A Phase I Study to Evaluate Safety and Immunogenicity of AERAS 404 (C-011-404)

NCT02109874 | Completed Phase 1 DMC

• 1 other identifier: C-011-404
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase I study will be conducted as a randomized, placebo-controlled, double-blind, dose-escalation study in four groups of healthy adult male and female subjects who are BCG-vaccinated, HIV-negative, and have no evidence of tuberculosis infection. The study will be conducted at one or two sites located in South Africa. The purpose is to evaluate the safety and immunogenicity of two injections of AERAS 404 prepared with four escalating amounts of antigen in healthy adult male and female subjects who are BCG-vaccinated, HIV-negative, and have no evidence of tuberculosis infection.

Conditions

Tuberculosis

Outcome Measures

Primary Outcomes (1)

• Evaluate the safety of two injections of AERAS 404 prepared with four escalating amounts of antigen in healthy adult subjects. Safety will be measured by number (percentage) and severity of SAEs.

  The safety profile will be described by treatment regimen. Serious adverse events (SAE) will be collected on subjects throughout their participation in the study. Solicited and unsolicited adverse events will be captured for 28 days after each vaccination. The number (percentage) of subjects with any adverse events (including solicited, unsolicited and serious adverse events) will be summarized by MedRA system organ class (SOC) and preferred term (PT). Additional summaries will present the number (percentage) of subjects with any adverse events by severity and by relationship to study vaccine. The number (percentage) of subjects with post-vaccination clinical laboratory values or vital sign values recorded as newly abnormal following study vaccination and meeting toxicity criteria will be tabulated at each post-vaccination point and overall.

  Solicited and unsolicited AEs until study day 182

Secondary Outcomes (1)

• Evaluate the immunogenicity of two injections of AERAS 404 prepared with four escalating amounts of antigen in healthy adult subjects. Immune response will be based on percentage of CD4+ and CD8+ cells.

  182 days

Study Arms (5)

AERAS-404 (mcg H4/nmol IC31) 5/500

EXPERIMENTAL

H4 antigen (supplied in 4 different concentrations): 1.0 mL containing H4 antigen at 50, 150, 500, or 1500 mcg/mL in 10 mmol/L tris and 5% glycerol IC31 Adjuvant (supplied in 1 concentration): 0.8 mL containing IC31 adjuvant at 1250 nmol/mL, in 10 mmol/L tris and 169 mmol/L NaCl

Biological: AERAS-404 (mcg H4/nmol IC31)

AERAS-404 (mcg H4/nmol IC31) 15/500

EXPERIMENTAL

H4 antigen (supplied in 4 different concentrations): 1.0 mL containing H4 antigen at 50, 150, 500, or 1500 mcg/mL in 10 mmol/L tris and 5% glycerol IC31 Adjuvant (supplied in 1 concentration): 0.8 mL containing IC31 adjuvant at 1250 nmol/mL, in 10 mmol/L tris and 169 mmol/L NaCl

Biological: AERAS-404 (mcg H4/nmol IC31)

AERAS-404 (mcg H4/nmol IC31) 50/500

EXPERIMENTAL

H4 antigen (supplied in 4 different concentrations): 1.0 mL containing H4 antigen at 50, 150, 500, or 1500 mcg/mL in 10 mmol/L tris and 5% glycerol IC31 Adjuvant (supplied in 1 concentration): 0.8 mL containing IC31 adjuvant at 1250 nmol/mL, in 10 mmol/L tris and 169 mmol/L NaCl

Biological: AERAS-404 (mcg H4/nmol IC31)

AERAS-404 (mcg H4/nmol IC31) 150/500

EXPERIMENTAL

H4 antigen (supplied in 4 different concentrations): 1.0 mL containing H4 antigen at 50, 150, 500, or 1500 mcg/mL in 10 mmol/L tris and 5% glycerol IC31 Adjuvant (supplied in 1 concentration): 0.8 mL containing IC31 adjuvant at 1250 nmol/mL, in 10 mmol/L tris and 169 mmol/L NaCl

Biological: AERAS-404 (mcg H4/nmol IC31)

Sterile buffer containing 10 mmol/L tris and 169 mmol/L NaCl

PLACEBO COMPARATOR

Placebo: Sterile buffer containing 10 mmol/L tris and 169 mmol/L NaCl. This is the identical buffer solution in which IC31 is formulated.

Biological: Sterile buffer containing 10 mmol/L tris and 169 mmol/L NaCl

Interventions

AERAS-404 (mcg H4/nmol IC31) BIOLOGICAL

Dose escalation

Also known as: H4, AERAS-404

AERAS-404 (mcg H4/nmol IC31) 15/500; AERAS-404 (mcg H4/nmol IC31) 150/500; AERAS-404 (mcg H4/nmol IC31) 5/500; AERAS-404 (mcg H4/nmol IC31) 50/500

Sterile buffer containing 10 mmol/L tris and 169 mmol/L NaCl BIOLOGICAL

Sterile buffer containing 10 mmol/L tris and 169 mmol/L NaCl

Eligibility Criteria

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

You may qualify if:

• Subjects must have met all of the following criteria:
• Had completed written informed consent
• Was male or female
• Was age 18 through 50 years on Study Day 0
• Had BCG vaccination at least 5 years ago, documented through medical history or presence of scar
• Had general good health, confirmed by medical history and physical examination
• Had a Body Mass Index (BMI) between 19 and 33 (weight in kg/\[height in m\]2)
• Agreed to complete a follow-up period of 182 days as required by the protocol
• Females: Agreed to avoid pregnancy from 28 days prior to Study Day 0 through the follow-up period of 182 days.
• Agreed to avoid elective surgery for the duration of the study
• Agreed to stay in contact with the investigative site for the duration of the study
• Had completed simultaneous enrollment in Aeras Vaccine Development Registry protocol

You may not qualify if:

• Subjects must not have:
• Acute illness on Study Day 0
• Oral temperature equal to or greater than 37.5 degrees C on Study Day 0
• Evidence of significant active infection
• 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 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 (the use of licensed drugs or vaccines medically indicated during the study interval was permitted)
• Current chronic drug therapy including hormone replacement such as thyroxin, insulin, etc. Estrogen and progesterone replacement and contraceptives were acceptable.
• History or laboratory evidence of any past, present or future possible immunodeficiency state which included (but was not limited to) any laboratory indication of HIV infection
• History of allergic disease or reactions, including eczema, likely to be exacerbated by any component of the study vaccine
• Previous medical history that may have compromised the safety of the subject in the study
• Evidence of a new acute illness that may have compromised the safety of the subject in the study
• Evidence of chronic hepatitis (e.g., hepatitis B core antibody or hepatitis C antibody)
• Inability to discontinue daily medications except contraceptives during the study period

Sponsors & Collaborators

• Aeras: lead
• Statens Serum Institut: collaborator

Study Sites (1)

South African Tuberculosis Vaccine Institute; Brewelskloof Hospital

Worcester, South Africa

Location

Related Publications (1)

• Geldenhuys H, Mearns H, Miles DJ, Tameris M, Hokey D, Shi Z, Bennett S, Andersen P, Kromann I, Hoff ST, Hanekom WA, Mahomed H, Hatherill M, Scriba TJ; H4:IC31 Trial Study Group; van Rooyen M, Bruce McClain J, Ryall R, de Bruyn G; H4:IC31 Trial Study Groupa. The tuberculosis vaccine H4:IC31 is safe and induces a persistent polyfunctional CD4 T cell response in South African adults: A randomized controlled trial. Vaccine. 2015 Jul 9;33(30):3592-9. doi: 10.1016/j.vaccine.2015.05.036. Epub 2015 Jun 3.

  PMID: 26048780 BACKGROUND

MeSH Terms

Conditions

Tuberculosis

Interventions

Tromethamine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Propylene Glycols; Glycols; Alcohols; Organic Chemicals

Study Officials

• Zhongkai Shi, MD

  Aeras

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: March 28, 2014
• First Posted: April 10, 2014
• Study Start: December 1, 2008
• Primary Completion: December 1, 2010
• Study Completion: September 1, 2012
• Last Updated: April 27, 2016

Record last verified: 2014-04

Locations

ZA (1)