A Randomized, Placebo Controlled, Partially Blinded Phase II Study to Evaluate Safety, Immunogenicity, and Prevention of Infection With Mycobacterium Tuberculosis of AERAS-404 and BCG Revaccination in Healthy Adolescents
Overview
- Phase
- Phase 2
- Intervention
- AERAS-404
- Conditions
- Tuberculosis
- Sponsor
- Aeras
- Enrollment
- 989
- Locations
- 2
- Primary Endpoint
- Safety Profile of H4:IC31 and BCG Revaccination in HIV-uninfected, Remotely BCG Vaccinated Adolescents.
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
Randomized, Placebo Controlled, Partially Blinded Phase II Study to Evaluate Safety, Immunogenicity, and Prevention of Infection with Mycobacterium tuberculosis of AERAS-404 and BCG Revaccination in Healthy Adolescents
Detailed Description
This Phase II, randomized, 3-arm, placebo controlled, partially blinded, clinical trial will be conducted in 990 healthy, HIV-uninfected, QFT-GIT negative, previously BCG vaccinated adolescents. The trial will be conducted at the South African Tuberculosis Vaccine Initiative (SATVI) site in the Western Cape region of South Africa, where epidemiological studies involving thousands of adolescents have been conducted over the last decade to characterize rates of Mtb infection and active TB disease in this age group. Subjects will be enrolled in two sequential cohorts and within each cohort subjects will be randomized in a 1:1:1 ratio to receive either AERAS-404 or saline placebo on Days 0 and 56, or BCG Vaccine SSI on Day 0. The first 90 subjects (30 from each arm) will form the Safety \& Immunogenicity Cohort and will be subject to more intensive collection of safety data, with data reviewed by the Data Monitoring Committee (DMC), principal investigator and local medical monitor. Selected immunogenicity assays, including whole blood intracellular cytokine staining (ICS), will also be performed in this cohort. The remaining 900 subjects will be enrolled into the Correlates Cohort. All 990 subjects in the study will be evaluated for safety and biomarker outcomes, and for prevention of Mtb infection. The primary Mtb infection endpoint will be QFT-GIT conversion from a negative to positive test, using the manufacturer's recommended threshold of 0.35 IU/mL, at any time-point after Day 84 and through end of follow-up for the primary endpoint. The 84-day 'wash-out' period is stipulated in order to exclude subjects who may have already been Mtb infected, but not yet converted their QFT-GIT test at screening, thus subjects who convert their QFT-GIT at Day 84 will not be included in the analyses of prevention of Mtb infection.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Has completed the written informed consent and assent process
- •Is age ≥ 12 years and ≤ 17 years on Study Day 0
- •Agrees to stay in contact with the study site for the duration of the study, provide updated contact information
- •For female subjects: agrees to avoid pregnancy from 28 days prior to Study Day 0 and for the full duration of the study.
- •Has general good health, confirmed by medical history and physical examination
- •Had BCG vaccination at least 5 years ago documented through medical history or by presence of healed BCG scar
- •Tests QFT-GIT negative at screening, using the manufacturer's recommended threshold of 0.35 IU/mL
Exclusion Criteria
- •Acute illness on Study Day 0
- •Oral temperature ≥37.5°C on Study Day 0
- •Clinically significant (and no more than Grade 1 on the Toxicity Scale) abnormal laboratory values from blood collected within 21 days
- •Evidence of clinically significant (and no more than Grade 1 on the Toxicity Scale) systemic or local disease on urinalysis
- •History or evidence of any clinically significant systemic disease, or any acute or chronic illness that might affect the safety, immunogenicity, or efficacy of study vaccine in the opinion of the investigator
- •History of treatment for active TB disease or latent Mtb infection
- •History or evidence, including chest X-ray, of active TB disease
- •Shared residence with an individual receiving anti-TB treatment, or known incompletely treated culture or smear positive TB
- •History of autoimmune disease or immunosuppression
- •Used immunosuppressive medication within 42 days before Study Day 0
Arms & Interventions
AERAS-404 (15 mcgH4/500 nmol IC31)
2 doses on Study Days 0 and 56
Intervention: AERAS-404
Bacillus Calmette-Guérin (BCG)
1 Dose on Study Day 0
Intervention: Bacillus Calmette-Guérin (BCG)
Placebo
2 Doses on Study Days 0 and 56
Intervention: Placebo
Outcomes
Primary Outcomes
Safety Profile of H4:IC31 and BCG Revaccination in HIV-uninfected, Remotely BCG Vaccinated Adolescents.
Time Frame: Study day 7 thru 6 months after last vaccination
Number of unsolicited and solicited adverse events recorded post vaccination. Unsolicited adverse events: 28 days post each vaccination Solicited adverse events: 7 days post each vaccination (with diary cards used for 7 days after each vaccination for Safety and Immunogenicity Cohort only) Solicited and unsolicited injection site reaction adverse events: BCG Group - 84 days post vaccination; H4:IC31/Placebo Groups - 28 days post each vaccination Serious adverse events, adverse events of special interest, and SUSARs: Entire study period, with a minimum of 6 months following the last dose of study vaccine
Number of Participants Testing Positive for Mtb at Day 84
Time Frame: Study day 84 through 6 months post-conversion
Rates of conversion to Mtb-positive measured by QuantiFERON-TB Gold In-tube (QFT-GIT) assay. The primary evaluation of Mtb infection was QFT-GIT conversion from a negative to positive test, using the manufacturer's recommended threshold of ≥0.35 IU/mL, at any time point after Day 84 and through end of follow-up for the primary endpoint. All participants with primary QFT-GIT conversion were followed for an additional 6 months post-conversion to ascertain the sustained QFT-GIT conversion and QFT-GIT reversion endpoints. Participants with an initial QFT-GIT conversion at Month 6 or 12 were asked to return for a final QFT-GIT evaluation and assessment for TB signs and symptoms at least 24 months after their initial vaccination. * H4:IC31 compared to placebo * BCG revaccination compared to placebo
Secondary Outcomes
- Rates of Sustained Conversion to Mtb-positive(6 months after initial conversion)
- Percentage of Participants With Immune Response to Vaccine in HIV-uninfected, Remotely BCG-vaccinated Adolescents: o H4:IC31 o BCG Revaccination(Study day 70)