A Phase I Study to Evaluate Safety and Immunogenicity of AERAS 404 Administered in Adults

NCT02074956 | Completed Phase 1 DMC

• 2 other identifiers: C 006 404C-006-404
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase I study will be conducted as a randomized, double-blind, dose-escalation study in five groups of healthy adult male and female subjects who are BCG-vaccinated, HIV-negative, and have no evidence of tuberculosis infection. Since BCG-vaccinated individuals are the target population for which AERAS 404 might be indicated, AERAS 404 will be administered to individuals already vaccinated with BCG

Conditions

Tuberculosis

Keywords

BCG Vaccinated; HIV Negative

Outcome Measures

Primary Outcomes (1)

• Safety profile of two injections of AERAS 404 at different dose levels of antigen and adjuvant.

  Serious Adverse Events (SAE) will be collected on subjects throughout their participation in the study. Solicited and unsolicited adverse events are captured 28 days post each vaccination. The safety profile of AERAS-404 will be summarized by treatment regimen. The number (percentage) of subjects with adverse events will be summarized by MedDRA system organ class (SOC), and preferred term (PT). Additional summaries will present the number (percentage) of subjects with adverse events by severity and by relationship to study vaccine.

  Total duration of study follow up for all subjects is 182 days.

Secondary Outcomes (1)

• Immunogenicity of two injections of AERAS 404 at different dose levels of antigen and adjuvant.

  Immunogenicity was evaluated from blood collected at Study Days 0, 7, 14, 28, 56, 63, 70, 84, and 182. For all subjects, a QuantiFERON-TB Gold test was performed during screening and at Study Day 182

Study Arms (5)

Cohort 1 AERAS-404

EXPERIMENTAL

H4 Antigen at 5 ug IC31 Adjuvant 500 nmol 2 doses at Study days 0 and 56

Biological: AERAS-404; Biological: Placebo

Cohort 2 AERAS-404

EXPERIMENTAL

H4 Antigen at 15 ug IC31 Adjuvant 500 nmol 2 doses at Study days 0 and 56

Biological: AERAS-404; Biological: Placebo

Cohort 3 AERAS-404

EXPERIMENTAL

H4 Antigen at 50 ug IC31 Adjuvant 500 nmol 2 doses at Study days 0 and 56

Biological: AERAS-404; Biological: Placebo

Cohort 4 AERAS-404

EXPERIMENTAL

H4 Antigen at 150 ug IC31 Adjuvant 500 nmol 2 doses at Study days 0 and 56

Biological: AERAS-404; Biological: Placebo

Cohort 5 AERAS-404

EXPERIMENTAL

H4 Antigen at 5 ug or 15 ug IC31 Adjuvant 100 nmol Placebo - sterile buffer 2 doses at Study days 0 and 56

Biological: AERAS-404; Biological: Placebo

Interventions

AERAS-404 BIOLOGICAL

AERAS-404 is comprised of the H4 antigen, a fusion protein of Mycobacterium tuberculosis antigens 85B and TB10.4; and IC31 adjuvant, a combination of a leucine-rich peptide and a synthetic oligonucleotide.

Also known as: H4

Cohort 1 AERAS-404; Cohort 2 AERAS-404; Cohort 3 AERAS-404; Cohort 4 AERAS-404; Cohort 5 AERAS-404

Placebo BIOLOGICAL

Sterile buffer containing 10 mmol Tris and 169 mmol of NaCl in 0.8 mL of aqueous solution. This is the identical buffer solution in which H4 and IC31 are formulated.

Also known as: Sterile Buffer

Cohort 1 AERAS-404; Cohort 2 AERAS-404; Cohort 3 AERAS-404; Cohort 4 AERAS-404; Cohort 5 AERAS-404

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Has completed written informed consent
• Is male or female
• Is age 18 through 45 years on Study Day 0
• Had BCG vaccination at least 5 years ago, documented through medical history or presence of scar
• Has general good health, confirmed by medical history and physical examination
• Has a Body Mass Index (BMI) between 19 and 33
• Agrees to complete a follow-up period of 182 days as required by the protocol
• Females: Agrees to avoid pregnancy from 28 days prior to Study Day 0 through the follow-up period of 182 days. Women physically capable of pregnancy (not sterilized and still menstruating or within 1 year of the last menses) must agree to avoid pregnancy using an acceptable method
• Agrees to avoid elective surgery for the duration of the study
• Agrees to stay in contact with the investigative site for the study duration
• Completed simultaneous enrollment in Aeras Vaccine Development Registry protocol

You may not qualify if:

• Acute illness on Study Day 0
• Axillary temperature \>=37.5 degrees Celsius on Study Day 0
• Evidence of significant active infection
• Used immunosuppressive medication within 42 days before Study Day 0
• Received immunoglobulin or blood products within 42 days before Study Day 0
• Received any investigational drug therapy or investigational vaccine within 182 days before Study Day 0
• Received inactivated influenza vaccine or inactivated tick-borne encephalitis vaccine within 14 days before entry into the study, or any other standard vaccine within 42 days before Study Day 0
• Current chronic drug therapy including hormone replacement such as thyroxin, insulin
• History or laboratory evidence of past, present or future possible immunodeficiency state which include any laboratory indication of HIV infection
• History of allergic disease or reactions, including eczema
• Previous medical history that may compromise safety of the subject in the study
• Evidence of new acute illness that may compromise the safety of subject in the study
• Evidence of chronic hepatitis
• Inability to discontinue daily medications except contraceptives during study period
• History of alcohol or drug abuse within past 2 years

Sponsors & Collaborators

• Aeras: lead
• Statens Serum Institut: collaborator

Study Sites (1)

University of Tampere Vaccine Research Clinic

Biokatu, Pirkanmaa, 33100, Finland

Location

Related Publications (1)

• Norrby M, Vesikari T, Lindqvist L, Maeurer M, Ahmed R, Mahdavifar S, Bennett S, McClain JB, Shepherd BM, Li D, Hokey DA, Kromann I, Hoff ST, Andersen P, de Visser AW, Joosten SA, Ottenhoff THM, Andersson J, Brighenti S. Safety and immunogenicity of the novel H4:IC31 tuberculosis vaccine candidate in BCG-vaccinated adults: Two phase I dose escalation trials. Vaccine. 2017 Mar 14;35(12):1652-1661. doi: 10.1016/j.vaccine.2017.01.055. Epub 2017 Feb 17.

  PMID: 28216183 DERIVED

MeSH Terms

Conditions

Tuberculosis

Condition Hierarchy (Ancestors)

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

Study Officials

• Zhongkai Shi, MD

  Aeras

  STUDY DIRECTOR

• Timo Vesikari, MD

  University of Tampere Vaccine Research Clinic

  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: February 27, 2014
• First Posted: February 28, 2014
• Study Start: May 1, 2008
• Primary Completion: October 1, 2009
• Study Completion: October 1, 2009
• Last Updated: March 17, 2014

Record last verified: 2014-03

Locations

FI (1)