- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02074956
A Phase I Study to Evaluate Safety and Immunogenicity of AERAS 404 Administered in Adults
A Phase I Randomized Placebo-Controlled, Double-Blind Study to Evaluate Safety and Immunogenicity of AERAS 404 When Administered as Different IC31 Adjuvant Amounts With Different AERAS-404 (HyVac4) Antigen Amounts in HIV-Negative BCG-Vaccinated Adults Without Evidence of Tuberculosis Infection
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Tampere
-
Biokatu, Tampere, Finland, 33100
- University of Tampere Vaccine Research Clinic
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
- Tobacco or cannabis smoking three or more days per week
- Positive urine test for illicit drugs
- History or evidence of any systemic disease on physical examination
- History or evidence of active tuberculosis
- Shared a residence within the last year with a individual on anti-tuberculosis treatment or with culture or smear positive tuberculosis
- All females: Positive urine pregnancy test during screening
- Abnormal (per local laboratory parameters) chemistry and hematology parameters
- QuantiFERON®-TB Gold evidence of Mtb infection
- Received a tuberculin skin test within 3 months (90 days) prior to Study Day 0
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Cohort 1 AERAS-404
H4 Antigen at 5 ug IC31 Adjuvant 500 nmol 2 doses at Study days 0 and 56 |
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.
Other Names:
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.
Other Names:
|
Experimental: Cohort 2 AERAS-404
H4 Antigen at 15 ug IC31 Adjuvant 500 nmol 2 doses at Study days 0 and 56 |
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.
Other Names:
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.
Other Names:
|
Experimental: Cohort 3 AERAS-404
H4 Antigen at 50 ug IC31 Adjuvant 500 nmol 2 doses at Study days 0 and 56 |
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.
Other Names:
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.
Other Names:
|
Experimental: Cohort 4 AERAS-404
H4 Antigen at 150 ug IC31 Adjuvant 500 nmol 2 doses at Study days 0 and 56 |
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.
Other Names:
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.
Other Names:
|
Experimental: Cohort 5 AERAS-404
H4 Antigen at 5 ug or 15 ug IC31 Adjuvant 100 nmol Placebo - sterile buffer 2 doses at Study days 0 and 56 |
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.
Other Names:
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.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety profile of two injections of AERAS 404 at different dose levels of antigen and adjuvant.
Time Frame: Total duration of study follow up for all subjects is 182 days.
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Immunogenicity of two injections of AERAS 404 at different dose levels of antigen and adjuvant.
Time Frame: 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
|
Intracellular cytokine staining will be used to assess immunogenicity.
Immune response based on percentages of CD4+ and CD8+ T cells that produced one, two, or three cytokines (IFN-γ, TNF-α, and/or IL-2) in response to stimulation with one of 2 antigenic peptide pools (Ag85B and TB10.4) derived from and representing the entire amino acid sequences of the mycobacterial antigens Ag85B and TB10.4,
respectively.
|
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
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Timo Vesikari, MD, University of Tampere Vaccine Research Clinic
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- C 006 404
- C-006-404 (Other Identifier: Aeras)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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