Safety and Immunogenicity Study of BCG, H4:IC31, and H56:IC31 Revaccination in Healthy Adolescents

NCT02378207 | Completed Phase 1 Results DMC

• 1 other identifier: HVTN 602 / AERAS A-042
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Tuberculosis

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Adverse Events

  The number of solicited and unsolicited adverse events (AEs), including serious adverse events (SAEs), recorded post-vaccination for all participants.

  Up to 8 months

• Percentage of Participants With Response Rates to TB Antigens as Compared to Baseline

  Flow cytometry was used to examine TB Mb-specific CD4+ and CD8+ T-cell responses using the ICS assay. The antigens used to stimulate cells in this assay included peptide pools for the vaccine-matched proteins (Ag85B, ESAT-6, Rv2660c, and TB 10.4) as well as complex TB antigens (TB whole cell lysate \[TB WCL\], and BCG Pasteur strain.

  Days 70 and 168

Secondary Outcomes (5)

• Evaluate Humoral Responses Elicited by the Different Vaccine Regimens.

  Up to day 168.

• * Evaluate Immune Response From Vaccine Regimens by Measuring Early (Innate) Vaccine-induced Peripheral Blood Transcription Profiles; Determine Which Responses Are Associated With Antigen-specific Adaptive Responses * Evaluate Adaptive Immune Response.

  Up to day 168

• Evaluate Changes in Innate Cells in Response to the Vaccine Regimens

  Up to day 168

• Measure Non-classical Major Histocompatibility Complex (MHC)-Restricted T-cell Vaccine-induced Responses, Such as to Mycobacterial Lipids (CD1-restricted) and Metabolites (MR1-restricted).

  Up to day 168

• Evaluate QFT-GIT and ESAT-6 Free IGRA Discordance and Conversion/Reversion Rate During the Course of the Trial.

  Up to day 168

Study Arms (4)

Group 1 H4:IC31

EXPERIMENTAL

15 mcg H4/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.

Biological: H4:IC31

Group 2 H56:IC31

EXPERIMENTAL

5 mcg H56/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.

Biological: H56:IC31

Group 3 BCG (2-8 x 105 CFU)

ACTIVE COMPARATOR

Administered IM as 0.1 mL in either deltoid muscle at Day 0.

Biological: BCG

Group 4 Control Sodium Chloride 0.9%

PLACEBO COMPARATOR

Administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.

Biological: Control Sodium Chloride 0.9%

Interventions

H4:IC31 BIOLOGICAL

H4 contains Mtb antigens Ag85B and TB10.4

Group 1 H4:IC31

H56:IC31 BIOLOGICAL

H56 contains Mtb antigens ESAT-6, and Rv2660c

Group 2 H56:IC31

BCG BIOLOGICAL

Group 3 BCG (2-8 x 105 CFU)

Control Sodium Chloride 0.9% BIOLOGICAL

Group 4 Control Sodium Chloride 0.9%

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Age of 12 to ≤ 17 years at enrollment
• Minimum weight ≥ 40 kg
• Previous BCG vaccination at least 5 years ago documented by scarification or medical card
• No evidence of active TB disease, as determined by history, physical examination and, if deemed appropriate, sputum investigation and / or chest x-ray.
• Negative QFT-GIT test at screening, using the manufacturer's recommended threshold of 0.35 IU/mL
• Assessed by the clinic staff as being at low risk for HIV infection
• Hemoglobin ≥ 11.7 g/dL for females, ≥ 12.5 g/dL for males
• Negative HIV-1 and -2 blood test
• 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)

You may not qualify if:

• Blood products received within 120 days before first vaccination
• Investigational research agents received within 182 days before first vaccination
• Intent to participate in another study of an investigational research agent during the planned duration of the HVTN 602 / AERAS A-042 study
• Pregnant or breastfeeding
• History of alcohol or drug abuse
• 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
• TB prophylaxis within 90 days prior to enrollment
• History of treatment for active TB disease or latent Mtb infection
• Positive and indeterminate QFT-GIT result
• Received a tuberculin skin test (TST) within 90 days prior to enrollment
• Vaccines and other Injections
• Immunosuppressive medications received within 168 days before first vaccination.
• Serious adverse reactions to vaccines including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain.
• Immunoglobulin received within 60 days before first vaccination
• Autoimmune disease Not excluded: mild, well-controlled psoriasis

Sponsors & Collaborators

• Aeras: lead
• HIV Vaccine Trials Network: collaborator
• Sanofi Pasteur, a Sanofi Company: collaborator
• Statens Serum Institut: collaborator

Study Sites (1)

Desmond Tutu HIV Foundation

Cape Town, South Africa

Location

Related Publications (1)

• Bekker LG, Dintwe O, Fiore-Gartland A, Middelkoop K, Hutter J, Williams A, Randhawa AK, Ruhwald M, Kromann I, Andersen PL, DiazGranados CA, Rutkowski KT, Tait D, Miner MD, Andersen-Nissen E, De Rosa SC, Seaton KE, Tomaras GD, McElrath MJ, Ginsberg A, Kublin JG; HVTN 602/Aeras A-042 Protocol Team. A phase 1b randomized study of the safety and immunological responses to vaccination with H4:IC31, H56:IC31, and BCG revaccination in Mycobacterium tuberculosis-uninfected adolescents in Cape Town, South Africa. EClinicalMedicine. 2020 Mar 18;21:100313. doi: 10.1016/j.eclinm.2020.100313. eCollection 2020 Apr.

  PMID: 32382714 DERIVED

MeSH Terms

Conditions

Tuberculosis

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Results Point of Contact

• Title: Dr. Linda-Gail Bekker
• Organization: Desmond Tutu HIV Foundation, Cape Town, South Africa

linda-gail.bekker@hiv-research.org.za

+27214066959

Study Officials

• Linda-Gail Bekker, MD

  Desmond Tutu HIV Centre

  STUDY CHAIR

• Jim Kublin, MD

  HVTN Core, FHCRC

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2015
• First Posted: March 4, 2015
• Study Start: May 1, 2015
• Primary Completion: October 31, 2016
• Study Completion: December 9, 2016
• Last Updated: November 18, 2019
• Results First Posted: November 18, 2019

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (1)