Overview

This trial is active, not recruiting.

Condition tuberculosis
Treatments aeras-404, placebo, bacillus calmette-guérin (bcg)
Phase phase 2
Sponsor Aeras
Collaborator Sanofi Pasteur, a Sanofi Company
Start date February 2014
End date September 2016
Trial size 990 participants
Trial identifier NCT02075203, C-040-404

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

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose prevention
Arm
(Experimental)
2 doses on Study Days 0 and 56
aeras-404 H4
The H4 antigen is a fusion protein created from two Mtb antigens: antigen Ag85B and TB10.4. Ag85B is also referred to as α-antigen and is a 30-kDa mycolyl transferase protein. TB10.4 is one of three members of the very similar ESAT-6 group of proteins found in Mtb culture supernatants. TB10.4 induces broad immune responses in T cells isolated from TB subjects compared to BCG-vaccinated donors and unvaccinated donors. IC31 is a combination of a leucine-rich peptide named KLK & a synthetic oligonucleotide named ODN1a. The optimal molar ratio of KLK to ODN1a in mice is 25:1. AERAS-404 & saline placebo trial arms will be double-blinded since BCG causes a recognizable local injection site reaction, the BCG revaccination trial arm will be unblinded.
(Active Comparator)
1 Dose on Study Day 0
bacillus calmette-guérin (bcg) BCG
BCG SSI Vaccine is registered in South Africa for prevention of TB in children and adults. BCG, an attenuated, live culture of the Bacillus Calmette-Guérin, was originally attenuated between 1906 and 1919 by serial passage of an M. bovis strain. The manufacturer Statens Serum Institut (SSI) in Copenhagen, Denmark derives this vaccine from the Danish BCG strain 1331. BCG SSI is supplied by the manufacturer in amber 10-dose vials containing 0.75 mg lyophilized SSI BCG. The BCG revaccination trial arm will be unblinded (open label).
(Placebo Comparator)
2 Doses on Study Days 0 and 56
placebo Tris buffered saline
Tris buffered saline (10mM Tris,pH 7.4, 150NM sodium chloride)

Primary Outcomes

Measure
Safety, in HIV-uninfected, remotely BCG vaccinated adolescents, of Aeras-404 or BCG revaccination; measured by the number and percentage of unsolicited and solicited adverse events recorded post vaccination.
time frame: Minimum follow-up time of 6 months
Prevention of Mtb infection, as measured by rates of conversion using a QFT-GIT assay (change from negative to positive), by AERAS-404 compared to placebo or BCG revaccination compared to placebo.
time frame: Minimum follow-up time of 6 months; median follow-up time at least 15 months; and a maximum individual follow-up to QFT-GIT conversion of 24 months.

Secondary Outcomes

Measure
Prevention of Mtb infection measured by rates of sustained conversion using a QFT-GIT assay, by AERAS-404 compared to placebo, or BCG revaccination compared to placebo.
time frame: Minimum follow-up time of 6 months; median follow-up time at least 15 months; and a maximum individual follow-up to QFT-GIT conversion of 24 months.
Immunogenicity in HIV-uninfected, remotely BCG vaccinated adolescents of AERAS-404 or BCG revaccination.
time frame: Minimum follow-up time of 6 months; median follow-up time at least 15 months; and a maximum individual follow-up to QFT-GIT conversion of 24 months.

Eligibility Criteria

Male or female participants from 12 years up to 17 years old.

Inclusion Criteria: 1. Has completed the written informed consent and assent process 2. Is age ≥ 12 years and ≤ 17 years on Study Day 0 3. Agrees to stay in contact with the study site for the duration of the study, provide updated contact information 4. For female subjects: agrees to avoid pregnancy from 28 days prior to Study Day 0 and for the full duration of the study. 5. Has general good health, confirmed by medical history and physical examination 6. Has body mass index (BMI) for age and sex between the 5th and 95th centiles by Centers for Disease Control nomogram 7. Had BCG vaccination at least 5 years ago documented through medical history or by presence of healed BCG scar 8. Tests QFT-GIT negative at screening, using the manufacturer's recommended threshold of 0.35 IU/mL Exclusion Criteria: 1. Acute illness on Study Day 0 2. Oral temperature ≥37.5°C on Study Day 0 3. Clinically significant (and no more than Grade 1 on the Toxicity Scale) abnormal laboratory values from blood collected within 21 days 4. Evidence of clinically significant (and no more than Grade 1 on the Toxicity Scale) systemic or local disease on urinalysis 5. 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 6. History of treatment for active TB disease or latent Mtb infection 7. History or evidence, including chest X-ray, of active TB disease 8. Shared residence with an individual receiving anti-TB treatment, or known incompletely treated culture or smear positive TB 9. History of autoimmune disease or immunosuppression 10. Used immunosuppressive medication within 42 days before Study Day 0 11. Received immunoglobulin or blood products within 42 days before Study Day 0 12. Received any investigational drug therapy or investigational vaccine within 182 days before Study Day 0 13. Received investigational TB vaccine, other than BCG 14. History or laboratory evidence of any past or present possible immunodeficiency state not limited to any lab indication of HIV-1 infection 15. History of allergic disease likely to be exacerbated by any component of the study vaccine 16. History of alcohol or drug abuse 17. All female subjects: currently pregnant or lactating/nursing; or positive urine pregnancy test during screening 18. Received a (TST) within 3 months (90 days) prior to Study Day 0. 19. Any current medical, psychiatric, occupational, substance abuse problems problems that in opinion of investigator will make unlikely for the subject to comply with the protocol

Additional Information

Official title 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
Principal investigator Mark Hatherill
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.
Trial information was received from ClinicalTrials.gov and was last updated in June 2016.
Information provided to ClinicalTrials.gov by Aeras.