Safety and Immunogenicity Study of AERAS-456 Vaccine for Tuberculosis

NCT01967134 | Completed Phase 1 Results DMC

• 1 other identifier: C-032-456
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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.

Conditions

Latent Tuberculosis; Latent Tuberculosis Bacteriology and Histology Unknown

Keywords

HIV Negative

Outcome Measures

Primary Outcomes (1)

• Number of Participants With at Least One Adverse Event (AE) Through 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

  Through Study Day 210

Secondary Outcomes (4)

• 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

• 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

• Number of Participants Who Received at Least Two Vaccinations and Tested Positive for Mtb Infection on Day 210

  Study Day 210

• Median % Change in Response to Peptides From Vaccine Antigen Ag85AB From Pre-vacc to Day 210

  Study Day 210

Study Arms (3)

H56:IC31 (50 ug H56) LTBI Neg

EXPERIMENTAL

LTBI Negative 3 Doses

Biological: H56:IC31

H56:IC31 (15 ug H56) LTBI Pos

EXPERIMENTAL

LTBI Positive 3 Doses

Biological: H56:IC31

H56:IC31 (50 ug H56) LTBI Pos

EXPERIMENTAL

LTBI Positive 3 Doses

Biological: H56:IC31

Interventions

H56:IC31 BIOLOGICAL

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.

Also known as: AERAS 456

H56:IC31 (15 ug H56) LTBI Pos; H56:IC31 (50 ug H56) LTBI Neg; H56:IC31 (50 ug H56) LTBI Pos

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Has completed the written informed consent process
• Is male or female
• Is aged 18 through 50 years on Study Day 0
• 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.
• Has general good health, confirmed by medical history and physical examination
• Is able and willing to complete the full follow-up period of 210 days as required by the protocol
• Is able and willing to commit to avoiding elective surgery for the duration of the study
• Is able and willing to stay in contact with the study site for the duration of the study
• \[Groups 2 \& 3\] Has latent tuberculosis infection (LTBI), diagnosed by a positive Quantiferon (QFT)
• Has completed simultaneous enrollment in the Registry Protocol

You may not qualify if:

• Axillary temperature 37.5 C
• 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.
• Abnormal urinalysis that, in the opinion of the investigator, indicates systemic or local disease.
• History or evidence of tuberculosis disease, including but not limited to pulmonary tuberculosis, pleural tuberculosis, lymph node tuberculosis or tuberculosis meningitis.
• \[Group 1\] Evidence of latent tuberculosis infection (LTBI), defined as a positive screening QFT or a history of a positive TST or QFT.
• Received a tuberculin skin test (TST) or bacillus Calmette-Guerin (BCG) within 45 days prior to Study Day 0.
• Received investigational Mtb vaccine at any time prior to Study Day 0.
• History or evidence of autoimmune disease.
• History or laboratory evidence of HIV infection.
• History or laboratory evidence of Hepatitis B or C.
• Used immunosuppressive medication (other than inhaled or topical immunosuppressants) within 45 days prior to Study Day 0.
• Received immunoglobulin or blood products within 45 days prior to Study Day 0

Sponsors & Collaborators

• Aeras: lead
• Statens Serum Institut: collaborator

Study Sites (1)

SATVI Project Office, Brewelskloof Hospital

Worcester, 6850, South Africa

Location

Related Publications (1)

• 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.

  PMID: 26095509 BACKGROUND

MeSH Terms

Conditions

Latent Tuberculosis

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Latent Infection

Results Point of Contact

• Title: Dr. Dereck Tait
• Organization: IAVI

dtait@iavi.org

27214424991

Study Officials

• Angelique Luabeya, MD

  University of Cape Town South African Tuberculosis Vaccine Initiative

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2013
• First Posted: October 22, 2013
• Study Start: November 1, 2011
• Primary Completion: December 1, 2012
• Study Completion: June 1, 2013
• Last Updated: August 21, 2019
• Results First Posted: August 21, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (1)