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

Archivel Farma S.L.0 sitesDecember 1, 2021

ConditionsTuberculosis

Overview

Phase: Phase 2
Intervention: Not specified
Conditions: Tuberculosis
Sponsor: Archivel Farma S.L.
Primary Endpoint: Early Bactericidal Activity (EBA) from day 0 to day 14
Status: Withdrawn
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief 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. 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.

Registry

clinicaltrials.gov

Start Date

December 1, 2021

End Date

December 31, 2022

Last Updated

3 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Archivel Farma S.L.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Adults (females and males) aged ≥
•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.

Exclusion Criteria

•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-
•Bodyweight \< 40kg.
•Evidence of rifampicin resistance via GeneXpert.
•Unstable Diabetes Mellitus as a poor metabolic control within the past 12 months.
•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);

Outcomes

Primary Outcomes

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.

Secondary Outcomes

Rate of Change in Time to Sputum Culture Positivity (TTP) in Liquid Culture Media (week 4, 8, 16 and 24 )(Up to week 24)
Number of patients with improvement of Health-related Quality of Life (HRQoL) comparing baseline measure with that over the course of therapy.(At week 8, week 24)
Early Bactericidal Activity (EBA) from 4 to 24 week(At week 4, 8, 16 and 24 after treatment initiation and RUTI®/placebo vaccination)
The proportion of patients with SAEs between each intervention arm and the control group(Up to week 24)
Hazard ratio for stable culture conversion (SCC).(24 weeks of TB treatment)
The proportion of patients with AEs between each intervention arm and the control group.(Up to week 24)
Proportion of patients with CLINICAL, X-ray or LABORATORY worsening(Through study completion, an average of 24 weeks)
Proportion of patients with improvement of clinical signs and symptoms, Bandim TB score(At weeks 2, 8, 24)
Early Bactericidal Activity (EBA) from 2 to 14 days(Daily between day 2 and day 14 after treatment initiation and RUTI®/placebo vaccination.)
Early Bactericidal Activity (EBA) from 7 to 14 days(Daily between day 7 and day 14 after treatment initiation and RUTI®/placebo vaccination.)
Rate of Change in Time to Sputum Culture Positivity (TTP) in Liquid Culture Media (Days 0-14).(14 days)