Safety of RUTI® Vaccination in MDR-TB Patients
Tuberculosis, Multidrug Resistant
About this trial
This is an interventional treatment trial for Tuberculosis, Multidrug Resistant
Eligibility Criteria
Inclusion criteria
In order to be eligible to participate in this study, a subject must meet all of the following criteria:
- Diagnosed with pulmonary MDR-TB, and therefore managed with second line TB drugs;
- Admitted in a TB unit / hospital routinely diagnosed with pulmonary MDR-TB with clinical status ≥ 6 with Bandim TB score combined with chest radiography; and microbiological criteria according to the medical history), using rapid genetic testing (GeneXpert TB test) and MGIT to confirm or Line Probe Assay; or classical diagnostic tools including sputum microscopy and culture followed by phenotypic drug susceptibility testing. All of this medical information will be in the medical history;
- 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 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 and for 30 days after end of the study for each group; males must agree to use a double barrier method of contraception (condom plus spermicide or diaphragm plus spermicide) while participating in the study and for 30 days after end of the study for the respective group; 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 provide written informed consent;
- The patient must be willing and able to attend all study visits and comply with all study procedures.
Inclusion criteria for vaccination
- Having successfully completed 16, 8 or 4 weeks (depending on the cohort) of MDR-TB treatment, fully supervised, and
- With beneficial initial response to therapy, evidenced by:
Clinical response criteria: patients admitted in a TB unit / hospital routinely diagnosed with pulmonary MDR-TB (according to clinical status ≤ 5 with Bandim TB score) (33).
Transient deterioration of chest radiographic abnormalities might be explained by a paradoxical inflammatory response, and this may therefore not necessarily be interpreted as treatment failure; such decision depends on consensus with the DSMB; evidence of improvement on chest x-ray.
• Microbiological response criteria: It has to be reported a reduction of the bacillary load in the sputum by means of the reduction of bacillary counts in GeneXpert TB test and liquid culture (MGIT) to confirm (diagnosis week 0 collected in the medical history) at week 4 in CohortsC, week 8 in both Cohorts (A-B) and week 12 and 16 in Cohort A.
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded from participation in this study:
- Inability 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; Central Nervous System involvement of TB (TB meningitis, intra-cranial tuberculomas) as there is too little evidence for effective drug penetration for second-line TB drugs;
- Major co-morbid conditions precluding full evaluation, i.e., active lung cancer, acute coronary syndrome, heart failure exceeding NYHA class 2; a diagnosis of metastasized malignancy; renal failure in excess of creatinine clearance < 30 mL/min calculated by the Cockcroft-Gault formula, which would severely complicate administration of aminoglycosides and capreomycin, considered as the major second-line TB drugs; obesity (BMI>30 kg/m2); chronic liver disease - Child-Pugh class C;
- Any of the following laboratory parameters:
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 x upper limit of normal (ULN) Total bilirubine > 2 x ULN Neutrophil count ≤ 500 neutrophils / mm3 Platelet count < 50,000 cells / mm3
- Receiving or anticipated to receive a daily dose of ≥ 10 mg of systemic prednisone or equivalent within the period starting 14 days prior to enrolment. Note: patients are allowed to receive an acute, short course of methylprednisolone or prednisone or equivalent for management of an acute exacerbation of COPD or reactive airway disease in asthmatics;
- Cytotoxic chemotherapy or radiation therapy within the previous 3 months;
- HIV co-infection, if CD4 count < 250 cells/mm3 at the diagnosis of HIV; those with > 250 copies/mL are expected to be able to mount a sufficient cellular immune response and will therefore be eligible;
- Blood transfusion in the last three weeks prior to the trial;
- Documented allergy to TB vaccines, notably, to the RUTI® vaccine.
Sites / Locations
- "Chernivtsi Regional Clinical TB Dispensary", II tuberculosis department of multidrug-resistant tuberculosis
- "Ivano-Frankivsk Regional Phthisiopulmonology Center of Ivano-Frankivsk Regional Council", Center for Pulmonary Diseases
- Medical Department #2 (resistant tuberculosis) of Kharkiv Regional Antituberculosis Dispensary No1
Arms of the Study
Arm 1
Arm 2
Active Comparator
Placebo Comparator
RUTI® vaccine
Matching RUTI® Placebo
Intervention: Patients randomized to receive RUTI® vaccine will receive one injection of RUTI® vaccine in their right or left deltoid muscle.
Intervention: Patients randomized to receive Placebo will receive one injection of Placebo in their right or left deltoid muscle.