Clinical Trial to Investigate Therapeutic Vaccine (RUTI) Against Tuberculosis (TB)

Double-Blind, Randomized, Placebo-Controlled, Phase IIb Clinical Trial to Investigate the Efficacy of RUTI® Therapeutic Vaccination as Adjuvant of Tuberculosis Chemotherapy

Prospective, randomized, double-blind, multicentre, placebo-controlled clinical phase IIb trial to evaluate efficacy of RUTI® vaccine in DS- (Drug-Sensitive) and MDR-TB (Multidrug-resistant) patients favourably responding to standard MDR-TB treatment. Time point of vaccination starts upon completion of 1 week of standard DS-TB treatment (cohort A), and another cohort of patients will be vaccinated upon completion of 1 month of standard MDR-TB treatment (cohort B). All the patients will be followed up to the end of the treatment.

Inclusion Criteria:

1. Diagnosed with pulmonary DS- or MDR-TB, and managed with standard-care TB drugs accordingly;

2. Attending a TB unit / hospital routinely diagnosed with pulmonary DS- or MDR-TB with clinical status ≥ 6 with Bandim TB score combined with chest radiography; and microbiological criteria (MGIT sputum culture), by using rapid genetic testing, gene Xpert;

3. Patients who have not received any anti-tubercular treatment in last 6 months

4. Females and males aged ≥ 18;

   • 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 postmenopausal) 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) while participating in the study; 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;

5. The patient must provide written informed consent;

6. The patient must be willing and able to attend all study visits and comply with all study procedures.

Inclusion criteria for vaccination

1. Having successfully completed 1 week or 1 month (depending on the cohort) of DS or MDR-TB treatment, respectively, fully supervised; and with beneficial initial response to therapy, evidenced by clinical response.

Exclusion Criteria:

1. Inability 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. Patients with extra-pulmonary tuberculosis

5. Major co-morbid conditions precluding full evaluation, i.e., HIV positive, chronic renal failure, chronic liver failure, Malignancy, patients taking any immunosuppressant drug, active lung cancer, acute coronary syndrome, heart failure exceeding NYHA class 2;

6. Presence of secondary immunodeficiency states: Organ transplantation, diabetes mellitus

7. 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 cells / mm3

8. Cytotoxic chemotherapy or radiation therapy within the previous 3 months;

9. Blood transfusion in the last three weeks prior to the trial; 10.Patients with history of alcohol or drug abuse

11. Documented allergy to TB vaccines, notably, to the RUTI® vaccine