A Phase I Study to Evaluate Safety and Immunogenicity of AERAS 404 Administered in Adults

Phase 1

Completed

• Conditions: Tuberculosis
• Interventions: Biological: AERAS-404; Biological: Placebo

• Registration Number: NCT02074956
• Lead Sponsor: Aeras

Brief Summary

This Phase I study will be conducted as a randomized, double-blind, dose-escalation study in five groups of healthy adult male and female subjects who are BCG-vaccinated, HIV-negative, and have no evidence of tuberculosis infection. Since BCG-vaccinated individuals are the target population for which AERAS 404 might be indicated, AERAS 404 will be administered to individuals already vaccinated with BCG

Detailed Description

Sixty subjects will be sequentially enrolled into one of five study groups (i.e., Group 1, Group 2, Group 3, Group 4, or Group 5) with 10 subjects per group in Groups 1-4 and 20 subjects in Group 5. Within each study group, subjects will be randomized to a treatment assignment of either AERAS-404 or placebo control at a ratio of 4:1 (Groups 1-4) or two different dose amounts of AERAS-404 or placebo control at a ratio of 9:9:2 (Group 5) administered by intramuscular injection on Study Day 0 and Study Day 56. The principal investigator will determine an appropriate interval between the vaccinations such that the entire group is not dosed at the same time. All subjects will receive the same treatment on Study Day 0 as they receive on Study Day 56. 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

Study Timeline

• Study Start: 2008-05
• Primary Completion: 2009-10
• Study Completion: 2009-10
• Study First Submitted: 2014-02-27
• Study First Submitted QC: 2014-02-27
• Study First Posted: 2014-02-28
• Status Verified: 2014-03
• Last Update Submitted: 2014-03-14
• Last Update Posted: 2014-03-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. Has completed written informed consent
2. Is male or female
3. Is age 18 through 45 years on Study Day 0
4. Had BCG vaccination at least 5 years ago, documented through medical history or presence of scar
5. Has general good health, confirmed by medical history and physical examination
6. Has a Body Mass Index (BMI) between 19 and 33
7. Agrees to complete a follow-up period of 182 days as required by the protocol
8. 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
9. Agrees to avoid elective surgery for the duration of the study
10. Agrees to stay in contact with the investigative site for the study duration
11. Completed simultaneous enrollment in Aeras Vaccine Development Registry protocol

Exclusion Criteria

1. Acute illness on Study Day 0
2. Axillary temperature >=37.5 degrees Celsius on Study Day 0
3. Evidence of significant active infection
4. Used immunosuppressive medication within 42 days before Study Day 0
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
8. Current chronic drug therapy including hormone replacement such as thyroxin, insulin
9. History or laboratory evidence of past, present or future possible immunodeficiency state which include any laboratory indication of HIV infection
10. History of allergic disease or reactions, including eczema
11. Previous medical history that may compromise safety of the subject in the study
12. Evidence of new acute illness that may compromise the safety of subject in the study
13. Evidence of chronic hepatitis
14. Inability to discontinue daily medications except contraceptives during study period
15. History of alcohol or drug abuse within past 2 years
16. Tobacco or cannabis smoking three or more days per week
17. Positive urine test for illicit drugs
18. History or evidence of any systemic disease on physical examination
19. History or evidence of active tuberculosis
20. Shared a residence within the last year with a individual on anti-tuberculosis treatment or with culture or smear positive tuberculosis
21. All females: Positive urine pregnancy test during screening
22. Abnormal (per local laboratory parameters) chemistry and hematology parameters
23. QuantiFERON®-TB Gold evidence of Mtb infection
24. Received a tuberculin skin test within 3 months (90 days) prior to Study Day 0

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1 AERAS-404	AERAS-404	H4 Antigen at 5 ug IC31 Adjuvant 500 nmol 2 doses at Study days 0 and 56
Cohort 1 AERAS-404	Placebo	H4 Antigen at 5 ug IC31 Adjuvant 500 nmol 2 doses at Study days 0 and 56
Cohort 2 AERAS-404	AERAS-404	H4 Antigen at 15 ug IC31 Adjuvant 500 nmol 2 doses at Study days 0 and 56
Cohort 2 AERAS-404	Placebo	H4 Antigen at 15 ug IC31 Adjuvant 500 nmol 2 doses at Study days 0 and 56
Cohort 3 AERAS-404	AERAS-404	H4 Antigen at 50 ug IC31 Adjuvant 500 nmol 2 doses at Study days 0 and 56
Cohort 3 AERAS-404	Placebo	H4 Antigen at 50 ug IC31 Adjuvant 500 nmol 2 doses at Study days 0 and 56
Cohort 4 AERAS-404	AERAS-404	H4 Antigen at 150 ug IC31 Adjuvant 500 nmol 2 doses at Study days 0 and 56
Cohort 4 AERAS-404	Placebo	H4 Antigen at 150 ug IC31 Adjuvant 500 nmol 2 doses at Study days 0 and 56
Cohort 5 AERAS-404	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
Cohort 5 AERAS-404	Placebo	H4 Antigen at 5 ug or 15 ug IC31 Adjuvant 100 nmol Placebo - sterile buffer 2 doses at Study days 0 and 56

Primary Outcome Measures

Name	Time	Method
Safety profile of two injections of AERAS 404 at different dose levels of antigen and adjuvant.	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.

Secondary Outcome Measures

Name	Time	Method
Immunogenicity of two injections of AERAS 404 at different dose levels of antigen and adjuvant.	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.

Trial Locations

Locations (1)

University of Tampere Vaccine Research Clinic; 🇫🇮 Biokatu, Tampere, Finland