Phase 1/II, Safety and Immunogenicity Study of AERAS-404 in BCG-Primed Infants
C-015-404
3 other identifiers
interventional
243
1 country
4
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jul 2013
Longer than P75 for phase_1
4 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 21, 2013
CompletedFirst Posted
Study publicly available on registry
May 24, 2013
CompletedStudy Start
First participant enrolled
July 1, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 22, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
December 22, 2017
CompletedApril 9, 2018
April 1, 2018
4.5 years
May 21, 2013
April 6, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Investigate the safety of AERAS-404 in HIV-uninfected, HIV-unexposed, BCG-primed infants.
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.
Subjects will be followed for up to 1 year and 4 months.
Secondary Outcomes (1)
Investigate the safety of a 3-dose AERAS-404 regimen in HIV-uninfected, HIV-unexposed, BCG-primed infants
Subjects will be followed for up to 1 year and 4 months.
Other Outcomes (4)
Assess the immunogenicity of a 3-dose AERAS-404 regimen in HIV-uninfected, HIV-unexposed, BCG-primed infants.
Subjects will be followed for up to 1 year and 4 months.
Select an appropriate dose regimen for AERAS-404 in HIV-uninfected, HIV-unexposed, BCG-primed infants.
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.
Explore interactions between AERAS-404 and EPI vaccines.
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.
- +1 more other outcomes
Study Arms (7)
Cohort 1 Aeras404 (5ug H4/100nmol IC31) or Placebo
EXPERIMENTAL1 Dose; Subject ≥ 168 to ≤ 196 days of age
Cohort 2 AERAS-404 (5ug H4/500nmol IC31) or Placebo
EXPERIMENTAL1 Dose; Subject ≥ 168 to ≤ 196 days of age
Cohort 3A AERAS-404 (5ug H4/500nmol IC31) or Placebo
EXPERIMENTAL2 Doses; Subject ≥ 168 to ≤ 189 days of age
Cohort 3B AERAS-404 (15ug H4/500nmol IC31) or Placebo
EXPERIMENTAL2 Doses; Subject ≥ 168 to ≤ 189 days of age
Cohort 4 AERAS-404 (15ug H4/500nmol IC31) or Placebo
EXPERIMENTAL3 Doses; Subject ≥ 84 to ≤ 98 days of age
Cohort 5 AERAS-404 (50ug H4/500nmol IC31) or Placebo
EXPERIMENTAL3 Doses; Subject ≥ 84 to ≤ 98 days of age
Cohort 6 AERAS-404 (dose level pending) or Placebo
EXPERIMENTAL3 Doses; Subject ≥ 64 to ≤ 83 days of age
Interventions
AERAS-404 has two components: the H4 antigen and the IC31 adjuvant. The reconstitution of the vaccine components, H4 antigen (manufactured at SP) and IC31 adjuvant (supplied by SSI), will take place at the clinical research site (CRS) prior to injection.
Tris buffered saline (10mM Tris, pH 7.4, 150nm sodium chloride).
Eligibility Criteria
You may qualify if:
- 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)
- Source documentation of birth weight ≥ 2.5 kg.
- Documented BCG vaccination within 72 hours of birth.
- Documented receipt of all age-appropriate EPI vaccines, except Rotavirus, for Cohorts 4 to 6 (see Appendix II).
- Source documentation of a negative HIV status in the mother, from any time during pregnancy with this child through randomization.
- Documentation of infant HIV negative exposure or infection status with negative HIV ELISA and HIV DNA PCR tests.
- Parent or legal guardian able and willing to provide signed informed consent.
- Participant/parent/legal guardian able to attend all scheduled visits and to comply with all trial procedures.
You may not qualify if:
- History of TB exposure in household or non-household contact.
- History/Evidence of TB disease or infection.
- Quantiferon positive.
- Prior TST test.
- Any one of Anemia, Neutropenia, Thrombocytopenia, SGPT (ALT), SGOT (AST) or Creatinine ≥ Grade 2
- Receipt of a live vaccine within 28 days prior to randomization.
- Receipt or planned receipt of any investigational vaccine.
- Known or suspected congenital immunodeficiency.
- Receipt of immunosuppressive therapy or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).
- Known or suspected autoimmune disease
- 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.
- Participation in another clinical trial for an investigational product (IP).
- Bleeding disorder or receipt of anticoagulants in the 3 weeks preceding randomization, contraindicating IM vaccination.
- Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion.
- Febrile illness (temperature ≥ 100.4°F \[≥ 38.0°C\]) within 24 hours prior to randomization.
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Aeraslead
- Statens Serum Institutcollaborator
- Sanofi Pasteur, a Sanofi Companycollaborator
- National Institute of Allergy and Infectious Diseases (NIAID)collaborator
- International Maternal Pediatric Adolescent AIDS Clinical Trials Groupcollaborator
Study Sites (4)
PHRU, Chris Hani Baragwanath Hospital
Johannesburg, Guateng, 2091, South Africa
Shandukani Research
Johannesburg, Hillbrow, 2001, South Africa
KID-CRU, Tygerberg Hospital
Cape Town, Tygerberg, 7505, South Africa
South African TB Vaccine Initiative (SATVI)
Worcester, South Africa
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Ann Ginsberg, MD, PhD
Aeras
- PRINCIPAL INVESTIGATOR
Avy Violari, MD
Perinatal HIV Research Unit
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 21, 2013
First Posted
May 24, 2013
Study Start
July 1, 2013
Primary Completion
December 22, 2017
Study Completion
December 22, 2017
Last Updated
April 9, 2018
Record last verified: 2018-04