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

This study has been completed.
Sponsor:
Collaborator:
Statens Serum Institut
Information provided by (Responsible Party):
Aeras
ClinicalTrials.gov Identifier:
NCT02109874
First received: March 28, 2014
Last updated: April 7, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Tuberculosis
Biological: AERAS-404 (mcg H4/nmol IC31)
Biological: Sterile buffer containing 10 mmol/L tris and 169 mmol/L NaCl
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: A Phase I Randomized Placebo-Controlled, Double-Blind Study to Evaluate Safety and Immunogenicity of AERAS 404 When Administered as a Single Adjuvant Amount With Different Antigen Amounts 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 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. [ Time Frame: Solicited and unsolicited AEs until study day 182 ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • 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. [ Time Frame: 182 days ] [ Designated as safety issue: No ]
    The primary response will be measured by flow cytometry in the Intracellular cytokine staining (ICS) assay. Immune responses will be based on percentage of CD4+ and CD8+ T cells that produced one, two, or three cytokines (IFN-gamma, TNF, and/or IL-2) in response to stimulation with one of the 2 antigenic peptide pool (Ag85B and TB10.4) derived from and representing the entire amino acid sequences of teh mycobacterial antigens Ag85B and TB10.4.


Enrollment: 40
Study Start Date: December 2008
Study Completion Date: September 2012
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AERAS-404 (mcg H4/nmol IC31) 5/500

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)
Dose escalation
Other Names:
  • H4
  • AERAS-404
Experimental: AERAS-404 (mcg H4/nmol IC31) 15/500

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)
Dose escalation
Other Names:
  • H4
  • AERAS-404
Experimental: AERAS-404 (mcg H4/nmol IC31) 50/500

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)
Dose escalation
Other Names:
  • H4
  • AERAS-404
Experimental: AERAS-404 (mcg H4/nmol IC31) 150/500

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)
Dose escalation
Other Names:
  • H4
  • AERAS-404
Placebo Comparator: Sterile buffer containing 10 mmol/L tris and 169 mmol/L NaCl
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

Detailed Description:

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.

Forty subjects will be sequentially enrolled into one of four study groups (i.e., Group 1, Group 2, Group 3, or Group 4) based on time of completion of screening, with 10 subjects enrolled into each group. Within each study group, subjects will be randomized to a treatment regimen of either AERAS-404 or placebo control administered by intramuscular injection on Study Day 0 and Study Day 56. All subjects will receive the same treatment on Study Day 0 as they receive on Study Day 56. The dose of antigen will increase between study groups. 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.

  Eligibility

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

Inclusion Criteria

Subjects must have met all of the following criteria:

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

Exclusion Criteria

Subjects must not have:

  1. Acute illness on Study Day 0
  2. Oral temperature equal to or greater than 37.5 degrees C on Study Day 0
  3. Evidence of significant active infection
  4. Used immunosuppressive medication within 42 days before Study Day 0 (inhaled and topical corticosteroids are permitted)
  5. Received immunoglobulin or blood products within 42 days before Study Day 0
  6. Received any investigational drug therapy or investigational vaccine within 182 days before Study Day 0
  7. 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)
  8. Current chronic drug therapy including hormone replacement such as thyroxin, insulin, etc. Estrogen and progesterone replacement and contraceptives were acceptable.
  9. 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
  10. History of allergic disease or reactions, including eczema, likely to be exacerbated by any component of the study vaccine
  11. Previous medical history that may have compromised the safety of the subject in the study
  12. Evidence of a new acute illness that may have compromised the safety of the subject in the study
  13. Evidence of chronic hepatitis (e.g., hepatitis B core antibody or hepatitis C antibody)
  14. Inability to discontinue daily medications except contraceptives during the study period
  15. History of alcohol or drug abuse within the past 2 years
  16. Tobacco or cannabis smoking 3 or more days per week
  17. Positive urine test for illicit drugs (opiates, cocaine, amphetamines)
  18. History or evidence of any systemic disease on physical examination or any acute or chronic illness that, in the opinion of the investigator, may have interfered with the evaluation of the safety or immunogenicity of the vaccine, including axillary lymphadenopathy
  19. History or evidence (including chest X-ray) of active tuberculosis
  20. Shared a residence within the last year with an individual on anti-tuberculosis treatment or with culture or smear positive tuberculosis
  21. All females: Positive urine pregnancy test during screening; positive serum pregnancy test on the day of study vaccination; were nursing
  22. Abnormal (per local laboratory parameters) chemistry, hematology or urinalysis obtained within 36 hours prior to randomization.
  23. Laboratory evidence of Mtb infection, defined as a positive QuantiFERON-TB Gold (QFT-G) test.
  24. History of a positive tuberculin skin test within the past ten years (defined according to local guidelines).
  25. Received a tuberculin skin test within 3 months (90 days) prior to Study Day 0.
  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: NCT02109874

Locations
South Africa
South African Tuberculosis Vaccine Institute; Brewelskloof Hospital
Worcester, South Africa
Sponsors and Collaborators
Aeras
Statens Serum Institut
Investigators
Study Director: Zhongkai Shi, MD Aeras
  More Information

No publications provided

Responsible Party: Aeras
ClinicalTrials.gov Identifier: NCT02109874     History of Changes
Other Study ID Numbers: C-011-404
Study First Received: March 28, 2014
Last Updated: April 7, 2014
Health Authority: South Africa: Medicines Control Council

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

ClinicalTrials.gov processed this record on November 25, 2014