Clinical Trial: A Phase I/IIa Safety & Immunogenicity of AERAS-456 in HIV-Negative Adults With & Without Latent Tuberculosis Infection (C-035-456)

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase I/IIa Double-Blind, Randomized, Placebo-controlled Dose-Finding Study to Evaluate the Safety and Immunogenicity of AERAS-456 in HIV-Negative Adults With and Without Laten

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.

Detailed Summary:

This is a Phase I/IIa, double-blind, randomized, placebo-controlled, dose- and regimen-finding study in healthy adults with and without latent Tuberculosis (TB) Infection, 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. The study will be conducted at two sites in South Africa.

A total of 98 subjects will be enrolled in 2 phases into 4 groups based on LTBI status. The initial phase will be a dose ranging study of a 2-dose regimen at 3 dosage levels in LTBI(-) subjects, to select a dosage for the second phase. In the second phase, the study will be expanded to evaluate both 2-dose and 3-dose regimens and to include LTBI(+) subjects. In the first phase, 50 LTBI(-) subjects will be enrolled in Group 1 and randomized at a ratio of 3:3:3:1 to receive 2 doses of 5/500, 15/500, or 50/500 of AERAS-456, or placebo given at Study Days 0 and 56 (Table 0 1).

One dose level of AERAS-456 will be selected by the sponsor and SSI for the second phase of the study, based on analysis of unblinded safety and immunogenicity data through 28 days after the second dose in the first phase, in conjunction with safety and immunogenicity data from study C-032-456. The criteria for dose-selection will be specified in a statistical analysis plan to be finalized prior to the unblinded review. The selected dose, in conjunction with the unblinded safety and immunogenicity data, will be submitted to the SMC for review. In the second phase, 48 subjects will be enrolled concurrently into Group 2 (LTBI[-]) and into Groups 3 and 4 (LTBI[+], Table 0 2). In each of Groups 2 and 4, 16 subjects will be randomized at a ratio of 3:1 to receive 3 doses of AERAS-456 or placebo giv
Sponsor: Aeras

Current Primary Outcome: Safety of AERAS-456 administered in HIV-negative, BCG-vaccinated adults with or without LTBI and no history of TB disease. [ Time Frame: Subjects will be followed for up to 10 months. ]

Serious Adverse Events (SAE) will be collected on subjects throughout their participation in the study. Solicited and unsolicited adverse events are captured 28 days post each vaccination. Evaluation of the safety profile of AERAS-456 will be performed using data from all subjects who received at least one dose, and will be summarized by cohort and treatment group. The number (percentage) of subjects with any adverse event (including solicited, unsolicited, and serious adverse events) will be summarized by Medical Dictionary for Regulatory Activities (MedDRA) system organ class and Preferred Term. Additional summaries will present the number (percentage) of subjects with any adverse events by severity and by relationship to study vaccine; parameters evaluable by the Aeras 456 Toxicity Table per US FDA guidance provided in the protocol, will be summarized by severity corresponding to Toxicity Grade, as appropriate.


Original Primary Outcome: Evaluate the safety profile of multiple dosage levels and dosing regimens of AERAS-456 administered to HIV-negative, BCG-vaccinated adults with and without LTBI and with no history or evidence of TB disease. [ Time Frame: June 2013 - July 2015 ]

The safety population will consist of all subjects who received at least one dose of study vaccine.

The safety profile of AERAS-456 will be described by study group and treatment assignment. The primary variable for evaluation of the safety profile will be the number and percentage of unsolicited and solicited adverse events recorded at all available post-vaccination time points. For all presentations of adverse events, additional summaries based on reporting period of adverse events following each study vaccination may also be presented.



Current Secondary Outcome: Immunogenicity of AERAS-456 administered in HIV-negative, BCG-vaccinated adults with or without LTBI and no history of TB disease. [ Time Frame: Subjects will have immunogencitiy assessments for up to 10 months. ]

T-cell response, as measured by Intracellular Cytokine Staining (ICS) and ELISpot.


Original Secondary Outcome: Evaluate the immunogenicity of multiple dosage levels and dosing regimens of AERAS-456 administered to HIV-negative, BCG-vaccinated adults with and without LTBI and with no history or evidence of TB disease. [ Time Frame: June 2013 - July 2015 ]

All immunogenicity analyses will be based on subjects who received at least one dose of study vaccine. Immunogenicity will be summarized for all time points as collected and as available. No imputation for missing data will be performed. Data will be transformed as appropriate prior to analysis.


Information By: Aeras

Dates:
Date Received: May 21, 2013
Date Started: August 2013
Date Completion:
Last Updated: January 4, 2016
Last Verified: January 2016