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

NCT ID: NCT02109874

Last Updated: 2016-04-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-31
• Study Completion Date: 2012-09-30

Brief Summary

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.

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.

Conditions

Tuberculosis

Study Design

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

Study Groups

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

Group Type: EXPERIMENTAL

AERAS-404 (mcg H4/nmol IC31)

Intervention Type: BIOLOGICAL

Dose escalation

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

Group Type: EXPERIMENTAL

AERAS-404 (mcg H4/nmol IC31)

Intervention Type: BIOLOGICAL

Dose escalation

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

Group Type: EXPERIMENTAL

AERAS-404 (mcg H4/nmol IC31)

Intervention Type: BIOLOGICAL

Dose escalation

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

Group Type: EXPERIMENTAL

AERAS-404 (mcg H4/nmol IC31)

Intervention Type: BIOLOGICAL

Dose escalation

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.

Group Type: PLACEBO_COMPARATOR

Sterile buffer containing 10 mmol/L tris and 169 mmol/L NaCl

Intervention Type: BIOLOGICAL

Interventions

AERAS-404 (mcg H4/nmol IC31)

Dose escalation

Intervention Type: BIOLOGICAL

Sterile buffer containing 10 mmol/L tris and 169 mmol/L NaCl

Intervention Type: BIOLOGICAL

Other Intervention Names

H4; AERAS-404

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 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

Locations

South African Tuberculosis Vaccine Institute; Brewelskloof Hospital

Worcester, , South Africa

Countries

South Africa

References

Geldenhuys H, Mearns H, Miles DJ, Tameris M, Hokey D, Shi Z, Bennett S, Andersen P, Kromann I, Hoff ST, Hanekom WA, Mahomed H, Hatherill M, Scriba TJ; H4:IC31 Trial Study Group; van Rooyen M, Bruce McClain J, Ryall R, de Bruyn G; H4:IC31 Trial Study Groupa. The tuberculosis vaccine H4:IC31 is safe and induces a persistent polyfunctional CD4 T cell response in South African adults: A randomized controlled trial. Vaccine. 2015 Jul 9;33(30):3592-9. doi: 10.1016/j.vaccine.2015.05.036. Epub 2015 Jun 3.

Reference Type: BACKGROUND

PMID: 26048780 (View on PubMed)

Other Identifiers

C-011-404

Identifier Type: -

Identifier Source: org_study_id