Clinical trial NCT00546273: Clinical Trial to Study 4 Different Doses of the Vaccine RUTI in Healthy Volunteers
Official title: Double-Blind, Randomized, Placebo-Controlled Phase I Study, to Study the Tolerability and Immunogenicity of 4 RUTI Antituberculous Vaccine Different Doses (5, 25, 100 y 200µg of FCMtb) in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Latent Tuberculosis Infection
Tuberculosis
Keywords: LTBI (Latent tuberculosis infection)
TB(Tuberculosis)
Vaccine
Lead sponsor: Germans Trias i Pujol Hospital
Sponsor class: OTHER
Collaborators: name: Archivel Farma S.L.
First posted: 2007-10-18
Enrollment: 24
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: TREATMENT

Brief summary: The aim of this study is to evaluate the safety of a new vaccine against Tuberculosis (RUTI) when administered to healthy adult volunteers, compared to placebo; and determine its safe dosage range. An initial evaluation of immune responses to the vaccine compared to placebo will also be undertaken.

In the present Phase I clinical trial, four increasing doses of RUTI will be tested, the groups composed by 6 volunteers each. (Total of 24 volunteers). The escalation to a new dose to test will be done after the safety of the previous dose has been ensured.

For each dose of FCMtb to test, each volunteer will be inoculated twice (at day 0 and day 28) with RUTI (4 volunteers) or placebo (2 volunteers) and will be followed-up up to 25 weeks from the first inoculation. The global length of the study will be approximately 15 months.

Detailed description: RUTI is a therapeutic vaccine made from virulent M.tuberculosis bacteria, grown in stressful conditions, fragmented, detoxified, heat inactivated (FCMtb) and liposomed. RUTI provides a strong humoral and cellular immune response against antigens from active growing and latent bacilli but also against structural antigens, as it has been proved in animal models of latent tuberculosis infection. The vaccine has been designed to be used against Latent Tuberculosis Infection as a therapeutic vaccine after 1-month of chemotheraputic treatment, instead the current treatment based on 6-9 months of chemotherapy.

Eligibility criteria: Inclusion Criteria:

* Signed informed consent
* Healthy, based on medical examination at inclusion
* Male Caucasian subjects, aged between 18 and 40 years
* Willing and likely to be able to comply with the trial procedures

Exclusion Criteria:

* Evidence of previous, current or latent tuberculosis, as radiological findings on chest X ray compatible with previous or current infection with tuberculosis
* Positive T-SPOT TB result
* BCG-vaccinated subjects
* History of severe organ-system diseases, including
* History of allergic disorders or known hypersensitivity to any drug or vaccine, or to any of the vaccine to be studied components
* Personal or familiar history of autoimmune diseases, or Positive Antinuclear Antibodies
* HIV, HBV and HCV sero-positive
* Suspected or known current drug and/or alcohol abuse (as defined by an alcohol intake of \> 50 g a day
* Lost of more than 400 mL of blood within 12 weeks, or more than 250 mL within 4 weeks, before the recruitment
* Laboratory parameters outside of normal ranges considered clinically significant
* Intake of trial medication in other clinical trials within 1 month of the first vaccination
* Intake of any other drugs that could not be eliminated of the body before the first vaccination, especially anti-inflammatory nonsteroid and corticosteroid drugs
* Acute disease with \> 37ºC temperature within 72 hours before the first vaccination

Primary outcomes:
measure: VAS Pain Score (Visual Analogic Scale, That Ranges From 0 to 100) to Evaluate Each Volunteer Subjective Pain Intensity at the Inoculation Point
timeFrame: at protocol defined timepoints: days 0, 1, 3, 7, 21, 28, 29, 31, 35, 56
measure: Occurrence, Intensity and Relationship to Vaccination of Local and Systemic Events
timeFrame: during the whole study
measure: Number of Clinically Relevant Abnormalities in the Laboratory Tests According to the Doctors' Impression
timeFrame: at protocol defined timepoints: days 0, 7, 21, 28, 35, 56, 112 & 156
Secondary outcomes:
measure: Evaluation of the Immunogenicity of the Different Doses of the Vaccine Tested
timeFrame: at protocol defined timepoints: days 0, 7, 21, 28, 35, 56, 112 & 156
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Experimental Tuberculosis Unit. Fundació Institut per la Investigació Germans Trias i Pujol
state: Barcelona
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
state: Barcelona
city: Badalona
country: Spain
facility: Pharmacology Department. Hospital Universitari Germans Trias i Pujol.
state: Barcelona
Study officials:
affiliation: Unitat de Tuberculosi Experimental. Fundació Institut per la Investigació en Ciències de la Salut Germans Trias i Pujol.
name: Pere-Joan Cardona, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Pharmacology Department. Hospital Universitari "Germans Trias i Pujol"
name: Joan Costa, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cardona PJ, Amat I, Gordillo S, Arcos V, Guirado E, Diaz J, Vilaplana C, Tapia G, Ausina V. Immunotherapy with fragmented Mycobacterium tuberculosis cells increases the effectiveness of chemotherapy against a chronical infection in a murine model of tuberculosis. Vaccine. 2005 Feb 3;23(11):1393-8. doi: 10.1016/j.vaccine.2004.09.008.
citation: Cardona PJ, Amat I. [Origin and development of RUTI, a new therapeutic vaccine against Mycobacterium tuberculosis infection]. Arch Bronconeumol. 2006 Jan;42(1):25-32. doi: 10.1016/s1579-2129(06)60110-9. Spanish.
citation: Cardona PJ. RUTI: a new chance to shorten the treatment of latent tuberculosis infection. Tuberculosis (Edinb). 2006 May-Jul;86(3-4):273-89. doi: 10.1016/j.tube.2006.01.024. Epub 2006 Mar 20.
citation: Vilaplana C, Ruiz-Manzano J, Gil O, Cuchillo F, Montane E, Singh M, Spallek R, Ausina V, Cardona PJ. The tuberculin skin test increases the responses measured by T cell interferon-gamma release assays. Scand J Immunol. 2008 Jun;67(6):610-7. doi: 10.1111/j.1365-3083.2008.02103.x. Epub 2008 Apr 4.
citation: Guirado E, Gil O, Caceres N, Singh M, Vilaplana C, Cardona PJ. Induction of a specific strong polyantigenic cellular immune response after short-term chemotherapy controls bacillary reactivation in murine and guinea pig experimental models of tuberculosis. Clin Vaccine Immunol. 2008 Aug;15(8):1229-37. doi: 10.1128/CVI.00094-08. Epub 2008 Jun 4.
citation: Gil O, Vilaplana C, Guirado E, Diaz J, Caceres N, Singh M, Cardona PJ. Enhanced gamma interferon responses of mouse spleen cells following immunotherapy for tuberculosis relapse. Clin Vaccine Immunol. 2008 Nov;15(11):1742-4. doi: 10.1128/CVI.00255-08. Epub 2008 Sep 30.