A Phase I/IIa AERAS-456 in HIV-Negative Adults With & Without Latent Tuberculosis Infection (C-035-456)

NCT01865487 | Completed Phase 1 Results DMC

• 1 other identifier: C-035-456
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 2

Brief Summary

This is a Phase I/IIa, double-blind, randomized, placebo-controlled, dose- and regimen-finding study in healthy adults with and without LTBI, who are BCG-vaccinated, HIV negative, and have no history or evidence of TB disease. The investigational product is AERAS-456 at 3 dose levels: 5, 15, and 50ug of H56 antigen with 500 nmol IC31. The vaccine is administered by IM injection.

Conditions

Latent Tuberculosis Bacteriology and Histology Unknown; Latent Tuberculosis

Keywords

BCG Vaccinated; HIV Negative

Outcome Measures

Primary Outcomes (1)

• Number and Percentage of Unsolicited and Solicited Adverse Events Recorded Post Day 0 Vaccination.

  Evaluation of unsolicited and solicited AEs was performed through 28 days after each study vaccination. Serious AEs were collected throughout the entire study period (i.e., 292 days). Evaluation of the safety profile of AERAS-456 was performed using data from all subjects who received at least one dose.

  Up to 10 months

Secondary Outcomes (4)

• Evaluate Immunogenicity of Multiple Dosage Levels and Dosing Regimens of H56:IC31 - CD4+ ICS (LTBI-negative)

  Day 292

• Evaluate Immunogenicity of Multiple Dosage Levels and Dosing Regimens of H56:IC31 - CD4+ ICS (LTBI-positive)

  Day 292

• Evaluate Immunogenicity of Multiple Dosage Levels and Dosing Regimens of H56:IC31 - IFN-gamma ELISpot

  Day 292

• Evaluate Kinetics of QuantiFERON®-TB Gold Test (QFT) Responses in LTBI-negative Participants

  Up to Study Day 292

Study Arms (6)

2-Dose Placebo

PLACEBO COMPARATOR

Placebo QFT Neg and Pos, 2 Doses, days 0,56

Biological: Placebo

2-Dose 5/500 H56ug/IC31nmol

EXPERIMENTAL

5/500 H56ug/IC31nmol QFT Neg and Pos, 2 Doses, days 0,56

Biological: H56ug/IC31nmol

2-Dose 15/500 H56ug/IC31nmol

EXPERIMENTAL

15/500 H56ug/IC31nmol QFT Negative 2 Doses, days 0,56

Biological: H56ug/IC31nmol

2-Dose 50/500 H56ug/IC31nmol

EXPERIMENTAL

50/500 H56ug/IC31nmol QFT Negative 2 Doses, days 0,56

Biological: H56ug/IC31nmol

3-Dose, Placebo

PLACEBO COMPARATOR

Placebo QFT Neg and Pos, 3 doses, days 0, 56, 112

Biological: Placebo

3-Dose, 5/500 H56ug/IC31nmol

EXPERIMENTAL

5/500 H56ug/IC31nmol QFT Neg and Pos, 3 Doses, days 0, 56, 112

Biological: H56ug/IC31nmol

Interventions

H56ug/IC31nmol BIOLOGICAL

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.

Also known as: AERAS-456

2-Dose 15/500 H56ug/IC31nmol; 2-Dose 5/500 H56ug/IC31nmol; 2-Dose 50/500 H56ug/IC31nmol; 3-Dose, 5/500 H56ug/IC31nmol

Placebo BIOLOGICAL

Sterile buffer consisting of 10mM Tris and 169mM NaCl at pH 7.4

2-Dose Placebo; 3-Dose, Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects must meet all of the following criteria prior to Study Day 0 vaccination:
• Has completed the written informed consent process prior to the start of screening evaluations.
• Is male or female.
• Is age 18 through 50 years at the time of randomization.
• Received BCG vaccination at least 5 years prior to randomization.
• 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 at screening.
• Is able and willing to complete the full follow-up period of 292 days as required by the protocol.
• Agrees to avoid elective surgery for the full duration of the study.
• \[Groups 1 and 2\] Does not have LTBI, determined by a negative QFT at screening or\[Groups 3 and 4\] Has LTBI, determined by a positive QFT at screening.

You may not qualify if:

• Subjects must meet none of the following criteria prior to Study Day 0 vaccination:
• Acute illness at the time of randomization.
• Oral temperature 37.5 degrees C at the time of randomization.
• Abnormal laboratory values from blood collected within 21 days prior to Study Day 0 vaccination.
• 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.
• Received a TST within 21 days prior to a scheduled study vaccination.
• Received investigational Mtb vaccine at any time prior to Study Day 0.
• History or evidence of autoimmune disease.
• History or laboratory evidence of HIV-1 infection at screening.
• Positive test for hepatitis B surface antigen or hepatitis C antibody at screening.
• Used immunosuppressive medication (other than inhaled or topical immunosuppressants) within 21 days prior to Study Day 0.
• Received immunoglobulin or blood products within 21 days prior to Study Day 0.
• Received any investigational product within 21 days prior to Study Day 0, or plans to participate in any other study involving administration of investigational product during the study period.
• Inability to discontinue current chronic prescription medications, except contraceptives, inhaled or topical immunosuppressants, or nutritional supplements, during the study period.

Sponsors & Collaborators

• Aeras: lead
• Statens Serum Institut: collaborator

Study Sites (2)

eKhayavac TB Vaccine Trial

Khayelitsha, Cape Town, 7784, South Africa

Location

SATVI Project Office, Brewelskloof Hospital

Worcester, 6850, South Africa

Location

Related Publications (1)

• Suliman S, Luabeya AKK, Geldenhuys H, Tameris M, Hoff ST, Shi Z, Tait D, Kromann I, Ruhwald M, Rutkowski KT, Shepherd B, Hokey D, Ginsberg AM, Hanekom WA, Andersen P, Scriba TJ, Hatherill M; H56-035 Trial Group. Dose Optimization of H56:IC31 Vaccine for Tuberculosis-Endemic Populations. A Double-Blind, Placebo-controlled, Dose-Selection Trial. Am J Respir Crit Care Med. 2019 Jan 15;199(2):220-231. doi: 10.1164/rccm.201802-0366OC.

  PMID: 30092143 RESULT

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: Aeras

dtait@aeras.org

27214424991

Study Officials

• Dereck Tait, MD

  Aeras

  STUDY DIRECTOR

• 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: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A 2 phase study based on LTBI status. Phase 1 is a dose ranging study of a 2 dose regimen at 3 dosage levels and placebo in LTBI negative participants. The second phase evaluated 2 and 3 dose regimens and included + and - LTBI participants.

Study Record Dates

• First Submitted: May 21, 2013
• First Posted: May 31, 2013
• Study Start: August 1, 2013
• Primary Completion: August 1, 2015
• Study Completion: November 1, 2015
• Last Updated: December 19, 2019
• Results First Posted: December 19, 2019

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (2)