Clinical trial NCT01198366: Study of AERAS-402 in Healthy Infants
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Tuberculosis
Keywords: Tuberculosis
Vaccine
Immunogenicity
Prevention of Tuberculosis
Lead sponsor: Aeras
Sponsor class: OTHER
Collaborators: name: European and Developing Countries Clinical Trials Partnership (EDCTP)
First posted: 2010-09-10
Enrollment: 487
Sex: ALL
Minimum age (years): 112
Maximum age (years): 182
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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 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

Primary outcomes:
measure: Adverse Events Collected Per Subject
timeFrame: Up to 24 months post vaccination
Secondary outcomes:
measure: Percentage of Cells Expressing Various Cytokines Will be Measured by Intracellular Cytokine Staining (ICS) in All Subjects
timeFrame: 28 days post last vaccination
measure: Interferon-gamma (IFN-gamma) Enzyme-linked Immunospot (ELISpot) Response: Spot Forming Units/10^6 PBMC According to ELISpot Assay
timeFrame: 28 days post last vaccination
measure: Antigen-specific Antibody Response - Mean Optical Density (Mean OD)
timeFrame: 28 day post last vaccination
measure: Percentage of Subjects Converting From a Negative QuantiFERON Test (QFT) to Positive QFT After Vaccination
timeFrame: up to 24 months post vaccination
Other outcomes:
Locations:
city: Boro
country: Kenya
facility: Boro Heath Center
city: Kisumu
country: Kenya
facility: KEMRI/CDC Research and Public Heath Collaboration
city: Siaya
country: Kenya
facility: Siaya District Hospital
city: Manhica
country: Mozambique
facility: CISM: Centro de Investigacao em Saude de Manhica
city: Cape Town
country: South Africa
facility: Univeristy of Cape Town
city: Soweto
country: South Africa
facility: Perinatal HIV Research Unit (PHRU) Chris Hani Baragwanath Hospital
city: Worcester
country: South Africa
facility: SATVI: Worcester
Study officials:
affiliation: Aeras
name: Robert Walker
role: STUDY_DIRECTOR
References:
citation: Tameris M, Hokey DA, Nduba V, Sacarlal J, Laher F, Kiringa G, Gondo K, Lazarus EM, Gray GE, Nachman S, Mahomed H, Downing K, Abel B, Scriba TJ, McClain JB, Pau MG, Hendriks J, Dheenadhayalan V, Ishmukhamedov S, Luabeya AK, Geldenhuys H, Shepherd B, Blatner G, Cardenas V, Walker R, Hanekom WA, Sadoff J, Douoguih M, Barker L, Hatherill M. A double-blind, randomised, placebo-controlled, dose-finding trial of the novel tuberculosis vaccine AERAS-402, an adenovirus-vectored fusion protein, in healthy, BCG-vaccinated infants. Vaccine. 2015 Jun 9;33(25):2944-54. doi: 10.1016/j.vaccine.2015.03.070. Epub 2015 Apr 28.