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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Latent Tuberculosis Infection, Tuberculosis

Intervention / Treatment
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* Biological: RUTI
* Biological: RUTI
* Biological: RUTI
* Biological: RUTI
* Biological: placebo of the vaccine RUTI


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RUTI 5 micrograms of FCMtb<br>RUTI dose: 5 micrograms of FCMtb (for fragmented cells of M. tuberculosis) (n=4) | Biological: RUTI<br>* dose: 5 micrograms of FCMtb; given subcutaneously twice, on days 0 and 28<br>* Other names: FCMtb is the active compound of the vaccine RUTI;|
| Experimental: RUTI 25 micrograms of FCMtb<br>RUTI dose: 25 micrograms of FCMtb (for fragmented cells of M. tuberculosis) (n=4) | Biological: RUTI<br>* dose: 25 micrograms of FCMtb; given subcutaneously twice, on days 0 and 28<br>* Other names: FCMtb is the active compound of the vaccine RUTI;|
| Experimental: RUTI 100 micrograms of FCMtb<br>RUTI dose: 100 micrograms of FCMtb (for fragmented cells of M. tuberculosis) (n=4) | Biological: RUTI<br>* dose: 100 micrograms of FCMtb; given subcutaneously twice, on days 0 and 28<br>* Other names: FCMtb is the active compound of the vaccine RUTI;|
| Experimental: RUTI 200 micrograms of FCMtb<br>RUTI 200 micrograms of FCMtb (for fragmented cells of M. tuberculosis) (n=4) | Biological: RUTI<br>* dose: 200 micrograms of FCMtb; given subcutaneously twice, on days 0 and 28<br>* Other names: FCMtb is the active compound of the vaccine RUTI;|
| Placebo Comparator: placebo<br>placebo of the vaccine RUTI (total n=8, n=2 for each period) | Biological: placebo of the vaccine RUTI<br>* placebo of the vaccine RUTI given subcutaneously twice, on days 0 and 28<br>* Other names: placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| VAS Pain Score (Visual Analogic Scale, That Ranges From 0 to 100) to Evaluate Each Volunteer Subjective Pain Intensity at the Inoculation Point |  | 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 |  | during the whole study | 
| Number of Clinically Relevant Abnormalities in the Laboratory Tests According to the Doctors' Impression | haematological and biochemical laboratory tests | at protocol defined timepoints: days 0, 7, 21, 28, 35, 56, 112 & 156 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the Immunogenicity of the Different Doses of the Vaccine Tested | Immunological assays are performed at all timepoints to determine vaccine immunogenicity | at protocol defined timepoints: days 0, 7, 21, 28, 35, 56, 112 & 156 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LTBI (Latent tuberculosis infection), TB(Tuberculosis), Vaccine