Clinical trial NCT00929396: A Safety and Immunogenicity Trial With an Adjuvanted Tuberculosis (TB) Subunit Vaccine in Purified Protein Derivative (PPD) Positive Volunteers
Official title: A Safety and Immunogenicity Phase 1 Trial With an Adjuvanted TB Subunit Vaccine (Ag85B-ESAT-6 + IC31)Administered in PPD Positive Volunteers at 0 and 2 Months
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Tuberculosis
Keywords: Tuberculosis
Vaccine
Ag85B
ESAT-6
IC31
Lead sponsor: Statens Serum Institut
Sponsor class: OTHER
First posted: 2009-06-29
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to evaluate the safety profile of an adjuvanted TB subunit vaccine administered at 0 and 2 months.


Eligibility criteria: Inclusion Criteria:

* Male and female between 18 and 55 years old
* BCG group: Known to be BCG-vaccinated over 2 years before, PPD positive (range 6-15 mm or any documented value between 6-15 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: Known to be treated for latent TB, PPDpositive (equal or over 10 mm or documented equal or over 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:

* Granulomatous disease (by chest X-ray)
* Vaccinated with live vaccine 3 months before first vaccination
* Administration of immune modulating drugs (steroids, immunosuppressive drugs or immunoglobulins) 3 months before the first vaccination
* 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 judged by PI to be clinically relevant
* Pregnant women/planned pregnancy and/or breastfeeding within the trial period

Primary outcomes:
measure: Physical examination. Local adverse events.Systemic adverse events. Laboratory safety tests including urine safety tests.
timeFrame: From first vaccination until 8 months after the first vaccination
Secondary outcomes:
measure: Detection by ELISPOT of IFNgamma spot-forming cells in PBMCs. Detection by ELISA of IFNgamma production in supernatants of PBMC. Detection by ELISA of IgG antibodies in serum/plasma. Detection by Elisa of TNFalfa and IFNgamma in serum
timeFrame: From first vaccination until 8 months after first vaccination
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Leiden University Medical Centre
state: RC Leiden
Study officials:
affiliation: Leiden University Medical Centre
name: Jaap van Dissel, MD, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: van Dissel JT, Soonawala D, Joosten SA, Prins C, Arend SM, Bang P, Tingskov PN, Lingnau K, Nouta J, Hoff ST, Rosenkrands I, Kromann I, Ottenhoff TH, Doherty TM, Andersen P. Ag85B-ESAT-6 adjuvanted with IC31(R) promotes strong and long-lived Mycobacterium tuberculosis specific T cell responses in volunteers with previous BCG vaccination or tuberculosis infection. Vaccine. 2011 Mar 3;29(11):2100-9. doi: 10.1016/j.vaccine.2010.12.135. Epub 2011 Jan 20.