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

NCT ID: NCT02066428

Last Updated: 2014-02-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

64 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-11-30

Study Completion Date

2009-05-31

Brief Summary

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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.

Detailed Description

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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%.

Conditions

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Tuberculosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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AERAS-404(50mcg H4/0nmol IC31) or Placebo

1 dose

Group Type EXPERIMENTAL

AERAS-404

Intervention Type BIOLOGICAL

AERAS 404 (H4:IC31) contains a fusion protein of 2 mycobacterial antigens (Ag85B and TB 10.4) formulated in IC31 adjuvant.

Placebo

Intervention Type BIOLOGICAL

Tris buffer saline consisting (10mM Tris and 169mM NaCI at pH7.4)

AERAS404 (50mcgH4/100nmol IC31) or Placebo

1 dose

Group Type EXPERIMENTAL

AERAS-404

Intervention Type BIOLOGICAL

AERAS 404 (H4:IC31) contains a fusion protein of 2 mycobacterial antigens (Ag85B and TB 10.4) formulated in IC31 adjuvant.

Placebo

Intervention Type BIOLOGICAL

Tris buffer saline consisting (10mM Tris and 169mM NaCI at pH7.4)

AERAS404 (50mcgH4/0nmol IC31) or Placebo

2 dose

Group Type EXPERIMENTAL

AERAS-404

Intervention Type BIOLOGICAL

AERAS 404 (H4:IC31) contains a fusion protein of 2 mycobacterial antigens (Ag85B and TB 10.4) formulated in IC31 adjuvant.

Placebo

Intervention Type BIOLOGICAL

Tris buffer saline consisting (10mM Tris and 169mM NaCI at pH7.4)

AERAS404 (150mcgH4/0nmol IC31) or Placebo

1 dose

Group Type EXPERIMENTAL

AERAS-404

Intervention Type BIOLOGICAL

AERAS 404 (H4:IC31) contains a fusion protein of 2 mycobacterial antigens (Ag85B and TB 10.4) formulated in IC31 adjuvant.

Placebo

Intervention Type BIOLOGICAL

Tris buffer saline consisting (10mM Tris and 169mM NaCI at pH7.4)

AERAS404 (50mcgH4/5000nmol IC31) or Placebo

1 dose

Group Type EXPERIMENTAL

AERAS-404

Intervention Type BIOLOGICAL

AERAS 404 (H4:IC31) contains a fusion protein of 2 mycobacterial antigens (Ag85B and TB 10.4) formulated in IC31 adjuvant.

Placebo

Intervention Type BIOLOGICAL

Tris buffer saline consisting (10mM Tris and 169mM NaCI at pH7.4)

AERAS404 (50mcgH4/500nmol IC31) or Placebo

2 dose

Group Type EXPERIMENTAL

AERAS-404

Intervention Type BIOLOGICAL

AERAS 404 (H4:IC31) contains a fusion protein of 2 mycobacterial antigens (Ag85B and TB 10.4) formulated in IC31 adjuvant.

Placebo

Intervention Type BIOLOGICAL

Tris buffer saline consisting (10mM Tris and 169mM NaCI at pH7.4)

AERAS404

2 dose placebo

Group Type EXPERIMENTAL

Placebo

Intervention Type BIOLOGICAL

Tris buffer saline consisting (10mM Tris and 169mM NaCI at pH7.4)

AERAS404 (50mcg H4/100nmol IC31) or Placebo

2 dose

Group Type EXPERIMENTAL

AERAS-404

Intervention Type BIOLOGICAL

AERAS 404 (H4:IC31) contains a fusion protein of 2 mycobacterial antigens (Ag85B and TB 10.4) formulated in IC31 adjuvant.

Placebo

Intervention Type BIOLOGICAL

Tris buffer saline consisting (10mM Tris and 169mM NaCI at pH7.4)

Interventions

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AERAS-404

AERAS 404 (H4:IC31) contains a fusion protein of 2 mycobacterial antigens (Ag85B and TB 10.4) formulated in IC31 adjuvant.

Intervention Type BIOLOGICAL

Placebo

Tris buffer saline consisting (10mM Tris and 169mM NaCI at pH7.4)

Intervention Type BIOLOGICAL

Other Intervention Names

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H4 Tris Buffered saline

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Statens Serum Institut

OTHER

Sponsor Role collaborator

Aeras

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Zhongkai SHI, MD

Role: STUDY_DIRECTOR

Aeras

Jan Andersson, MD

Role: PRINCIPAL_INVESTIGATOR

Karolinska Institutet

Locations

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Karolinska Institutet, Karolinska University Hospital

Huddinge, Stockholm County, Sweden

Site Status

Countries

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Sweden

References

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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

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C-005-404

Identifier Type: -

Identifier Source: org_study_id

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