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

Tuberculosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02066428
• Other study ID #: C-005-404
• Status: Completed
• Phase: Phase 1
• First received: February 17, 2014
• Last updated: February 18, 2014
• Start date: November 2007
• Est. completion date: May 2009

Study information

• Verified date: February 2014
• Source: Aeras
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationSweden: Medical Products Agency
• Study type: Interventional

Clinical Trial 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.

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%.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: May 2009
• Est. primary completion date: May 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Tuberculosis

Intervention

Biological:
• AERAS-404
AERAS 404 (H4:IC31) contains a fusion protein of 2 mycobacterial antigens (Ag85B and TB 10.4) formulated in IC31 adjuvant.
• Placebo
Tris buffer saline consisting (10mM Tris and 169mM NaCI at pH7.4)

Locations

Country	Name	City	State
Sweden	Karolinska Institutet, Karolinska University Hospital	Huddinge	Stockholm

Sponsors (2)

Lead Sponsor	Collaborator
Aeras	Statens Serum Institut

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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	Yes
Secondary	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-?; tumor necrosis factor alpha, TNF-a; 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	all subjects will have immunology samples taken at 9 time points over 182 days	No