Safety and Efficacy of RUTI® With the Standard of Treatment for Tuberculosis (CONSTAN-ARG)
Primary Purpose
Tuberculosis, Pulmonary
Status
Recruiting
Phase
Phase 2
Locations
Argentina
Study Type
Interventional
Intervention
RUTI® Vaccine
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Tuberculosis, Pulmonary focused on measuring Tuberculosis, immunotherapy, drug-susceptible
Eligibility Criteria
Inclusion Criteria:
- Men and women aged 18 or older
- Written informed consent
- Laboratory confirmed pulmonary TB
- Clinical symptoms compatible with pulmonary TB and/or X-ray evidence of pulmonary TB
- Women of non-childbearing potential: at least 2 years post-menopausal or surgically sterile (e.g. tubal ligation)
- Women of childbearing potential (including women less than 2 years past menopause) must have a negative pregnancy test at enrollment and must agree to use dual-barrier methods of contraception, intrauterine device (IUD), bilateral tubal occlusion, sexual abstinence, or vasectomized partner.
- Males must agree to use a double barrier method of contraception at least 1 month after RUTI/placebo vaccination; or the male patient or his female partner must be surgically sterile or the female partner must be post-menopausal
- Willing and able to attend all study visits and comply with all study procedures
- Verifiable address or place of residence easy accessible to perform visits and willing to inform the research team of any change during the treatment and follow-up period
Exclusion Criteria:
- Unable to provide written informed consent
- Women reported, or detected, or willing to be pregnant during the trial period; Men willing to conceive a child during the study or 6 months after end of treatment
- Severity of illness precluding full evaluation: expected early death, evidenced by respiratory failure, low blood pressure, WHO performance score 3-4
- Evidence or suspicion of resistance to rifampin, isoniazid, pyrazinamide, and ethambutol, either laboratory-confirmed or based on epidemiological history at screening
- Previous treatment for M. tuberculosis in the previous 24 months.
- Bodyweight < 40kg
- Unstable Diabetes Mellitus as a poor metabolic control within the past 12 months
- HIV-infected subjects
- 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
- HIstory of severe mental ilness which, in the opinion of the investigator, may exclude the participant from participating in the trial.
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)
- Known allergy or any hipersensitivity to study mediactions, including rifampin, isoniazid, pyrazinamide, and ethambutol, or any of its excipients.
- Documented allergy to anti-TB vaccines or any excipient of the RUTI vaccine.
- Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
Sites / Locations
- Hospital José Nestor LencinasRecruiting
- Hospital de Clínicas Presidente Dr. Nicolás AvellanedaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
RUTI
Placebo
Arm Description
Single injection of RUTI 25µg of FCMtb at day 0.
Single injection of saline at day 0.
Outcomes
Primary Outcome Measures
Early bactericidal activity (EBA) 0-14
Change in EBA, using the time to positivity (TTP) of sputum in liquid Mycobacteria Growth Indicator Tube (MGIT)
Adverse events
Proportion of patients with treatment-emergent adverse events (TEAE)
Grade 3-4 adverse events
Total number of grade 3 and 4 adverse events (AE)
Secondary Outcome Measures
Time to sputum culture conversion (SCC)
Time to SCC, in liquid MGIT
Proportion of SCC at week 16
Proportion of participants with SCC, in liquid MGIT
Proportion of SCC at week 16
Proportion of participants with SCC, in liquid MGIT
Early bactericidal activity (EBA) 2-14
Change in EBA, using the TTP of sputum in liquid MGIT
Early bactericidal activity (EBA) 7-14
Change in EBA, using the TTP of sputum in liquid MGIT
Early bactericidal activity (EBA) 24 weeks
Change in EBA, using the TTP of sputum in liquid MGIT
Proportion of SCC per weeks
Proportion of participants with SCC, in liquid MGIT
Clinical worsening
Proportion of participants with clinical, X-ray, or laboratory worsening
Improvement of clinical signs and symptoms
Proportion of participants with improvement on Bandim TB score
Improvement of quality of life
Proportion of participants with improvement on health-related quality of life (HRQOL)
Discontinuation of TB treatment
Proportion of participants who discontinue treatment due to failure, resistance, other.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05455112
Brief Title
Safety and Efficacy of RUTI® With the Standard of Treatment for Tuberculosis
Acronym
CONSTAN-ARG
Official Title
Phase IIb Clinical Trial to Evaluate the Efficacy and Safety of the Administration of RUTI® Immunotherapy With the Standard Treatment in Patients With Tuberculosis
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 29, 2022 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
July 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Archivel Farma S.L.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study is proposed to evaluate the safety and efficacy of the RUTI vaccine in patients with pulmonary tuberculosis. Therapeutic vaccination of RUTI would stimulate the immune response not only against growing bacteria, but also against bacteria in a latent state that are less sensitive to antibiotic treatments. Therapeutic vaccination in patients with pulmonary tuberculosis could improve the speed of recovery of patients without inducing the appearance of drug resistance.
Detailed Description
The safety and immunogenicity of RUTI was established in healthy volunteers, patients with latent tuberculosis (TB); and Drug Susceptible (DS) -TB and Drug resistance (DR)-TB. This study proposed to evaluate the safety and efficacy of the RUTI vaccine in patients with active pulmonary TB. Immunotherapy for TB could shorten the sputum culture conversion, therefore reduce the time required to cure. Therapeutic vaccines do not interfere directly with the causative organism and hence, they are not involved in the development of drug resistance. Therapeutic vaccination would also be beneficial for DS-TB as it could increase the response to the standard therapy and help diminish the development of drug resistance. The vaccination stimulates the immune response during the continuation phase of TB treatment in which the remaining bacteria are poorly sensitive, if not refractory, to antimycobacterial agents, and potentiate chemotherapy. Reducing the huge reservoir of mycobacterium tuberculosis (DS or not) by vaccination strategies could ultimately accelerate elimination of the disease worldwide.
As per the results of the Phase II clinical trial in patients with latent TB, the best polyantigenic response was obtained with a dose of 25µg of RUTI vaccine and the second inoculation did not further increase the response. Based on these findings, a single dose of 25µg of vaccine will be used in the study.
The objective of this study is to i) explore the efficacy as reduction of bacillary load through the study of early bactericidal activity (EBA) in patients with DS-TB; and ii) provide data from safety perspective of the vaccine RUTI (25 µg FCMtb) in patients with TB, when given concomitant with the standard of care treatment initiation.
The study will include patients diagnosed with pulmonary DS-TB, candidate to start treatment with standard-care TB drugs and without any disease that could compromise the assessment of the response to the vaccination, or increase the risk of adverse events. RUTI will be administered on the day of TB treatment start, EBA will be measured on days 2, 4, 7, 10, 12, and 14, and adverse events will be collected up to week 24. Other measurements will be performed to assess the sputum culture conversion (SCC), clinical, X-ray or laboratory worsening, improvement of clinical signs and symptoms, and health-related quality-of-life (HRQOL).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculosis, Pulmonary
Keywords
Tuberculosis, immunotherapy, drug-susceptible
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
44 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
RUTI
Arm Type
Experimental
Arm Description
Single injection of RUTI 25µg of FCMtb at day 0.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Single injection of saline at day 0.
Intervention Type
Biological
Intervention Name(s)
RUTI® Vaccine
Intervention Description
One subcutaneous injection of RUTI 25µg FCMtb
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
One subcutaneous injection of saline
Primary Outcome Measure Information:
Title
Early bactericidal activity (EBA) 0-14
Description
Change in EBA, using the time to positivity (TTP) of sputum in liquid Mycobacteria Growth Indicator Tube (MGIT)
Time Frame
From day 0 to day 14
Title
Adverse events
Description
Proportion of patients with treatment-emergent adverse events (TEAE)
Time Frame
From day 0 to week 24
Title
Grade 3-4 adverse events
Description
Total number of grade 3 and 4 adverse events (AE)
Time Frame
From day 0 to week 24
Secondary Outcome Measure Information:
Title
Time to sputum culture conversion (SCC)
Description
Time to SCC, in liquid MGIT
Time Frame
From day 0 to week 16
Title
Proportion of SCC at week 16
Description
Proportion of participants with SCC, in liquid MGIT
Time Frame
From day 0 to week 16
Title
Proportion of SCC at week 16
Description
Proportion of participants with SCC, in liquid MGIT
Time Frame
From day 0 to week 8
Title
Early bactericidal activity (EBA) 2-14
Description
Change in EBA, using the TTP of sputum in liquid MGIT
Time Frame
From day 2 to day 14
Title
Early bactericidal activity (EBA) 7-14
Description
Change in EBA, using the TTP of sputum in liquid MGIT
Time Frame
From day 7 to day 14
Title
Early bactericidal activity (EBA) 24 weeks
Description
Change in EBA, using the TTP of sputum in liquid MGIT
Time Frame
From day 0 to week 24
Title
Proportion of SCC per weeks
Description
Proportion of participants with SCC, in liquid MGIT
Time Frame
Weeks 4, 12, 16, and 24
Title
Clinical worsening
Description
Proportion of participants with clinical, X-ray, or laboratory worsening
Time Frame
From day 0 to week 24
Title
Improvement of clinical signs and symptoms
Description
Proportion of participants with improvement on Bandim TB score
Time Frame
Weeks 1, 2, 8, 12, 16, and 24.
Title
Improvement of quality of life
Description
Proportion of participants with improvement on health-related quality of life (HRQOL)
Time Frame
Weeks 8 and 24
Title
Discontinuation of TB treatment
Description
Proportion of participants who discontinue treatment due to failure, resistance, other.
Time Frame
From day 0 to week 24.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Men and women aged 18 or older
Written informed consent
Laboratory confirmed pulmonary TB
Clinical symptoms compatible with pulmonary TB and/or X-ray evidence of pulmonary TB
Women of non-childbearing potential: at least 2 years post-menopausal or surgically sterile (e.g. tubal ligation)
Women of childbearing potential (including women less than 2 years past menopause) must have a negative pregnancy test at enrollment and must agree to use dual-barrier methods of contraception, intrauterine device (IUD), bilateral tubal occlusion, sexual abstinence, or vasectomized partner.
Males must agree to use a double barrier method of contraception at least 1 month after RUTI/placebo vaccination; or the male patient or his female partner must be surgically sterile or the female partner must be post-menopausal
Willing and able to attend all study visits and comply with all study procedures
Verifiable address or place of residence easy accessible to perform visits and willing to inform the research team of any change during the treatment and follow-up period
Exclusion Criteria:
Unable to provide written informed consent
Women reported, or detected, or willing to be pregnant during the trial period; Men willing to conceive a child during the study or 6 months after end of treatment
Severity of illness precluding full evaluation: expected early death, evidenced by respiratory failure, low blood pressure, WHO performance score 3-4
Evidence or suspicion of resistance to rifampin, isoniazid, pyrazinamide, and ethambutol, either laboratory-confirmed or based on epidemiological history at screening
Previous treatment for M. tuberculosis in the previous 24 months.
Bodyweight < 40kg
Unstable Diabetes Mellitus as a poor metabolic control within the past 12 months
HIV-infected subjects
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
HIstory of severe mental ilness which, in the opinion of the investigator, may exclude the participant from participating in the trial.
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)
Known allergy or any hipersensitivity to study mediactions, including rifampin, isoniazid, pyrazinamide, and ethambutol, or any of its excipients.
Documented allergy to anti-TB vaccines or any excipient of the RUTI vaccine.
Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Leylen Colmegna
Email
leylen.colmegna@latresearch.com
Facility Information:
Facility Name
Hospital José Nestor Lencinas
City
Godoy Cruz
State/Province
Mendoza
ZIP/Postal Code
M5547
Country
Argentina
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
María Andrea Villalba
Facility Name
Hospital de Clínicas Presidente Dr. Nicolás Avellaneda
City
San Miguel De Tucumán
State/Province
Tucumán
ZIP/Postal Code
T4001KKP
Country
Argentina
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Conrado Juan Llapur
12. IPD Sharing Statement
Learn more about this trial
Safety and Efficacy of RUTI® With the Standard of Treatment for Tuberculosis
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