Safety and Immunogenicity Study of AERAS-456 Vaccine for Tuberculosis

• Sponsor: Aeras (Other)
• Overall Status: Completed
• CT.gov ID: NCT01967134
• Collaborator: Statens Serum Institut (Other)
• Enrollment: 25
• Location: 1
• Arms: 3
• Duration (Months): 19
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

This is a Phase I, open-label, dose-escalation study with three study groups. This study will be conducted in 25 HIV negative subjects, 17 of whom will have Latent Tuberculosis Infection (LTBI) and 8 of whom will not have LTBI at study enrollment. The investigational product is AERAS-456 at a dose of 15 ug of H56 antigen with IC31 500 nmol KLK (15/500), and a dose of 50 ug of H56 antigen with IC31 500 nmol KLK (50/500). The vaccine is administered by intramuscular injection.

Condition or Disease	Intervention/Treatment	Phase
Latent Tuberculosis; Latent Tuberculosis Bacteriology and Histology Unknown	Biological: H56:IC31	Phase 1

Detailed Description

This is a Phase I, open-label, dose-escalation study with three study groups. This study will be conducted in 25 HIV negative subjects, 17 of whom will have Latent Tuberculosis Infection (LTBI) and 8 of whom will not have LTBI at study enrollment. The investigational product is H56:IC31 (AERAS-456) at a dose of 15 ug of H56 antigen with IC31 500 nmol KLK (15/500), and a dose of 50 ug of H56 antigen with IC31 500 nmol KLK (50/500). The vaccine is administered by intramuscular (IM) injection.

Subjects will be assigned to a study group based on LTBI status at enrollment and time of completion of screening. Subjects without LTBI will be assigned to Group 1. Subjects with LTBI will be sequentially assigned to Groups 2 and 3 based on the order in which they complete screening. All subjects will receive a first dose of study vaccine on Study Day 0, a second dose of study vaccine on Study Day 56, and a third dose of study vaccine on Study Day 112. Enrollment of subjects into Group 2 will begin only after a review of safety data from the 14-day period after initial vaccination of all subjects in Group 1. Likewise, enrollment of subjects into Group 3 will begin only after the corresponding review of safety data from Group 2.

The total duration of study follow-up for all subjects is 210 days. Study groups 1-2 will enroll 8 subjects each and study group 3 will enroll 9 subjects. This study is planned at a single clinical site in South Africa. The sizes specified for each study group were selected because they are judged to be adequate for preliminary safety and immunogenicity evaluations for a Phase I study rather than for statistical reasons.

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Phase I Open Label Dose-Escalation Study to Evaluate the Safety and Immunogenicity of H56:IC31 (AERAS-456) in HIV-negative Adults With and Without Latent Tuberculosis Infection
• Study Start Date: Nov 1, 2011
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: H56:IC31 (50 ug H56) LTBI Neg LTBI Negative 3 Doses	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) formulated in the Th1-stimulating IC31 adjuvant.; Other Names: AERAS 456
Experimental: H56:IC31 (15 ug H56) LTBI Pos LTBI Positive 3 Doses	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) formulated in the Th1-stimulating IC31 adjuvant.; Other Names: AERAS 456
Experimental: H56:IC31 (50 ug H56) LTBI Pos LTBI Positive 3 Doses	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) formulated in the Th1-stimulating IC31 adjuvant.; Other Names: AERAS 456

Outcome Measures

Primary Outcome Measures

1. Number of Participants With at Least One Adverse Event (AE) Through Day 210 [Through Study Day 210]

   Solicited AEs: through 14 days after each vaccination Unsolicited AEs: post-vaccination on Study Days 0, 56, and 112 through 28 days after vaccination Injection site reactions and axillary lymphadenopathy: post-injection on the day of each vaccination, and Study Days 2 , 7, 14, and 28 days after each vaccination Serious adverse events (SAE): through Study Day 210

Secondary Outcome Measures

1. Median % Change in Response to Peptides From Vaccine Antigen Ag85B From Pre-vaccination to Day 70 in Participants Who Received Two Vaccinations [Study Day 70]

   Whole blood ICS Percent Antigen-Specific T Cell UNS-subtracted Cytokine Response Antigen: Ag85B Cytokine(s): G+2+17+T+ %CD4+ T Cell Response

2. Median % Change in Response to Peptides From Vaccine Antigen ESAT-6 From Pre-vaccination to Day 70 in Participants Who Received Two Vaccinations [Study Day 70]

   Percent Antigen-Specific T Cell UNS-subtracted Cytokine Response 12-Hour Whole Blood Intracellular Cytokine Staining (ICS) Assay Antigen: ESAT6 Cytokine(s): G+2+17+T+ %CD4+ T Cell Response

3. Number of Participants Who Received at Least Two Vaccinations and Tested Positive for Mtb Infection on Day 210 [Study Day 210]

   Measure of Mtb positivity by QuantiFERON-TB Gold In-Tube Number of Positive Responses and Shift from Screening to Study Day 210 Post-Vaccination Responses

4. Median % Change in Response to Peptides From Vaccine Antigen Ag85AB From Pre-vacc to Day 210 [Study Day 210]

   Responses to vaccine antigen Ag85B measure by Interferon gamma (IFN-γ) ELISpot assay Unstimulated-subtracted IFN-γ ELISpot Response (Spot forming units/10^6 PBMC) Antigen: Ag85B

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Has completed the written informed consent process

2. Is male or female

3. Is aged 18 through 50 years on Study Day 0

4. Females: Ability to avoid pregnancy during the trial: 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 avoid pregnancy with an acceptable method of avoiding pregnancy from 28 days prior to administration of the study vaccine through the end of the study.

5. Has general good health, confirmed by medical history and physical examination

6. Is able and willing to complete the full follow-up period of 210 days as required by the protocol

7. Is able and willing to commit to avoiding elective surgery for the duration of the study

8. Is able and willing to stay in contact with the study site for the duration of the study

9. [Groups 2 & 3] Has latent tuberculosis infection (LTBI), diagnosed by a positive Quantiferon (QFT)

10. Has completed simultaneous enrollment in the Registry Protocol

Exclusion Criteria:

1. Axillary temperature 37.5 C

2. Abnormal laboratory values from blood collected within 7 days prior to Study Day 0 vaccination as follows:

• hemoglobin, hematocrit, platelet count, absolute neutrophil count, or absolute lymphocyte count below lower limit of normal (LLN).

• white blood cell count above upper limit of normal (ULN) or below LLN

• alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, alkaline phosphatase (ALP), or creatinine above ULN.

1. Abnormal urinalysis that, in the opinion of the investigator, indicates systemic or local disease.

2. History or evidence of tuberculosis disease, including but not limited to pulmonary tuberculosis, pleural tuberculosis, lymph node tuberculosis or tuberculosis meningitis.

3. [Group 1] Evidence of latent tuberculosis infection (LTBI), defined as a positive screening QFT or a history of a positive TST or QFT.

4. Received a tuberculin skin test (TST) or bacillus Calmette-Guerin (BCG) within 45 days prior to Study Day 0.

5. Received investigational Mtb vaccine at any time prior to Study Day 0.

6. History or evidence of autoimmune disease.

7. History or laboratory evidence of HIV infection.

8. History or laboratory evidence of Hepatitis B or C.

9. Used immunosuppressive medication (other than inhaled or topical immunosuppressants) within 45 days prior to Study Day 0.

10. Received immunoglobulin or blood products within 45 days prior to Study Day 0

11. Received any investigational product within 45 days prior to Study Day 0, or plans to participate in any other study involving administration of investigational product during the study period.

12. Inability to discontinue daily medications, except contraceptives, inhaled or topical immunosuppressants, or nutritional supplements, during the study period.

13. Documented history of allergic reaction or hypersensitivity to any component of the study vaccine.

14. Female subjects: currently pregnant or lactating/nursing; or positive serum pregnancy test during screening; or positive urine pregnancy test on the day of Study Day 0, Study Day 56, or Study Day 112 vaccination.

15. History or evidence of any systemic disease or any acute or chronic illness that, in the opinion of the investigator, may compromise the safety of the subject in the study or interfere with the evaluation of the safety or immunogenicity of the vaccine.

16. History of dermatologic disease or skin features that, in the opinion of the investigator, may interfere with the assessment of injection site reactions.

17. History or evidence of any medical, psychiatric, occupational, or substance abuse problems that, in the opinion of the investigator, will make it unlikely that the subject will comply with the protocol.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	SATVI Project Office, Brewelskloof Hospital	Worcester		South Africa	6850

Sponsors and Collaborators

• Aeras
• Statens Serum Institut

Investigators

• Principal Investigator: Angelique Luabeya, MD, University of Cape Town South African Tuberculosis Vaccine Initiative

Study Documents (Full-Text)

None provided.

More Information

Publications

• Luabeya AK, Kagina BM, Tameris MD, Geldenhuys H, Hoff ST, Shi Z, Kromann I, Hatherill M, Mahomed H, Hanekom WA, Andersen P, Scriba TJ; H56-032 Trial Study Group, Schoeman E, Krohn C, Day CL, Africa H, Makhethe L, Smit E, Brown Y, Suliman S, Hughes EJ, Bang P, Snowden MA, McClain B, Hussey GD. First-in-human trial of the post-exposure tuberculosis vaccine H56:IC31 in Mycobacterium tuberculosis infected and non-infected healthy adults. Vaccine. 2015 Aug 7;33(33):4130-40. doi: 10.1016/j.vaccine.2015.06.051. Epub 2015 Jun 19.

• Responsible Party: Aeras
• ClinicalTrials.gov Identifier: NCT01967134
• Other Study ID Numbers: C-032-456
• First Posted: Oct 22, 2013
• Last Update Posted: Aug 21, 2019
• Last Verified: Jun 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Aeras: HIV Negative
• Additional relevant MeSH terms: Tuberculosis; Latent Tuberculosis

Study Results

Participant Flow

Arm/Group Title	H56:IC31 (50 ug H56) LTBI Neg	H56:IC31 (15 ug H56) LTBI Pos	H56:IC31 (50 ug H56) LTBI Pos
Arm/Group Description	LTBI Negative 3 Doses 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) formulated in the Th1-stimulating IC31 adjuvant.	LTBI Positive 3 Doses 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) formulated in the Th1-stimulating IC31 adjuvant.	LTBI Positive 3 Doses 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) formulated in the Th1-stimulating IC31 adjuvant.
Period Title: Overall Study
STARTED	8	8	9
COMPLETED	8	7	9
NOT COMPLETED	0	1	0

Baseline Characteristics

Arm/Group Title	H56:IC31 (50 ug H56) LTBI Neg	H56:IC31 (15 ug H56) LTBI Pos	H56:IC31 (50 ug H56) LTBI Pos	Total
Arm/Group Description	LTBI Negative 3 Doses 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) formulated in the Th1-stimulating IC31 adjuvant.	LTBI Positive 3 Doses 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) formulated in the Th1-stimulating IC31 adjuvant.	LTBI Positive 3 Doses 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) formulated in the Th1-stimulating IC31 adjuvant.	Total of all reporting groups
Overall Participants	8	8	9	25
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	8 100%	8 100%	9 100%	25 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	4 50%	6 75%	5 55.6%	15 60%
Male	4 50%	2 25%	4 44.4%	10 40%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	8 100%	8 100%	9 100%	25 100%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	3 37.5%	1 12.5%	1 11.1%	5 20%
White	0 0%	0 0%	0 0%	0 0%
More than one race	5 62.5%	7 87.5%	8 88.9%	20 80%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
South Africa	8 100%	8 100%	9 100%	25 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With at Least One Adverse Event (AE) Through Day 210
Description	Solicited AEs: through 14 days after each vaccination Unsolicited AEs: post-vaccination on Study Days 0, 56, and 112 through 28 days after vaccination Injection site reactions and axillary lymphadenopathy: post-injection on the day of each vaccination, and Study Days 2 , 7, 14, and 28 days after each vaccination Serious adverse events (SAE): through Study Day 210
Time Frame	Through Study Day 210

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	H56:IC31 (50 ug H56) LTBI Neg	H56:IC31 (15 ug H56) LTBI Pos	H56:IC31 (50 ug H56) LTBI Pos
Arm/Group Description	LTBI Negative 3 Doses 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) formulated in the Th1-stimulating IC31 adjuvant.	LTBI Positive 3 Doses 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) formulated in the Th1-stimulating IC31 adjuvant.	LTBI Positive 3 Doses 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) formulated in the Th1-stimulating IC31 adjuvant.
Measure Participants	8	8	9
Participants with at least one AE after any dose	8 100%	8 100%	9 100%
Participants with at least one AE after 3rd dose	6 75%	7 87.5%	4 44.4%

2. Secondary Outcome

Title	Median % Change in Response to Peptides From Vaccine Antigen Ag85B From Pre-vaccination to Day 70 in Participants Who Received Two Vaccinations
Description	Whole blood ICS Percent Antigen-Specific T Cell UNS-subtracted Cytokine Response Antigen: Ag85B Cytokine(s): G+2+17+T+ %CD4+ T Cell Response
Time Frame	Study Day 70

Outcome Measure Data

Analysis Population Description

All vaccinated subjects

Arm/Group Title	H56:IC31 (50 ug H56) LTBI Neg	H56:IC31 (15 ug H56) LTBI Pos	H56:IC31 (50 ug H56) LTBI Pos
Arm/Group Description	LTBI Negative 3 Doses 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) formulated in the Th1-stimulating IC31 adjuvant.	LTBI Positive 3 Doses 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) formulated in the Th1-stimulating IC31 adjuvant.	LTBI Positive 3 Doses 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) formulated in the Th1-stimulating IC31 adjuvant.
Measure Participants	8	8	9
Median (95% Confidence Interval) [% change from pre-vacc to day 70]	0.0008	0.0050	0.0019

3. Secondary Outcome

Title	Median % Change in Response to Peptides From Vaccine Antigen ESAT-6 From Pre-vaccination to Day 70 in Participants Who Received Two Vaccinations
Description	Percent Antigen-Specific T Cell UNS-subtracted Cytokine Response 12-Hour Whole Blood Intracellular Cytokine Staining (ICS) Assay Antigen: ESAT6 Cytokine(s): G+2+17+T+ %CD4+ T Cell Response
Time Frame	Study Day 70

Outcome Measure Data

Analysis Population Description

All vaccinated subjects

Arm/Group Title	H56:IC31 (50 ug H56) LTBI Neg	H56:IC31 (15 ug H56) LTBI Pos	H56:IC31 (50 ug H56) LTBI Pos
Arm/Group Description	LTBI Negative 3 Doses 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) formulated in the Th1-stimulating IC31 adjuvant.	LTBI Positive 3 Doses 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) formulated in the Th1-stimulating IC31 adjuvant.	LTBI Positive 3 Doses 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) formulated in the Th1-stimulating IC31 adjuvant.
Measure Participants	8	8	9
Median (95% Confidence Interval) [% change from pre-vacc to day 70]	0.0000	0.0005	0.0005

4. Secondary Outcome

Title	Number of Participants Who Received at Least Two Vaccinations and Tested Positive for Mtb Infection on Day 210
Description	Measure of Mtb positivity by QuantiFERON-TB Gold In-Tube Number of Positive Responses and Shift from Screening to Study Day 210 Post-Vaccination Responses
Time Frame	Study Day 210

Outcome Measure Data

Analysis Population Description

All vaccinated subjects

Arm/Group Title	H56:IC31 (50 ug H56) LTBI Neg	H56:IC31 (15 ug H56) LTBI Pos	H56:IC31 (50 ug H56) LTBI Pos
Arm/Group Description	LTBI Negative 3 Doses 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) formulated in the Th1-stimulating IC31 adjuvant.	LTBI Positive 3 Doses 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) formulated in the Th1-stimulating IC31 adjuvant.	LTBI Positive 3 Doses 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) formulated in the Th1-stimulating IC31 adjuvant.
Measure Participants	8	8	9
Count of Participants [Participants]	2 25%	6 75%	9 100%

5. Secondary Outcome

Title	Median % Change in Response to Peptides From Vaccine Antigen Ag85AB From Pre-vacc to Day 210
Description	Responses to vaccine antigen Ag85B measure by Interferon gamma (IFN-γ) ELISpot assay Unstimulated-subtracted IFN-γ ELISpot Response (Spot forming units/10^6 PBMC) Antigen: Ag85B
Time Frame	Study Day 210

Outcome Measure Data

Analysis Population Description

Subjects in all vaccinated population with available data

Arm/Group Title	H56:IC31 (50 ug H56) LTBI Neg	H56:IC31 (15 ug H56) LTBI Pos	H56:IC31 (50 ug H56) LTBI Pos
Arm/Group Description	LTBI Negative 3 Doses 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) formulated in the Th1-stimulating IC31 adjuvant.	LTBI Positive 3 Doses 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) formulated in the Th1-stimulating IC31 adjuvant.	LTBI Positive 3 Doses 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) formulated in the Th1-stimulating IC31 adjuvant.
Measure Participants	7	1	7
Median (95% Confidence Interval) [percent change]	36.6667	-8.3333	80.0000

Adverse Events

Time Frame	Solicited AEs: Thru 14 days after each vaccination Unsolicited AEs: 28 days after each vaccination SAEs: Days 0-210
Arm/Group Title	Aeras-456 (50 ug H56/500 Nmol IC31) LTBI Negative		Aeras-456 (15 ug H56/500 Nmol IC31) LTBI Positive		Aeras-456 (50 ug H56 / 500 Nmol IC31) LTBI Positive
Arm/Group Description	LTBI Negative 3 Doses Aeras-456: H56:IC31 (designated as AERAS-456 for Aeras-sponsored clinical development) 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) formulated in the Th1-stimulating IC31 adjuvant.		LTBI Positive 3 Doses Aeras-456: H56:IC31 (designated as AERAS-456 for Aeras-sponsored clinical development) 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) formulated in the Th1-stimulating IC31 adjuvant.		LTBI Positive 3 Doses Aeras-456: H56:IC31 (designated as AERAS-456 for Aeras-sponsored clinical development) 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) formulated in the Th1-stimulating IC31 adjuvant.
All Cause Mortality
	Aeras-456 (50 ug H56/500 Nmol IC31) LTBI Negative		Aeras-456 (15 ug H56/500 Nmol IC31) LTBI Positive		Aeras-456 (50 ug H56 / 500 Nmol IC31) LTBI Positive
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)		0/9 (0%)
Serious Adverse Events
	Aeras-456 (50 ug H56/500 Nmol IC31) LTBI Negative		Aeras-456 (15 ug H56/500 Nmol IC31) LTBI Positive		Aeras-456 (50 ug H56 / 500 Nmol IC31) LTBI Positive
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)		0/9 (0%)
Other (Not Including Serious) Adverse Events
	Aeras-456 (50 ug H56/500 Nmol IC31) LTBI Negative		Aeras-456 (15 ug H56/500 Nmol IC31) LTBI Positive		Aeras-456 (50 ug H56 / 500 Nmol IC31) LTBI Positive
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/8 (100%)		8/8 (100%)		9/9 (100%)
Cardiac disorders
Bradycardia	4/8 (50%)	5	2/8 (25%)	2	0/9 (0%)	0
Gastrointestinal disorders
Abdominal pain	1/8 (12.5%)	1	0/8 (0%)	0	0/9 (0%)	0
Dyspepsia	0/8 (0%)	0	1/8 (12.5%)	1	0/9 (0%)	0
Nausea	2/8 (25%)	2	2/8 (25%)	7	1/9 (11.1%)	1
General disorders
Chills	0/8 (0%)	0	0/8 (0%)	0	2/9 (22.2%)	2
Fatigue	3/8 (37.5%)	9	4/8 (50%)	8	2/9 (22.2%)	3
Injection site erythema	0/8 (0%)	0	0/8 (0%)	0	2/9 (22.2%)	2
Injection site pain	5/8 (62.5%)	12	7/8 (87.5%)	18	6/9 (66.7%)	11
Injection site pruritus	1/8 (12.5%)	1	0/8 (0%)	0	0/9 (0%)	0
Injection site swelling	1/8 (12.5%)	1	2/8 (25%)	2	4/9 (44.4%)	5
Injection site warmth	5/8 (62.5%)	9	6/8 (75%)	10	6/9 (66.7%)	10
Pyrexia	0/8 (0%)	0	1/8 (12.5%)	1	0/9 (0%)	0
Immune system disorders
Seasonal allergy	0/8 (0%)	0	1/8 (12.5%)	1	0/9 (0%)	0
Infections and infestations
Bronchitis	0/8 (0%)	0	1/8 (12.5%)	1	0/9 (0%)	0
Rhinitis	2/8 (25%)	2	2/8 (25%)	3	0/9 (0%)	0
Sinusitis	0/8 (0%)	0	0/8 (0%)	0	2/9 (22.2%)	2
Upper respiratory tract infection	1/8 (12.5%)	1	5/8 (62.5%)	5	1/9 (11.1%)	1
Injury, poisoning and procedural complications
Arthropod bite	0/8 (0%)	0	1/8 (12.5%)	1	1/9 (11.1%)	1
Muscle strain	0/8 (0%)	0	0/8 (0%)	0	1/9 (11.1%)	1
Investigations
Alanine aminotransferase increased	0/8 (0%)	0	0/8 (0%)	0	2/9 (22.2%)	3
Aspartate aminotransferase increased	0/8 (0%)	0	0/8 (0%)	0	1/9 (11.1%)	1
Haemoglobin decreased	1/8 (12.5%)	2	0/8 (0%)	0	2/9 (22.2%)	2
Neutrophil count decreased	1/8 (12.5%)	1	0/8 (0%)	0	0/9 (0%)	0
Protein urine	5/8 (62.5%)	6	0/8 (0%)	0	0/9 (0%)	0
Red blood cells urine	2/8 (25%)	2	2/8 (25%)	2	2/9 (22.2%)	2
White blood cell count increased	1/8 (12.5%)	1	1/8 (12.5%)	1	1/9 (11.1%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/8 (12.5%)	1	3/8 (37.5%)	4	0/9 (0%)	0
Back pain	0/8 (0%)	0	0/8 (0%)	0	1/9 (11.1%)	1
Joint stiffness	1/8 (12.5%)	1	0/8 (0%)	0	0/9 (0%)	0
Musculoskeletal pain	0/8 (0%)	0	0/8 (0%)	0	1/9 (11.1%)	1
Myalgia	2/8 (25%)	2	2/8 (25%)	7	1/9 (11.1%)	4
Pain in extremity	0/8 (0%)	0	1/8 (12.5%)	1	0/9 (0%)	0
Nervous system disorders
Dizziness	2/8 (25%)	2	1/8 (12.5%)	1	0/9 (0%)	0
Headache	3/8 (37.5%)	10	2/8 (25%)	5	3/9 (33.3%)	4
Hypoaesthesia	0/8 (0%)	0	2/8 (25%)	2	0/9 (0%)	0
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/8 (12.5%)	1	0/8 (0%)	0	0/9 (0%)	0
Nasal congestion	0/8 (0%)	0	1/8 (12.5%)	1	0/9 (0%)	0
Oropharyngeal pain	1/8 (12.5%)	1	0/8 (0%)	0	0/9 (0%)	0
Skin and subcutaneous tissue disorders
Skin lesion	0/8 (0%)	0	1/8 (12.5%)	1	0/9 (0%)	0
Vascular disorders
Hot flush	1/8 (12.5%)	1	0/8 (0%)	0	0/9 (0%)	0
Hypertension	2/8 (25%)	4	2/8 (25%)	3	1/9 (11.1%)	1

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.