Latent Tuberculosis Infection, Tuberculosis
Conditions
Keywords
LTBI (Latent tuberculosis infection), TB(Tuberculosis), Vaccine
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.
Interventions
BIOLOGICALRUTI
dose: 5 micrograms of FCMtb; given subcutaneously twice, on days 0 and 28
BIOLOGICALplacebo of the vaccine RUTI
placebo of the vaccine RUTI given subcutaneously twice, on days 0 and 28
Sponsors
Archivel Farma S.L.
Germans Trias i Pujol Hospital
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | at protocol defined timepoints: days 0, 7, 21, 28, 35, 56, 112 & 156 | haematological and biochemical laboratory tests |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of the Immunogenicity of the Different Doses of the Vaccine Tested | at protocol defined timepoints: days 0, 7, 21, 28, 35, 56, 112 & 156 | Immunological assays are performed at all timepoints to determine vaccine immunogenicity |
Countries
Spain
Participant flow
Recruitment details
Four RUTI doses were tested, in a sequencial way (n=6 each). 14 days before starting each level of treatment, subjects, after signing the informed consent, were screened in the Phase 1 Unit (Hospital Germans Trias i Pujol) in order to decide if they were elegible to be part of the study.
Pre-assignment details
24 volunteers were enrolled and distributed in 4 groups, one group for every period (each period: 6 new volunteers). There was one period per dose tested, and doses were tested increasingly, not beginning to test one dose until clinically ensured the safety of the previous dose. The double blind was opened at the end of the study.
Participants by arm
| Arm | Count |
|---|---|
| RUTI 5 Micrograms of FCMtb RUTI dose: 5 micrograms of FCMtb | 4 |
| RUTI 25 Micrograms of FCMtb RUTI dose: 25 micrograms of FCMtb | 4 |
| RUTI 100 Micrograms of FCMtb RUTI dose: 100 micrograms of FCMtb | 4 |
| RUTI 200 Micrograms of FCMtb RUTI dose: 200 micrograms of FCMtb | 4 |
| Placebo placebo of the vaccine RUTI, given subcutaneously twice, on days 0 and 28 | 8 |
| Total | 24 |
Baseline characteristics
| Characteristic | RUTI 25 Micrograms of FCMtb | RUTI 100 Micrograms of FCMtb | RUTI 200 Micrograms of FCMtb | RUTI 5 Micrograms of FCMtb | Placebo | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 4 Participants | 4 Participants | 4 Participants | 8 Participants | 24 Participants |
| Age Continuous | 26 years STANDARD_DEVIATION 2.94 | 23 years STANDARD_DEVIATION 2.16 | 22.25 years STANDARD_DEVIATION 2.22 | 25.25 years STANDARD_DEVIATION 2.87 | 24 years STANDARD_DEVIATION 4.75 | 24.08 years STANDARD_DEVIATION 3.46 |
| Region of Enrollment Spain | 4 participants | 4 participants | 4 participants | 4 participants | 8 participants | 24 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 4 Participants | 4 Participants | 8 Participants | 24 Participants |
Outcome results
Primary
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
Population: All the participants of the study were analyzed for this specific outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RUTI 5 Micrograms of FCMtb | Number of Clinically Relevant Abnormalities in the Laboratory Tests According to the Doctors' Impression | 0 number of abnormalities |
| RUTI 25 Micrograms of FCMtb | Number of Clinically Relevant Abnormalities in the Laboratory Tests According to the Doctors' Impression | 0 number of abnormalities |
| RUTI 100 Micrograms of FCMtb | Number of Clinically Relevant Abnormalities in the Laboratory Tests According to the Doctors' Impression | 0 number of abnormalities |
| RUTI 200 Micrograms of FCMtb | Number of Clinically Relevant Abnormalities in the Laboratory Tests According to the Doctors' Impression | 0 number of abnormalities |
| Placebo | Number of Clinically Relevant Abnormalities in the Laboratory Tests According to the Doctors' Impression | 0 number of abnormalities |
Primary
Occurrence, Intensity and Relationship to Vaccination of Local and Systemic Events
Time frame: during the whole study
Primary
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
Secondary
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