Back to results

Phase 1/II, Safety and Immunogenicity Study of AERAS-404 in BCG-Primed Infants (C-015-404)

Primary Purpose

Tuberculosis

Status

Completed

Phase

Phase 1

Locations

South Africa

Study Type

Interventional

Intervention

AERAS-404

Placebo

About this trial

This is an interventional prevention trial for Tuberculosis focused on measuring BCG Vaccinated, HIV Negative

Eligibility Criteria

64 Days - 196 Days (Child)All SexesAccepts Healthy Volunteers

INCLUSION CRITERIA

Age at time of entry:
Cohorts 1 to 6
- Cohorts 1 and 2: ≥ 168 to ≤ 196 days
- Cohorts 3A and 3B: ≥ 168 to ≤ 189 days
- Cohorts 4 and 5: ≥ 84 to ≤ 98 days (≥ 2 weeks after receipt of EPI vaccine doses at 10 weeks of age)
- Cohort 6 - coincident with EPI vaccine doses at 10 weeks of age (≥ 64 to ≤ 83 days of age)
Source documentation of birth weight ≥ 2.5 kg.
Documented BCG vaccination within 72 hours of birth.
Documented receipt of all age-appropriate EPI vaccines, except Rotavirus, for Cohorts 4 to 6 (see Appendix II).
Source documentation of a negative HIV status in the mother, from any time during pregnancy with this child through randomization.
Documentation of infant HIV negative exposure or infection status with negative HIV ELISA and HIV DNA PCR tests.
Parent or legal guardian able and willing to provide signed informed consent.
Participant/parent/legal guardian able to attend all scheduled visits and to comply with all trial procedures.

EXCLUSION CRITERIA

History of TB exposure in household or non-household contact.
History/Evidence of TB disease or infection.
Quantiferon positive.
Prior TST test.
Any one of Anemia, Neutropenia, Thrombocytopenia, SGPT (ALT), SGOT (AST) or Creatinine ≥ Grade 2
Receipt of a live vaccine within 28 days prior to randomization.
Receipt or planned receipt of any investigational vaccine.
Known or suspected congenital immunodeficiency.
Receipt of immunosuppressive therapy or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).
Known or suspected autoimmune disease
Hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to a vaccine containing any of the same substances as the vaccine used in the trial.
Participation in another clinical trial for an investigational product (IP).
Bleeding disorder or receipt of anticoagulants in the 3 weeks preceding randomization, contraindicating IM vaccination.
Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion.
Febrile illness (temperature ≥ 100.4°F [≥ 38.0°C]) within 24 hours prior to randomization.
Note: A subject may enroll after recovery from febrile illness if the subject is still within the age window.
Systemic antibiotic use within 48 hours prior to randomization.

Sites / Locations

PHRU, Chris Hani Baragwanath Hospital
Shandukani Research
KID-CRU, Tygerberg Hospital
South African TB Vaccine Initiative (SATVI)

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Experimental

Arm Label

Cohort 1 Aeras404 (5ug H4/100nmol IC31) or Placebo

Cohort 2 AERAS-404 (5ug H4/500nmol IC31) or Placebo

Cohort 3A AERAS-404 (5ug H4/500nmol IC31) or Placebo

Cohort 3B AERAS-404 (15ug H4/500nmol IC31) or Placebo

Cohort 4 AERAS-404 (15ug H4/500nmol IC31) or Placebo

Cohort 5 AERAS-404 (50ug H4/500nmol IC31) or Placebo

Cohort 6 AERAS-404 (dose level pending) or Placebo

Arm Description

1 Dose; Subject ≥ 168 to ≤ 196 days of age

2 Doses; Subject ≥ 168 to ≤ 189 days of age

3 Doses; Subject ≥ 84 to ≤ 98 days of age

3 Doses; Subject ≥ 64 to ≤ 83 days of age

Outcomes

Primary Outcome Measures

Investigate the safety of AERAS-404 in HIV-uninfected, HIV-unexposed, BCG-primed infants.

Adverse Events and Serious Adverse Events (SAE) will be collected on subjects throughout their participation in the study. Solicited adverse events are captured 28 days post each vaccination. Evaluation of the safety profile of AERAS-404 will be performed using data from all subjects who received at least one dose and has 7 days of safety data, and will be summarized by cohort and treatment group. The number (percentage) of subjects with any adverse event (including solicited, unsolicited, and serious adverse events) will be summarized by Medical Dictionary for Regulatory Activities (MedDRA) system organ class and Preferred Term. Additional summaries will present the number (percentage) of subjects with any adverse events by severity and by relationship to study vaccine; parameters evaluable by the Aeras 404 Pediatric Toxicity Table provided in the protocol, will be summarized by severity corresponding to Toxicity Grade, as appropriate.

Secondary Outcome Measures

Investigate the safety of a 3-dose AERAS-404 regimen in HIV-uninfected, HIV-unexposed, BCG-primed infants

The number and percentage of subjects who are enrolled into the three-dose regimen (Cohorts 4-6) with solicited and unsolicited AEs (including serious adverse events [SAEs], local and systemic reactions, and clinical laboratory values or vital sign values recorded as newly abnormal following study vaccination) recorded post-vaccination will be summarized to address the secondary safety objective of the study. Subjects in Cohorts 4 and 5 will be followed for : 1 year and 3 months, Cohort 6: 1 year 4 months and Solicited adverse events are captured 28 days post each vaccination.

Full Information

NCT ID

NCT01861730

First Posted

May 21, 2013

Last Updated

April 6, 2018

Sponsor

Aeras

Collaborators

Statens Serum Institut, Sanofi Pasteur, a Sanofi Company, National Institute of Allergy and Infectious Diseases (NIAID), International Maternal Pediatric Adolescent AIDS Clinical Trials Group

1. Study Identification

Unique Protocol Identification Number

NCT01861730

Brief Title

Phase 1/II, Safety and Immunogenicity Study of AERAS-404 in BCG-Primed Infants

Acronym

C-015-404

Official Title

Phase 1/II, Safety and Immunogenicity Study of a Recombinant Protein Tuberculosis Vaccine (AERAS-404) in BCG-Primed Infants

Study Type

Interventional

2. Study Status

Record Verification Date

April 2018

Overall Recruitment Status

Completed

Study Start Date

July 1, 2013 (Actual)

Primary Completion Date

December 22, 2017 (Actual)

Study Completion Date

December 22, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Aeras

Collaborators

Statens Serum Institut, Sanofi Pasteur, a Sanofi Company, National Institute of Allergy and Infectious Diseases (NIAID), International Maternal Pediatric Adolescent AIDS Clinical Trials Group

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Phase I/II, randomized, double-blind, placebo-controlled, safety, immunogenicity and dose-range finding study of AERAS-404 Tuberculosis (TB) vaccine administered intramuscularly in Bacille Calmette-Guerin (BCG) primed infants.

Detailed Description

This is a Phase I/II, randomized, double-blind, placebo-controlled, safety, immunogenicity and dose-range finding study in HIV-uninfected, HIV-unexposed, BCG-primed infants. The study vaccine AERAS-404 or placebo will be administered without concomitant EPI vaccines (Cohorts 1 to 5, N = 159 subjects) and with concomitant EPI vaccines (Cohort 6, N = 70 subjects). Study vaccine or placebo will be administered as a single dose (injection) at Study Day 0 ( ≥168 to ≤ 196 days of age, Cohorts 1 and 2), a 2-dose schedule at Study Day 0 (≥ 168 to ≤ 189 days of age) and Study Day 28 (Cohorts 3A and 3B) or a 3-dose schedule at Study Day 0 (≥ 84 to ≤ 98 days of age), Study Day 42 and Study Day 98 (Cohorts 4 and 5). Subjects in Cohort 6 will receive the study vaccine or placebo at Study Day 0 (≥ 64 to ≤ 83 days of age), Study Day 28 (≥ 91 to ≤ 105 days of age), and Study Day 210 (≥ 273 to ≤ 287 days of age). A cohort will enroll once safety in the previous cohort has been established. AERAS-404 is an investigational vaccine manufactured by Sanofi Pasteur (SP) and Statens Serum Institute (SSI).

6. Conditions and Keywords

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

Tuberculosis

Keywords

BCG Vaccinated, HIV Negative

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

243 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cohort 1 Aeras404 (5ug H4/100nmol IC31) or Placebo

Arm Type

Experimental

Arm Description

1 Dose; Subject ≥ 168 to ≤ 196 days of age

Arm Title

Cohort 2 AERAS-404 (5ug H4/500nmol IC31) or Placebo

Arm Type

Experimental

Arm Description

1 Dose; Subject ≥ 168 to ≤ 196 days of age

Arm Title

Cohort 3A AERAS-404 (5ug H4/500nmol IC31) or Placebo

Arm Type

Experimental

Arm Description

2 Doses; Subject ≥ 168 to ≤ 189 days of age

Arm Title

Cohort 3B AERAS-404 (15ug H4/500nmol IC31) or Placebo

Arm Type

Experimental

Arm Description

2 Doses; Subject ≥ 168 to ≤ 189 days of age

Arm Title

Cohort 4 AERAS-404 (15ug H4/500nmol IC31) or Placebo

Arm Type

Experimental

Arm Description

3 Doses; Subject ≥ 84 to ≤ 98 days of age

Arm Title

Cohort 5 AERAS-404 (50ug H4/500nmol IC31) or Placebo

Arm Type

Experimental

Arm Description

3 Doses; Subject ≥ 84 to ≤ 98 days of age

Arm Title

Cohort 6 AERAS-404 (dose level pending) or Placebo

Arm Type

Experimental

Arm Description

3 Doses; Subject ≥ 64 to ≤ 83 days of age

Intervention Type

Biological

Intervention Name(s)

AERAS-404

Other Intervention Name(s)

Intervention Description

AERAS-404 has two components: the H4 antigen and the IC31 adjuvant. The reconstitution of the vaccine components, H4 antigen (manufactured at SP) and IC31 adjuvant (supplied by SSI), will take place at the clinical research site (CRS) prior to injection.

Intervention Type

Biological

Intervention Name(s)

Placebo

Other Intervention Name(s)

Tris buffered saline

Intervention Description

Tris buffered saline (10mM Tris, pH 7.4, 150nm sodium chloride).

Primary Outcome Measure Information:

Title

Investigate the safety of AERAS-404 in HIV-uninfected, HIV-unexposed, BCG-primed infants.

Description

Time Frame

Subjects will be followed for up to 1 year and 4 months.

Secondary Outcome Measure Information:

Title

Investigate the safety of a 3-dose AERAS-404 regimen in HIV-uninfected, HIV-unexposed, BCG-primed infants

Description

Time Frame

Subjects will be followed for up to 1 year and 4 months.

Other Pre-specified Outcome Measures:

Title

Assess the immunogenicity of a 3-dose AERAS-404 regimen in HIV-uninfected, HIV-unexposed, BCG-primed infants.

Description

T-cell response, as measured by Intracellular Cytokine Staining (ICS) following stimulation with peptide pools spanning the vaccine antigens, will be used to assess immunogenicity.

Time Frame

Subjects will be followed for up to 1 year and 4 months.

Title

Select an appropriate dose regimen for AERAS-404 in HIV-uninfected, HIV-unexposed, BCG-primed infants.

Description

Safety and immunogenicity analyses will be reviewed for the selection of the appropriate dose regimen

Time Frame

After all subjects in Cohorts 4 and 5 have completed Study Day 126, the safety and immunogenicity data from these Cohorts will be evaluated. The data will inform the decision on the study vaccine dose for Cohort 6.

Title

Explore interactions between AERAS-404 and EPI vaccines.

Description

Antibody concentration levels at 12 months of age for all Cohorts, and in addition at 28 days post second study vaccine dose (Study Day 56) for Cohort 6 will be presented. Summaries will include antibody titers to Tetanus toxoid vaccine (tetanus; given at 6, 10, 14 weeks of age), and Haemophilus influenza B conjugate vaccine (given at 6, 10, 14 weeks of age). Responses to other EPI vaccines may also be assessed.

Time Frame

Antibody concentration blood samples taken when subjects reach 12 months of age for all Cohorts and in addition, 28 post second study vaccine dose (Study Day 56) for subjects in Cohort 6 only.

Title

Assess the immunogenicity of a 2-dose AERAS-404 regimen in HIV-uninfected, HIV-unexposed, BCG-primed infants.

Time Frame

Subjects will have Immunology samples taken at multiple time points for up to 1 year and 4 months.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

64 Days

Maximum Age & Unit of Time

196 Days

Accepts Healthy Volunteers

Eligibility Criteria

INCLUSION CRITERIA Age at time of entry: Cohorts 1 to 6 Cohorts 1 and 2: ≥ 168 to ≤ 196 days Cohorts 3A and 3B: ≥ 168 to ≤ 189 days Cohorts 4 and 5: ≥ 84 to ≤ 98 days (≥ 2 weeks after receipt of EPI vaccine doses at 10 weeks of age) Cohort 6 - coincident with EPI vaccine doses at 10 weeks of age (≥ 64 to ≤ 83 days of age) Source documentation of birth weight ≥ 2.5 kg. Documented BCG vaccination within 72 hours of birth. Documented receipt of all age-appropriate EPI vaccines, except Rotavirus, for Cohorts 4 to 6 (see Appendix II). Source documentation of a negative HIV status in the mother, from any time during pregnancy with this child through randomization. Documentation of infant HIV negative exposure or infection status with negative HIV ELISA and HIV DNA PCR tests. Parent or legal guardian able and willing to provide signed informed consent. Participant/parent/legal guardian able to attend all scheduled visits and to comply with all trial procedures. EXCLUSION CRITERIA History of TB exposure in household or non-household contact. History/Evidence of TB disease or infection. Quantiferon positive. Prior TST test. Any one of Anemia, Neutropenia, Thrombocytopenia, SGPT (ALT), SGOT (AST) or Creatinine ≥ Grade 2 Receipt of a live vaccine within 28 days prior to randomization. Receipt or planned receipt of any investigational vaccine. Known or suspected congenital immunodeficiency. Receipt of immunosuppressive therapy or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months). Known or suspected autoimmune disease Hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to a vaccine containing any of the same substances as the vaccine used in the trial. Participation in another clinical trial for an investigational product (IP). Bleeding disorder or receipt of anticoagulants in the 3 weeks preceding randomization, contraindicating IM vaccination. Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion. Febrile illness (temperature ≥ 100.4°F [≥ 38.0°C]) within 24 hours prior to randomization. Note: A subject may enroll after recovery from febrile illness if the subject is still within the age window. Systemic antibiotic use within 48 hours prior to randomization.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ann Ginsberg, MD, PhD

Organizational Affiliation

Aeras

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Avy Violari, MD

Organizational Affiliation

Perinatal HIV Research Unit

Official's Role

Principal Investigator

Facility Information:

Facility Name

PHRU, Chris Hani Baragwanath Hospital

City

Johannesburg

State/Province

Guateng

ZIP/Postal Code

2091

Country

South Africa

Facility Name

Shandukani Research

City

Johannesburg

State/Province

Hillbrow

ZIP/Postal Code

2001

Country

South Africa

Facility Name

KID-CRU, Tygerberg Hospital

City

Cape Town

State/Province

Tygerberg

ZIP/Postal Code

7505

Country

South Africa

Facility Name

South African TB Vaccine Initiative (SATVI)

City

Worcester

Country

South Africa

12. IPD Sharing Statement

Learn more about this trial

Phase 1/II, Safety and Immunogenicity Study of AERAS-404 in BCG-Primed Infants

We'll reach out to this number within 24 hrs