TuberculosisPhase 2CONSTANNCT05136833
Evaluation of Efficacy and Safety of the Concomitant of RUTI® Immunotherapy With the Standard Treatment in TB Patients
A Phase 2 study testing RUTI® vaccine in people with Tuberculosis, run by Archivel Farma S.L..
Trial summary
The study is an exploratory clinical trial to evaluate the efficacy and safety of the treatment with a vaccine against tuberculosis (RUTI®) given at the same time as standard treatment in patients with tuberculosis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tuberculosis
- What is being tested?
- RUTI® vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Dec 2021to 31 Dec 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults (females and males) aged ≥ 18.
- Written informed consent in a language they understand. This includes informed consent to be in the trial and informed consent to collect specimens.
- Laboratory confirmed pulmonary TB (with or without extrapulmonary involvement) defined as a hard copy of a sputum laboratory result that reports Mtb detection by sputum-microscopy smear-positive at least 1+, rapid molecular assay or mycobacterial culture.
- Patients who have not received any anti-tubercular treatment in the last 24 hours.
- Females of non-childbearing potential: at least 2 years post-menopausal or surgically sterile (e.g. tubal ligation).
- Females of childbearing potential (including females less than 2 years post-menopausal) must have a negative pregnancy test at enrolment and must agree to use highly effective methods of birth control (i.e. diaphragm plus spermicide or male condom plus spermicide, oral contraceptive in combination with a second method, contraceptive implant, injectable contraceptive, indwelling intrauterine device, sexual abstinence, or a vasectomized partner) while participating in the study.
- Males must agree to use a double-barrier method of contraception (condom plus spermicide or diaphragm plus spermicide) at least 1 month after RUTI/placebo vaccination; or the male patient or his female partner must be surgically sterile (e.g. vasectomy, tubal ligation) or the female partner must be post-menopausal.
- The patient must be willing and able to attend all study visits and comply with all study procedures.
Who cannot join
- Unable to provide written informed consent.
- Women reported, or detected, or willing to be pregnant during the trial period.
- Severity of illness precluding full evaluation: expected early death, evidenced by respiratory failure, low blood pressure, WHO performance score 3-4.
- Bodyweight < 40kg.
- Evidence of rifampicin resistance via GeneXpert.
- Unstable Diabetes Mellitus as a poor metabolic control within the past 12 months.
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- For HIV infected subjects if the CD4+ count <250 cells/μL.
- Major co-morbid conditions or any other finding which in the opinion of the investigator would compromise the protocol compliance or significantly influence the interpretation of results (i.e. cancer, immunodeficiency of any nature including treatment with immunosuppressant drugs and excluding HIV infection).
- Any of the following laboratory parameters:
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 x upper limit of normal (ULN);
- Total bilirubin > 2 x ULN;
- Neutrophil count ≤ 500 neutrophils / mm3;
- Platelet count < 50,000 platelets / mm3.
- Alcohol use: potential participant either self-reports or in the investigator's opinion that the patient drinks more than an average of four units/day over a usual week or is a binge drinker (men: 5 or more drinks; women: consume 4 or more drinks, in about 2 hours).
- Documented allergy to TB vaccines or any of the study treatment excipients, notably, to the RUTI® vaccine.
- Concurrent enrolment in another clinical study, unless it is an observational (noninterventional) clinical study or during the follow-up period of an interventional study.
About this study
Official title: A Phase IIb Study to Explore the Efficacy and Safety of the Concomitant Administration of RUTI® Immunotherapy With the Standard Treatment in Patients With TB
The study is an exploratory clinical trial to evaluate the efficacy and safety of the treatment with a vaccine against tuberculosis (RUTI®) given at the same time as standard treatment in patients with tuberculosis. It is a prospective, randomized (1:1), double-blind, multicentre, placebo-controlled clinical phase IIb trial.
Read the detailed description
Patients will be randomized (1: 1) to receive an inoculation of RUTI® or placebo at the same time that standard treatment is started.
The standard TB treatment will continue after RUTI® or placebo administration according to SOC guidelines. All the patients will be followed up 6 months after the vaccination or until the end of SOC treatment.
Once all the patients have completed the week 2 follow-up, a Data Safety Monitoring Board (DSMB) will be established to review all relevant safety and toxicity data.
- Conditions
- Tuberculosis
- Being tested
- RUTI® vaccine, Placebo
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RUTI® vaccineBiological
Each dose of the RUTI® vaccine contains 25 µg of fragmented, purified and liposomed heat-inactivated Mycobacterium tuberculosis bacilli (FCMtb) in a total volum of 0.3mL.
PlaceboBiological
Normal saline will be used as a placebo.
| Study group | Role | What they receive |
|---|---|---|
| Group A (RUTI) | Experimental | Subjets will receive one inoculation of the RUTI® vaccine at the same time as standard treatment is started. It will be administered subcutaneously in the deltoid region at a dose of 25 µg of fragmented, purified and liposomed heat-inactivated Mycobacterium tuberculosis bacilli (FCMtb) in an injection volume of 0.3 mL Receives: Biological: RUTI® vaccine |
| Group B (Placebo) | Placebo comparator | Subjets will receive one inoculation of normal saline at the same time as standard treatment is started. It will be administered subcutaneously in the deltoid region. Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Early Bactericidal Activity (EBA) from day 0 to day 14
Measured as the reduction of bacillary load of M. Tuberculosis based upon Time to detection (TTD) signal in MGIT.
Measured: Daily between day 0 and day 14 after treatment initiation and RUTI®/placebo vaccination.
Secondary outcomes (11)
Early Bactericidal Activity (EBA) from 2 to 14 days
Measured as the reduction of bacillary load of M. Tuberculosis based upon Time to detection (TTD) signal in MGIT. Difference between each intervention arm and control group.
Measured: Daily between day 2 and day 14 after treatment initiation and RUTI®/placebo vaccination.
Early Bactericidal Activity (EBA) from 7 to 14 days
Measured as the reduction of the bacillary load of M. Tuberculosis based upon Time to detection (TTD) signal in MGIT.
Measured: Daily between day 7 and day 14 after treatment initiation and RUTI®/placebo vaccination.
Early Bactericidal Activity (EBA) from 4 to 24 week
Measured as the reduction of the bacillary load of M. Tuberculosis based upon Time to detection (TTD) signal in MGIT
Measured: At week 4, 8, 16 and 24 after treatment initiation and RUTI®/placebo vaccination
Hazard ratio for stable culture conversion (SCC).
Difference between each intervention arm and control group.
Measured: 24 weeks of TB treatment
Rate of Change in Time to Sputum Culture Positivity (TTP) in Liquid Culture Media (Days 0-14).
Difference between each intervention arm and control group.
Measured: 14 days
Rate of Change in Time to Sputum Culture Positivity (TTP) in Liquid Culture Media (week 4, 8, 16 and 24 )
Difference between each intervention arm and control group.
Measured: Up to week 24
The proportion of patients with AEs between each intervention arm and the control group.
Difference of patients with AEs between each intervention arm and control group.
Measured: Up to week 24
The proportion of patients with SAEs between each intervention arm and the control group
Difference of patients with SAEs between each intervention arm and control group.
Measured: Up to week 24
Proportion of patients with CLINICAL, X-ray or LABORATORY worsening
Difference of patients with Clinical, X-ray or Laboratory worsening between each intervention arm and control group.
Measured: Through study completion, an average of 24 weeks
Proportion of patients with improvement of clinical signs and symptoms, Bandim TB score
Difference of patients with improvement of clinical signs and symptoms between intervention and control group.
Measured: At weeks 2, 8, 24
Number of patients with improvement of Health-related Quality of Life (HRQoL) comparing baseline measure with that over the course of therapy.
Difference f patients with improvement of HRQoL between each intervention arm and control group.
Measured: At week 8, week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2021
- Study start1 Dec 2021
- Primary completion30 Jun 2022
- Study completion31 Dec 2022 (estimated)
Why it stopped: Covid-19 pandemia
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for TuberculosisStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Archivel Farma S.L.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Fundació Institut Germans Trias i Pujol
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05136833
- Sponsor's protocol ID
- AC-R6
- Other IDs
- 2021-003301-22
- Acronym
- CONSTAN
- Status last verified
- Jul 2022
- First submitted
- 10 Nov 2021
- Last updated
- 13 Jul 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIb Study to Explore the Efficacy and Safety of the Concomitant Administration of RUTI® Immunotherapy With the Standard Treatment in Patients With TB
- ClinicalTrials.gov ID
- NCT05136833
- Acronym / sponsor ID
- CONSTAN / AC-R6
- Conditions
- Tuberculosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Covid-19 pandemia
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Archivel Farma S.L.Industry (pharma, biotech, devices)
- Collaborators
- Fundació Institut Germans Trias i Pujol
- Study start
- 1 Dec 2021 (actual)
- Primary completion
- 30 Jun 2022 (actual)
- Study completion
- 31 Dec 2022 (estimated)
- First posted
- 29 Nov 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study is an exploratory clinical trial to evaluate the efficacy and safety of the treatment with a vaccine against tuberculosis (RUTI®) given at the same time as standard treatment in patients with tuberculosis. It is a prospective, randomized (1:1), double-blind, multicentre, placebo-controlled clinical phase IIb trial.
Detailed description
Patients will be randomized (1: 1) to receive an inoculation of RUTI® or placebo at the same time that standard treatment is started.
The standard TB treatment will continue after RUTI® or placebo administration according to SOC guidelines. All the patients will be followed up 6 months after the vaccination or until the end of SOC treatment.
Once all the patients have completed the week 2 follow-up, a Data Safety Monitoring Board (DSMB) will be established to review all relevant safety and toxicity data.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A (RUTI) | Experimental | Biological: RUTI® vaccineSubjets will receive one inoculation of the RUTI® vaccine at the same time as standard treatment is started. It will be administered subcutaneously in the deltoid region at a dose of 25 µg of fragmented, purified and liposomed heat-inactivated Mycobacterium tuberculosis bacilli (FCMtb) in an injection volume of 0.3 mL |
| Group B (Placebo) | Placebo comparator | Biological: PlaceboSubjets will receive one inoculation of normal saline at the same time as standard treatment is started. It will be administered subcutaneously in the deltoid region. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Adults (females and males) aged ≥ 18.
- Written informed consent in a language they understand. This includes informed consent to be in the trial and informed consent to collect specimens.
- Laboratory confirmed pulmonary TB (with or without extrapulmonary involvement) defined as a hard copy of a sputum laboratory result that reports Mtb detection by sputum-microscopy smear-positive at least 1+, rapid molecular assay or mycobacterial culture.
- Patients who have not received any anti-tubercular treatment in the last 24 hours.
- Females of non-childbearing potential: at least 2 years post-menopausal or surgically sterile (e.g. tubal ligation).
Key exclusion criteria (16 listed)
- Unable to provide written informed consent.
- Women reported, or detected, or willing to be pregnant during the trial period.
- Severity of illness precluding full evaluation: expected early death, evidenced by respiratory failure, low blood pressure, WHO performance score 3-4.
- Bodyweight < 40kg.
- Evidence of rifampicin resistance via GeneXpert.
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 |
|---|---|---|
| RUTI® vaccineEach dose of the RUTI® vaccine contains 25 µg of fragmented, purified and liposomed heat-inactivated Mycobacterium tuberculosis bacilli (FCMtb) in a total volum of 0.3mL. | Biological | Group A (RUTI) |
| PlaceboNormal saline will be used as a placebo. | Biological | Group B (Placebo) |
Primary outcome
Early Bactericidal Activity (EBA) from day 0 to day 14
Time frame: Daily between day 0 and day 14 after treatment initiation and RUTI®/placebo vaccination.
Measured as the reduction of bacillary load of M. Tuberculosis based upon Time to detection (TTD) signal in MGIT.
11 secondary outcomes
Early Bactericidal Activity (EBA) from 2 to 14 days
Time frame: Daily between day 2 and day 14 after treatment initiation and RUTI®/placebo vaccination.
Early Bactericidal Activity (EBA) from 7 to 14 days
Time frame: Daily between day 7 and day 14 after treatment initiation and RUTI®/placebo vaccination.
Early Bactericidal Activity (EBA) from 4 to 24 week
Time frame: At week 4, 8, 16 and 24 after treatment initiation and RUTI®/placebo vaccination
Hazard ratio for stable culture conversion (SCC).
Time frame: 24 weeks of TB treatment
Rate of Change in Time to Sputum Culture Positivity (TTP) in Liquid Culture Media (Days 0-14).
Time frame: 14 days
Rate of Change in Time to Sputum Culture Positivity (TTP) in Liquid Culture Media (week 4, 8, 16 and 24 )
Time frame: Up to week 24
The proportion of patients with AEs between each intervention arm and the control group.
Time frame: Up to week 24
The proportion of patients with SAEs between each intervention arm and the control group
Time frame: Up to week 24
Proportion of patients with CLINICAL, X-ray or LABORATORY worsening
Time frame: Through study completion, an average of 24 weeks
Proportion of patients with improvement of clinical signs and symptoms, Bandim TB score
Time frame: At weeks 2, 8, 24
Number of patients with improvement of Health-related Quality of Life (HRQoL) comparing baseline measure with that over the course of therapy.
Time frame: At week 8, week 24
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2022.
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing RUTI® vaccine in people with Tuberculosis, run by Archivel Farma S.L..
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 8 inclusion and 16 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: withdrawn, as of the sponsor's last update on 13 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Early Bactericidal Activity (EBA) from day 0 to day 14 (time frame: Daily between day 0 and day 14 after treatment initiation and RUTI®/placebo vaccination.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Jul 2022.