Latent Tuberculosis InfectionPhase 1NCT00546273
Clinical Trial to Study 4 Different Doses of the Vaccine RUTI in Healthy Volunteers
A Phase 1 study testing RUTI in people with Latent Tuberculosis Infection and Tuberculosis, run by Germans Trias i Pujol Hospital at 3 sites in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 40 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Latent Tuberculosis Infection, Tuberculosis
- What is being tested?
- RUTI
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 3 sitesSpain
- Study dates
- Apr 2007to Jun 2008
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
3 sites in 1 country.
Spain3 sites
Experimental Tuberculosis Unit. Fundació Institut per la Investigació Germans Trias i Pujol
Badalona, Barcelona, 08916
Hospital Germans Trias i Pujol
Badalona, Barcelona, 08916
Pharmacology Department. Hospital Universitari Germans Trias i Pujol.
Badalona, Barcelona, 08916
About this study
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
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.
Read the 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.
- Conditions
- Latent Tuberculosis Infection, Tuberculosis
- Being tested
- RUTI, placebo of the vaccine RUTI
- Keywords
- LTBI (Latent tuberculosis infection), TB(Tuberculosis), Vaccine
- Medical subject headings
- Latent Tuberculosis, Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RUTIBiological
Also called FCMtb is the active compound of the vaccine RUTI
dose: 5 micrograms of FCMtb; given subcutaneously twice, on days 0 and 28
RUTIBiological
Also called FCMtb is the active compound of the vaccine RUTI
dose: 25 micrograms of FCMtb; given subcutaneously twice, on days 0 and 28
RUTIBiological
Also called FCMtb is the active compound of the vaccine RUTI
dose: 100 micrograms of FCMtb; given subcutaneously twice, on days 0 and 28
RUTIBiological
Also called FCMtb is the active compound of the vaccine RUTI
dose: 200 micrograms of FCMtb; given subcutaneously twice, on days 0 and 28
placebo of the vaccine RUTIBiological
Also called placebo
placebo of the vaccine RUTI given subcutaneously twice, on days 0 and 28
| Study group | Role | What they receive |
|---|---|---|
| RUTI 5 micrograms of FCMtb | Experimental | RUTI dose: 5 micrograms of FCMtb (for fragmented cells of M. tuberculosis) (n=4) Receives: Biological: RUTI |
| RUTI 25 micrograms of FCMtb | Experimental | RUTI dose: 25 micrograms of FCMtb (for fragmented cells of M. tuberculosis) (n=4) Receives: Biological: RUTI |
| RUTI 100 micrograms of FCMtb | Experimental | RUTI dose: 100 micrograms of FCMtb (for fragmented cells of M. tuberculosis) (n=4) Receives: Biological: RUTI |
| RUTI 200 micrograms of FCMtb | Experimental | RUTI 200 micrograms of FCMtb (for fragmented cells of M. tuberculosis) (n=4) Receives: Biological: RUTI |
| placebo | Placebo comparator | placebo of the vaccine RUTI (total n=8, n=2 for each period) Receives: Biological: placebo of the vaccine RUTI |
What is being measured
The primary outcome is the main question the study is designed to answer.
VAS Pain Score (Visual Analogic Scale, That Ranges From 0 to 100) to Evaluate Each Volunteer Subjective Pain Intensity at the Inoculation Point
Measured: 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
Measured: during the whole study
Number of Clinically Relevant Abnormalities in the Laboratory Tests According to the Doctors' Impression
haematological and biochemical laboratory tests
Measured: at protocol defined timepoints: days 0, 7, 21, 28, 35, 56, 112 & 156
Secondary outcomes (1)
Evaluation of the Immunogenicity of the Different Doses of the Vaccine Tested
Immunological assays are performed at all timepoints to determine vaccine immunogenicity
Measured: at protocol defined timepoints: days 0, 7, 21, 28, 35, 56, 112 & 156
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2007 (estimated)
- Study startApr 2007
- Primary completionJun 2008
- Study completionJun 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Latent Tuberculosis InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Germans Trias i Pujol Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Archivel Farma S.L.
- Investigators
- Pere-Joan Cardona, MD, PhD, Principal investigator, Unitat de Tuberculosi Experimental. Fundació Institut per la Investigació en Ciències de la Salut Germans Trias i Pujol.Joan Costa, MD, PhD, Principal investigator, Pharmacology Department. Hospital Universitari "Germans Trias i Pujol"
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00546273
- Sponsor's protocol ID
- FA/MI/01
- Other IDs
- EudraCT Number: 2006-000690-29
- Status last verified
- May 2009
- First submitted
- 16 Oct 2007
- Last updated
- 27 May 2009
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 15661388Cardona 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.
PubMed 16426520Cardona 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.
PubMed 16545981Vilaplana 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.
PubMed 18397200Guirado 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.
PubMed 18524883Gil 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.
PubMed 18827194
Study at a glance
From the registry record, last updated by the sponsor on 27 May 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00546273
- Acronym / sponsor ID
- FA/MI/01
- Conditions
- Latent Tuberculosis Infection, Tuberculosis
- Keywords
- LTBI (Latent tuberculosis infection), TB(Tuberculosis), Vaccine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Germans Trias i Pujol HospitalUniversity, hospital or other
- Collaborators
- Archivel Farma S.L.
- Study start
- Apr 2007
- Primary completion
- Jun 2008 (actual)
- Study completion
- Jun 2008 (actual)
- First posted
- 18 Oct 2007 (estimated)
- Results
- Posted 25 Mar 2009
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| RUTI 5 micrograms of FCMtb | Experimental | Biological: RUTIRUTI dose: 5 micrograms of FCMtb (for fragmented cells of M. tuberculosis) (n=4) |
| RUTI 25 micrograms of FCMtb | Experimental | Biological: RUTIRUTI dose: 25 micrograms of FCMtb (for fragmented cells of M. tuberculosis) (n=4) |
| RUTI 100 micrograms of FCMtb | Experimental | Biological: RUTIRUTI dose: 100 micrograms of FCMtb (for fragmented cells of M. tuberculosis) (n=4) |
| RUTI 200 micrograms of FCMtb | Experimental | Biological: RUTIRUTI 200 micrograms of FCMtb (for fragmented cells of M. tuberculosis) (n=4) |
| placebo | Placebo comparator | Biological: placebo of the vaccine RUTIplacebo of the vaccine RUTI (total n=8, n=2 for each period) |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RUTIAlso: FCMtb is the active compound of the vaccine RUTIdose: 5 micrograms of FCMtb; given subcutaneously twice, on days 0 and 28 | Biological | RUTI 5 micrograms of FCMtb |
| RUTIAlso: FCMtb is the active compound of the vaccine RUTIdose: 25 micrograms of FCMtb; given subcutaneously twice, on days 0 and 28 | Biological | RUTI 25 micrograms of FCMtb |
| RUTIAlso: FCMtb is the active compound of the vaccine RUTIdose: 100 micrograms of FCMtb; given subcutaneously twice, on days 0 and 28 | Biological | RUTI 100 micrograms of FCMtb |
| RUTIAlso: FCMtb is the active compound of the vaccine RUTIdose: 200 micrograms of FCMtb; given subcutaneously twice, on days 0 and 28 | Biological | RUTI 200 micrograms of FCMtb |
| placebo of the vaccine RUTIAlso: placeboplacebo of the vaccine RUTI given subcutaneously twice, on days 0 and 28 | Biological | placebo |
Primary outcome
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
Time frame: at protocol defined timepoints: days 0, 7, 21, 28, 35, 56, 112 & 156
haematological and biochemical laboratory tests
1 secondary outcome
Evaluation of the Immunogenicity of the Different Doses of the Vaccine Tested
Time frame: at protocol defined timepoints: days 0, 7, 21, 28, 35, 56, 112 & 156
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 May 2009.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 15661388Cardona 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.
- Background: PubMed 16426520Cardona 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.
- Background: PubMed 16545981Cardona 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.
- Background: PubMed 18397200Vilaplana 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.
- Background: PubMed 18524883Guirado 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.
- Background: PubMed 18827194Gil 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.
- Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol homepageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pere-Joan Cardona, MD, PhD principal investigator
Unitat de Tuberculosi Experimental. Fundació Institut per la Investigació en Ciències de la Salut Germans Trias i Pujol.
Joan Costa, MD, PhD principal investigator
Pharmacology Department. Hospital Universitari "Germans Trias i Pujol"
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RUTI in people with Latent Tuberculosis Infection and Tuberculosis, run by Germans Trias i Pujol Hospital at 3 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 May 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Mar 2009). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00546273, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 May 2009.