Clinical trial NCT01049282: A Safety and Immunogenicity Trial With an Adjuvanted TB Subunit Vaccine (Ag85B-ESAT-6 + IC31)
Official title: A Safety and Immunogenicity Phase 1 Trial With an Adjuvanted TB Subunit Vaccine (Ag85B-ESAT-6 + IC31) Administered in Different Antigen/Adjuvant Formulations in TST Negative and TST Positive Volunteers at 0 and 2 Months
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Tuberculosis
Keywords: safety
immunogenicity
adjuvanted TB subunit vaccine
Lead sponsor: Statens Serum Institut
Sponsor class: OTHER
First posted: 2010-01-14
Enrollment: 39
Sex: MALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: The study has the following objectives:

Primary objective To evaluate the safety profile of an adjuvanted TB subunit vaccine administered in different antigen/adjuvant formulations at 0 and 2 months Secondary objective To determine the immunogenicity profile of an adjuvanted TB subunit vaccine administered in different antigen/adjuvant formulations at 0 and 2 months.

Detailed description: Number of trial subjects=48 Investigational product=Ag85B - ESAT-6 + IC31 Dosage Group 1: TST negative, 50 µg antigen Group 2: TST negative, 50 µg antigen + fixed adjuvant Group 3: BCG vaccinated, 50 µg antigen + fixed adjuvant Group 4 : Latent TB, 50 µg antigen + fixed adjuvant Dosage volume 0.5 ml Administration Intramuscularly into deltoid muscle, alternate arms at day 0 (right) and day 56 (left).

Eligibility criteria: Inclusion Criteria:

* Male between 18 and 40 years old
* TST negative groups: TST- and negative QuantiFERON-TB Gold In tube test
* BCG group: known to be BCG-vaccinated \> 2 years before(scar, vaccination card), TST+ (\> 6 or any documented value \> 6 mm on medical file in the past), with no active, chronic or past TB disease as confirmed by chest X ray, negative QuantiFERON-TB Gold In Tube test and negative 6-day lymphocyte tests.
* Infection group: latent TB, TST+ ( = or \> 10 mm or documented = or \> 10 mm positive on medical file in the past), previously TB infected but with no active disease confirmed by chest X ray, may have received chemoprophylaxis but with no TB treatment/chemoprophylaxis within the preceding 2 years, positive QuantiFERON-TB Gold In Tube test and/or positive 6-day lymphocyte test.
* Healthy based on medical examination/history at the inclusion
* Signed informed consent
* Prepared to grant authorized persons access to the medical records
* The volunteer is likely to comply with instructions

Exclusion Criteria:

* Confirmed active TB based on clinical evaluation(history, physical findings and investigations)
* Vaccinated with any vaccine 3 months before first vaccination
* Administration of immune modulating drugs (steroids, immunosuppressive drugs or immunoglobulins)
* HBV, HCV or HIV sero-positive
* Participation in other clinical trials
* Known hypersensitivity to any of the vaccine components
* Laboratory parameters outside of normal range considered clinically relevant

Primary outcomes:
measure: Safety on Physical examination , and Laboratory safety tests of hematology clinical chemistry
timeFrame: 12 visits in a total of 224 days duratiion from the day of first vaccinantion
Secondary outcomes:
measure: Immunogenicity assessment by: A.Detection of IFN gama production after stimulation with Ag85B, ESAT-6 and H1. B.Detection of IgG antibodies to recombinant proteins Ag85B, ESAT-6 and H1 in serum/plasma.
timeFrame: 12 visits in a total of 224 days duratiion from the day of first vaccinantion
Other outcomes:
Locations:
Study officials:
affiliation: Armauer Hansen Research Institue/AHRI/,Ethiopia
name: Jemal Hussein, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Statens serum Institute/SSI/,Denamrk
name: Peter Bang, Msc
role: STUDY_DIRECTOR
References:
citation: Hussein J, Zewdie M, Yamuah L, Bedru A, Abebe M, Dagnew AF, Chanyalew M, Yohannes AG, Ahmed J, Engers H, Doherty TM, Bang P, Kromann I, Hoff ST, Aseffa A. A phase I, open-label trial on the safety and immunogenicity of the adjuvanted tuberculosis subunit vaccine H1/IC31(R) in people living in a TB-endemic area. Trials. 2018 Jan 10;19(1):24. doi: 10.1186/s13063-017-2354-0.