A Phase II Study of H56:IC31 in Healthy Adolescents

NCT03265977 | Withdrawn Phase 2 DMC

• 1 other identifier: A-043
• Study Type: interventional
• Target: N/A
• Locations: 2 countries
• Sites: 4

Brief Summary

This clinical trial will evaluate safety, immunogenicity, and efficacy (prevention of Mtb infection as measured by IGRA conversions) of H56:IC31 in remotely BCG vaccinated adolescents.

Conditions

Tuberculosis Infection

Outcome Measures

Primary Outcomes (2)

• Frequency and severity of adverse events

  To evaluate the safety profile of H56:IC31 compared to placebo in HIV-uninfected, previously BCG vaccinated adolescents.

  Day 0 through month 24

• ESAT-6 free IGRA conversion from a negative to positive test at any time point after Day 84 and through end of follow-up for the primary endpoint.

  To evaluate prevention of Mtb infection by H56:IC31 compared to placebo, as measured by rates of conversion using an ESAT-6 free IGRA.

  Day 84 through month 24

Secondary Outcomes (4)

• Primary ESAT-6 free IGRA conversion from a negative to a positive test

  Day 84 through month 24

• Primary ESAT-6 free IGRA conversion from a negative to a positive test

  Day 84 through end of study (approximately 24 months)

• Initial ESAT-6 free IGRA reversion from a positive to a negative test at any time point after primary ESAT-6 free IGRA conversion through the end of follow up.

  Day 84 through month 24

• Percentage of CD4+ and CD8+ T cells that express IFN-γ, TNF, and/or IL-2 alone or in combination in response to stimulation with peptide pools representing the entire amino acid sequence of the vaccine antigens.

  Day 0 through month 24

Study Arms (2)

H56:IC31

EXPERIMENTAL

5 ug H56/500 nmol IC31, 0.5 mL Intramuscular (IM), Days 0 and 56

Biological: H56:IC31

Placebo

PLACEBO COMPARATOR

Normal saline, 0.5 mL IM, Days 0 and 56

Other: Placebo

Interventions

H56:IC31 BIOLOGICAL

The H56 antigen is a fusion protein created from 3 Mtb antigens: antigen 85B (Ag85B), ESAT-6, and Rv2660c.

H56:IC31

Placebo OTHER

Normal saline

Placebo

Eligibility Criteria

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

You may qualify if:

• Has completed the written informed consent and assent process
• Is age ≥12 years and ≤17 years on Study Day 0
• Agrees to stay in contact with the study site for the duration of the study, provide updated contact information as necessary, and has no current plans to move from the study area for the duration of the study
• For female participants: agrees to avoid pregnancy from 21 days prior to Study Day 0 through 6 months after the last study vaccination. Women physically capable of pregnancy (not sterilized and still menstruating or within 1 year of the last menses) in sexual relationships with men must use an acceptable method of avoiding pregnancy during this period. Acceptable methods of avoiding pregnancy include a sterile sexual partner, sexual abstinence (not engaging in sexual intercourse), hormonal contraceptives (oral, injection, transdermal patch, or implant), vaginal ring, or intrauterine device (IUD)
• Has general good health, confirmed by medical history and physical examination
• Had BCG vaccination at least 5 years ago documented by confirmation of parent/guardian that the participant received all childhood vaccines or by presence of healed BCG scar
• Tests ESAT-6 free IGRA and QFT-Plus negative at screening, using a pre-determined threshold for ESAT-6 free IGRA and the manufacturer's recommended threshold for QFT-Plus of 0.35 IU/mL in either of the TB antigen tubes after nil-subtraction

You may not qualify if:

• Acute illness on Study Day 0
• Axillary temperature ≥37.5 °C on Study Day 0
• Abnormal laboratory values from the most recent blood collected prior to randomization as follows (abnormal results may be repeated once and if found to be resolved the participant will not be excluded):
• Laboratory evidence of hematologic disease (white blood cell count \<3000/mm\^3 or \>11,500/mm\^3; hemoglobin \<0.9 times the lower limit of normal of the testing laboratory, by age and gender; absolute neutrophil count \<1300/mm\^3; absolute lymphocyte count \<1000/mm\^3).
• ALT, AST, alkaline phosphatase, total bilirubin, creatinine, blood urea nitrogen (BUN) \>1.25 times the ULN
• Urinalysis abnormality greater than Grade 1 on the Toxicity Scale (with the exception of hematuria in a menstruating female), or urinalysis abnormality judged clinically significant by the investigator
• History or evidence of any clinically significant systemic disease, or any acute or chronic illness that might affect the safety, immunogenicity, or efficacy of investigational product in the opinion of the investigator
• History of treatment for active TB disease or latent Mtb infection
• History or evidence, including chest X-ray, of active TB disease
• Shared household with an individual receiving anti-TB treatment, or known to have incompletely treated culture or smear positive TB, at screening
• History of autoimmune disease or immunosuppression
• Used immunosuppressive medication within 42 days before Study Day 0 (inhaled and topical corticosteroids are permitted)
• Received immunoglobulin or blood products within 42 days before Study Day 0
• Received any investigational drug or investigational vaccine within 180 days before Study Day 0, or planned participation in any other clinical trial during the study period
• Received investigational TB vaccine at any time prior to Study Day 0

Sponsors & Collaborators

• Aeras: lead
• Statens Serum Institut: collaborator
• Aurum Institute: collaborator
• South African Tuberculosis Vaccine Initiative: collaborator
• Oslo University Hospital: collaborator
• University of Copenhagen: collaborator
• University of Bergen: collaborator
• National Institute for Medical Research, Tanzania: collaborator

Study Sites (4)

Aurum Institute - Klerksdorp

Klerksdorp, 2571, South Africa

Location

Aurum Institute - Rustenburg

Rustenburg, 0300, South Africa

Location

Aurum Institute - Tembisa

Tembisa, 1632, South Africa

Location

National Institute for Medical Research

Mwanza, Isamilo Area, Tanzania

Location

MeSH Terms

Conditions

Latent Tuberculosis

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Latent Infection

Study Officials

• Dereck Tait, MD

  Aeras

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Random numbers generated by IWRS; Stratified by site. Syringes are masked with a translucent colored label, in order to maintain the study blind.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be enrolled in two cohorts. Within each cohort participants will be randomized in a 1:1 ratio to receive either H56:IC31 (5 ug H56/500 nmol IC31) or placebo intramuscularly (IM) on Days 0 and 56.

Study Record Dates

• First Submitted: August 24, 2017
• First Posted: August 29, 2017
• Study Start: June 1, 2018
• Primary Completion: April 30, 2021
• Study Completion: June 30, 2021
• Last Updated: April 10, 2018

Record last verified: 2018-04

Locations

TA (1); ZA (3)