Evaluation of Efficacy and Safety of the Concomitant of RUTI® Immunotherapy With the Standard Treatment in TB Patients

NCT05136833 | Withdrawn Phase 2

• 2 other identifiers: AC-R62021-003301-22
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Tuberculosis

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  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.

• Early Bactericidal Activity (EBA) from 4 to 24 week

  At week 4, 8, 16 and 24 after treatment initiation and RUTI®/placebo vaccination

• Hazard ratio for stable culture conversion (SCC).

  24 weeks of TB treatment

• Rate of Change in Time to Sputum Culture Positivity (TTP) in Liquid Culture Media (Days 0-14).

  14 days

Other Outcomes (2)

• IFN-γ production of ex vivo stimulated peripheral blood mononuclear cells (PBMC) (Exploratory endpoint for immunogenicity outcomes 1)

  Up to week 24

• The summative ability of PBMCs to control mycobacterial growth inhibition assay (MGIA) (Exploratory endpoint for immunogenicity outcomes 2)

  Up to week 24

Study Arms (2)

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

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.

Biological: Placebo

Interventions

RUTI® vaccine BIOLOGICAL

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.

Group A (RUTI)

Placebo BIOLOGICAL

Normal saline will be used as a placebo.

Group B (Placebo)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Archivel Farma S.L.: lead
• Fundació Institut Germans Trias i Pujol: collaborator

MeSH Terms

Conditions

Tuberculosis

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2021
• First Posted: November 29, 2021
• Study Start: December 1, 2021
• Primary Completion: June 30, 2022
• Study Completion: December 31, 2022
• Last Updated: July 13, 2022

Record last verified: 2022-07