Clinical trial NCT01861730: Phase 1/II, Safety and Immunogenicity Study of AERAS-404 in BCG-Primed Infants
Official title: Phase 1/II, Safety and Immunogenicity Study of a Recombinant Protein Tuberculosis Vaccine (AERAS-404) in BCG-Primed Infants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Tuberculosis
Keywords: BCG Vaccinated
HIV Negative
Lead sponsor: Aeras
Sponsor class: OTHER
Collaborators: name: Statens Serum Institut
name: Sanofi Pasteur, a Sanofi Company
name: National Institute of Allergy and Infectious Diseases (NIAID)
name: International Maternal Pediatric Adolescent AIDS Clinical Trials Group
First posted: 2013-05-24
Enrollment: 243
Sex: ALL
Minimum age (years): 64
Maximum age (years): 196
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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).

Eligibility criteria: INCLUSION CRITERIA

1. Age at time of entry:

   Cohorts 1 to 6
   * Cohorts 1 and 2: ≥ 168 to ≤ 196 days
   * Cohorts 3A and 3B: ≥ 168 to ≤ 189 days
   * Cohorts 4 and 5: ≥ 84 to ≤ 98 days (≥ 2 weeks after receipt of EPI vaccine doses at 10 weeks of age)
   * Cohort 6 - coincident with EPI vaccine doses at 10 weeks of age (≥ 64 to ≤ 83 days of age)
2. Source documentation of birth weight ≥ 2.5 kg.
3. Documented BCG vaccination within 72 hours of birth.
4. Documented receipt of all age-appropriate EPI vaccines, except Rotavirus, for Cohorts 4 to 6 (see Appendix II).
5. Source documentation of a negative HIV status in the mother, from any time during pregnancy with this child through randomization.
6. Documentation of infant HIV negative exposure or infection status with negative HIV ELISA and HIV DNA PCR tests.
7. Parent or legal guardian able and willing to provide signed informed consent.
8. Participant/parent/legal guardian able to attend all scheduled visits and to comply with all trial procedures.

EXCLUSION CRITERIA

1. History of TB exposure in household or non-household contact.
2. History/Evidence of TB disease or infection.
3. Quantiferon positive.
4. Prior TST test.
5. Any one of Anemia, Neutropenia, Thrombocytopenia, SGPT (ALT), SGOT (AST) or Creatinine ≥ Grade 2
6. Receipt of a live vaccine within 28 days prior to randomization.
7. Receipt or planned receipt of any investigational vaccine.
8. Known or suspected congenital immunodeficiency.
9. Receipt of immunosuppressive therapy or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).
10. Known or suspected autoimmune disease
11. Hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to a vaccine containing any of the same substances as the vaccine used in the trial.
12. Participation in another clinical trial for an investigational product (IP).
13. Bleeding disorder or receipt of anticoagulants in the 3 weeks preceding randomization, contraindicating IM vaccination.
14. Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion.
15. Febrile illness (temperature ≥ 100.4°F \[≥ 38.0°C\]) within 24 hours prior to randomization.

    Note: A subject may enroll after recovery from febrile illness if the subject is still within the age window.
16. Systemic antibiotic use within 48 hours prior to randomization.

Primary outcomes:
measure: Investigate the safety of AERAS-404 in HIV-uninfected, HIV-unexposed, BCG-primed infants.
timeFrame: Subjects will be followed for up to 1 year and 4 months.
Secondary outcomes:
measure: Investigate the safety of a 3-dose AERAS-404 regimen in HIV-uninfected, HIV-unexposed, BCG-primed infants
timeFrame: Subjects will be followed for up to 1 year and 4 months.
Other outcomes:
measure: Assess the immunogenicity of a 3-dose AERAS-404 regimen in HIV-uninfected, HIV-unexposed, BCG-primed infants.
timeFrame: Subjects will be followed for up to 1 year and 4 months.
measure: Select an appropriate dose regimen for AERAS-404 in HIV-uninfected, HIV-unexposed, BCG-primed infants.
timeFrame: After all subjects in Cohorts 4 and 5 have completed Study Day 126, the safety and immunogenicity data from these Cohorts will be evaluated. The data will inform the decision on the study vaccine dose for Cohort 6.
measure: Explore interactions between AERAS-404 and EPI vaccines.
timeFrame: Antibody concentration blood samples taken when subjects reach 12 months of age for all Cohorts and in addition, 28 post second study vaccine dose (Study Day 56) for subjects in Cohort 6 only.
measure: Assess the immunogenicity of a 2-dose AERAS-404 regimen in HIV-uninfected, HIV-unexposed, BCG-primed infants.
timeFrame: Subjects will have Immunology samples taken at multiple time points for up to 1 year and 4 months.
Locations:
city: Johannesburg
country: South Africa
facility: PHRU, Chris Hani Baragwanath Hospital
state: Guateng
city: Johannesburg
country: South Africa
facility: Shandukani Research
state: Hillbrow
city: Cape Town
country: South Africa
facility: KID-CRU, Tygerberg Hospital
state: Tygerberg
city: Worcester
country: South Africa
facility: South African TB Vaccine Initiative (SATVI)
Study officials:
affiliation: Aeras
name: Ann Ginsberg, MD, PhD
role: STUDY_DIRECTOR
affiliation: Perinatal HIV Research Unit
name: Avy Violari, MD
role: PRINCIPAL_INVESTIGATOR
References: