Study of AERAS-402 in Healthy Infants - Full Text View

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	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:

MedlinePlus related topics: Tuberculosis

U.S. FDA Resources

Further study details as provided by Aeras:

Primary Outcome Measures:

Adverse Events collected per subject [ Time Frame: 6 to 24 months post vaccination ] [ Designated as safety issue: Yes ]
AEs are recorded for 28 days post vaccination SAEs are recorded for the entire study period to assess the safety profile
Number of cases of TB are collected in the subjects entered in the study [ Time Frame: 24 months post vaccination ] [ Designated as safety issue: No ]
To evaluate the efficacy of AERAS-402 in the prevention of TB in infants based on TB case definition endpoint #1 as described in the protocol.

Secondary Outcome Measures:

Percentage of cells expressing various cytokines will be measured in all subjects [ Time Frame: 24 months post vaccination ] [ Designated as safety issue: No ]
To evaluate the immunogenicity of AERAS-402 compared to controls, flow cytometric intracellular cytokine staining (ICS) of CD4 and CD8 T cells producing one, two or three cytokines (IFN-γ, TNF-α, and/or IL-2) simultaneously after stimulation with a peptide pool of mycobacterial peptides.
Number of subjects that have positive QuantiFERON tests after vaccination [ Time Frame: 24 months post vaccination ] [ Designated as safety issue: No ]
To evaluate the proportion of on-study QuantiFERON conversions in infants that received AERAS-402 compared to controls.
Number of subjects with probable TB [ Time Frame: 24 months post vaccination ] [ Designated as safety issue: No ]
To evaluate the efficacy of AERAS-402 in the prevention of TB in infants based on TB case definition endpoints #2 and #3 as specified in the protocol.

Enrollment:	487
Study Start Date:	September 2010
Estimated Study Completion Date:	March 2014
Estimated Primary Completion Date:	December 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Group One - Dose Finding - Low Dose Subjects enrolled in Study Group 1 will be randomized in a ratio of 3:1 to receive two doses of AERAS-402 at the lowest dose level or placebo, once on Study Day 0 and again on Study Day 28.	Biological: AERAS-402 Live recombinant serotype 35 replication deficient adenovirus vector expressing a fusion protein of three Mycobacterium tuberculosis antigens
Experimental: Group 2 - Dose Finding - Middle dose - Subjects enrolled in Study Group 2 will be randomized in a ratio of 3:1 to receive two doses of AERAS-402 at the middle dose level or placebo, once on Study Day 0 and again on Study Day 28.	Biological: AERAS-402 Live recombinant serotype 35 replication deficient adenovirus vector expressing a fusion protein of three Mycobacterium tuberculosis antigens
Experimental: Group 3 - Dose Finding - High Dose Subjects enrolled in Study Group 3 will be randomized in a ratio of 3:1 to receive two doses of AERAS-402 at the highest dose level or placebo, once on Study Day 0 and again on Study Day 28.	Biological: AERAS-402 Live recombinant serotype 35 replication deficient adenovirus vector expressing a fusion protein of three Mycobacterium tuberculosis antigens
Experimental: Group 5 - Safety Cohort Subjects will receive three doses of AERAS-402 at the selected dose level or placebo, once on Study Day 0, again on Study Day 28, and again on Study Day 280.	Biological: AERAS-402 Live recombinant serotype 35 replication deficient adenovirus vector expressing a fusion protein of three Mycobacterium tuberculosis antigens
Experimental: Group 4 - Dose Finding Group 2 These additional 96 subjects will be randomized (1:1:1:1) in a parallel design to receive two doses of either AERAS-402 (1.5 x 1010, 3.0 x 1010, or 1.0 x 1011 vp) or placebo, once on Study Day 0 and again on Study Day 28.	Biological: AERAS-402 Live recombinant serotype 35 replication deficient adenovirus vector expressing a fusion protein of three Mycobacterium tuberculosis antigens

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 presents Mycobacterium tuberculosis (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:

Parent/legal guardian has completed the written informed consent process
Is age greater than or equal to 112 days (16 weeks) and less than or equal 182 days (26 weeks) on Study Day 0
Has general good health, confirmed by medical history and physical examination
Is up to date on all 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
Has ability to complete follow-up period of 728 days as required by the protocol
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
Has completed simultaneous enrollment in Aeras Vaccine Development Registry protocol
Had BCG vaccination ≥ 3 months prior to randomization documented by medical card

Exclusion Criteria:

Acute illness, evidence of any significant active infection or temperature >=37.5°C on the day of randomization
Used immunosuppressive medication within 45 days before entry into the study (inhaled and topical corticosteroids are permitted)
Received immunoglobulin or blood products within 45 days before entry into the study
Ever received any investigational drug therapy or investigational vaccine
History or laboratory evidence of individual immunodeficiency virus (HIV-1) infection
History of allergic disease or reactions to any component of the study vaccine
Previous medical history that may compromise the safety of the participant in the study
Evidence of a new acute illness that may compromise the safety of the participant in the study
Inability to discontinue daily medications during the study
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)
History or evidence of active tuberculosis
A positive QuantiFERON®-TB Gold In-Tube test
A household contact with active TB disease

Contacts and Locations

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
Last Updated:	November 12, 2012
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
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections

ClinicalTrials.gov processed this record on May 21, 2013