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

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.

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.

Inclusion Criteria:

1. Adults (females and males) aged ≥ 18.
2. Written informed consent in a language they understand. This includes informed consent to be in the trial and informed consent to collect specimens.
3. 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.
4. Patients who have not received any anti-tubercular treatment in the last 24 hours.
5. Females of non-childbearing potential: at least 2 years post-menopausal or surgically sterile (e.g. tubal ligation).
6. 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.
7. 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.
8. The patient must be willing and able to attend all study visits and comply with all study procedures.

Exclusion Criteria:

1. Unable to provide written informed consent.

2. Women reported, or detected, or willing to be pregnant during the trial period.

3. Severity of illness precluding full evaluation: expected early death, evidenced by respiratory failure, low blood pressure, WHO performance score 3-4.

4. Bodyweight < 40kg.

5. Evidence of rifampicin resistance via GeneXpert.

6. Unstable Diabetes Mellitus as a poor metabolic control within the past 12 months.

7. For HIV infected subjects if the CD4+ count <250 cells/μL.

8. 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).

9. 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.

10. 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).

11. Documented allergy to TB vaccines or any of the study treatment excipients, notably, to the RUTI® vaccine.

12. Concurrent enrolment in another clinical study, unless it is an observational (noninterventional) clinical study or during the follow-up period of an interventional study.