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A Phase I Randomized Placebo-Controlled, Double-Blind Study to Evaluate Safety and Immunogenicity of AERAS-404 Administered as Different Amounts of Antigen and Adjuvant Combinations in HIV-Negative BCG-Vaccinated Adults Without Evidence of Tuberculosis Infection

Primary Purpose

Tuberculosis

Status
Completed
Phase
Phase 1
Locations
Sweden
Study Type
Interventional
Intervention
AERAS-404
Placebo
Sponsored by
Aeras
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Tuberculosis focused on measuring BCG Vaccinated, HIV Negative

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  1. Male or female
  2. Age 18 through 50 years on Study Day 0
  3. Completed wriiten Informed Consent
  4. BCG vaccination at least 5 years ago,
  5. General good health, confirmed by medical history
  6. (BMI) between 19 and 33 (kg/m2)
  7. Has ability to complete follow-up period of 182 days as required
  8. Females must be physically incapable of conception
  9. Avoiding elective surgery for the duration of the study
  10. Stay in contact with the investigative site for the duration of the study
  11. Complete simultaneous enrollment in Aeras Vaccine Development Registry protocol

Exclusion Criteria:

  1. Acute illness on the day of randomization
  2. Oral temperature >=37.5 degree Celcius on the day of randomization
  3. Evidence of significant active infection
  4. Used immunosuppressive medication within 42 days before entry into the study
  5. Received immunoglobulin or blood products within 42 days before entry into the study
  6. Received any investigational drug therapy or investigational vaccine within 182 days
  7. Received inactivated influenza vaccine or inactivated tick-borne encephalitis vaccine within 14 days before entry into the study.
  8. Current chronic drug therapy including hormone replacement such as thyroxin, insulin, etc.
  9. History or laboratory evidence of any past, present or future possible immunodeficiency state which will include any laboratory indication of virus type 1 (HIV-1) infection
  10. History of allergic disease or reactions, including eczema.
  11. Previous medical history that may compromise safety of subject
  12. Evidence of new acute illness that may compromise safety of subject
  13. Evidence of chronic hepatitis
  14. Inability to discontinue daily medication except contraception
  15. History of alcohol or drug abuse within 2yrs
  16. Tobacco or cannabis smoking three
  17. Positive urine test for illicit drugs
  18. History or evidence of any systemic disease on physical examination
  19. History of active TB
  20. Shared residence within 1 year with an individual on anti-TB treatment
  21. All females: nursing
  22. Abnormal hemoglobin,hematocrit etc drawn within 36 hours prior to randomization
  23. Laboratory test evidence of Mtb infection
  24. History of positive tuberculin skin test within past 10 years
  25. Received a tuberculin skin test within 3 years
  26. History of autoimmune disease

Sites / Locations

  • Karolinska Institutet, Karolinska University Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

AERAS-404(50mcg H4/0nmol IC31) or Placebo

AERAS404 (50mcgH4/100nmol IC31) or Placebo

AERAS404 (50mcgH4/0nmol IC31) or Placebo

AERAS404 (150mcgH4/0nmol IC31) or Placebo

AERAS404 (50mcgH4/5000nmol IC31) or Placebo

AERAS404 (50mcgH4/500nmol IC31) or Placebo

AERAS404

AERAS404 (50mcg H4/100nmol IC31) or Placebo

Arm Description

1 dose

1 dose

2 dose

1 dose

1 dose

2 dose

2 dose placebo

2 dose

Outcomes

Primary Outcome Measures

Evaluate the safety of one or two injections of two AERAS 404 antigen amounts administered with three different amounts of adjuvant
Serious adverse events (SAE) will be collected on subjects throughout their participation in the study. Solicited and unsolicited AEs will be collected through 28 days after each vaccination.The safety profile of the different antigen/adjuvant treatment regimens will be described. Listings will be provided for all subjects with serious adverse events (SAE). All adverse events and clinically relevant laboratory results will be summarized across time points to examine the relationship between treatment regimens (i.e., number of doses and level of antigen/adjuvant) and key safety endpoints including number (percentage) of solicited and spontaneous adverse events and number (percentage) of subjects with newly abnormal post-vaccination laboratory values based on predefined toxicity criteria. Adverse events will also be summarized by severity and relationship to study vaccine by treatment regimen.

Secondary Outcome Measures

Evaluate the immunogenicity of one or two injections of two AERAS 404 antigen amounts administered with three different amounts of adjuvant.
Assessment of immune response will be based on the percentage of CD4 and CD8 T cells producing any of three cytokines (interferon gamma, IFN-γ; tumor necrosis factor alpha, TNF-α; and/or interleukin-2, IL-2) or any combination of these three cytokines simultaneously in response to stimulation with two the antigenic peptide pools contains 85B and TB10.4 representing the entire amino acid sequences of mycobacterial antigens Ag85B and TB10.4, respectively. Responses will be measured by flow cytometry using a qualified intracellular cytokine staining (ICS) assay

Full Information

First Posted
February 17, 2014
Last Updated
February 18, 2014
Sponsor
Aeras
Collaborators
Statens Serum Institut
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1. Study Identification

Unique Protocol Identification Number
NCT02066428
Brief Title
A Phase I Randomized Placebo-Controlled, Double-Blind Study to Evaluate Safety and Immunogenicity of AERAS-404 Administered as Different Amounts of Antigen and Adjuvant Combinations in HIV-Negative BCG-Vaccinated Adults Without Evidence of Tuberculosis Infection
Official Title
A Phase I Randomized Placebo-Controlled, Double-Blind Study to Evaluate Safety and Immunogenicity of AERAS-404 Administered as Different Amounts of Antigen and Adjuvant Combinations in HIV-Negative BCG-Vaccinated Adults Without Evidence of Tuberculosis Infection
Study Type
Interventional

2. Study Status

Record Verification Date
February 2014
Overall Recruitment Status
Completed
Study Start Date
November 2007 (undefined)
Primary Completion Date
May 2009 (Actual)
Study Completion Date
May 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Aeras
Collaborators
Statens Serum Institut

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Phase I, randomized, double blinded, Placebo-controlled, immunogenicity and dose-range finding study of AERAS-404 in Bacille Calmette-Guerin (BCG) healthy adult male and sterile females.
Detailed Description
This ia a Phase I, randomized, placebo-controlled, double-blind study in three groups of healthy adult males or sterile females who are BCG-vaccinated, HIV-negative, and have no evidence of tuberculosis infection. Sixty-four subjects assigned to one of eight treatment groups to receive one of four different antigen/adjuvant combinations of study vaccine, or placebo control. Within each study group, subjects will be randomized to receive either a single-dose antigen/adjuvant regimen of study vaccine (vaccination with study vaccine on Study Day 0 followed by vaccination with placebo control on Study Day 56) or a two-dose antigen/adjuvant regimen of study vaccine (vaccination with study vaccine on Study Days 0 and 56). All subjects will be followed for safety and immunogenicity evaluations for 182 days. The sample sizes specified for each study group were selected because they are judged to be adequate for preliminary safety and immunogenicity evaluations for a Phase I study rather than for statistical reasons. If no SAE are observed among 56 subjects receiving active study vaccine, an approximation to the upper 95% confidence bound on the rate of SAE occurrence would be 5.4%.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculosis
Keywords
BCG Vaccinated, HIV Negative

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
64 (Actual)

8. Arms, Groups, and Interventions

Arm Title
AERAS-404(50mcg H4/0nmol IC31) or Placebo
Arm Type
Experimental
Arm Description
1 dose
Arm Title
AERAS404 (50mcgH4/100nmol IC31) or Placebo
Arm Type
Experimental
Arm Description
1 dose
Arm Title
AERAS404 (50mcgH4/0nmol IC31) or Placebo
Arm Type
Experimental
Arm Description
2 dose
Arm Title
AERAS404 (150mcgH4/0nmol IC31) or Placebo
Arm Type
Experimental
Arm Description
1 dose
Arm Title
AERAS404 (50mcgH4/5000nmol IC31) or Placebo
Arm Type
Experimental
Arm Description
1 dose
Arm Title
AERAS404 (50mcgH4/500nmol IC31) or Placebo
Arm Type
Experimental
Arm Description
2 dose
Arm Title
AERAS404
Arm Type
Experimental
Arm Description
2 dose placebo
Arm Title
AERAS404 (50mcg H4/100nmol IC31) or Placebo
Arm Type
Experimental
Arm Description
2 dose
Intervention Type
Biological
Intervention Name(s)
AERAS-404
Other Intervention Name(s)
H4
Intervention Description
AERAS 404 (H4:IC31) contains a fusion protein of 2 mycobacterial antigens (Ag85B and TB 10.4) formulated in IC31 adjuvant.
Intervention Type
Biological
Intervention Name(s)
Placebo
Other Intervention Name(s)
Tris Buffered saline
Intervention Description
Tris buffer saline consisting (10mM Tris and 169mM NaCI at pH7.4)
Primary Outcome Measure Information:
Title
Evaluate the safety of one or two injections of two AERAS 404 antigen amounts administered with three different amounts of adjuvant
Description
Serious adverse events (SAE) will be collected on subjects throughout their participation in the study. Solicited and unsolicited AEs will be collected through 28 days after each vaccination.The safety profile of the different antigen/adjuvant treatment regimens will be described. Listings will be provided for all subjects with serious adverse events (SAE). All adverse events and clinically relevant laboratory results will be summarized across time points to examine the relationship between treatment regimens (i.e., number of doses and level of antigen/adjuvant) and key safety endpoints including number (percentage) of solicited and spontaneous adverse events and number (percentage) of subjects with newly abnormal post-vaccination laboratory values based on predefined toxicity criteria. Adverse events will also be summarized by severity and relationship to study vaccine by treatment regimen.
Time Frame
All subjects will be followed for safety and immunogenicity evaluations for 182 days. A total of eleven clinic visits are planned (excluding screening) for all subjects
Secondary Outcome Measure Information:
Title
Evaluate the immunogenicity of one or two injections of two AERAS 404 antigen amounts administered with three different amounts of adjuvant.
Description
Assessment of immune response will be based on the percentage of CD4 and CD8 T cells producing any of three cytokines (interferon gamma, IFN-γ; tumor necrosis factor alpha, TNF-α; and/or interleukin-2, IL-2) or any combination of these three cytokines simultaneously in response to stimulation with two the antigenic peptide pools contains 85B and TB10.4 representing the entire amino acid sequences of mycobacterial antigens Ag85B and TB10.4, respectively. Responses will be measured by flow cytometry using a qualified intracellular cytokine staining (ICS) assay
Time Frame
all subjects will have immunology samples taken at 9 time points over 182 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Male or female Age 18 through 50 years on Study Day 0 Completed wriiten Informed Consent BCG vaccination at least 5 years ago, General good health, confirmed by medical history (BMI) between 19 and 33 (kg/m2) Has ability to complete follow-up period of 182 days as required Females must be physically incapable of conception Avoiding elective surgery for the duration of the study Stay in contact with the investigative site for the duration of the study Complete simultaneous enrollment in Aeras Vaccine Development Registry protocol Exclusion Criteria: Acute illness on the day of randomization Oral temperature >=37.5 degree Celcius on the day of randomization Evidence of significant active infection Used immunosuppressive medication within 42 days before entry into the study Received immunoglobulin or blood products within 42 days before entry into the study Received any investigational drug therapy or investigational vaccine within 182 days Received inactivated influenza vaccine or inactivated tick-borne encephalitis vaccine within 14 days before entry into the study. Current chronic drug therapy including hormone replacement such as thyroxin, insulin, etc. History or laboratory evidence of any past, present or future possible immunodeficiency state which will include any laboratory indication of virus type 1 (HIV-1) infection History of allergic disease or reactions, including eczema. Previous medical history that may compromise safety of subject Evidence of new acute illness that may compromise safety of subject Evidence of chronic hepatitis Inability to discontinue daily medication except contraception History of alcohol or drug abuse within 2yrs Tobacco or cannabis smoking three Positive urine test for illicit drugs History or evidence of any systemic disease on physical examination History of active TB Shared residence within 1 year with an individual on anti-TB treatment All females: nursing Abnormal hemoglobin,hematocrit etc drawn within 36 hours prior to randomization Laboratory test evidence of Mtb infection History of positive tuberculin skin test within past 10 years Received a tuberculin skin test within 3 years History of autoimmune disease
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhongkai SHI, MD
Organizational Affiliation
Aeras
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Jan Andersson, MD
Organizational Affiliation
Karolinska Institutet
Official's Role
Principal Investigator
Facility Information:
Facility Name
Karolinska Institutet, Karolinska University Hospital
City
Huddinge
State/Province
Stockholm
ZIP/Postal Code
14186
Country
Sweden

12. IPD Sharing Statement

Citations:
PubMed Identifier
28216183
Citation
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.
Results Reference
derived

Learn more about this trial

A Phase I Randomized Placebo-Controlled, Double-Blind Study to Evaluate Safety and Immunogenicity of AERAS-404 Administered as Different Amounts of Antigen and Adjuvant Combinations in HIV-Negative BCG-Vaccinated Adults Without Evidence of Tuberculosis Infection

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