Clinical Trial to Study 4 Different Doses of the Vaccine RUTI in Healthy Volunteers

Germans Trias i Pujol Hospital24 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Latent Tuberculosis Infection

Interventions

RUTIBIOLOGICAL

dose: 5 micrograms of FCMtb; given subcutaneously twice, on days 0 and 28

RUTIBIOLOGICAL

dose: 25 micrograms of FCMtb; given subcutaneously twice, on days 0 and 28

RUTIBIOLOGICAL

dose: 100 micrograms of FCMtb; given subcutaneously twice, on days 0 and 28

RUTIBIOLOGICAL

dose: 200 micrograms of FCMtb; given subcutaneously twice, on days 0 and 28

placebo of the vaccine RUTIBIOLOGICAL

placebo of the vaccine RUTI given subcutaneously twice, on days 0 and 28

Eligibility

Sex: MALEMin age: 18 YearsMax age: 40 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (3)

Experimental Tuberculosis Unit. Fundació Institut per la Investigació Germans Trias i Pujol

Badalona, Barcelona, Spain

Hospital Germans Trias i Pujol

Badalona, Barcelona, Spain

Pharmacology Department. Hospital Universitari Germans Trias i Pujol.

Badalona, Barcelona, Spain

Outcomes

Primary Outcomes

VAS Pain Score (Visual Analogic Scale, That Ranges From 0 to 100) to Evaluate Each Volunteer Subjective Pain Intensity at the Inoculation Point

Time frame: at protocol defined timepoints: days 0, 1, 3, 7, 21, 28, 29, 31, 35, 56

Occurrence, Intensity and Relationship to Vaccination of Local and Systemic Events

Time frame: during the whole study

Number of Clinically Relevant Abnormalities in the Laboratory Tests According to the Doctors' Impression

haematological and biochemical laboratory tests

Time frame: at protocol defined timepoints: days 0, 7, 21, 28, 35, 56, 112 & 156

Secondary Outcomes

Evaluation of the Immunogenicity of the Different Doses of the Vaccine Tested

Immunological assays are performed at all timepoints to determine vaccine immunogenicity

Time frame: at protocol defined timepoints: days 0, 7, 21, 28, 35, 56, 112 & 156