A Study for Safety and Immunogenicity of BCG and AERAS-404 in HIV-Negative, TB-Negative, BCG-Naive Adults

NCT02420444 | Completed Phase 1

• 1 other identifier: C-013-404
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

70 subjects received BCG intradermally at Study Day -42, then at Study Day 0 were randomized to receive AERAS-404 50 mcg H4/500 nmol IC31 intramuscularly as a 3-dose (N=30) or 2-dose (N=30) regimen, or placebo (N=10). Subjects were vaccinated on Study Days 0, 56, and 231, and followed through Study Day 259.

Conditions

Tuberculosis

Outcome Measures

Primary Outcomes (1)

• Number of unsolicited, solicited, and serious adverse events (SAEs).

  Includes injection site AEs and systemic AEs.

  259 days

Secondary Outcomes (1)

• Immunogenicity of BCG and a 2- or 3-dose regimen of AERAS-404 measured by intracellular staining assay (ICS).

  259 Days

Study Arms (3)

BCG SSI prime with Placebo

PLACEBO COMPARATOR

All subjects received BCG Vaccine SSI, 2-8 x 10\^5 CFU (BCG) on Study Day -42. Placebo containing 0,8 mL sterile buffer consisting of 10 mmol Tris and 169 mmol NaCl aqueous solution was administered on Study Days 0, 56, and 231.

Biological: BCG SSI; Biological: Placebo

BCG SSI prime with Placebo and AERAS-404

EXPERIMENTAL

All subjects received BCG Vaccine SSI, 2-8 x 10\^5 CFU (BCG) on Study Day -42. Placebo on Study Day 0 followed by AERAS-404 50/500 on Study Days 56 and 231. AERAS-404 50/500 was a fixed dose combination of H4 50 mcg and IC31 500 nmol (KLK equivalent). H4 and IC31 adjuvant were supplied as separate single-dose vials containing frozen product as follows: * H4 antigen: 500 mcg/mL (100 mcg/0.2 mL), in 10 mmol/L Tris-HCl, pH 8.3. * IC31 adjuvant: 1250 nmol/mL (1000 nmol/0.8 mL) KLK equivalent, in 10 mmol/L Tris-HCl and 169 mmol/L NaCl.

Biological: BCG SSI; Biological: Placebo; Biological: AERAS-404

BCG SSI prime with AERAS-404

EXPERIMENTAL

All subjects received BCG Vaccine SSI, 2-8 x 10\^5 CFU (BCG) on Study Day -42. AERAS-404 50/500 on Study Days 0, 56, and 231. AERAS-404 50/500 was a fixed dose combination of H4 50 mcg and IC31 500 nmol (KLK equivalent). H4 and IC31 adjuvant were supplied as separate single-dose vials containing frozen product as follows: * H4 antigen: 500 mcg/mL (100 mcg/0.2 mL), in 10 mmol/L Tris-HCl, pH 8.3. * IC31 adjuvant: 1250 nmol/mL (1000 nmol/0.8 mL) KLK equivalent, in 10 mmol/L Tris-HCl and 169 mmol/L NaCl.

Biological: BCG SSI; Biological: AERAS-404

Interventions

BCG SSI BIOLOGICAL

The dose volume administered for BCG was 0.1 mL, and the mode of administration was ID injection to the deltoid area.

Also known as: BCG Vaccine SSI Danish, bacillus Calmette-Guérin

BCG SSI prime with AERAS-404; BCG SSI prime with Placebo; BCG SSI prime with Placebo and AERAS-404

Placebo BIOLOGICAL

This is the identical buffer solution in which H4:IC31 was formulated. The dose volume administered for Placebo was 0.5mL, and the mode of administration was an IM injection.

Also known as: Sterile buffered saline

BCG SSI prime with Placebo; BCG SSI prime with Placebo and AERAS-404

AERAS-404 BIOLOGICAL

AERAS-404 vaccine was reconstituted on site by adding 0.2 mL H4 antigen solution to 0.8 mL IC31 adjuvant solution. The dose volume administered for AERAS-404 was 0.5mL, and the mode of administration was an IM injection.

Also known as: H4:IC31

BCG SSI prime with AERAS-404; BCG SSI prime with Placebo and AERAS-404

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Had completed the written informed consent process.
• Was male or female.
• Was age ≥ 18 years and ≤ 50 years.
• Agreed to stay in contact with the study site for the duration of the study, provide updated contact information as necessary, and had no current plans to move from the study area for the duration of the study.
• Agreed to avoid elective surgery for the duration of the study.
• Had completed simultaneous enrollment in Aeras Vaccine Development Registry protocol.
• For female subjects: agreed to avoid pregnancy from 28 days prior to Study Day 0 through the duration of the study.
• Had general good health, confirmed by medical history and physical examination.
• Had body mass index (BMI) between 18 and 33 (weight/height2) by nomogram.

You may not qualify if:

• Oral temperature ≥37.5°C.
• Abnormal CBC laboratory values (per local laboratory parameters) from blood collected at screening (\>5% above ULN or \>5% below LLN).
• Abnormally elevated laboratory values (per local laboratory parameters) from blood collected at screening for ALT, AST, GGT, total bilirubin, alkaline phosphatase (ALP), blood urea nitrogen (BUN), creatinine, prothrombin time (PT), or partial thromboplastin time (PTT) (\>10% above ULN).
• Abnormal urinalysis that, in the opinion of the investigator, was clinically significant.
• Positive screening urine test for illicit drugs (opiates, cocaine, amphetamines).
• History or evidence of active or latent tuberculosis infection, including a positive QuantiFERON-TB test, a history of a positive TST, or abnormal chest X-ray findings that in the opinion of the investigator were evidence of tuberculosis.
• Residence longer than 6 months in a high-burden country (per WHO 2010 TB Report).
• Shared a residence within 1 year prior to Study Day -42 with an individual on anti-tuberculosis treatment or with culture- or smear-positive pulmonary tuberculosis.
• Previous treatment for active or latent tuberculosis infection.
• History or evidence of autoimmune disease.
• History or evidence of any past, present, or future possible immunodeficiency state, including laboratory evidence of HIV 1 infection.
• History or evidence of chronic hepatitis, including hepatitis B core antibody or hepatitis C antibody.
• Received a TST within 90 days prior to Study Day -42.
• Received a systemic antibiotic with 14 days prior to Study Day -42.
• Received BCG vaccination or BCG immunotherapy prior to Study Day -42.

Sponsors & Collaborators

• Aeras: lead
• Sanofi Pasteur, a Sanofi Company: collaborator

Study Sites (1)

Centre Hosptialier Universitaire Vaudois (CHUV)

Lausanne, Canton of Vaud, Switzerland

Location

MeSH Terms

Conditions

Tuberculosis

Condition Hierarchy (Ancestors)

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

Study Officials

• Giuseppe Pantaleo, MD

  Centre Hosptialier Universitaire Vaudois (CHUV)

  PRINCIPAL INVESTIGATOR

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: April 15, 2015
• First Posted: April 17, 2015
• Study Start: January 1, 2011
• Primary Completion: May 1, 2012
• Study Completion: November 1, 2013
• Last Updated: January 24, 2017

Record last verified: 2017-01

Locations

CH (1)