C-037-456: A Phase I Study of Safety & Immunogenicity of AERAS-456 in HIV-Neg. Adults Treated for Drug-susceptible Pulmonary TB

• Sponsor: Aeras (Other)
• Overall Status: Completed
• CT.gov ID: NCT02375698
• Collaborator: Statens Serum Institut (Other)
• Enrollment: 22
• Locations: 3
• Arms: 2
• Actual Duration (Months): 23.1
• Patients Per Site: 7.3
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This is a Phase I, double-blind, randomized, placebo-controlled safety and immunogenicity study in adults who have recently been successfully treated for drug-susceptible pulmonary Tuberculosis (TB). The safety and immunogenicity profile of escalating doses of AERAS-456 in HIV-negative subjects recently treated for drug-susceptible pulmonary TB will be investigated. The study will be conducted at three sites in South Africa.

Condition or Disease	Intervention/Treatment	Phase
Tuberculosis	Biological: H56:IC31; Biological: Placebo	Phase 1

Detailed Description

This study will be the first evaluation of AERAS-456 in subjects who have completed a full course of treatment prescribed for pulmonary TB. Subjects will begin screening for study participation when they have completed 4 calendar months of TB treatment. Subjects meeting the inclusion/exclusion criteria will be randomized within a study group in a 3:1 ratio (N=18 AERAS-456; N=6 placebo) to receive two 0.5 mL intramuscular injections of AERAS-456 or placebo eight weeks apart, on Study Day 0 and Study Day 56.

Study Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: A Phase I, Double-blind, Randomized, Placebo-controlled, Study to Evaluate the Safety and Immunogenicity of AERAS-456 in HIV Negative Adults Successfully Treated for Drug-susceptible Pulmonary Tuberculosis
• Actual Study Start Date: Nov 21, 2014
• Actual Primary Completion Date: Jun 24, 2016
• Actual Study Completion Date: Oct 24, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Gr 1 H56:IC31 5/500 5ug H56 + 500 ug IC31	Biological: H56:IC31; H56:IC31 contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c).; Other Names: AERAS-456
Placebo Comparator: Placebo The placebo consists of 10mM Tris and 169 mM NaCl pH 7.4.	Biological: Placebo; The placebo consists of 10mM Tris and 169 mM NaCl pH 7.4.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Day 0 to Day 420]

   Unsolicited AEs: 28 days after each vaccination Solicited AEs: 7 days after each vaccination SAEs: through Day 420 Adverse events of special interest: through Day 420

Secondary Outcome Measures

1. Mean Percent Change From Baseline of Participants' Responses to TB Antigens Ag85A and ESAT-6 [Day 224]

   13-Color PBMC Intracellular Cytokine Staining (ICS) Assay using PBMCs Percent Antigen-specific T Cell DMSO-subtracted, ANY Cytokine Response - Change from Baseline T Cell: CD4

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Is HIV-negative.

2. Is male or female aged 18 through 60 years on Study Day 0.

3. Has completed the written informed consent process.

4. Has a diagnosis of confirmed pulmonary tuberculosis and is on standard TB treatment.

5. Is confirmed to be Mtb negative by either 2 GeneXpert tests or 2 cultures from sputum samples taken on 2 different days at least 1 week apart, the first after at least 4 calendar months of TB treatment and the second day not later than after 5 calendar months (with a window of plus 1 week) of treatment.

6. Agrees to complete the prescribed course of TB treatment (completion of TB treatment can occur after vaccination on Study Day 0; subject must have completed at least 5 calendar months of TB treatment on Study Day 0; if TB treatment is completed before randomization/vaccination then the time from completion of TB treatment to randomization/vaccination should not exceed 28 days).

7. For female subjects: agrees to avoid pregnancy between screening and up until two months after last vaccination. Women physically capable of pregnancy (not sterilized and still menstruating or within 1 year of the last menses if menopausal) in sexual relationships with men must use an acceptable method of avoiding pregnancy from 28 days prior to administration of study vaccine up until two months after the last vaccination. Acceptable methods of avoiding pregnancy include a sterile sexual partner, sexual abstinence (not engaging in sexual intercourse), hormonal contraceptives (oral, injection, transdermal patch, or implant), vaginal ring, or intrauterine device (IUD).

8. Agrees to stay in contact with the study site for the full duration of the study, providing updated contact information as necessary, and has no current plans to move from the study area during the duration of the study.

Exclusion Criteria:

1. Evidence of a new acute illness that may compromise the safety of the subject in the study on Study Day 0.

2. History of TB prior to current episode.

3. TB meningitis or other forms of severe TB with high risk of a poor outcome.

4. Previous medical history that may compromise the safety of the subject in the study, including but not limited to severe impairment of pulmonary function from tuberculosis infection or other pulmonary disease; chronic illness with signs of cardiac or renal failure; suspected progressive neurological disease; or uncontrolled epilepsy.

5. Evidence of any systemic disease or any acute or chronic illness that may interfere with the evaluation of the safety of the vaccine.

6. History or laboratory evidence of any possible immunodeficiency state.

7. History of allergic disease or reactions likely to be exacerbated by any component of the study vaccine.

8. Received any non-BCG TB vaccine previously.

9. For female subjects: Currently pregnant, lactating/nursing, or a positive urine HCG.

10. Severe anemia, defined as hemoglobin less than 10 g/dL or a hematocrit less than 30 percent based on screening hematology obtained within 7 days before randomization on Study Day 0.

11. History of autoimmune disease or immunosuppression.

12. Used immunosuppressive medication within 42 days before Study Day 0 (inhaled and topical corticosteroids are permitted).

13. Received immunoglobulin or blood products within 42 days before Study Day 0.

14. Received any investigational drug therapy or investigational vaccine within 6 months before Study Day 0, or planned participation in any other investigational study during the study period.

15. Received any licensed vaccine within 28 days before Study Day 0, or receipt of any vaccine or immunomodulating agent through Study Day 63.

16. Is, in the judgment of the principal investigator, not suitable to participate in this clinical study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Task Clinical Research Centre	Bellville 7530	Cape Town	South Africa
2	University of Cape Town Lung Institute	Mowbray	Cape Town	South Africa
3	The Aurum Institue	Johannesburg		South Africa

Sponsors and Collaborators

• Aeras
• Statens Serum Institut

Investigators

• Study Director: Dereck Tait, MBChB, Aeras

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Aeras
• ClinicalTrials.gov Identifier: NCT02375698
• Other Study ID Numbers: C-037-456
• First Posted: Mar 3, 2015
• Last Update Posted: Nov 18, 2019
• Last Verified: Aug 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Tuberculosis

Study Results

Participant Flow

Arm/Group Title	H56:IC31 5/500	Placebo
Arm/Group Description	5ug H56 + 500 ug IC31 H56:IC31: H56:IC31 contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c).	The placebo consists of 10mM Tris and 169 mM NaCl pH 7.4.
Period Title: Overall Study
STARTED	16	6
COMPLETED	14	4
NOT COMPLETED	2	2

Baseline Characteristics

Arm/Group Title	H56:IC31 5/500	Placebo	Total
Arm/Group Description	5ug H56 + 500 ug IC31 H56:IC31: H56:IC31 contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c).	The placebo consists of 10mM Tris and 169 mM NaCl pH 7.4.	Total of all reporting groups
Overall Participants	16	6	22
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	16 100%	6 100%	22 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	3 18.8%	1 16.7%	4 18.2%
Male	13 81.3%	5 83.3%	18 81.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	16 100%	6 100%	22 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	8 50%	5 83.3%	13 59.1%
White	0 0%	0 0%	0 0%
More than one race	8 50%	1 16.7%	9 40.9%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
South Africa	16 100%	6 100%	22 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	Unsolicited AEs: 28 days after each vaccination Solicited AEs: 7 days after each vaccination SAEs: through Day 420 Adverse events of special interest: through Day 420
Time Frame	Day 0 to Day 420

Outcome Measure Data

Analysis Population Description

Safety analysis set

Arm/Group Title	H56:IC31 5/500	Placebo
Arm/Group Description	5ug H56 + 500 ug IC31 H56:IC31: H56:IC31 contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c).	The placebo consists of 10mM Tris and 169 mM NaCl pH 7.4.
Measure Participants	16	6
Participants with any AE	14 87.5%	6 100%
Participants with SAEs	0 0%	0 0%

2. Secondary Outcome

Title	Mean Percent Change From Baseline of Participants' Responses to TB Antigens Ag85A and ESAT-6
Description	13-Color PBMC Intracellular Cytokine Staining (ICS) Assay using PBMCs Percent Antigen-specific T Cell DMSO-subtracted, ANY Cytokine Response - Change from Baseline T Cell: CD4
Time Frame	Day 224

Outcome Measure Data

Analysis Population Description

Immunogenicity analysis set

Arm/Group Title	H56:IC31 5/500	Placebo
Arm/Group Description	5ug H56 + 500 ug IC31 H56:IC31: H56:IC31 contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c).	The placebo consists of 10mM Tris and 169 mM NaCl pH 7.4.
Measure Participants	14	4
Stimulation Ag: Ag85B	0.014 (0.0375)	-0.029 (0.0405)
Stimulation Ag: ESAT-6	0.026 (0.0384)	-0.018 (0.0037)

Adverse Events

Time Frame	Unsolicited AEs: for 28 days after each vaccination. Solicited AEs: for 7 days after each vaccination (with diary cards). SAEs: for entire study period (i.e., Study Days 0 to 420). Adverse events of special interest: for entire study period (i.e., Study Days 0 to 420).
Arm/Group Title	Gr 1 H56:IC31 5/500		Placebo
Arm/Group Description	5ug H56 + 500 ug IC31 H56:IC31: H56:IC31 contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c).		The placebo consists of 10mM Tris and 169 mM NaCl pH 7.4. Placebo: The placebo consists of 10mM Tris and 169 mM NaCl pH 7.4.
All Cause Mortality
	Gr 1 H56:IC31 5/500		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/6 (0%)
Serious Adverse Events
	Gr 1 H56:IC31 5/500		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Gr 1 H56:IC31 5/500		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/16 (87.5%)		6/6 (100%)
Blood and lymphatic system disorders
EOSINOPHILIA	1/16 (6.3%)	1	0/6 (0%)	0
NEUTROPENIA	0/16 (0%)	0	1/6 (16.7%)	1
Cardiac disorders
BRADYCARDIA	4/16 (25%)	4	3/6 (50%)	3
TACHYCARDIA	2/16 (12.5%)	3	1/6 (16.7%)	1
Gastrointestinal disorders
NAUSEA	2/16 (12.5%)	2	0/6 (0%)	0
General disorders
FATIGUE	4/16 (25%)	5	3/6 (50%)	4
INJECTION SITE ERYTHEMA	3/16 (18.8%)	3	0/6 (0%)	0
INJECTION SITE PAIN	6/16 (37.5%)	8	0/6 (0%)	0
INJECTION SITE SWELLING	4/16 (25%)	4	0/6 (0%)	0
PYREXIA	2/16 (12.5%)	2	0/6 (0%)	0
Infections and infestations
BRONCHITIS	1/16 (6.3%)	1	0/6 (0%)	0
CONJUNCTIVITIS VIRAL	0/16 (0%)	0	1/6 (16.7%)	1
INFLUENZA	1/16 (6.3%)	1	0/6 (0%)	0
TONSILLITIS	1/16 (6.3%)	1	0/6 (0%)	0
URINARY TRACT INFECTION	1/16 (6.3%)	1	0/6 (0%)	0
Injury, poisoning and procedural complications
CONTUSION	1/16 (6.3%)	1	0/6 (0%)	0
Investigations
ALANINE AMINOTRANSFERASE INCREASED	4/16 (25%)	4	1/6 (16.7%)	1
ASPARTATE AMINOTRANSFERASE INCREASED	5/16 (31.3%)	5	0/6 (0%)	0
BLOOD BILIRUBIN INCREASED	1/16 (6.3%)	1	0/6 (0%)	0
BLOOD PRESSURE DIASTOLIC INCREASED	5/16 (31.3%)	7	0/6 (0%)	0
BLOOD PRESSURE SYSTOLIC INCREASED	1/16 (6.3%)	1	0/6 (0%)	0
GAMMA-GLUTAMYLTRANSFERASE INCREASED	4/16 (25%)	4	2/6 (33.3%)	2
HAEMOGLOBIN DECREASED	3/16 (18.8%)	4	0/6 (0%)	0
NEUTROPHIL COUNT DECREASED	2/16 (12.5%)	2	1/6 (16.7%)	1
WHITE BLOOD CELL COUNT DECREASED	0/16 (0%)	0	1/6 (16.7%)	1
WHITE BLOOD CELL COUNT INCREASED	3/16 (18.8%)	3	0/6 (0%)	0
Musculoskeletal and connective tissue disorders
ARTHRALGIA	0/16 (0%)	0	1/6 (16.7%)	1
FLANK PAIN	1/16 (6.3%)	1	0/6 (0%)	0
MUSCULOSKELETAL PAIN	0/16 (0%)	0	1/6 (16.7%)	2
MYALGIA	2/16 (12.5%)	2	0/6 (0%)	0
Renal and urinary disorders
HAEMATURIA	1/16 (6.3%)	1	1/6 (16.7%)	1
PROTEINURIA	3/16 (18.8%)	4	1/6 (16.7%)	1
Skin and subcutaneous tissue disorders
HIDRADENITIS	1/16 (6.3%)	1	0/6 (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.