Study of AERAS-402 in Healthy Infants

NCT ID: NCT01198366

Last Updated: 2017-05-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 487 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-09-30
• Study Completion Date: 2014-04-30

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.

Conditions

Tuberculosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Dose Finding Gr 1 placebo x 2

Subjects received two doses (x2) of placebo (sterile buffer) on study days 0 and 28.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

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.

Group Type: EXPERIMENTAL

AERAS-402 1.5 x 10^10 vp

Intervention Type: BIOLOGICAL

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.

Group Type: EXPERIMENTAL

AERAS-402 3.0 x 10^10 vp

Intervention Type: BIOLOGICAL

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.

Group Type: EXPERIMENTAL

AERAS-402 1.0 x 10^11 vp

Intervention Type: BIOLOGICAL

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.

Group Type: EXPERIMENTAL

AERAS-402 1.5 x 10^10 vp

Intervention Type: BIOLOGICAL

Expanded Safety Phase Gr 5 Placebo x3

Subjects received 3 doses (x3) of placebo (sterile buffer) on days 0, 28 and 280.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

Interventions

AERAS-402 1.5 x 10^10 vp

Intervention Type: BIOLOGICAL

AERAS-402 3.0 x 10^10 vp

Intervention Type: BIOLOGICAL

AERAS-402 1.0 x 10^11 vp

Intervention Type: BIOLOGICAL

Placebo

Intervention Type: BIOLOGICAL

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

• Minimum Eligible Age: 112 Days
• Maximum Eligible Age: 182 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

European and Developing Countries Clinical Trials Partnership (EDCTP)

OTHER_GOV

Sponsor Role: collaborator

Aeras

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert Walker

Role: STUDY_DIRECTOR

Aeras

Locations

Boro Heath Center

Boro, , Kenya

KEMRI/CDC Research and Public Heath Collaboration

Kisumu, , Kenya

Siaya District Hospital

Siaya, , Kenya

CISM: Centro de Investigacao em Saude de Manhica

Manhiça, , Mozambique

Univeristy of Cape Town

Cape Town, , South Africa

Perinatal HIV Research Unit (PHRU) Chris Hani Baragwanath Hospital

Soweto, , South Africa

SATVI: Worcester

Worcester, , South Africa

Countries

Kenya; Mozambique; South Africa

References

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.

Reference Type: BACKGROUND

PMID: 25936724 (View on PubMed)

Other Identifiers

C-029-402

Identifier Type: -

Identifier Source: org_study_id