A Phase I Study to Evaluate Safety and Immunogenicity of AERAS 404 (C-011-404)
- Conditions
- Tuberculosis
- Interventions
- Biological: AERAS-404 (mcg H4/nmol IC31)Biological: Sterile buffer containing 10 mmol/L tris and 169 mmol/L NaCl
- Registration Number
- NCT02109874
- Lead Sponsor
- Aeras
- Brief Summary
This Phase I study will be conducted as a randomized, placebo-controlled, double-blind, dose-escalation study in four groups of healthy adult male and female subjects who are BCG-vaccinated, HIV-negative, and have no evidence of tuberculosis infection. The study will be conducted at one or two sites located in South Africa. The purpose is to evaluate the safety and immunogenicity of two injections of AERAS 404 prepared with four escalating amounts of antigen in healthy adult male and female subjects who are BCG-vaccinated, HIV-negative, and have no evidence of tuberculosis infection.
- Detailed Description
This Phase I study will be conducted as a randomized, placebo-controlled, double-blind, dose-escalation study in four groups of healthy adult male and female subjects who are BCG-vaccinated, HIV-negative, and have no evidence of tuberculosis infection. The study will be conducted at one or two sites located in South Africa.
Forty subjects will be sequentially enrolled into one of four study groups (i.e., Group 1, Group 2, Group 3, or Group 4) based on time of completion of screening, with 10 subjects enrolled into each group. Within each study group, subjects will be randomized to a treatment regimen of either AERAS-404 or placebo control administered by intramuscular injection on Study Day 0 and Study Day 56. All subjects will receive the same treatment on Study Day 0 as they receive on Study Day 56. The dose of antigen will increase between study groups. All subjects will be followed for safety and immunogenicity evaluations for 182 days. A total of eleven clinic visits are planned (excluding screening) for all subjects.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 40
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description AERAS-404 (mcg H4/nmol IC31) 50/500 AERAS-404 (mcg H4/nmol IC31) H4 antigen (supplied in 4 different concentrations): 1.0 mL containing H4 antigen at 50, 150, 500, or 1500 mcg/mL in 10 mmol/L tris and 5% glycerol IC31 Adjuvant (supplied in 1 concentration): 0.8 mL containing IC31 adjuvant at 1250 nmol/mL, in 10 mmol/L tris and 169 mmol/L NaCl AERAS-404 (mcg H4/nmol IC31) 150/500 AERAS-404 (mcg H4/nmol IC31) H4 antigen (supplied in 4 different concentrations): 1.0 mL containing H4 antigen at 50, 150, 500, or 1500 mcg/mL in 10 mmol/L tris and 5% glycerol IC31 Adjuvant (supplied in 1 concentration): 0.8 mL containing IC31 adjuvant at 1250 nmol/mL, in 10 mmol/L tris and 169 mmol/L NaCl AERAS-404 (mcg H4/nmol IC31) 5/500 AERAS-404 (mcg H4/nmol IC31) H4 antigen (supplied in 4 different concentrations): 1.0 mL containing H4 antigen at 50, 150, 500, or 1500 mcg/mL in 10 mmol/L tris and 5% glycerol IC31 Adjuvant (supplied in 1 concentration): 0.8 mL containing IC31 adjuvant at 1250 nmol/mL, in 10 mmol/L tris and 169 mmol/L NaCl Sterile buffer containing 10 mmol/L tris and 169 mmol/L NaCl Sterile buffer containing 10 mmol/L tris and 169 mmol/L NaCl Placebo: Sterile buffer containing 10 mmol/L tris and 169 mmol/L NaCl. This is the identical buffer solution in which IC31 is formulated. AERAS-404 (mcg H4/nmol IC31) 15/500 AERAS-404 (mcg H4/nmol IC31) H4 antigen (supplied in 4 different concentrations): 1.0 mL containing H4 antigen at 50, 150, 500, or 1500 mcg/mL in 10 mmol/L tris and 5% glycerol IC31 Adjuvant (supplied in 1 concentration): 0.8 mL containing IC31 adjuvant at 1250 nmol/mL, in 10 mmol/L tris and 169 mmol/L NaCl
- Primary Outcome Measures
Name Time Method Evaluate the safety of two injections of AERAS 404 prepared with four escalating amounts of antigen in healthy adult subjects. Safety will be measured by number (percentage) and severity of SAEs. Solicited and unsolicited AEs until study day 182 The safety profile will be described by treatment regimen. Serious adverse events (SAE) will be collected on subjects throughout their participation in the study. Solicited and unsolicited adverse events will be captured for 28 days after each vaccination. The number (percentage) of subjects with any adverse events (including solicited, unsolicited and serious adverse events) will be summarized by MedRA system organ class (SOC) and preferred term (PT). Additional summaries will present the number (percentage) of subjects with any adverse events by severity and by relationship to study vaccine. The number (percentage) of subjects with post-vaccination clinical laboratory values or vital sign values recorded as newly abnormal following study vaccination and meeting toxicity criteria will be tabulated at each post-vaccination point and overall.
- Secondary Outcome Measures
Name Time Method Evaluate the immunogenicity of two injections of AERAS 404 prepared with four escalating amounts of antigen in healthy adult subjects. Immune response will be based on percentage of CD4+ and CD8+ cells. 182 days The primary response will be measured by flow cytometry in the Intracellular cytokine staining (ICS) assay. Immune responses will be based on percentage of CD4+ and CD8+ T cells that produced one, two, or three cytokines (IFN-gamma, TNF, and/or IL-2) in response to stimulation with one of the 2 antigenic peptide pool (Ag85B and TB10.4) derived from and representing the entire amino acid sequences of teh mycobacterial antigens Ag85B and TB10.4.
Trial Locations
- Locations (1)
South African Tuberculosis Vaccine Institute; Brewelskloof Hospital
🇿🇦Worcester, South Africa