Study of AERAS-402 in Healthy Infants

This study has been completed.
Sponsor:
Collaborator:
European and Developing Countries Clinical Trials Partnership (EDCTP)
Information provided by (Responsible Party):
Aeras
ClinicalTrials.gov Identifier:
NCT01198366
First received: September 7, 2010
Last updated: August 3, 2015
Last verified: August 2015
  Purpose

AERAS-402 will be given to infants of at least 16 weeks of age who have already been vaccinated with BCG to determine if AERAS-402 will increase protection of infants to tuberculosis.


Condition Intervention Phase
Tuberculosis
Biological: AERAS-402 1.5 x 10^10 vp
Biological: AERAS-402 3.0 x 10^10 vp
Biological: AERAS-402 1.0 x 10^11 vp
Biological: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Phase II, Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate the Safety and Immunogenicity of AERAS-402 in BCG-vaccinated, HIV-uninfected Infants Without Evidence of Tuberculosis

Resource links provided by NLM:


Further study details as provided by Aeras:

Primary Outcome Measures:
  • Adverse Events Collected Per Subject [ Time Frame: Up to 24 months post vaccination ] [ Designated as safety issue: Yes ]
    Adverse Events (AEs) are recorded for 28 days post vaccination Serious Adverse Events (SAEs) are recorded for the entire study period to assess the safety profile


Secondary Outcome Measures:
  • Percentage of Cells Expressing Various Cytokines Will be Measured by Intracellular Cytokine Staining (ICS) in All Subjects [ Time Frame: 28 days post last vaccination ] [ Designated as safety issue: No ]
    To evaluate the immunogenicity of AERAS-402 compared to controls, flow cytometric ICS of CD4 and CD8 T cells producing any of three cytokines (IFN-γ, TNF-α, and/or IL-2) alone or in combination after stimulation with a peptide pool of mycobacterial peptides. Dimethylsulfoxide (DMSO) subtracted responses are presented.

  • Interferon-gamma (IFN-gamma) Enzyme-linked Immunospot (ELISpot) Response: Spot Forming Units/10^6 PBMC According to ELISpot Assay [ Time Frame: 28 days post last vaccination ] [ Designated as safety issue: No ]
    To evaluate the immunogenicity of AERAS-402 compared to controls. ELISpot assay of specific T cell responses after stimulation with a peptide pool of mycobacterial peptides. Values presented have been corrected for background readings.

  • Antigen-specific Antibody Response - Mean Optical Density (Mean OD) [ Time Frame: 28 day post last vaccination ] [ Designated as safety issue: No ]
    To evaluate the immunogenicity of AERAS-402 compared to controls by ELISA Assay for Antigen-specific Antibody Response. Median responses of individual Mean OD (absorbance at 450nm) by study group is presented. Higher OD values suggests the presence of antibody to each of the Mtb antigens (Ag85A, Ag85B and TB10.4).

  • Percentage of Subjects Converting From a Negative QuantiFERON Test (QFT) to Positive QFT After Vaccination [ Time Frame: up to 24 months post vaccination ] [ Designated as safety issue: No ]
    To evaluate the proportion of on-study QuantiFERON conversions from negative to positive in infants that received AERAS-402 compared to controls. A QFT value of on >= 0.35IU/mL was considered positive for this study.


Enrollment: 487
Study Start Date: September 2010
Study Completion Date: April 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Dose Finding Gr 1 placebo x 2
Subjects received two doses (x2) of placebo (sterile buffer) on study days 0 and 28.
Biological: Placebo
Experimental: Dose Finding Gr 2 AERAS-402 (1.5 x 10^10 vp) x2
Subjects received two doses (x2) of AERAS-402 (1.5 x 10^10 vp) on study days 0 and 28.
Biological: AERAS-402 1.5 x 10^10 vp
Experimental: Dose Finding Gr 3 AERAS-402 (3.0 x 10^10 vp) x 2
Subjects received two doses (x2) of AERAS-402 (3.0 x 10^10 vp) on study days 0 and 28.
Biological: AERAS-402 3.0 x 10^10 vp
Experimental: Dose Finding Gr 4 AERAS-402 (1.0 x 10^11 vp) x 2
Subjects received two doses (x2) of AERAS-402 (1.0 x 10^11 vp) on study days 0 and 28.
Biological: AERAS-402 1.0 x 10^11 vp
Experimental: Expanded Safety Phase Gr 5 AERAS-402 (1.0 X 10^11 vp) x 3
Subjects received 3 doses (x3) of AERAS-402 (1.0 X 10^11 vp) on days 0, 28 and 280.
Biological: AERAS-402 1.5 x 10^10 vp
Placebo Comparator: Expanded Safety Phase Gr 5 Placebo x3
Subjects received 3 doses (x3) of placebo (sterile buffer) on days 0, 28 and 280.
Biological: Placebo

Detailed Description:

The only currently available tuberculosis vaccine, bacillus Calmette-Guérin (BCG), is estimated to reduce the risk of tuberculosis (TB) in children by up to 70-80%, but protection is incomplete. Efforts to increase TB protection in children include new vaccines for primary immunizations as well as combinations of vaccines given as primary and boosting vaccinations.

AERAS 402 is a live recombinant serotype 35 replication deficient adenovirus vector expressing a fusion protein of three Mycobacterium tuberculosis (Mtb) antigens (Ag85A, Ag85B and TB10.4). It presents Mtb antigens in the setting of a new, live, replication-deficient adenovirus vaccine that may increase T cell-mediated immunity and thus protection from tuberculosis. AERAS-402 appears safe and immunogenic in adults. Since BCG-vaccinated infants are the population for which AERAS-402 might be indicated, AERAS-402 will be administered to infants of at least 16 weeks of age who have already been vaccinated with BCG. This is the first Phase II study of AERAS-402 in infants.

  Eligibility

Ages Eligible for Study:   112 Days to 182 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Parent/legal guardian has completed the written informed consent process
  2. Is age greater than or equal to 112 days (16 weeks) and less than or equal 182 days (26 weeks) on Study Day 0
  3. Has general good health, confirmed by medical history and physical examination
  4. Is up to date on all Expanded Program of Immunization (EPI) immunizations for his/her age with a minimum of 14 days between the last EPI vaccination and administration of study vaccine on Study Day 0
  5. Has ability to complete follow-up period of 728 days as required by the protocol
  6. Parent/legal guardian is able and willing to stay in contact with the study site for the duration of the study and to provide updated contact information as necessary, and has no current plans to move from the study area for the duration of the study
  7. Has completed simultaneous enrollment in Aeras Vaccine Development Registry protocol
  8. Had BCG vaccination ≥ 3 months prior to randomization documented by medical card

Exclusion Criteria:

  1. Acute illness, evidence of any significant active infection or temperature >=37.5°C on the day of randomization
  2. Used immunosuppressive medication within 45 days before entry into the study (inhaled and topical corticosteroids are permitted)
  3. Received immunoglobulin or blood products within 45 days before entry into the study
  4. Ever received any investigational drug therapy or investigational vaccine
  5. History or laboratory evidence of individual immunodeficiency virus (HIV-1) infection
  6. History of allergic disease or reactions to any component of the study vaccine
  7. Previous medical history that may compromise the safety of the participant in the study
  8. Evidence of a new acute illness that may compromise the safety of the participant in the study
  9. Inability to discontinue daily medications during the study
  10. History or evidence of any systemic disease on physical examination or any acute or chronic illness that may interfere with the evaluation of the safety or immunogenicity of the vaccine, e.g., including masses between the leg and abdomen (e.g., inguinal hernia or lymphadenopathy)
  11. History or evidence of active tuberculosis
  12. A positive QuantiFERON®-TB Gold In-Tube test
  13. A household contact with active TB disease
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01198366

Locations
Kenya
Boro Heath Center
Boro, Kenya
KEMRI/CDC Research and Public Heath Collaboration
Kisumu, Kenya, 40100
Siaya District Hospital
Siaya, Kenya
Mozambique
CISM: Centro de Investigacao em Saude de Manhica
Manhica, Mozambique, 1929
South Africa
Univeristy of Cape Town
Cape Town, South Africa, 7925
Perinatal HIV Research Unit (PHRU) Chris Hani Baragwanath Hospital
Soweto, South Africa, 1864
SATVI: Worcester
Worcester, South Africa, 6850
Sponsors and Collaborators
Aeras
European and Developing Countries Clinical Trials Partnership (EDCTP)
Investigators
Study Director: Robert Walker Aeras
  More Information

No publications provided

Responsible Party: Aeras
ClinicalTrials.gov Identifier: NCT01198366     History of Changes
Other Study ID Numbers: C-029-402
Study First Received: September 7, 2010
Results First Received: June 10, 2015
Last Updated: August 3, 2015
Health Authority: Kenya: Pharmacy and Poisons Board
South Africa: Medicines Control Council
Mozambique: Ministry of Health (MISAU)

Keywords provided by Aeras:
Tuberculosis
Vaccine
Immunogenicity
Prevention of Tuberculosis

Additional relevant MeSH terms:
Tuberculosis
Actinomycetales Infections
Bacterial Infections
Gram-Positive Bacterial Infections
Mycobacterium Infections

ClinicalTrials.gov processed this record on September 03, 2015