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Study of AERAS-402 in Healthy Infants

Primary Purpose

Tuberculosis

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

AERAS-402 1.5 x 10^10 vp

AERAS-402 3.0 x 10^10 vp

AERAS-402 1.0 x 10^11 vp

Placebo

About this trial

This is an interventional prevention trial for Tuberculosis focused on measuring Tuberculosis, Vaccine, Immunogenicity, Prevention of Tuberculosis

Eligibility Criteria

112 Days - 182 Days (Child)All SexesAccepts Healthy Volunteers

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 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
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

Sites / Locations

Boro Heath Center
KEMRI/CDC Research and Public Heath Collaboration
Siaya District Hospital
CISM: Centro de Investigacao em Saude de Manhica
Univeristy of Cape Town
Perinatal HIV Research Unit (PHRU) Chris Hani Baragwanath Hospital
SATVI: Worcester

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

Dose Finding Gr 1 placebo x 2

Dose Finding Gr 2 AERAS-402 (1.5 x 10^10 vp) x2

Dose Finding Gr 3 AERAS-402 (3.0 x 10^10 vp) x 2

Dose Finding Gr 4 AERAS-402 (1.0 x 10^11 vp) x 2

Expanded Safety Phase Gr 5 AERAS-402 (1.0 X 10^11 vp) x 3

Expanded Safety Phase Gr 5 Placebo x3

Arm Description

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

Subjects received two doses (x2) of AERAS-402 (1.5 x 10^10 vp) on study days 0 and 28.

Subjects received two doses (x2) of AERAS-402 (3.0 x 10^10 vp) on study days 0 and 28.

Subjects received two doses (x2) of AERAS-402 (1.0 x 10^11 vp) on study days 0 and 28.

Subjects received 3 doses (x3) of AERAS-402 (1.0 X 10^11 vp) on days 0, 28 and 280.

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

Outcomes

Primary Outcome Measures

Adverse Events Collected Per Subject

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

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

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)

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

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.

Full Information

NCT ID

NCT01198366

First Posted

September 7, 2010

Last Updated

March 31, 2017

Sponsor

Aeras

Collaborators

European and Developing Countries Clinical Trials Partnership (EDCTP)

1. Study Identification

Unique Protocol Identification Number

NCT01198366

Brief Title

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

2. Study Status

Record Verification Date

March 2017

Overall Recruitment Status

Completed

Study Start Date

September 2010 (undefined)

Primary Completion Date

January 2014 (Actual)

Study Completion Date

April 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Aeras

Collaborators

European and Developing Countries Clinical Trials Partnership (EDCTP)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Tuberculosis

Keywords

Tuberculosis, Vaccine, Immunogenicity, Prevention of Tuberculosis

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

487 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dose Finding Gr 1 placebo x 2

Arm Type

Placebo Comparator

Arm Description

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

Arm Title

Dose Finding Gr 2 AERAS-402 (1.5 x 10^10 vp) x2

Arm Type

Experimental

Arm Description

Subjects received two doses (x2) of AERAS-402 (1.5 x 10^10 vp) on study days 0 and 28.

Arm Title

Dose Finding Gr 3 AERAS-402 (3.0 x 10^10 vp) x 2

Arm Type

Experimental

Arm Description

Subjects received two doses (x2) of AERAS-402 (3.0 x 10^10 vp) on study days 0 and 28.

Arm Title

Dose Finding Gr 4 AERAS-402 (1.0 x 10^11 vp) x 2

Arm Type

Experimental

Arm Description

Subjects received two doses (x2) of AERAS-402 (1.0 x 10^11 vp) on study days 0 and 28.

Arm Title

Expanded Safety Phase Gr 5 AERAS-402 (1.0 X 10^11 vp) x 3

Arm Type

Experimental

Arm Description

Subjects received 3 doses (x3) of AERAS-402 (1.0 X 10^11 vp) on days 0, 28 and 280.

Arm Title

Expanded Safety Phase Gr 5 Placebo x3

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Biological

Intervention Name(s)

AERAS-402 1.5 x 10^10 vp

Intervention Type

Biological

Intervention Name(s)

AERAS-402 3.0 x 10^10 vp

Intervention Type

Biological

Intervention Name(s)

AERAS-402 1.0 x 10^11 vp

Intervention Type

Biological

Intervention Name(s)

Placebo

Primary Outcome Measure Information:

Title

Adverse Events Collected Per Subject

Description

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

Time Frame

Up to 24 months post vaccination

Secondary Outcome Measure Information:

Title

Percentage of Cells Expressing Various Cytokines Will be Measured by Intracellular Cytokine Staining (ICS) in All Subjects

Description

Time Frame

28 days post last vaccination

Title

Interferon-gamma (IFN-gamma) Enzyme-linked Immunospot (ELISpot) Response: Spot Forming Units/10^6 PBMC According to ELISpot Assay

Description

Time Frame

28 days post last vaccination

Title

Antigen-specific Antibody Response - Mean Optical Density (Mean OD)

Description

Time Frame

28 day post last vaccination

Title

Percentage of Subjects Converting From a Negative QuantiFERON Test (QFT) to Positive QFT After Vaccination

Description

Time Frame

up to 24 months post vaccination

10. Eligibility

Sex

All

Minimum Age & Unit of Time

112 Days

Maximum Age & Unit of Time

182 Days

Accepts Healthy Volunteers

Eligibility 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 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 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Robert Walker

Organizational Affiliation

Aeras

Official's Role

Study Director

Facility Information:

Facility Name

Boro Heath Center

City

Boro

Country

Kenya

Facility Name

KEMRI/CDC Research and Public Heath Collaboration

City

Kisumu

ZIP/Postal Code

40100

Country

Kenya

Facility Name

Siaya District Hospital

City

Siaya

Country

Kenya

Facility Name

CISM: Centro de Investigacao em Saude de Manhica

City

Manhica

ZIP/Postal Code

1929

Country

Mozambique

Facility Name

Univeristy of Cape Town

City

Cape Town

ZIP/Postal Code

7925

Country

South Africa

Facility Name

Perinatal HIV Research Unit (PHRU) Chris Hani Baragwanath Hospital

City

Soweto

ZIP/Postal Code

1864

Country

South Africa

Facility Name

SATVI: Worcester

City

Worcester

ZIP/Postal Code

6850

Country

South Africa

12. IPD Sharing Statement

Citations:

PubMed Identifier

25936724

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.

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Study of AERAS-402 in Healthy Infants

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