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

NCT ID: NCT00546273

Last Updated: 2009-05-27

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-04-30

Study Completion Date

2008-06-30

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.

Conditions

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Latent Tuberculosis Infection Tuberculosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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RUTI 5 micrograms of FCMtb

RUTI dose: 5 micrograms of FCMtb (for fragmented cells of M. tuberculosis) (n=4)

Group Type EXPERIMENTAL

RUTI

Intervention Type BIOLOGICAL

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

RUTI 25 micrograms of FCMtb

RUTI dose: 25 micrograms of FCMtb (for fragmented cells of M. tuberculosis) (n=4)

Group Type EXPERIMENTAL

RUTI

Intervention Type BIOLOGICAL

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

RUTI 100 micrograms of FCMtb

RUTI dose: 100 micrograms of FCMtb (for fragmented cells of M. tuberculosis) (n=4)

Group Type EXPERIMENTAL

RUTI

Intervention Type BIOLOGICAL

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

RUTI 200 micrograms of FCMtb

RUTI 200 micrograms of FCMtb (for fragmented cells of M. tuberculosis) (n=4)

Group Type EXPERIMENTAL

RUTI

Intervention Type BIOLOGICAL

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

placebo

placebo of the vaccine RUTI (total n=8, n=2 for each period)

Group Type PLACEBO_COMPARATOR

placebo of the vaccine RUTI

Intervention Type BIOLOGICAL

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

Interventions

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RUTI

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

Intervention Type BIOLOGICAL

RUTI

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

Intervention Type BIOLOGICAL

RUTI

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

Intervention Type BIOLOGICAL

RUTI

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

Intervention Type BIOLOGICAL

placebo of the vaccine RUTI

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

Intervention Type BIOLOGICAL

Other Intervention Names

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FCMtb is the active compound of the vaccine RUTI FCMtb is the active compound of the vaccine RUTI FCMtb is the active compound of the vaccine RUTI FCMtb is the active compound of the vaccine RUTI placebo

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

40 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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Archivel Farma S.L.

INDUSTRY

Sponsor Role collaborator

Germans Trias i Pujol Hospital

OTHER

Sponsor Role lead

Responsible Party

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Fundacio Institut Germans Trias i Pujol

Principal Investigators

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Pere-Joan Cardona, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Unitat de Tuberculosi Experimental. Fundació Institut per la Investigació en Ciències de la Salut Germans Trias i Pujol.

Joan Costa, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Pharmacology Department. Hospital Universitari "Germans Trias i Pujol"

Locations

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

Badalona, Barcelona, Spain

Site Status

Hospital Germans Trias i Pujol

Badalona, Barcelona, Spain

Site Status

Pharmacology Department. Hospital Universitari Germans Trias i Pujol.

Badalona, Barcelona, Spain

Site Status

Countries

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Spain

References

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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.

Reference Type BACKGROUND
PMID: 15661388 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16426520 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16545981 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18397200 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18524883 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18827194 (View on PubMed)

Related Links

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http://www.germanstrias.org/

Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol homepage

Other Identifiers

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EudraCT Number: 2006-000690-29

Identifier Type: -

Identifier Source: secondary_id

FA/MI/01

Identifier Type: -

Identifier Source: org_study_id

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