Population Description
"Overall Number of Participants Analyzed" includes those with samples collected at the month 6.5 immunogenicity timepoint, who were HIV-uninfected and received the first 4 vaccinations. "Number Analyzed" shows the number of participants with available data after filtering for assay-specific quality control criteria.
Arm/Group Title Part A, Group 1: Vaccine Part A, Group 2: Placebo
Arm/Group Description ALVAC-HIV at months 0 and 1, and ALVAC-HIV + bivalent subtype C gp120/MF59 at months 3, 6, and 12 Placebo for ALVAC-HIV at months 0 and 1, and placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at months 3, 6, and 12
Measure Participants 185 37
C.1086C_V1_V2 Tags
129
87.8%
0
0%
gp70-96ZM651.02 V1v2
88
59.9%
0
0%
gp70-TV1.21 V1V2
113
76.9%
0
0%
12. Primary Outcome
Title Part A: Level of IgG Binding Antibodies to 3 V1V2-scaffolded Env Proteins After the Primary Vaccine Regimen
Description Serum HIV-1-specific IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. The measure unit fluorescence units are relative to assay background, not relative to the placebo arm. Background is used here rather than negative control stimulation, since the antigens are used as bead coating rather than stimulation.
Time Frame Measured at Month 6.5

Outcome Measure Data

Analysis Population Description
"Overall Number of Participants Analyzed" includes those with samples collected at the month 6.5 immunogenicity timepoint, who were HIV-uninfected and received the first 4 vaccinations. "Number Analyzed" shows the number of participants with available data after filtering for assay-specific quality control criteria.
Arm/Group Title Part A, Group 1: Vaccine Part A, Group 2: Placebo
Arm/Group Description ALVAC-HIV at months 0 and 1, and ALVAC-HIV + bivalent subtype C gp120/MF59 at months 3, 6, and 12 Placebo for ALVAC-HIV at months 0 and 1, and placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at months 3, 6, and 12
Measure Participants 185 37
C.1086C_V1_V2 Tags
562
1
gp70-96ZM651.02 V1v2
392.5
1
gp70-TV1.21 V1V2
338.25
1
13. Primary Outcome
Title Part A: Occurrence of CD4+ T Cell Responses to the HIV Proteins Included in the Vaccine After the Primary Vaccine Regimen. Measured by Flow Cytometry.
Description PBMC samples are stimulated with synthetic peptide pools or left unstimulated as a negative control. For each sample, T-cell subset, and peptide pool, response magnitude is % cells expressing markers after peptide stimulation minus % cells expressing markers after no stimulation. A contingency table is constructed to assess response: stimulation (peptide/none) vs. marker expression (yes/no). A one-sided Fisher's exact test is applied, testing if the number of cells positive for the marker is equal in the stimulated vs. unstimulated cells. A discrete Bonferroni adjustment is made over the peptide pools. Response is positive if p<=0.00001. Data are excluded if the blood draw date was outside the visit window, the participant was HIV-infected, PBMC viability or T-cell count were low, or negative control was high.
Time Frame Measured at Month 6.5

Outcome Measure Data

Analysis Population Description
"Overall Number of Participants Analyzed" includes those with samples collected at the month 6.5 immunogenicity timepoint, who were HIV-uninfected and received the first 4 vaccinations. "Number Analyzed" shows the number of participants with available data after filtering for assay-specific quality control criteria.
Arm/Group Title Part A, Group 1: Vaccine Part A, Group 2: Placebo
Arm/Group Description ALVAC-HIV at months 0 and 1, and ALVAC-HIV + bivalent subtype C gp120/MF59 at months 3, 6, and 12 Placebo for ALVAC-HIV at months 0 and 1, and placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at months 3, 6, and 12
Measure Participants 185 37
Any gp120
120
81.6%
1
2.9%
1086 gp120
82
55.8%
1
2.9%
TV1 gp120
112
76.2%
1
2.9%
ZM96 gp120
102
69.4%
0
0%
14. Primary Outcome
Title Part A: Level of CD4+ T Cell Responses to the HIV Proteins Included in the Vaccine After the Primary Vaccine Regimen.
Description Measured by flow cytometry ICS assay: refer to earlier description for assay methods and analysis variable derivation. Percentage of T-cells expressing cytokines are summarized for positive responders only.
Time Frame Measured at Month 6.5

Outcome Measure Data

Analysis Population Description
"Overall Number of Participants Analyzed" includes those with samples collected at the month 6.5 immunogenicity timepoint, who were HIV-uninfected and received the first 4 vaccinations. "Number Analyzed" shows the number of participants with available data after filtering for assay-specific quality control criteria.
Arm/Group Title Part A, Group 1: Vaccine Part A, Group 2: Placebo
Arm/Group Description ALVAC-HIV at months 0 and 1, and ALVAC-HIV + bivalent subtype C gp120/MF59 at months 3, 6, and 12 Placebo for ALVAC-HIV at months 0 and 1, and placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at months 3, 6, and 12
Measure Participants 185 37
Any gp120
0.11501130
0.003579320
1086 gp120
0.06613413
-0.00296204
TV1 gp120
0.09629575
-0.002244635
ZM96 gp120
0.0889934
-0.002505630
15. Primary Outcome
Title Part B: Number of Participants Reporting Local Reactogenicity Signs and Symptoms in the Extension Study
Description Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [March 2017]. For each participant, the maximum grade observed for each symptom over the time frame is presented.
Time Frame Measured through 3 days after the Month 30 vaccination

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Part B, Group 1a: Vaccine Part B, Group 1b: Vaccine/Placebo Part B, Group 2: Placebo
Arm/Group Description Participants originally in Part A Group 1 (Vaccine) receive ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 1 (Vaccine) receive placebo for ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 2 (Placebo) receive placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at month 30
Measure Participants 32 31 7
None
16
10.9%
18
51.4%
7
21.9%
Mild
12
8.2%
11
31.4%
0
0%
Moderate
4
2.7%
2
5.7%
0
0%
Severe
0
0%
0
0%
0
0%
Life Threatening
0
0%
0
0%
0
0%
None
21
14.3%
25
71.4%
7
21.9%
Mild
7
4.8%
5
14.3%
0
0%
Moderate
4
2.7%
1
2.9%
0
0%
Severe
0
0%
0
0%
0
0%
Life Threatening
0
0%
0
0%
0
0%
None
14
9.5%
17
48.6%
7
21.9%
Mild
11
7.5%
12
34.3%
0
0%
Moderate
7
4.8%
2
5.7%
0
0%
Severe
0
0%
0
0%
0
0%
Life Threatening
0
0%
0
0%
0
0%
None
28
19%
27
77.1%
7
21.9%
Mild
1
0.7%
3
8.6%
0
0%
Moderate
3
2%
1
2.9%
0
0%
Severe
0
0%
0
0%
0
0%
Life Threatening
0
0%
0
0%
0
0%
None
28
19%
25
71.4%
7
21.9%
Mild
1
0.7%
4
11.4%
0
0%
Moderate
2
1.4%
1
2.9%
0
0%
Severe
1
0.7%
1
2.9%
0
0%
Life Threatening
0
0%
0
0%
0
0%
None
28
19%
24
68.6%
7
21.9%
Mild
0
0%
4
11.4%
0
0%
Moderate
3
2%
2
5.7%
0
0%
Severe
1
0.7%
1
2.9%
0
0%
Life Threatening
0
0%
0
0%
0
0%
16. Primary Outcome
Title Part B: Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms in the Extension Study
Description Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [March 2017]. For each participant, the maximum grade observed for each symptom over the time frame is presented.
Time Frame Measured through 3 days after the Month 30 vaccination

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Part B, Group 1a: Vaccine Part B, Group 1b: Vaccine/Placebo Part B, Group 2: Placebo
Arm/Group Description Participants originally in Part A Group 1 (Vaccine) receive ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 1 (Vaccine) receive placebo for ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 2 (Placebo) receive placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at month 30
Measure Participants 32 31 7
None
21
14.3%
24
68.6%
7
21.9%
Mild
9
6.1%
7
20%
0
0%
Moderate
2
1.4%
0
0%
0
0%
Severe
0
0%
0
0%
0
0%
Potentially Life-threatening
0
0%
0
0%
0
0%
None
21
14.3%
24
68.6%
7
21.9%
Mild
7
4.8%
7
20%
0
0%
Moderate
4
2.7%
0
0%
0
0%
Severe
0
0%
0
0%
0
0%
Potentially Life-threatening
0
0%
0
0%
0
0%
None
26
17.7%
29
82.9%
6
18.8%
Mild
6
4.1%
2
5.7%
1
3.1%
Moderate
0
0%
0
0%
0
0%
Severe
0
0%
0
0%
0
0%
Potentially Life-threatening
0
0%
0
0%
0
0%
None
31
21.1%
30
85.7%
7
21.9%
Mild
1
0.7%
1
2.9%
0
0%
Moderate
0
0%
0
0%
0
0%
Severe
0
0%
0
0%
0
0%
Potentially Life-threatening
0
0%
0
0%
0
0%
None
32
21.8%
30
85.7%
7
21.9%
Mild
0
0%
1
2.9%
0
0%
Moderate
0
0%
0
0%
0
0%
Severe
0
0%
0
0%
0
0%
Potentially Life-threatening
0
0%
0
0%
0
0%
None
28
19%
29
82.9%
7
21.9%
Mild
4
2.7%
2
5.7%
0
0%
Moderate
0
0%
0
0%
0
0%
Severe
0
0%
0
0%
0
0%
Potentially Life-threatening
0
0%
0
0%
0
0%
None
25
17%
28
80%
7
21.9%
Mild
6
4.1%
3
8.6%
0
0%
Moderate
1
0.7%
0
0%
0
0%
Severe
0
0%
0
0%
0
0%
Potentially Life-threatening
0
0%
0
0%
0
0%
None
16
10.9%
21
60%
6
18.8%
Mild
11
7.5%
10
28.6%
1
3.1%
Moderate
5
3.4%
0
0%
0
0%
Severe
0
0%
0
0%
0
0%
Potentially Life-threatening
0
0%
0
0%
0
0%
None
32
21.8%
31
88.6%
7
21.9%
Mild
0
0%
0
0%
0
0%
Moderate
0
0%
0
0%
0
0%
Severe
0
0%
0
0%
0
0%
Potentially Life-threatening
0
0%
0
0%
0
0%
17. Primary Outcome
Title Part B: Number of Participants With Early Study Termination Associated With an AE or Reactogenicity
Description From the study termination form, early termination reasons associated with an AE are tabulated by treatment arm
Time Frame Measured through Month 36

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Part B, Group 1a: Vaccine Part B, Group 1b: Vaccine/Placebo Part B, Group 2: Placebo
Arm/Group Description Participants originally in Part A Group 1 (Vaccine) receive ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 1 (Vaccine) receive placebo for ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 2 (Placebo) receive placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at month 30
Measure Participants 32 31 7
Termination not due to AE/Reactogenicity
0
0%
0
0%
0
0%
Other reason
32
21.8%
31
88.6%
7
21.9%
18. Primary Outcome
Title Part B: Chemistry and Hematology Laboratory Results of Grade 1 or Higher
Description Laboratory results are summarized by analyte and timepoint. Analytes and timepoint combinations with no grade 1 or higher results are not shown.
Time Frame Time Frame: Measured during screening for part B, and 2 weeks after vaccination at Month 30

Outcome Measure Data

Analysis Population Description
The "overall number of participants analyzed" represents participants enrolled and eligible for laboratory assessment. Participants do not have laboratory assessments if they attended the visit but laboratory specimens were not collected, or they missed the scheduled visit, or they terminated participation in the study prior to the scheduled visit.
Arm/Group Title Part B, Group 1a: Vaccine Part B, Group 1b: Vaccine/Placebo Part B, Group 2: Placebo
Arm/Group Description Participants originally in Part A Group 1 (Vaccine) receive ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 1 (Vaccine) receive placebo for ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 2 (Placebo) receive placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at month 30
Measure Participants 32 31 7
WBC (1000/cubic mm)-Part B Screening
0
0%
0
0%
0
0%
WBC (1000/cubic mm)-Day 924
0
0%
0
0%
0
0%
Neutrophils (1000/cubic mm)-Part B Screening
0
0%
0
0%
0
0%
Neutrophils (1000/cubic mm)-Day 924
0
0%
0
0%
0
0%
Hemoglobin (g/dL)-Part B Screening
0
0%
0
0%
0
0%
Hemoglobin (g/dL)-Day 924
0
0%
0
0%
0
0%
Lymphocytes (1000/cubic mm)-Part B Screening
0
0%
0
0%
0
0%
Lymphocytes (1000/cubic mm)-Day 924
0
0%
0
0%
0
0%
Platelets (1000/cubic mm)-Part B Screening
0
0%
0
0%
0
0%
Platelets (1000/cubic mm)-Day 924
0
0%
0
0%
0
0%
ALT (SGPT) (U/L)-Part B Screening
0
0%
0
0%
0
0%
ALT (SGPT) (U/L)-Day 924
0
0%
0
0%
0
0%
AST (U/L)-Part B Screening
0
0%
0
0%
0
0%
AST (U/L)-Day 924
0
0%
0
0%
0
0%
Alkaline Phosphatase (U/L)-Part B Screening
0
0%
0
0%
0
0%
Alkaline Phosphatase (U/L)-Day 924
0
0%
0
0%
0
0%
Creatinine (g/dL)-Part B Screening
1
0.7%
2
5.7%
0
0%
Creatinine (g/dL)-Day 924
1
0.7%
6
17.1%
1
3.1%
19. Primary Outcome
Title Part B Chemistry Laboratory Measures: Alkaline Phosphatase, AST, and ALT
Description For each chemistry laboratory measure, summary statistics were presented by analyte and treatment group for the overall population.
Time Frame Measured during screening for part B, and 2 weeks after vaccination at Month 30

Outcome Measure Data

Analysis Population Description
The "overall number of participants analyzed" represents participants enrolled and eligible for laboratory assessment. Participants do not have laboratory assessments if they attended the visit but laboratory specimens were not collected, or they missed the scheduled visit, or they terminated participation in the study prior to the scheduled visit.
Arm/Group Title Part B, Group 1a: Vaccine Part B, Group 1b: Vaccine/Placebo Part B, Group 2: Placebo
Arm/Group Description Participants originally in Part A Group 1 (Vaccine) receive ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 1 (Vaccine) receive placebo for ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 2 (Placebo) receive placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at month 30
Measure Participants 32 31 7
ALT (SGPT) (U/L)-Part B Screening
17
18
20
ALT (SGPT) (U/L)-Day 924
16
15
16.5
AST (U/L)-Part B Screening
22.5
23
20
AST (U/L)-Day 924
20.5
21
22
Alkaline Phosphatase (U/L)-Part B Screening
73
74
68
Alkaline Phosphatase (U/L)-Day 924
76.5
69
59.5
20. Primary Outcome
Title Part B Chemistry Laboratory Measures: Hemoglobin, Creatinine
Description For each chemistry laboratory measure, summary statistics were presented by analyte and treatment group for the overall population.
Time Frame Measured during screening for part B, and 2 weeks after vaccination at Month 30

Outcome Measure Data

Analysis Population Description
The "overall number of participants analyzed" represents participants enrolled and eligible for laboratory assessment. Participants do not have laboratory assessments if they attended the visit but laboratory specimens were not collected, or they missed the scheduled visit, or they terminated participation in the study prior to the scheduled visit.
Arm/Group Title Part B, Group 1a: Vaccine Part B, Group 1b: Vaccine/Placebo Part B, Group 2: Placebo
Arm/Group Description Participants originally in Part A Group 1 (Vaccine) receive ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 1 (Vaccine) receive placebo for ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 2 (Placebo) receive placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at month 30
Measure Participants 32 31 7
Hemoglobin (g/dL)-Part B Screening
14.85
14.6
13.8
Hemoglobin (g/dL)-Day 924
14.65
13.965
13.7
Creatinine (g/dL)-Part B Screening
0.00085
0.0007
0.0007
Creatinine (g/dL)-Day 924
0.0009
0.0008
0.00075
21. Primary Outcome
Title Part B Chemistry Laboratory Measures: WBC, Platelets, Lymphocytes, Neutrophils
Description For each chemistry laboratory measure, summary statistics were presented by analyte and treatment group for the overall population.
Time Frame Measured during screening for part B, and 2 weeks after vaccination at Month 30

Outcome Measure Data

Analysis Population Description
The "overall number of participants analyzed" represents participants enrolled and eligible for laboratory assessment. Participants do not have laboratory assessments if they attended the visit but laboratory specimens were not collected, or they missed the scheduled visit, or they terminated participation in the study prior to the scheduled visit.
Arm/Group Title Part B, Group 1a: Vaccine Part B, Group 1b: Vaccine/Placebo Part B, Group 2: Placebo
Arm/Group Description Participants originally in Part A Group 1 (Vaccine) receive ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 1 (Vaccine) receive placebo for ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 2 (Placebo) receive placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at month 30
Measure Participants 32 31 7
WBC (1000/cubic mm)-Part B Screening
6.4
6.59
7.1
WBC (1000/cubic mm)-Day 924
6.28
6.355
6.505
Neutrophils (1000/cubic mm)-Part B Screening
3.499
3.41
3.38
Neutrophils (1000/cubic mm)-Day 924
3.577
3.7825
3.031
Lymphocytes (1000/cubic mm)-Part B Screening
2.2295
1.941
2.559
Lymphocytes (1000/cubic mm)-Day 924
2.031
1.9295
2.541
Platelets (1000/cubic mm)-Part B Screening
264
256
311
Platelets (1000/cubic mm)-Day 924
279
248.5
281.5
22. Primary Outcome
Title Part B: Occurrence of IgG Binding Antibodies to 3 V1V2-scaffolded Env Proteins in the Extension Study
Description Measured by HIV-1 multiplex Ab assay: refer to earlier description for assay methods and analysis variable derivation. The number and percentage of participants with positive responses are summarized by antigen.
Time Frame Measured at Month 30.5

Outcome Measure Data

Analysis Population Description
"Overall Number of Participants Analyzed" includes those with samples collected at month 30.5, who were HIV-uninfected and received the all vaccinations. "Number Analyzed" counts participants with available data after filtering for assay-specific quality control criteria.
Arm/Group Title Part B, Group 1a: Vaccine Part B, Group 1b: Vaccine/Placebo Part B, Group 2: Placebo
Arm/Group Description Participants originally in Part A Group 1 (Vaccine) receive ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 1 (Vaccine) receive placebo for ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 2 (Placebo) receive placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at month 30
Measure Participants 28 30 6
C.1086C_V1_V2 Tags
19
12.9%
23
65.7%
0
0%
gp70-96ZM651.02 V1v2
14
9.5%
15
42.9%
0
0%
gp70-TV1.GSKvacV1V2/293F
15
10.2%
18
51.4%
0
0%
23. Primary Outcome
Title Part B: Level of IgG Binding Antibodies to 3 V1V2-scaffolded Env Proteins in the Extension Study
Description Serum HIV-1-specific IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. The measure unit fluorescence units are relative to assay background, not relative to the placebo arm. Background is used here rather than negative control stimulation, since the antigens are used as bead coating rather than stimulation.
Time Frame Measured at Month 30.5

Outcome Measure Data

Analysis Population Description
"Overall Number of Participants Analyzed" includes those with samples collected at month 30.5, who were HIV-uninfected and received the all vaccinations. "Number Analyzed" counts participants with available data after filtering for assay-specific quality control criteria.
Arm/Group Title Part B, Group 1a: Vaccine Part B, Group 1b: Vaccine/Placebo Part B, Group 2: Placebo
Arm/Group Description Participants originally in Part A Group 1 (Vaccine) receive ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 1 (Vaccine) receive placebo for ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 2 (Placebo) receive placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at month 30
Measure Participants 28 30 6
C.1086C_V1_V2 Tags
527.375
562.25
1
gp70-96ZM651.02 V1v2
858.125
1015.625
1
gp70-TV1.GSKvacV1V2/293F
924.75
1537
1
24. Primary Outcome
Title Part B: Occurrence of IgG Ab Binding to gp120 Env Proteins Contained in the Vaccine (ZM96, TV1.C, 1086.C) in the Extension Study
Description Measured by HIV-1 multiplex Ab assay: refer to earlier description for assay methods and analysis variable derivation. The number and percentage of participants with positive responses are summarized by antigen.
Time Frame Measured at Month 30.5

Outcome Measure Data

Analysis Population Description
"Overall Number of Participants Analyzed" includes those with samples collected at month 30.5, who were HIV-uninfected and received the all vaccinations. "Number Analyzed" counts participants with available data after filtering for assay-specific quality control criteria.
Arm/Group Title Part B, Group 1a: Vaccine Part B, Group 1b: Vaccine/Placebo Part B, Group 2: Placebo
Arm/Group Description Participants originally in Part A Group 1 (Vaccine) receive ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 1 (Vaccine) receive placebo for ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 2 (Placebo) receive placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at month 30
Measure Participants 28 30 6
1086C_D7gp120.avi/293F
26
17.7%
30
85.7%
0
0%
96ZM651.D11gp120.avi
25
17%
29
82.9%
0
0%
TV1c8_D11gp120.avi/293F
26
17.7%
30
85.7%
0
0%
25. Primary Outcome
Title Part B: Level of IgG Ab Binding to gp120 Env Proteins Contained in the Vaccine (ZM96, TV1.C, 1086.C) in the Extension Study
Description Serum HIV-1-specific IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. The measure unit fluorescence units are relative to assay background, not relative to the placebo arm. Background is used here rather than negative control stimulation, since the antigens are used as bead coating rather than stimulation.
Time Frame Measured at Month 30.5

Outcome Measure Data

Analysis Population Description
"Overall Number of Participants Analyzed" includes those with samples collected at month 30.5, who were HIV-uninfected and received the all vaccinations. "Number Analyzed" counts participants with available data after filtering for assay-specific quality control criteria.
Arm/Group Title Part B, Group 1a: Vaccine Part B, Group 1b: Vaccine/Placebo Part B, Group 2: Placebo
Arm/Group Description Participants originally in Part A Group 1 (Vaccine) receive ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 1 (Vaccine) receive placebo for ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 2 (Placebo) receive placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at month 30
Measure Participants 28 30 6
1086C_D7gp120.avi/293F
31063.875
30887.75
1
96ZM651.D11gp120.avi
30006.875
30137.5
1
TV1c8_D11gp120.avi/293F
30864.875
30674.125
1
26. Primary Outcome
Title Part B: Occurrence of CD4+ T Cell Responses to the HIV Proteins Included in the Vaccine in the Extension Study
Description Measured by flow cytometry ICS assay: refer to earlier description for assay methods and analysis variable derivation. The number and percentage of participants with positive responses are summarized by peptide pool.
Time Frame Measured at Month 30.5

Outcome Measure Data

Analysis Population Description
"Overall Number of Participants Analyzed" includes those with samples collected at month 30.5, who were HIV-uninfected and received the all vaccinations. "Number Analyzed" counts participants with available data after filtering for assay-specific quality control criteria.
Arm/Group Title Part B, Group 1a: Vaccine Part B, Group 1b: Vaccine/Placebo Part B, Group 2: Placebo
Arm/Group Description Participants originally in Part A Group 1 (Vaccine) receive ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 1 (Vaccine) receive placebo for ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 2 (Placebo) receive placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at month 30
Measure Participants 28 30 6
Any gp120
25
17%
26
74.3%
0
0%
1086 gp120
22
15%
23
65.7%
0
0%
TV1 gp120
24
16.3%
25
71.4%
0
0%
ZM96 gp120
23
15.6%
22
62.9%
0
0%
27. Primary Outcome
Title Part B: Level of CD4+ T Cell Responses to the HIV Proteins Included in the Vaccine in the Extension Study
Description Measured by flow cytometry ICS assay: refer to earlier description for assay methods and analysis variable derivation. Percentage of T-cells expressing cytokines are summarized for positive responders only.
Time Frame Measured at Month 30.5

Outcome Measure Data

Analysis Population Description
"Overall Number of Participants Analyzed" includes those with samples collected at month 30.5, who were HIV-uninfected and received the all vaccinations. "Number Analyzed" counts participants with available data after filtering for assay-specific quality control criteria.
Arm/Group Title Part B, Group 1a: Vaccine Part B, Group 1b: Vaccine/Placebo Part B, Group 2: Placebo
Arm/Group Description Participants originally in Part A Group 1 (Vaccine) receive ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 1 (Vaccine) receive placebo for ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 2 (Placebo) receive placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at month 30
Measure Participants 28 30 6
Any gp120
0.284956245
0.18676016
0.00889506
1086 gp120
0.1299094
0.11812899
-0.00507644
TV1 gp120
0.23924445
0.180244495
0.00889506
ZM96 gp120
0.25434725
0.13517637
-0.00325229
28. Secondary Outcome
Title Part A: Frequency of Severe Local Reactogenicity Signs and Symptoms, Through the Fifth Vaccination
Description Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [March 2017]. The maximum grade observed for each symptom over the time frame is presented.
Time Frame Measured through 3 days after each vaccination at Month 0, 1, 3, 6, and 12

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Part A, Group 1: Vaccine Part A, Group 2: Placebo
Arm/Group Description ALVAC-HIV at months 0 and 1, and ALVAC-HIV + bivalent subtype C gp120/MF59 at months 3, 6, and 12 Placebo for ALVAC-HIV at months 0 and 1, and placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at months 3, 6, and 12
Measure Participants 210 42
None
37
25.2%
24
68.6%
Mild
120
81.6%
17
48.6%
Moderate
50
34%
1
2.9%
Severe
3
2%
0
0%
Life Threatening
0
0%
0
0%
None
60
40.8%
33
94.3%
Mild
114
77.6%
8
22.9%
Moderate
35
23.8%
1
2.9%
Severe
1
0.7%
0
0%
Life Threatening
0
0%
0
0%
None
30
20.4%
24
68.6%
Mild
123
83.7%
17
48.6%
Moderate
54
36.7%
1
2.9%
Severe
3
2%
0
0%
Life Threatening
0
0%
0
0%
None
196
133.3%
42
120%
Mild
8
5.4%
0
0%
Moderate
3
2%
0
0%
Severe
3
2%
0
0%
Life Threatening
0
0%
0
0%
None
178
121.1%
42
120%
Mild
17
11.6%
0
0%
Moderate
12
8.2%
0
0%
Severe
3
2%
0
0%
Life Threatening
0
0%
0
0%
None
176
119.7%
42
120%
Mild
17
11.6%
0
0%
Moderate
14
9.5%
0
0%
Severe
3
2%
0
0%
Life Threatening
0
0%
0
0%
29. Secondary Outcome
Title Part A: Frequency of Severe Systemic Reactogenicity Signs and Symptoms, Through the Fifth Vaccination
Description Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [March 2017]. The maximum grade observed for each symptom over the time frame is presented.
Time Frame Measured through 3 days after each vaccination at Month 0, 1, 3, 6, and 12

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Part A, Group 1: Vaccine Part A, Group 2: Placebo
Arm/Group Description ALVAC-HIV at months 0 and 1, and ALVAC-HIV + bivalent subtype C gp120/MF59 at months 3, 6, and 12 Placebo for ALVAC-HIV at months 0 and 1, and placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at months 3, 6, and 12
Measure Participants 210 42
None
121
82.3%
26
74.3%
Mild
74
50.3%
14
40%
Moderate
15
10.2%
1
2.9%
Severe
0
0%
1
2.9%
Potentially Life-threatening
0
0%
0
0%
None
124
84.4%
34
97.1%
Mild
64
43.5%
7
20%
Moderate
22
15%
1
2.9%
Severe
0
0%
0
0%
Potentially Life-threatening
0
0%
0
0%
None
130
88.4%
19
54.3%
Mild
62
42.2%
17
48.6%
Moderate
17
11.6%
6
17.1%
Severe
1
0.7%
0
0%
Potentially Life-threatening
0
0%
0
0%
None
174
118.4%
38
108.6%
Mild
34
23.1%
4
11.4%
Moderate
2
1.4%
0
0%
Severe
0
0%
0
0%
Potentially Life-threatening
0
0%
0
0%
None
200
136.1%
41
117.1%
Mild
9
6.1%
1
2.9%
Moderate
1
0.7%
0
0%
Severe
0
0%
0
0%
Potentially Life-threatening
0
0%
0
0%
None
187
127.2%
40
114.3%
Mild
21
14.3%
2
5.7%
Moderate
2
1.4%
0
0%
Severe
0
0%
0
0%
Potentially Life-threatening
0
0%
0
0%
None
143
97.3%
33
94.3%
Mild
57
38.8%
8
22.9%
Moderate
8
5.4%
1
2.9%
Severe
2
1.4%
0
0%
Potentially Life-threatening
0
0%
0
0%
None
63
42.9%
14
40%
Mild
104
70.7%
19
54.3%
Moderate
40
27.2%
8
22.9%
Severe
3
2%
1
2.9%
Potentially Life-threatening
0
0%
0
0%
None
192
130.6%
41
117.1%
Mild
11
7.5%
0
0%
Moderate
7
4.8%
1
2.9%
Severe
0
0%
0
0%
Potentially Life-threatening
0
0%
0
0%
30. Secondary Outcome
Title Part A: Compare the Occurrence of IgG Ab Binding to gp120 Env Proteins Contained in the Vaccine (ZM96, TV1.C, 1086.C) After the Fourth Versus the Fifth Vaccination
Description Serum HIV-1-specific IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. Samples from post-enrollment visits have positive responses if they meet three conditions: (1) net MFI greater than or equal to an antigen-specific response threshold (defined as the maximum of 100 and the 95th percentile of pre-vaccination net MFI), (2) net MFI values are greater than 3 times pre-vaccination net MFI, and (3) experimental antigen MFI values are greater than 3 times pre-vaccination MFI. Data are excluded if the blood draw date was outside the allowable window, a participant was HIV-infected, or the reference antigen exceeds 5000 MFI.
Time Frame Measured at Month 6.5 and 12.5

Outcome Measure Data

Analysis Population Description
The durability cohort was randomly selected from those in the month 6.5 cohort with samples collected at month 12.5. Selection was stratified by gender to match the overall protocol. "Overall Number of Participants Analyzed" represents the durability cohort. "Number Analyzed" counts participants with data meeting assay-specific quality criteria.
Arm/Group Title Part A, Group 1: Vaccine
Arm/Group Description ALVAC-HIV at months 0 and 1, and ALVAC-HIV + bivalent subtype C gp120/MF59 at months 3, 6, and 12
Measure Participants 65
1086C_D7gp120.avi/293F (Month 6.5)
64
43.5%
1086C_D7gp120.avi/293F (Month 12.5)
64
43.5%
96ZM651.D11gp120.avi (Month 6.5)
59
40.1%
96ZM651.D11gp120.avi (Month 12.5)
59
40.1%
TV1c8_D11gp120.avi/293F (Month 6.5)
64
43.5%
TV1c8_D11gp120.avi/293F (Month 12.5)
64
43.5%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part A, Group 1: Vaccine
Comments IgG Ab binding to 1086C_D7gp120.avi/293F after the fourth (month 6.5) versus the fifth vaccination (month 12.5)
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 1.0000
Comments The threshold for statistical significance was p = 0.05.
Method McNemar
Comments
Method of Estimation Estimation Parameter Proportion Difference (Net)
Estimated Value -0.015
Confidence Interval (2-Sided) %
to
Parameter Dispersion Type:
Value:
Estimation Comments Difference = Month 12.5 (5th vaccination) - Month 6.5 (4th vaccination)
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part A, Group 1: Vaccine
Comments IgG Ab binding to 96ZM651.D11gp120.avi after the fourth (month 6.5) versus the fifth vaccination (month 12.5)
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 1.0000
Comments The threshold for statistical significance was p = 0.05.
Method McNemar
Comments
Method of Estimation Estimation Parameter Proportion Difference (Net)
Estimated Value -0.015
Confidence Interval (2-Sided) %
to
Parameter Dispersion Type:
Value:
Estimation Comments Difference = Month 12.5 (5th vaccination) - Month 6.5 (4th vaccination)
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part A, Group 1: Vaccine
Comments IgG Ab binding to TV1c8_D11gp120.avi/293F after the fourth (month 6.5) versus the fifth vaccination (month 12.5)
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 1.0000
Comments The threshold for statistical significance was p = 0.05.
Method McNemar
Comments
Method of Estimation Estimation Parameter Proportion Difference (Net)
Estimated Value -0.015
Confidence Interval (2-Sided) %
to
Parameter Dispersion Type:
Value:
Estimation Comments Difference = Month 12.5 (5th vaccination) - Month 6.5 (4th vaccination)
31. Secondary Outcome
Title Part A: Compare the Level of IgG Ab Binding to gp120 Env Proteins Contained in the Vaccine (ZM96, TV1.C, 1086.C) After the Fourth Versus the Fifth Vaccination
Description Serum HIV-1-specific IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. The measure unit fluorescence units are relative to assay background, not relative to the placebo arm. Background is used here rather than negative control stimulation, since the antigens are used as bead coating rather than stimulation. Comparisons were performed among positive responders only (positivity criteria is described in Outcome 30).
Time Frame Measured at Month 6.5 and 12.5

Outcome Measure Data

Analysis Population Description
The durability cohort was randomly selected from those in the month 6.5 cohort with samples collected at month 12.5. Selection was stratified by gender to match the overall protocol. "Overall Number of Participants Analyzed" represents the durability cohort. "Number Analyzed" counts participants with data meeting assay-specific quality criteria.
Arm/Group Title Part A, Group 1: Vaccine
Arm/Group Description ALVAC-HIV at months 0 and 1, and ALVAC-HIV + bivalent subtype C gp120/MF59 at months 3, 6, and 12
Measure Participants 65
1086C_D7gp120.avi/293F (Month 6.5)
29317.375
1086C_D7gp120.avi/293F (Month 12.5)
31407.349999
96ZM651.D11gp120.avi (Month 6.5)
26437.25
96ZM651.D11gp120.avi (Month 12.5)
31378.5
TV1c8_D11gp120.avi/293F (Month 6.5)
28365.625
TV1c8_D11gp120.avi/293F (Month 12.5)
31425.5
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part A, Group 1: Vaccine
Comments IgG Ab binding to 1086C_D7gp120.avi/293F after the fourth (month 6.5) versus the fifth vaccination (month 12.5)
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value <.0001
Comments The threshold for statistical significance was p = 0.05.
Method Wilcoxon Signed-Rank
Comments
Method of Estimation Estimation Parameter Geometric Mean difference (Net)
Estimated Value 0.914
Confidence Interval (2-Sided) %
to
Parameter Dispersion Type:
Value:
Estimation Comments Difference = Month 12.5 (5th vaccination) - Month 6.5 (4th vaccination)
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part A, Group 1: Vaccine
Comments IgG Ab binding to 96ZM651.D11gp120.avi after the fourth (month 6.5) versus the fifth vaccination (month 12.5)
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value <.0001
Comments The threshold for statistical significance was p = 0.05.
Method Wilcoxon Signed-Rank
Comments
Method of Estimation Estimation Parameter Geometric Mean difference (Net)
Estimated Value 0.945
Confidence Interval (2-Sided) %
to
Parameter Dispersion Type:
Value:
Estimation Comments Difference = Month 12.5 (5th vaccination) - Month 6.5 (4th vaccination)
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part A, Group 1: Vaccine
Comments IgG Ab binding to TV1c8_D11gp120.avi/293F after the fourth (month 6.5) versus the fifth vaccination (month 12.5)
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value <.0001
Comments The threshold for statistical significance was p = 0.05.
Method Wilcoxon Signed-Rank
Comments
Method of Estimation Estimation Parameter Geometric Mean difference (Net)
Estimated Value 0.895
Confidence Interval (2-Sided) %
to
Parameter Dispersion Type:
Value:
Estimation Comments Difference = Month 12.5 (5th vaccination) - Month 6.5 (4th vaccination)
32. Secondary Outcome
Title Part A: Compare the Occurrence of IgG Binding Antibodies to 3 V1V2-scaffolded Env Proteins After the Fourth Versus the Fifth Vaccination
Description Serum HIV-1-specific IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. Samples from post-enrollment visits have positive responses if they meet three conditions: (1) net MFI greater than or equal to an antigen-specific response threshold (defined as the maximum of 100 and the 95th percentile of pre-vaccination net MFI), (2) net MFI values are greater than 3 times pre-vaccination net MFI, and (3) experimental antigen MFI values are greater than 3 times pre-vaccination MFI. Data are excluded if the blood draw date was outside the allowable window, a participant was HIV-infected, or the reference antigen exceeds 5000 MFI.
Time Frame Measured at Month 6.5 and 12.5

Outcome Measure Data

Analysis Population Description
The durability cohort was randomly selected from those in the month 6.5 cohort with samples collected at month 12.5. Selection was stratified by gender to match the overall protocol. "Overall Number of Participants Analyzed" represents the durability cohort. "Number Analyzed" counts participants with data meeting assay-specific quality criteria.
Arm/Group Title Part A, Group 1: Vaccine
Arm/Group Description ALVAC-HIV at months 0 and 1, and ALVAC-HIV + bivalent subtype C gp120/MF59 at months 3, 6, and 12
Measure Participants 65
C.1086C_V1_V2 Tags (Month 6.5)
49
33.3%
C.1086C_V1_V2 Tags (Month 12.5)
57
38.8%
gp70-96ZM651.02 V1v2 (Month 6.5)
29
19.7%
gp70-96ZM651.02 V1v2 (Month 12.5)
44
29.9%
gp70-TV1.GSKvacV1V2/293F (Month 6.5)
36
24.5%
gp70-TV1.GSKvacV1V2/293F (Month 12.5)
50
34%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part A, Group 1: Vaccine
Comments IgG Ab binding to C.1086C_V1_V2 Tags after the fourth (month 6.5) versus the fifth vaccination (month 12.5)
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.0215
Comments The threshold for statistical significance was p = 0.05.
Method McNemar
Comments
Method of Estimation Estimation Parameter Proportion Difference (Net)
Estimated Value 0
Confidence Interval (2-Sided) %
to
Parameter Dispersion Type:
Value:
Estimation Comments Difference = Month 12.5 (5th vaccination) - Month 6.5 (4th vaccination)
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part A, Group 1: Vaccine
Comments IgG Ab binding to gp70-96ZM651.02 V1v2 after the fourth (month 6.5) versus the fifth vaccination (month 12.5)
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.0003
Comments The threshold for statistical significance was p = 0.05.
Method McNemar
Comments
Method of Estimation Estimation Parameter Proportion Difference (Net)
Estimated Value 0
Confidence Interval (2-Sided) %
to
Parameter Dispersion Type:
Value:
Estimation Comments Difference = Month 12.5 (5th vaccination) - Month 6.5 (4th vaccination)
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part A, Group 1: Vaccine
Comments IgG Ab binding to gp70-TV1.GSKvacV1V2/293F after the fourth (month 6.5) versus the fifth vaccination (month 12.5)
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.0010
Comments The threshold for statistical significance was p = 0.05.
Method McNemar
Comments
Method of Estimation Estimation Parameter Proportion Difference (Net)
Estimated Value 0.228
Confidence Interval (2-Sided) %
to
Parameter Dispersion Type:
Value:
Estimation Comments Difference = Month 12.5 (5th vaccination) - Month 6.5 (4th vaccination)
33. Secondary Outcome
Title Part A: Compare the Level of IgG Binding Antibodies to 3 V1V2-scaffolded Env Proteins After the Fourth Versus the Fifth Vaccination
Description Serum HIV-1-specific IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. The measure unit fluorescence units are relative to assay background, not relative to the placebo arm. Background is used here rather than negative control stimulation, since the antigens are used as bead coating rather than stimulation. Comparisons were performed among positive responders only (positivity criteria is described in Outcome 32).
Time Frame Measured at Month 6.5 and 12.5

Outcome Measure Data

Analysis Population Description
The durability cohort was randomly selected from those in the month 6.5 cohort with samples collected at month 12.5. Selection was stratified by gender to match the overall protocol. "Overall Number of Participants Analyzed" represents the durability cohort. "Number Analyzed" counts participants with data meeting assay-specific quality criteria.
Arm/Group Title Part A, Group 1: Vaccine
Arm/Group Description ALVAC-HIV at months 0 and 1, and ALVAC-HIV + bivalent subtype C gp120/MF59 at months 3, 6, and 12
Measure Participants 65
C.1086C_V1_V2 Tags (Month 6.5)
1281.5
C.1086C_V1_V2 Tags (Month 12.5)
2938.5
gp70-96ZM651.02 V1v2 (Month 6.5)
1747.5
gp70-96ZM651.02 V1v2 (Month 12.5)
3821.75
gp70-TV1.GSKvacV1V2/293F (Month 6.5)
3082.625
gp70-TV1.GSKvacV1V2/293F (Month 12.5)
4207.8499015
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part A, Group 1: Vaccine
Comments IgG Ab binding to C.1086C_V1_V2 Tags after the fourth (month 6.5) versus the fifth vaccination (month 12.5)
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value <.0001
Comments The threshold for statistical significance was p = 0.05.
Method Wilcoxon Signed-Rank
Comments
Method of Estimation Estimation Parameter Geometric Mean difference (Net)
Estimated Value 0
Confidence Interval (2-Sided) %
to
Parameter Dispersion Type:
Value:
Estimation Comments Difference = Month 12.5 (5th vaccination) - Month 6.5 (4th vaccination)
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part A, Group 1: Vaccine
Comments IgG Ab binding to gp70-96ZM651.02 V1v2 after the fourth (month 6.5) versus the fifth vaccination (month 12.5)
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value <.0001
Comments The threshold for statistical significance was p = 0.05.
Method Wilcoxon Signed-Rank
Comments
Method of Estimation Estimation Parameter Geometric Mean difference (Net)
Estimated Value 0
Confidence Interval (2-Sided) %
to
Parameter Dispersion Type:
Value:
Estimation Comments Difference = Month 12.5 (5th vaccination) - Month 6.5 (4th vaccination)
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part A, Group 1: Vaccine
Comments IgG Ab binding to gp70-TV1.GSKvacV1V2/293F after the fourth (month 6.5) versus the fifth vaccination (month 12.5)
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.0002
Comments The threshold for statistical significance was p = 0.05.
Method Wilcoxon Signed-Rank
Comments
Method of Estimation Estimation Parameter Geometric Mean difference (Net)
Estimated Value 6.099
Confidence Interval (2-Sided) %
to
Parameter Dispersion Type:
Value:
Estimation Comments Difference = Month 12.5 (5th vaccination) - Month 6.5 (4th vaccination)
34. Secondary Outcome
Title Part A: Compare the Occurrence of CD4+ T Cell Responses to the HIV Proteins Included in the Vaccine After the Fourth Versus the Fifth Vaccinations
Description PBMC samples are stimulated with synthetic peptide pools or left unstimulated as a negative control. For each sample, T-cell subset, and peptide pool, response magnitude is % cells expressing markers after peptide stimulation minus % cells expressing markers after no stimulation. A contingency table is constructed to assess response: stimulation (peptide/none) vs. marker expression (yes/no). A one-sided Fisher's exact test is applied, testing if the number of cells positive for the marker is equal in the stimulated vs. unstimulated cells. A discrete Bonferroni adjustment is made over the peptide pools. Response is positive if p<=0.00001. Data are excluded if the blood draw date was outside the visit window, the participant was HIV-infected, PBMC viability or T-cell count were low, or negative control was high.
Time Frame Measured at Month 6.5 and 12.5

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Part A, Group 1: Vaccine
Arm/Group Description ALVAC-HIV at months 0 and 1, and ALVAC-HIV + bivalent subtype C gp120/MF59 at months 3, 6, and 12
Measure Participants 56
1086 gp120 (Month 6.5)
24
16.3%
1086 gp120 (Month 12.5)
23
15.6%
TV1 gp120 (Month 6.5)
32
21.8%
TV1 gp120 (Month 12.5)
31
21.1%
ZM96 gp120 (Month 6.5)
30
20.4%
ZM96 gp120 (Month 12.5)
34
23.1%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part A, Group 1: Vaccine
Comments CD4+ T Cell Responses to 1086 gp120 after the fourth (month 6.5) versus the fifth vaccination (month 12.5)
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 1.0000
Comments The threshold for statistical significance was p = 0.05.
Method McNemar
Comments
Method of Estimation Estimation Parameter Proportion Difference (Net)
Estimated Value 0.018
Confidence Interval (2-Sided) %
to
Parameter Dispersion Type:
Value:
Estimation Comments Difference = Month 12.5 (5th vaccination) - Month 6.5 (4th vaccination)
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part A, Group 1: Vaccine
Comments CD4+ T Cell Responses to TV1 gp120 after the fourth (month 6.5) versus the fifth vaccination (month 12.5)
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.6698
Comments The threshold for statistical significance was p = 0.05.
Method McNemar
Comments
Method of Estimation Estimation Parameter Proportion Difference (Net)
Estimated Value 0.036
Confidence Interval (2-Sided) %
to
Parameter Dispersion Type:
Value:
Estimation Comments Difference = Month 12.5 (5th vaccination) - Month 6.5 (4th vaccination)
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part A, Group 1: Vaccine
Comments CD4+ T Cell Responses to ZM96 gp120 after the fourth (month 6.5) versus the fifth vaccination (month 12.5)
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.1435
Comments The threshold for statistical significance was p = 0.05.
Method McNemar
Comments
Method of Estimation Estimation Parameter Proportion Difference (Net)
Estimated Value 0.125
Confidence Interval (2-Sided) %
to
Parameter Dispersion Type:
Value:
Estimation Comments Difference = Month 12.5 (5th vaccination) - Month 6.5 (4th vaccination)
35. Secondary Outcome
Title Part A: Compare the Level of CD4+ T Cell Responses to the HIV Proteins Included in the Vaccine After the Fourth Versus the Fifth Vaccinations
Description PBMC samples are stimulated with synthetic peptide pools or left unstimulated as a negative control. For each sample, T-cell subset, and peptide pool, response magnitude is % cells expressing markers after peptide stimulation minus % cells expressing markers after no stimulation. A contingency table is constructed to assess response: stimulation (peptide/none) vs. marker expression (yes/no). A one-sided Fisher's exact test is applied, testing if the number of cells positive for the marker is equal in the stimulated vs. unstimulated cells. A discrete Bonferroni adjustment is made over the peptide pools. Response is positive if p<=0.00001. Data are excluded if the blood draw date was outside the visit window, the participant was HIV-infected, PBMC viability or T-cell count were low, or negative control was high. Comparisons were performed among positive responders only.
Time Frame Measured at Month 6.5 and 12.5

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Part A, Group 1: Vaccine
Arm/Group Description ALVAC-HIV at months 0 and 1, and ALVAC-HIV + bivalent subtype C gp120/MF59 at months 3, 6, and 12
Measure Participants 56
1086 gp120 (Month 6.5)
0.17577251
1086 gp120 (Month 12.5)
0.14932756
TV1 gp120 (Month 6.5)
0.158423055
TV1 gp120 (Month 12.5)
0.22183561
ZM96 gp120 (Month 6.5)
0.17436147
ZM96 gp120 (Month 12.5)
0.203201925
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part A, Group 1: Vaccine
Comments CD4+ T Cell Responses to 1086 gp120 after the fourth (month 6.5) versus the fifth vaccination (month 12.5)
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.9661
Comments The threshold for statistical significance was p = 0.05.
Method Wilcoxon Signed-Rank
Comments
Method of Estimation Estimation Parameter Geometric Mean difference (Net)
Estimated Value 0.965
Confidence Interval (2-Sided) %
to
Parameter Dispersion Type:
Value:
Estimation Comments Difference = Month 12.5 (5th vaccination) - Month 6.5 (4th vaccination)
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part A, Group 1: Vaccine
Comments CD4+ T Cell Responses to TV1 gp120 after the fourth (month 6.5) versus the fifth vaccination (month 12.5)
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.8593
Comments The threshold for statistical significance was p = 0.05.
Method Wilcoxon Signed-Rank
Comments
Method of Estimation Estimation Parameter Geometric Mean difference (Net)
Estimated Value 1.118
Confidence Interval (2-Sided) %
to
Parameter Dispersion Type:
Value:
Estimation Comments Difference = Month 12.5 (5th vaccination) - Month 6.5 (4th vaccination)
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part A, Group 1: Vaccine
Comments CD4+ T Cell Responses to ZM96 gp120 after the fourth (month 6.5) versus the fifth vaccination (month 12.5)
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.4396
Comments The threshold for statistical significance was p = 0.05.
Method Wilcoxon Signed-Rank
Comments
Method of Estimation Estimation Parameter Geometric Mean difference (Net)
Estimated Value 1.138
Confidence Interval (2-Sided) %
to
Parameter Dispersion Type:
Value:
Estimation Comments Difference = Month 12.5 (5th vaccination) - Month 6.5 (4th vaccination)
36. Secondary Outcome
Title Part B: Occurrence of IgG Ab Binding to gp120 Env Proteins Contained in the Vaccine (ZM96, TV1.C, 1086.C) in the Extension Study, at 6 Months After the Month 30 Vaccination
Description Serum HIV-1-specific IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. Samples from post-enrollment visits have positive responses if they meet three conditions: (1) net MFI greater than or equal to an antigen-specific response threshold (defined as the maximum of 100 and the 95th percentile of pre-vaccination net MFI), (2) net MFI values are greater than 3 times pre-vaccination net MFI, and (3) experimental antigen MFI values are greater than 3 times pre-vaccination MFI. Data are excluded if the blood draw date was outside the allowable window, a participant was HIV-infected, or the reference antigen exceeds 5000 MFI.
Time Frame Measured at Month 30 and 36

Outcome Measure Data

Analysis Population Description
"Overall Number of Participants Analyzed" represents Part B participants. "Number Analyzed" counts participants with data meeting assay-specific quality criteria.
Arm/Group Title Part B, Group 1a: Vaccine Part B, Group 1b: Vaccine/Placebo Part B, Group 2: Placebo
Arm/Group Description Participants originally in Part A Group 1 (Vaccine) receive ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 1 (Vaccine) receive placebo for ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 2 (Placebo) receive placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at month 30
Measure Participants 32 31 7
1086C_D7gp120.avi/293F (Month 30)
31
21.1%
30
85.7%
0
0%
1086C_D7gp120.avi/293F (Month 36)
31
21.1%
30
85.7%
0
0%
96ZM651.D11gp120.avi (Month 30)
2
1.4%
2
5.7%
0
0%
96ZM651.D11gp120.avi (Month 36)
24
16.3%
25
71.4%
0
0%
TV1c8_D11gp120.avi/293F (Month 30)
27
18.4%
30
85.7%
0
0%
TV1c8_D11gp120.avi/293F (Month 36)
31
21.1%
30
85.7%
0
0%
37. Secondary Outcome
Title Part B: Level of IgG Ab Binding to gp120 Env Proteins Contained in the Vaccine (ZM96, TV1.C, 1086.C) in the Extension Study, at 6 Months After the Month 30 Vaccination
Description Serum HIV-1-specific IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. The measure unit fluorescence units are relative to assay background, not relative to the placebo arm. Background is used here rather than negative control stimulation, since the antigens are used as bead coating rather than stimulation.
Time Frame Measured at Month 30 and 36

Outcome Measure Data

Analysis Population Description
"Overall Number of Participants Analyzed" represents Part B participants. "Number Analyzed" counts participants with data meeting assay-specific quality criteria.
Arm/Group Title Part B, Group 1a: Vaccine Part B, Group 1b: Vaccine/Placebo Part B, Group 2: Placebo
Arm/Group Description Participants originally in Part A Group 1 (Vaccine) receive ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 1 (Vaccine) receive placebo for ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 2 (Placebo) receive placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at month 30
Measure Participants 32 31 7
1086C_D7gp120.avi/293F (Month 30)
6664
4415
1
1086C_D7gp120.avi/293F (Month 36)
25399
24763.625
1
96ZM651.D11gp120.avi (Month 30)
895.25
706.5
1
96ZM651.D11gp120.avi (Month 36)
9750
7324.75
2.75
TV1c8_D11gp120.avi/293F (Month 30)
937
616.25
1
TV1c8_D11gp120.avi/293F (Month 36)
17175.5
17192.375
1
38. Secondary Outcome
Title Part B: Occurrence of IgG Binding Antibodies to 3 V1V2-scaffolded Env Proteins in the Extension Study, at 6 Months After the Month 30 Vaccination
Description Serum HIV-1-specific IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. Samples from post-enrollment visits have positive responses if they meet three conditions: (1) net MFI greater than or equal to an antigen-specific response threshold (defined as the maximum of 100 and the 95th percentile of pre-vaccination net MFI), (2) net MFI values are greater than 3 times pre-vaccination net MFI, and (3) experimental antigen MFI values are greater than 3 times pre-vaccination MFI. Data are excluded if the blood draw date was outside the allowable window, a participant was HIV-infected, or the reference antigen exceeds 5000 MFI.
Time Frame Measured at Month 30 and 36

Outcome Measure Data

Analysis Population Description
"Overall Number of Participants Analyzed" represents Part B participants. "Number Analyzed" counts participants with data meeting assay-specific quality criteria.
Arm/Group Title Part B, Group 1a: Vaccine Part B, Group 1b: Vaccine/Placebo Part B, Group 2: Placebo
Arm/Group Description Participants originally in Part A Group 1 (Vaccine) receive ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 1 (Vaccine) receive placebo for ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 2 (Placebo) receive placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at month 30
Measure Participants 32 31 7
C.1086C_V1_V2 Tags (Month 30)
7
4.8%
6
17.1%
0
0%
C.1086C_V1_V2 Tags (Month 36)
9
6.1%
12
34.3%
1
3.1%
gp70-96ZM651.02 V1v2 (Month 30)
2
1.4%
1
2.9%
0
0%
gp70-96ZM651.02 V1v2 (Month 36)
7
4.8%
3
8.6%
1
3.1%
gp70-TV1.GSKvacV1V2/293F (Month 30)
0
0%
2
5.7%
0
0%
gp70-TV1.GSKvacV1V2/293F (Month 36)
4
2.7%
4
11.4%
0
0%
39. Secondary Outcome
Title Part B: Level of IgG Binding Antibodies to 3 V1V2-scaffolded Env Proteins in the Extension Study, at 6 Months After the Month 30 Vaccination
Description Serum HIV-1-specific IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. The measure unit fluorescence units are relative to assay background, not relative to the placebo arm. Background is used here rather than negative control stimulation, since the antigens are used as bead coating rather than stimulation.
Time Frame Measured at Month 30 and 36

Outcome Measure Data

Analysis Population Description
"Overall Number of Participants Analyzed" represents Part B participants. "Number Analyzed" counts participants with data meeting assay-specific quality criteria.
Arm/Group Title Part B, Group 1a: Vaccine Part B, Group 1b: Vaccine/Placebo Part B, Group 2: Placebo
Arm/Group Description Participants originally in Part A Group 1 (Vaccine) receive ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 1 (Vaccine) receive placebo for ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 2 (Placebo) receive placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at month 30
Measure Participants 32 31 7
C.1086C_V1_V2 Tags (Month 30)
13.5
23
2.75
C.1086C_V1_V2 Tags (Month 36)
47.25
79.25
4.75
gp70-96ZM651.02 V1v2 (Month 30)
1
1
1
gp70-96ZM651.02 V1v2 (Month 36)
19.75
35.375
1
gp70-TV1.GSKvacV1V2/293F (Month 30)
1
1
1
gp70-TV1.GSKvacV1V2/293F (Month 36)
1
7.625
1
40. Secondary Outcome
Title Part B: Occurrence of CD4+ T Cell Responses to the HIV Proteins Included in the Vaccine in the Extension Study, at 6 Months After the Month 30 Vaccination
Description PBMC samples are stimulated with synthetic peptide pools or left unstimulated as a negative control. For each sample, T-cell subset, and peptide pool, response magnitude is % cells expressing markers after peptide stimulation minus % cells expressing markers after no stimulation. A contingency table is constructed to assess response: stimulation (peptide/none) vs. marker expression (yes/no). A one-sided Fisher's exact test is applied, testing if the number of cells positive for the marker is equal in the stimulated vs. unstimulated cells. A discrete Bonferroni adjustment is made over the peptide pools. Response is positive if p<=0.00001. Data are excluded if the blood draw date was outside the visit window, the participant was HIV-infected, PBMC viability or T-cell count were low, or negative control was high.
Time Frame Measured at Month 30 and 36

Outcome Measure Data

Analysis Population Description
"Overall Number of Participants Analyzed" represents Part B participants. "Number Analyzed" counts participants with data meeting assay-specific quality criteria.
Arm/Group Title Part B, Group 1a: Vaccine Part B, Group 1b: Vaccine/Placebo Part B, Group 2: Placebo
Arm/Group Description Participants originally in Part A Group 1 (Vaccine) receive ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 1 (Vaccine) receive placebo for ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 2 (Placebo) receive placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at month 30
Measure Participants 32 31 7
Any gp120 (Month 30)
18
12.2%
17
48.6%
0
0%
Any gp120 (Month 36)
18
12.2%
16
45.7%
0
0%
1086 gp120 (Month 30)
12
8.2%
8
22.9%
0
0%
1086 gp120 (Month 36)
11
7.5%
12
34.3%
0
0%
TV1 gp120 (Month 30)
16
10.9%
15
42.9%
0
0%
TV1 gp120 (Month 36)
17
11.6%
12
34.3%
0
0%
ZM96 gp120 (Month 30)
15
10.2%
14
40%
0
0%
ZM96 gp120 (Month 36)
15
10.2%
13
37.1%
0
0%
41. Secondary Outcome
Title Part B: Level of CD4+ T Cell Responses to the HIV Proteins Included in the Vaccine in the Extension Study, at 6 Months After the Month 30 Vaccination
Description PBMC samples are stimulated with synthetic peptide pools or left unstimulated as a negative control. For each sample, T-cell subset, and peptide pool, response magnitude is % cells expressing markers after peptide stimulation minus % cells expressing markers after no stimulation. A contingency table is constructed to assess response: stimulation (peptide/none) vs. marker expression (yes/no). A one-sided Fisher's exact test is applied, testing if the number of cells positive for the marker is equal in the stimulated vs. unstimulated cells. A discrete Bonferroni adjustment is made over the peptide pools. Response is positive if p<=0.00001. Data are excluded if the blood draw date was outside the visit window, the participant was HIV-infected, PBMC viability or T-cell count were low, or negative control was high.
Time Frame Measured at Month 30 and 36

Outcome Measure Data

Analysis Population Description
"Overall Number of Participants Analyzed" represents Part B participants. "Number Analyzed" counts participants with data meeting assay-specific quality criteria.
Arm/Group Title Part B, Group 1a: Vaccine Part B, Group 1b: Vaccine/Placebo Part B, Group 2: Placebo
Arm/Group Description Participants originally in Part A Group 1 (Vaccine) receive ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 1 (Vaccine) receive placebo for ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 2 (Placebo) receive placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at month 30
Measure Participants 32 31 7
Any gp120 (Month 30)
0.128764915
0.10384047
0.00929931
Any gp120 (Month 36)
0.115994935
0.09751639
0.007663255
1086 gp120 (Month 30)
0.07396858
0.05696544
0.00878693
1086 gp120 (Month 36)
0.064916705
0.06119621
0.001323895
TV1 gp120 (Month 30)
0.114625195
0.077949675
-0.00139331
TV1 gp120 (Month 36)
0.106333215
0.04974197
-0.00506502
ZM96 gp120 (Month 30)
0.09879441
0.08841848
-0.006057945
ZM96 gp120 (Month 36)
0.104756745
0.10113899
-0.001777015

Adverse Events

Time Frame Serious adverse events are collected throughout the study (months 0-18 for Part A, and months 30-36 for Part B). Non-serious adverse events are collected through 30 days after each vaccination (at months 0, 1, 3, 6, and 12 for Part A, and month 30 for Part B).
Adverse Event Reporting Description
Arm/Group Title Part A, Group 1: Vaccine Part A, Group 2: Placebo Part B, Group 1a: Vaccine Part B, Group 1b: Vaccine/Placebo Part B, Group 2: Placebo
Arm/Group Description ALVAC-HIV at months 0 and 1, and ALVAC-HIV + bivalent subtype C gp120/MF59 at months 3, 6, and 12 Placebo for ALVAC-HIV at months 0 and 1, and placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at months 3, 6, and 12 Participants originally in Part A Group 1 (Vaccine) receive ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 1 (Vaccine) receive placebo for ALVAC-HIV + bivalent subtype C gp120/MF59 at month 30 Participants originally in Part A Group 2 (Placebo) receive placebo for ALVAC-HIV + placebo for bivalent subtype C gp120/MF59 at month 30
All Cause Mortality
Part A, Group 1: Vaccine Part A, Group 2: Placebo Part B, Group 1a: Vaccine Part B, Group 1b: Vaccine/Placebo Part B, Group 2: Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 2/210 (1%) 0/42 (0%) 0/32 (0%) 0/31 (0%) 0/7 (0%)
Serious Adverse Events
Part A, Group 1: Vaccine Part A, Group 2: Placebo Part B, Group 1a: Vaccine Part B, Group 1b: Vaccine/Placebo Part B, Group 2: Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 7/210 (3.3%) 0/42 (0%) 0/32 (0%) 0/31 (0%) 0/7 (0%)
Infections and infestations
Any Event in SOC 2/210 (1%) 2 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Gastrointestinal infection 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Hepatitis C 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Injury, poisoning and procedural complications
Any Event in SOC 1/210 (0.5%) 3 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Multiple injuries 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Soft tissue injury 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Subdural haematoma 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Musculoskeletal and connective tissue disorders
Any Event in SOC 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Rheumatic fever 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Nervous system disorders
Any Event in SOC 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Transient ischaemic attack 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Psychiatric disorders
Any Event in SOC 2/210 (1%) 2 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Bipolar disorder 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Completed suicide 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Other (Not Including Serious) Adverse Events
Part A, Group 1: Vaccine Part A, Group 2: Placebo Part B, Group 1a: Vaccine Part B, Group 1b: Vaccine/Placebo Part B, Group 2: Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 147/210 (70%) 34/42 (81%) 15/32 (46.9%) 18/31 (58.1%) 1/7 (14.3%)
Blood and lymphatic system disorders
Any Event in SOC 5/210 (2.4%) 5 2/42 (4.8%) 2 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Iron deficiency anaemia 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Lymphadenopathy 2/210 (1%) 2 1/42 (2.4%) 1 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Neutropenia 1/210 (0.5%) 1 1/42 (2.4%) 1 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Thrombocytopenia 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Cardiac disorders
Any Event in SOC 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Sinus bradycardia 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Ear and labyrinth disorders
Any Event in SOC 1/210 (0.5%) 1 1/42 (2.4%) 1 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Ear pain 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Tinnitus 0/210 (0%) 0 1/42 (2.4%) 1 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Eye disorders
Any Event in SOC 1/210 (0.5%) 1 1/42 (2.4%) 1 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Conjunctivitis allergic 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Eye pruritus 0/210 (0%) 0 1/42 (2.4%) 1 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Gastrointestinal disorders
Any Event in SOC 20/210 (9.5%) 23 7/42 (16.7%) 10 1/32 (3.1%) 1 1/31 (3.2%) 1 0/7 (0%) 0
Abdominal distension 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Abdominal pain 1/210 (0.5%) 1 2/42 (4.8%) 3 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Abdominal pain lower 2/210 (1%) 2 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Abdominal pain upper 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Aphthous ulcer 0/210 (0%) 0 1/42 (2.4%) 1 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Dental caries 0/210 (0%) 0 1/42 (2.4%) 1 1/32 (3.1%) 1 0/31 (0%) 0 0/7 (0%) 0
Diarrhoea 3/210 (1.4%) 3 2/42 (4.8%) 2 0/32 (0%) 0 1/31 (3.2%) 1 0/7 (0%) 0
Dyspepsia 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Enteritis 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Gastritis 2/210 (1%) 2 1/42 (2.4%) 1 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Haemorrhoids 2/210 (1%) 2 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Mouth ulceration 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Nausea 2/210 (1%) 2 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Paraesthesia oral 0/210 (0%) 0 1/42 (2.4%) 1 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Toothache 4/210 (1.9%) 4 1/42 (2.4%) 1 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Vomiting 2/210 (1%) 2 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
General disorders
Any Event in SOC 22/210 (10.5%) 29 7/42 (16.7%) 8 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Chest pain 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Influenza like illness 18/210 (8.6%) 21 5/42 (11.9%) 5 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Injection site nodule 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Injection site pruritus 2/210 (1%) 2 2/42 (4.8%) 2 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Pain 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Suprapubic pain 0/210 (0%) 0 1/42 (2.4%) 1 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Vessel puncture site bruise 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Vessel puncture site pain 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Vessel puncture site swelling 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Infections and infestations
Any Event in SOC 81/210 (38.6%) 112 24/42 (57.1%) 27 10/32 (31.3%) 12 10/31 (32.3%) 10 0/7 (0%) 0
Abscess limb 2/210 (1%) 2 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Acarodermatitis 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Anal abscess 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Bacterial vaginosis 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Blister infected 0/210 (0%) 0 1/42 (2.4%) 1 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Body tinea 4/210 (1.9%) 4 0/42 (0%) 0 1/32 (3.1%) 1 0/31 (0%) 0 0/7 (0%) 0
Chlamydial infection 1/210 (0.5%) 1 0/42 (0%) 0 1/32 (3.1%) 1 0/31 (0%) 0 0/7 (0%) 0
Conjunctivitis 2/210 (1%) 2 3/42 (7.1%) 3 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Cystitis 2/210 (1%) 2 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Dysentery 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Escherichia urinary tract infection 0/210 (0%) 0 1/42 (2.4%) 1 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Folliculitis 2/210 (1%) 2 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Fungal skin infection 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Furuncle 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Gastroenteritis 6/210 (2.9%) 6 1/42 (2.4%) 1 0/32 (0%) 0 2/31 (6.5%) 2 0/7 (0%) 0
Genitourinary chlamydia infection 0/210 (0%) 0 0/42 (0%) 0 3/32 (9.4%) 3 4/31 (12.9%) 4 0/7 (0%) 0
Genitourinary tract gonococcal infection 0/210 (0%) 0 0/42 (0%) 0 1/32 (3.1%) 1 0/31 (0%) 0 0/7 (0%) 0
Gingivitis 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Hepatitis C 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Influenza 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Nasal herpes 0/210 (0%) 0 1/42 (2.4%) 1 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Nasopharyngitis 1/210 (0.5%) 2 1/42 (2.4%) 1 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Oral herpes 2/210 (1%) 2 1/42 (2.4%) 1 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Otitis media 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Pelvic inflammatory disease 0/210 (0%) 0 1/42 (2.4%) 1 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Pharyngitis 5/210 (2.4%) 5 0/42 (0%) 0 1/32 (3.1%) 1 0/31 (0%) 0 0/7 (0%) 0
Postoperative wound infection 0/210 (0%) 0 1/42 (2.4%) 1 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Pulmonary tuberculosis 0/210 (0%) 0 1/42 (2.4%) 1 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Respiratory tract infection bacterial 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Rhinitis 8/210 (3.8%) 9 1/42 (2.4%) 1 1/32 (3.1%) 1 0/31 (0%) 0 0/7 (0%) 0
Sinusitis 3/210 (1.4%) 3 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Subcutaneous abscess 3/210 (1.4%) 3 0/42 (0%) 0 1/32 (3.1%) 1 1/31 (3.2%) 1 0/7 (0%) 0
Tinea versicolour 1/210 (0.5%) 1 2/42 (4.8%) 2 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Tonsillitis 0/210 (0%) 0 0/42 (0%) 0 1/32 (3.1%) 1 0/31 (0%) 0 0/7 (0%) 0
Upper respiratory tract infection 32/210 (15.2%) 35 4/42 (9.5%) 5 1/32 (3.1%) 1 1/31 (3.2%) 1 0/7 (0%) 0
Urethritis 2/210 (1%) 2 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Urinary tract infection 6/210 (2.9%) 7 2/42 (4.8%) 2 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Urogenital trichomoniasis 0/210 (0%) 0 0/42 (0%) 0 1/32 (3.1%) 1 1/31 (3.2%) 1 0/7 (0%) 0
Vaginal infection 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Varicella 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Viral infection 2/210 (1%) 2 1/42 (2.4%) 1 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Viral pharyngitis 0/210 (0%) 0 0/42 (0%) 0 0/32 (0%) 0 1/31 (3.2%) 1 0/7 (0%) 0
Viral upper respiratory tract infection 5/210 (2.4%) 5 3/42 (7.1%) 4 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Vulvovaginal candidiasis 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Vulvovaginitis trichomonal 2/210 (1%) 2 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Wound infection 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Injury, poisoning and procedural complications
Any Event in SOC 23/210 (11%) 26 3/42 (7.1%) 3 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Animal bite 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Arthropod bite 2/210 (1%) 2 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Buttock injury 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Ear canal abrasion 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Face injury 3/210 (1.4%) 4 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Foreign body in eye 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Injury 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Ligament sprain 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Limb injury 2/210 (1%) 2 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Muscle strain 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Post procedural contusion 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Procedural dizziness 2/210 (1%) 2 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Procedural pain 1/210 (0.5%) 1 1/42 (2.4%) 1 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Skin abrasion 1/210 (0.5%) 1 2/42 (4.8%) 2 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Skin laceration 4/210 (1.9%) 4 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Stab wound 2/210 (1%) 2 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Investigations
Any Event in SOC 48/210 (22.9%) 75 8/42 (19%) 11 1/32 (3.1%) 1 7/31 (22.6%) 7 1/7 (14.3%) 1
Alanine aminotransferase increased 19/210 (9%) 22 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Aspartate aminotransferase increased 22/210 (10.5%) 26 2/42 (4.8%) 2 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Blood alkaline phosphatase increased 2/210 (1%) 2 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Blood creatinine increased 7/210 (3.3%) 9 0/42 (0%) 0 1/32 (3.1%) 1 6/31 (19.4%) 6 1/7 (14.3%) 1
Blood pressure increased 4/210 (1.9%) 5 1/42 (2.4%) 1 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Haemoglobin decreased 2/210 (1%) 2 4/42 (9.5%) 5 0/32 (0%) 0 1/31 (3.2%) 1 0/7 (0%) 0
Neutrophil count decreased 5/210 (2.4%) 5 1/42 (2.4%) 2 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Platelet count decreased 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Urobilinogen urine increased 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Weight decreased 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
White blood cell count decreased 1/210 (0.5%) 1 1/42 (2.4%) 1 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Musculoskeletal and connective tissue disorders
Any Event in SOC 14/210 (6.7%) 15 0/42 (0%) 0 1/32 (3.1%) 1 0/31 (0%) 0 0/7 (0%) 0
Arthralgia 2/210 (1%) 2 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Back pain 2/210 (1%) 2 0/42 (0%) 0 1/32 (3.1%) 1 0/31 (0%) 0 0/7 (0%) 0
Muscle spasms 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Musculoskeletal chest pain 2/210 (1%) 2 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Musculoskeletal pain 3/210 (1.4%) 3 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Myalgia 4/210 (1.9%) 4 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Pain in extremity 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Nervous system disorders
Any Event in SOC 18/210 (8.6%) 21 4/42 (9.5%) 4 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Dizziness 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Headache 14/210 (6.7%) 15 4/42 (9.5%) 4 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Presyncope 2/210 (1%) 2 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Somnolence 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Tension headache 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Tremor 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Psychiatric disorders
Any Event in SOC 4/210 (1.9%) 4 2/42 (4.8%) 2 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Anxiety 0/210 (0%) 0 1/42 (2.4%) 1 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Depression 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Premature ejaculation 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Stress 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Substance abuse 0/210 (0%) 0 1/42 (2.4%) 1 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Substance-induced psychotic disorder 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Renal and urinary disorders
Any Event in SOC 19/210 (9%) 23 3/42 (7.1%) 4 2/32 (6.3%) 2 2/31 (6.5%) 2 0/7 (0%) 0
Dysuria 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Glycosuria 4/210 (1.9%) 4 1/42 (2.4%) 1 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Haematuria 3/210 (1.4%) 4 1/42 (2.4%) 1 0/32 (0%) 0 1/31 (3.2%) 1 0/7 (0%) 0
Proteinuria 13/210 (6.2%) 14 2/42 (4.8%) 2 2/32 (6.3%) 2 1/31 (3.2%) 1 0/7 (0%) 0
Reproductive system and breast disorders
Any Event in SOC 14/210 (6.7%) 16 3/42 (7.1%) 4 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Abnormal withdrawal bleeding 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Amenorrhoea 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Dysmenorrhoea 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Dyspareunia 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Menorrhagia 3/210 (1.4%) 3 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Metrorrhagia 8/210 (3.8%) 8 1/42 (2.4%) 1 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Vaginal discharge 1/210 (0.5%) 1 2/42 (4.8%) 2 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Vulvovaginal pruritus 0/210 (0%) 0 1/42 (2.4%) 1 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Respiratory, thoracic and mediastinal disorders
Any Event in SOC 7/210 (3.3%) 7 1/42 (2.4%) 1 1/32 (3.1%) 1 0/31 (0%) 0 0/7 (0%) 0
Epistaxis 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Nasal congestion 1/210 (0.5%) 1 1/42 (2.4%) 1 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Nasal septum ulceration 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Oropharyngeal pain 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Rhinitis allergic 0/210 (0%) 0 0/42 (0%) 0 1/32 (3.1%) 1 0/31 (0%) 0 0/7 (0%) 0
Rhinorrhoea 2/210 (1%) 2 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Throat irritation 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Skin and subcutaneous tissue disorders
Any Event in SOC 13/210 (6.2%) 19 1/42 (2.4%) 1 2/32 (6.3%) 2 1/31 (3.2%) 1 0/7 (0%) 0
Acne 2/210 (1%) 2 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Dermatitis 2/210 (1%) 3 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Pruritus 1/210 (0.5%) 1 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Pruritus generalised 3/210 (1.4%) 4 0/42 (0%) 0 1/32 (3.1%) 1 0/31 (0%) 0 0/7 (0%) 0
Rash generalised 2/210 (1%) 2 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Rash macular 1/210 (0.5%) 2 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Rash maculo-papular 2/210 (1%) 2 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Rash papular 3/210 (1.4%) 3 1/42 (2.4%) 1 0/32 (0%) 0 1/31 (3.2%) 1 0/7 (0%) 0
Skin ulcer 0/210 (0%) 0 0/42 (0%) 0 1/32 (3.1%) 1 0/31 (0%) 0 0/7 (0%) 0
Vascular disorders
Any Event in SOC 1/210 (0.5%) 3 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0
Hypertension 1/210 (0.5%) 3 0/42 (0%) 0 0/32 (0%) 0 0/31 (0%) 0 0/7 (0%) 0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title Jessica Andriesen, PhD, Associate Director of HVTN SDMC Operations
Organization Fred Hutchinson Cancer Research Center
Phone 206-667-5812
Email jandries@fredhutch.org
Responsible Party:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT02404311
Other Study ID Numbers:
  • HVTN 100
First Posted:
Mar 31, 2015
Last Update Posted:
Nov 5, 2021
Last Verified:
Jul 1, 2020