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

NCT ID: NCT02074956

Last Updated: 2014-03-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-05-31
• Study Completion Date: 2009-10-31

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

Conditions

Tuberculosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Cohort 1 AERAS-404

H4 Antigen at 5 ug IC31 Adjuvant 500 nmol

2 doses at Study days 0 and 56

Group Type: EXPERIMENTAL

AERAS-404

Intervention Type: BIOLOGICAL

AERAS-404 is comprised of the H4 antigen, a fusion protein of Mycobacterium tuberculosis antigens 85B and TB10.4; and IC31 adjuvant, a combination of a leucine-rich peptide and a synthetic oligonucleotide.

Placebo

Intervention Type: BIOLOGICAL

Sterile buffer containing 10 mmol Tris and 169 mmol of NaCl in 0.8 mL of aqueous solution. This is the identical buffer solution in which H4 and IC31 are formulated.

Cohort 2 AERAS-404

H4 Antigen at 15 ug IC31 Adjuvant 500 nmol

2 doses at Study days 0 and 56

Group Type: EXPERIMENTAL

AERAS-404

Intervention Type: BIOLOGICAL

AERAS-404 is comprised of the H4 antigen, a fusion protein of Mycobacterium tuberculosis antigens 85B and TB10.4; and IC31 adjuvant, a combination of a leucine-rich peptide and a synthetic oligonucleotide.

Placebo

Intervention Type: BIOLOGICAL

Sterile buffer containing 10 mmol Tris and 169 mmol of NaCl in 0.8 mL of aqueous solution. This is the identical buffer solution in which H4 and IC31 are formulated.

Cohort 3 AERAS-404

H4 Antigen at 50 ug IC31 Adjuvant 500 nmol

2 doses at Study days 0 and 56

Group Type: EXPERIMENTAL

AERAS-404

Intervention Type: BIOLOGICAL

AERAS-404 is comprised of the H4 antigen, a fusion protein of Mycobacterium tuberculosis antigens 85B and TB10.4; and IC31 adjuvant, a combination of a leucine-rich peptide and a synthetic oligonucleotide.

Placebo

Intervention Type: BIOLOGICAL

Sterile buffer containing 10 mmol Tris and 169 mmol of NaCl in 0.8 mL of aqueous solution. This is the identical buffer solution in which H4 and IC31 are formulated.

Cohort 4 AERAS-404

H4 Antigen at 150 ug IC31 Adjuvant 500 nmol

2 doses at Study days 0 and 56

Group Type: EXPERIMENTAL

AERAS-404

Intervention Type: BIOLOGICAL

AERAS-404 is comprised of the H4 antigen, a fusion protein of Mycobacterium tuberculosis antigens 85B and TB10.4; and IC31 adjuvant, a combination of a leucine-rich peptide and a synthetic oligonucleotide.

Placebo

Intervention Type: BIOLOGICAL

Sterile buffer containing 10 mmol Tris and 169 mmol of NaCl in 0.8 mL of aqueous solution. This is the identical buffer solution in which H4 and IC31 are formulated.

Cohort 5 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

Group Type: EXPERIMENTAL

AERAS-404

Intervention Type: BIOLOGICAL

AERAS-404 is comprised of the H4 antigen, a fusion protein of Mycobacterium tuberculosis antigens 85B and TB10.4; and IC31 adjuvant, a combination of a leucine-rich peptide and a synthetic oligonucleotide.

Placebo

Intervention Type: BIOLOGICAL

Sterile buffer containing 10 mmol Tris and 169 mmol of NaCl in 0.8 mL of aqueous solution. This is the identical buffer solution in which H4 and IC31 are formulated.

Interventions

AERAS-404

AERAS-404 is comprised of the H4 antigen, a fusion protein of Mycobacterium tuberculosis antigens 85B and TB10.4; and IC31 adjuvant, a combination of a leucine-rich peptide and a synthetic oligonucleotide.

Intervention Type: BIOLOGICAL

Placebo

Sterile buffer containing 10 mmol Tris and 169 mmol of NaCl in 0.8 mL of aqueous solution. This is the identical buffer solution in which H4 and IC31 are formulated.

Intervention Type: BIOLOGICAL

Other Intervention Names

H4; Sterile Buffer

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Statens Serum Institut

OTHER

Sponsor Role: collaborator

Aeras

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Zhongkai Shi, MD

Role: STUDY_DIRECTOR

Aeras

Timo Vesikari, MD

Role: PRINCIPAL_INVESTIGATOR

University of Tampere Vaccine Research Clinic

Locations

University of Tampere Vaccine Research Clinic

Biokatu, Pirkanmaa, Finland

Countries

Finland

References

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.

Reference Type: DERIVED

PMID: 28216183 (View on PubMed)

Other Identifiers

C-006-404

Identifier Type: OTHER

Identifier Source: secondary_id

C 006 404

Identifier Type: -

Identifier Source: org_study_id