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

This study has been completed.
Sponsor:
Collaborator:
Statens Serum Institut
Information provided by (Responsible Party):
Aeras
ClinicalTrials.gov Identifier:
NCT02066428
First received: February 17, 2014
Last updated: February 18, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Tuberculosis
Biological: AERAS-404
Biological: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by Aeras:

Primary Outcome Measures:
  • Evaluate the safety of one or two injections of two AERAS 404 antigen amounts administered with three different amounts of adjuvant [ 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 ] [ Designated as safety issue: Yes ]
    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. [ Time Frame: all subjects will have immunology samples taken at 9 time points over 182 days ] [ Designated as safety issue: No ]
    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


Enrollment: 64
Study Start Date: November 2007
Study Completion Date: May 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AERAS-404(50mcg H4/0nmol IC31) or Placebo
1 dose
Biological: AERAS-404
AERAS 404 (H4:IC31) contains a fusion protein of 2 mycobacterial antigens (Ag85B and TB 10.4) formulated in IC31 adjuvant.
Other Name: H4
Biological: Placebo
Tris buffer saline consisting (10mM Tris and 169mM NaCI at pH7.4)
Other Name: Tris Buffered saline
Experimental: AERAS404 (50mcgH4/100nmol IC31) or Placebo
1 dose
Biological: AERAS-404
AERAS 404 (H4:IC31) contains a fusion protein of 2 mycobacterial antigens (Ag85B and TB 10.4) formulated in IC31 adjuvant.
Other Name: H4
Biological: Placebo
Tris buffer saline consisting (10mM Tris and 169mM NaCI at pH7.4)
Other Name: Tris Buffered saline
Experimental: AERAS404 (50mcgH4/0nmol IC31) or Placebo
2 dose
Biological: AERAS-404
AERAS 404 (H4:IC31) contains a fusion protein of 2 mycobacterial antigens (Ag85B and TB 10.4) formulated in IC31 adjuvant.
Other Name: H4
Biological: Placebo
Tris buffer saline consisting (10mM Tris and 169mM NaCI at pH7.4)
Other Name: Tris Buffered saline
Experimental: AERAS404 (150mcgH4/0nmol IC31) or Placebo
1 dose
Biological: AERAS-404
AERAS 404 (H4:IC31) contains a fusion protein of 2 mycobacterial antigens (Ag85B and TB 10.4) formulated in IC31 adjuvant.
Other Name: H4
Biological: Placebo
Tris buffer saline consisting (10mM Tris and 169mM NaCI at pH7.4)
Other Name: Tris Buffered saline
Experimental: AERAS404 (50mcgH4/5000nmol IC31) or Placebo
1 dose
Biological: AERAS-404
AERAS 404 (H4:IC31) contains a fusion protein of 2 mycobacterial antigens (Ag85B and TB 10.4) formulated in IC31 adjuvant.
Other Name: H4
Biological: Placebo
Tris buffer saline consisting (10mM Tris and 169mM NaCI at pH7.4)
Other Name: Tris Buffered saline
Experimental: AERAS404 (50mcgH4/500nmol IC31) or Placebo
2 dose
Biological: AERAS-404
AERAS 404 (H4:IC31) contains a fusion protein of 2 mycobacterial antigens (Ag85B and TB 10.4) formulated in IC31 adjuvant.
Other Name: H4
Biological: Placebo
Tris buffer saline consisting (10mM Tris and 169mM NaCI at pH7.4)
Other Name: Tris Buffered saline
Experimental: AERAS404
2 dose placebo
Biological: Placebo
Tris buffer saline consisting (10mM Tris and 169mM NaCI at pH7.4)
Other Name: Tris Buffered saline
Experimental: AERAS404 (50mcg H4/100nmol IC31) or Placebo
2 dose
Biological: AERAS-404
AERAS 404 (H4:IC31) contains a fusion protein of 2 mycobacterial antigens (Ag85B and TB 10.4) formulated in IC31 adjuvant.
Other Name: H4
Biological: Placebo
Tris buffer saline consisting (10mM Tris and 169mM NaCI at pH7.4)
Other Name: Tris Buffered saline

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%.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02066428

Locations
Sweden
Karolinska Institutet, Karolinska University Hospital
Huddinge, Stockholm, Sweden, 14186
Sponsors and Collaborators
Aeras
Statens Serum Institut
Investigators
Study Director: Zhongkai SHI, MD Aeras
Principal Investigator: Jan Andersson, MD Karolinska Institutet
  More Information

No publications provided

Responsible Party: Aeras
ClinicalTrials.gov Identifier: NCT02066428     History of Changes
Other Study ID Numbers: C-005-404
Study First Received: February 17, 2014
Last Updated: February 18, 2014
Health Authority: United States: Food and Drug Administration
Sweden: Medical Products Agency

Keywords provided by Aeras:
BCG Vaccinated
HIV Negative

Additional relevant MeSH terms:
Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections

ClinicalTrials.gov processed this record on July 22, 2014