Back to resultsClinical Trial to Study 4 Different Doses of the Vaccine RUTI in Healthy Volunteers
Primary Purpose
Latent Tuberculosis Infection, Tuberculosis
Status
Completed
Phase
Phase 1
Locations
Spain
Study Type
Interventional
Intervention
RUTI
RUTI
RUTI
RUTI
placebo of the vaccine RUTI
Sponsored by
About this trial
This is an interventional treatment trial for Latent Tuberculosis Infection focused on measuring LTBI (Latent tuberculosis infection), TB(Tuberculosis), Vaccine
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
Sites / Locations
- Experimental Tuberculosis Unit. Fundació Institut per la Investigació Germans Trias i Pujol
- Hospital Germans Trias i Pujol
- Pharmacology Department. Hospital Universitari Germans Trias i Pujol.
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
RUTI 5 micrograms of FCMtb
RUTI 25 micrograms of FCMtb
RUTI 100 micrograms of FCMtb
RUTI 200 micrograms of FCMtb
placebo
Arm Description
RUTI dose: 5 micrograms of FCMtb (for fragmented cells of M. tuberculosis) (n=4)
RUTI dose: 25 micrograms of FCMtb (for fragmented cells of M. tuberculosis) (n=4)
RUTI dose: 100 micrograms of FCMtb (for fragmented cells of M. tuberculosis) (n=4)
RUTI 200 micrograms of FCMtb (for fragmented cells of M. tuberculosis) (n=4)
placebo of the vaccine RUTI (total n=8, n=2 for each period)
Outcomes
Primary Outcome Measures
VAS Pain Score (Visual Analogic Scale, That Ranges From 0 to 100) to Evaluate Each Volunteer Subjective Pain Intensity at the Inoculation Point
Occurrence, Intensity and Relationship to Vaccination of Local and Systemic Events
Number of Clinically Relevant Abnormalities in the Laboratory Tests According to the Doctors' Impression
haematological and biochemical laboratory tests
Secondary Outcome Measures
Evaluation of the Immunogenicity of the Different Doses of the Vaccine Tested
Immunological assays are performed at all timepoints to determine vaccine immunogenicity
Full Information
NCT ID
NCT00546273
First Posted
October 16, 2007
Last Updated
May 14, 2009
Sponsor
Germans Trias i Pujol Hospital
Collaborators
Archivel Farma S.L.
1. Study Identification
Unique Protocol Identification Number
NCT00546273
Brief Title
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
2. Study Status
Record Verification Date
May 2009
Overall Recruitment Status
Completed
Study Start Date
April 2007 (undefined)
Primary Completion Date
June 2008 (Actual)
Study Completion Date
June 2008 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Germans Trias i Pujol Hospital
Collaborators
Archivel Farma S.L.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Latent Tuberculosis Infection, Tuberculosis
Keywords
LTBI (Latent tuberculosis infection), TB(Tuberculosis), Vaccine
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
RUTI 5 micrograms of FCMtb
Arm Type
Experimental
Arm Description
RUTI dose: 5 micrograms of FCMtb (for fragmented cells of M. tuberculosis) (n=4)
Arm Title
RUTI 25 micrograms of FCMtb
Arm Type
Experimental
Arm Description
RUTI dose: 25 micrograms of FCMtb (for fragmented cells of M. tuberculosis) (n=4)
Arm Title
RUTI 100 micrograms of FCMtb
Arm Type
Experimental
Arm Description
RUTI dose: 100 micrograms of FCMtb (for fragmented cells of M. tuberculosis) (n=4)
Arm Title
RUTI 200 micrograms of FCMtb
Arm Type
Experimental
Arm Description
RUTI 200 micrograms of FCMtb (for fragmented cells of M. tuberculosis) (n=4)
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
placebo of the vaccine RUTI (total n=8, n=2 for each period)
Intervention Type
Biological
Intervention Name(s)
RUTI
Other Intervention Name(s)
FCMtb is the active compound of the vaccine RUTI
Intervention Description
dose: 5 micrograms of FCMtb; given subcutaneously twice, on days 0 and 28
Intervention Type
Biological
Intervention Name(s)
RUTI
Other Intervention Name(s)
FCMtb is the active compound of the vaccine RUTI
Intervention Description
dose: 25 micrograms of FCMtb; given subcutaneously twice, on days 0 and 28
Intervention Type
Biological
Intervention Name(s)
RUTI
Other Intervention Name(s)
FCMtb is the active compound of the vaccine RUTI
Intervention Description
dose: 100 micrograms of FCMtb; given subcutaneously twice, on days 0 and 28
Intervention Type
Biological
Intervention Name(s)
RUTI
Other Intervention Name(s)
FCMtb is the active compound of the vaccine RUTI
Intervention Description
dose: 200 micrograms of FCMtb; given subcutaneously twice, on days 0 and 28
Intervention Type
Biological
Intervention Name(s)
placebo of the vaccine RUTI
Other Intervention Name(s)
placebo
Intervention Description
placebo of the vaccine RUTI given subcutaneously twice, on days 0 and 28
Primary Outcome Measure Information:
Title
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
Title
Occurrence, Intensity and Relationship to Vaccination of Local and Systemic Events
Time Frame
during the whole study
Title
Number of Clinically Relevant Abnormalities in the Laboratory Tests According to the Doctors' Impression
Description
haematological and biochemical laboratory tests
Time Frame
at protocol defined timepoints: days 0, 7, 21, 28, 35, 56, 112 & 156
Secondary Outcome Measure Information:
Title
Evaluation of the Immunogenicity of the Different Doses of the Vaccine Tested
Description
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
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pere-Joan Cardona, MD, PhD
Organizational Affiliation
Unitat de Tuberculosi Experimental. Fundació Institut per la Investigació en Ciències de la Salut Germans Trias i Pujol.
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Joan Costa, MD, PhD
Organizational Affiliation
Pharmacology Department. Hospital Universitari "Germans Trias i Pujol"
Official's Role
Principal Investigator
Facility Information:
Facility Name
Experimental Tuberculosis Unit. Fundació Institut per la Investigació Germans Trias i Pujol
City
Badalona
State/Province
Barcelona
ZIP/Postal Code
08916
Country
Spain
Facility Name
Hospital Germans Trias i Pujol
City
Badalona
State/Province
Barcelona
ZIP/Postal Code
08916
Country
Spain
Facility Name
Pharmacology Department. Hospital Universitari Germans Trias i Pujol.
City
Badalona
State/Province
Barcelona
ZIP/Postal Code
08916
Country
Spain
12. IPD Sharing Statement
Citations:
PubMed Identifier
15661388
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.
Results Reference
background
PubMed Identifier
16426520
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.
Results Reference
background
PubMed Identifier
16545981
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.
Results Reference
background
PubMed Identifier
18397200
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.
Results Reference
background
PubMed Identifier
18524883
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.
Results Reference
background
PubMed Identifier
18827194
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.
Results Reference
background
Links:
URL
http://www.germanstrias.org/
Description
Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol homepage
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Clinical Trial to Study 4 Different Doses of the Vaccine RUTI in Healthy Volunteers
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