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Phase 1/II, Safety and Immunogenicity Study of AERAS-404 in BCG-Primed Infants

Phase 1
Completed
Conditions
Tuberculosis
Interventions
Biological: AERAS-404
Biological: Placebo
Registration Number
NCT01861730
Lead Sponsor
Aeras
Brief Summary

Phase I/II, randomized, double-blind, placebo-controlled, safety, immunogenicity and dose-range finding study of AERAS-404 Tuberculosis (TB) vaccine administered intramuscularly in Bacille Calmette-Guerin (BCG) primed infants.

Detailed Description

This is a Phase I/II, randomized, double-blind, placebo-controlled, safety, immunogenicity and dose-range finding study in HIV-uninfected, HIV-unexposed, BCG-primed infants. The study vaccine AERAS-404 or placebo will be administered without concomitant EPI vaccines (Cohorts 1 to 5, N = 159 subjects) and with concomitant EPI vaccines (Cohort 6, N = 70 subjects). Study vaccine or placebo will be administered as a single dose (injection) at Study Day 0 ( ≥168 to ≤ 196 days of age, Cohorts 1 and 2), a 2-dose schedule at Study Day 0 (≥ 168 to ≤ 189 days of age) and Study Day 28 (Cohorts 3A and 3B) or a 3-dose schedule at Study Day 0 (≥ 84 to ≤ 98 days of age), Study Day 42 and Study Day 98 (Cohorts 4 and 5). Subjects in Cohort 6 will receive the study vaccine or placebo at Study Day 0 (≥ 64 to ≤ 83 days of age), Study Day 28 (≥ 91 to ≤ 105 days of age), and Study Day 210 (≥ 273 to ≤ 287 days of age). A cohort will enroll once safety in the previous cohort has been established. AERAS-404 is an investigational vaccine manufactured by Sanofi Pasteur (SP) and Statens Serum Institute (SSI).

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
243
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Cohort 4 AERAS-404 (15ug H4/500nmol IC31) or PlaceboAERAS-4043 Doses; Subject ≥ 84 to ≤ 98 days of age
Cohort 1 Aeras404 (5ug H4/100nmol IC31) or PlaceboAERAS-4041 Dose; Subject ≥ 168 to ≤ 196 days of age
Cohort 3A AERAS-404 (5ug H4/500nmol IC31) or PlaceboPlacebo2 Doses; Subject ≥ 168 to ≤ 189 days of age
Cohort 5 AERAS-404 (50ug H4/500nmol IC31) or PlaceboAERAS-4043 Doses; Subject ≥ 84 to ≤ 98 days of age
Cohort 6 AERAS-404 (dose level pending) or PlaceboAERAS-4043 Doses; Subject ≥ 64 to ≤ 83 days of age
Cohort 1 Aeras404 (5ug H4/100nmol IC31) or PlaceboPlacebo1 Dose; Subject ≥ 168 to ≤ 196 days of age
Cohort 4 AERAS-404 (15ug H4/500nmol IC31) or PlaceboPlacebo3 Doses; Subject ≥ 84 to ≤ 98 days of age
Cohort 5 AERAS-404 (50ug H4/500nmol IC31) or PlaceboPlacebo3 Doses; Subject ≥ 84 to ≤ 98 days of age
Cohort 6 AERAS-404 (dose level pending) or PlaceboPlacebo3 Doses; Subject ≥ 64 to ≤ 83 days of age
Cohort 3B AERAS-404 (15ug H4/500nmol IC31) or PlaceboAERAS-4042 Doses; Subject ≥ 168 to ≤ 189 days of age
Cohort 3B AERAS-404 (15ug H4/500nmol IC31) or PlaceboPlacebo2 Doses; Subject ≥ 168 to ≤ 189 days of age
Cohort 2 AERAS-404 (5ug H4/500nmol IC31) or PlaceboAERAS-4041 Dose; Subject ≥ 168 to ≤ 196 days of age
Cohort 2 AERAS-404 (5ug H4/500nmol IC31) or PlaceboPlacebo1 Dose; Subject ≥ 168 to ≤ 196 days of age
Cohort 3A AERAS-404 (5ug H4/500nmol IC31) or PlaceboAERAS-4042 Doses; Subject ≥ 168 to ≤ 189 days of age
Primary Outcome Measures
NameTimeMethod
Investigate the safety of AERAS-404 in HIV-uninfected, HIV-unexposed, BCG-primed infants.Subjects will be followed for up to 1 year and 4 months.

Adverse Events and Serious Adverse Events (SAE) will be collected on subjects throughout their participation in the study. Solicited adverse events are captured 28 days post each vaccination. Evaluation of the safety profile of AERAS-404 will be performed using data from all subjects who received at least one dose and has 7 days of safety data, 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 404 Pediatric Toxicity Table provided in the protocol, will be summarized by severity corresponding to Toxicity Grade, as appropriate.

Secondary Outcome Measures
NameTimeMethod
Investigate the safety of a 3-dose AERAS-404 regimen in HIV-uninfected, HIV-unexposed, BCG-primed infantsSubjects will be followed for up to 1 year and 4 months.

The number and percentage of subjects who are enrolled into the three-dose regimen (Cohorts 4-6) with solicited and unsolicited AEs (including serious adverse events \[SAEs\], local and systemic reactions, and clinical laboratory values or vital sign values recorded as newly abnormal following study vaccination) recorded post-vaccination will be summarized to address the secondary safety objective of the study. Subjects in Cohorts 4 and 5 will be followed for : 1 year and 3 months, Cohort 6: 1 year 4 months and Solicited adverse events are captured 28 days post each vaccination.

Trial Locations

Locations (4)

PHRU, Chris Hani Baragwanath Hospital

🇿🇦

Johannesburg, Guateng, South Africa

Shandukani Research

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Johannesburg, Hillbrow, South Africa

KID-CRU, Tygerberg Hospital

🇿🇦

Cape Town, Tygerberg, South Africa

South African TB Vaccine Initiative (SATVI)

🇿🇦

Worcester, South Africa

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