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Phase 1b Safety and Immunogenicity Trial of BCG Revaccination, H4:IC31, and H56:IC31 in Healthy, HIV-1-Uninfected Adolescents (A-042)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02378207
First Posted: March 4, 2015
Last Update Posted: January 24, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
HIV Vaccine Trials Network
Sanofi Pasteur, a Sanofi Company
Statens Serum Institut
Information provided by (Responsible Party):
Aeras
  Purpose
The aims of the phase 1b trial described here are to facilitate identification of assays and immune responses that could then be evaluated as correlates of risk and correlates of protection in efficacy studies and ultimately to provide leads for biomarkers of protection against tuberculosis. This study will complement one ongoing study (NCT02075203) evaluating the prevention of M. Tuberculosis infection using H4:IC31 (also known as AERAS-404).

Condition Intervention Phase
Tuberculosis Biological: H4:IC31 Biological: H56:IC31 Biological: BCG Biological: Control Sodium Chloride 0.9% Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Randomized, Placebo-controlled, Partially Blinded Phase 1b Clinical Trial to Evaluate the Safety and Immunogenicity of BCG Revaccination, H4:IC31, and H56:IC31 in Healthy, HIV-1-Uninfected Adolescent Participants

Resource links provided by NLM:


Further study details as provided by Aeras:

Primary Outcome Measures:
  • Safety and tolerability of the different vaccine regimens in adolescents [ Time Frame: Up to 8 months ]
    The number and percentage of solicited and unsolicited adverse events (AEs), recorded postvaccination for all participants.

  • Cellular immune responses of the different vaccine regimens in adolescents compared to those measured at baseline. [ Time Frame: Up to day 70 ]
    T-cell responses by flow cytometric intracellular cytokine staining (ICS) of CD4+ T cells after stimulation with a pool of mycobacterial peptides and/or PPD (purified protein derivative) using cryopreserved peripheral blood mononuclear cells (PBMC).

  • Cellular immune responses of the different vaccine regimens in adolescents compared to those measured at baseline. [ Time Frame: Up to day 70 ]
    T-cell responses by flow cytometric intracellular cytokine staining (ICS) of CD8+ T cells after stimulation with a pool of mycobacterial peptides and/or PPD (purified protein derivative) using cryopreserved peripheral blood mononuclear cells (PBMC).


Enrollment: 84
Study Start Date: May 2015
Study Completion Date: December 9, 2016
Primary Completion Date: October 31, 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1 H4:IC31
15 mcg H4/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.
Biological: H4:IC31
Experimental: Group 2 H56:IC31
5 mcg H56/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.
Biological: H56:IC31
Active Comparator: Group 3 BCG (2-8 x 105 CFU)
Administered ID as 0.1 mL in either deltoid muscle at Day 0.
Biological: BCG
Placebo Comparator: Group 4 Control Sodium Chloride 0.9%
Administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.
Biological: Control Sodium Chloride 0.9%

Detailed Description:

This study proposes to further evaluate the safety and immunogenicity of H4:IC31, H56:IC31, and BCG revaccination. The study will be conducted in previously BCG vaccinated healthy adolescents, and will entail a thorough immunogenicity evaluation of these regimens incorporating unbiased systems vaccinology approaches and novel assessments of baseline and elicited responses that may impact vaccine responses. A major goal for this study is to generate immunological data on a wide range of immune responses using a variety of approaches including validated assessments, unbiased strategies, and novel exploratory assays to increase the likelihood of detecting responses correlating with risk or protection in the prevention of infection study. Investigators contributing to the proposed study have participated in a correlates analysis for an HIV vaccine exhibiting modest efficacy in which 2 correlates of risk were identified.

An additional aim of this study is to explore factors affecting vaccine induced responses that may also impact efficacy. For example, it is hypothesized that exposure to environmental mycobacteria may alter protection provided by BCG vaccination. Reagents for evaluating levels of exposure to environmental mycobacteria are in development as part of a concurrent collaborative study. An exploratory objective for this trial is to apply these reagents to examine whether such exposures influence immune responses elicited by these regimens.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Age of 12 to ≤ 17 years at enrollment
  2. Minimum weight ≥ 40 kg
  3. Previous BCG vaccination at least 5 years ago documented by scarification or medical card
  4. No evidence of active TB disease, as determined by history, physical examination and, if deemed appropriate, sputum investigation and / or chest x-ray.
  5. Negative QFT-GIT test at screening, using the manufacturer's recommended threshold of 0.35 IU/mL
  6. Assessed by the clinic staff as being at low risk for HIV infection
  7. Hemoglobin ≥ 11.7 g/dL for females, ≥ 12.5 g/dL for males
  8. Negative HIV-1 and -2 blood test
  9. Agree to consistently use effective contraception for sexual activity that could lead to pregnancy from at least 20 days prior to enrollment through the last required protocol clinic visit.

(additional minor criteria not added due to space constraints)

Exclusion Criteria:

  1. Blood products received within 120 days before first vaccination
  2. Investigational research agents received within 182 days before first vaccination
  3. Intent to participate in another study of an investigational research agent during the planned duration of the HVTN 602 / AERAS A-042 study
  4. Pregnant or breastfeeding
  5. History of alcohol or drug abuse
  6. A significant contact with active TB disease: for example, shared residency with an individual receiving anti-TB treatment, or with an individual known to have incompletely treated culture or smear positive TB
  7. TB prophylaxis within 90 days prior to enrollment
  8. History of treatment for active TB disease or latent Mtb infection
  9. Positive and indeterminate QFT-GIT result
  10. Received a tuberculin skin test (TST) within 90 days prior to enrollment
  11. Vaccines and other Injections
  12. Immunosuppressive medications received within 168 days before first vaccination.
  13. Serious adverse reactions to vaccines including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain.
  14. Immunoglobulin received within 60 days before first vaccination
  15. Autoimmune disease Not excluded: mild, well-controlled psoriasis
  16. Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health. Including but not limited to: Diabetes mellitus type 1 or type 2, Thyroidectomy, or Thyroid disease, Asthma, Asplenia, Bleeding disorders, malignancy, Seizure disorder, and Angioedema

(additional minor criteria not added due to space constraints)

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02378207


Locations
South Africa
Desmond Tutu HIV Foundation
Cape Town, South Africa
Sponsors and Collaborators
Aeras
HIV Vaccine Trials Network
Sanofi Pasteur, a Sanofi Company
Statens Serum Institut
Investigators
Study Chair: Linda-Gail Bekker, MD Desmond Tutu HIV Centre
Study Chair: Jim Kublin, MD HVTN Core, FHCRC
  More Information

Responsible Party: Aeras
ClinicalTrials.gov Identifier: NCT02378207     History of Changes
Other Study ID Numbers: HVTN 602 / AERAS A-042
First Submitted: February 12, 2015
First Posted: March 4, 2015
Last Update Posted: January 24, 2017
Last Verified: January 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections