Double-Blind, Randomized, Placebo-Controlled Phase IIa Clinical Trial to Investigate the Safety and Immunogenicity of RUTI® Therapeutic Vaccination in Patients with Multi-Drug Resistant Tuberculosis after successful intensive-phase treatment.

Phase 2

Withdrawn

Conditions: Infection with Mycobacterium tuberculosis resistant to at least the two first line antibiotics
Multidrug-resistant Tuberculosis
10028440
10024970

Registration Number: NL-OMON43117

Lead Sponsor: Archivel Farma S.L.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Withdrawn

Sex: Not specified

Target Recruitment: 5

Inclusion Criteria

- Female or Male patients (aged * 18);- Females of childbearing potential must have a negative pregnancy test at enrolment and must agree to use highly effective methods of birth control during and 30 days after the study;- 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;- diagnosed with active MDR-TB and therefore treated with second-line TB drugs;- MDR-TB patients with Mycobacterium tuberculosis (or Mycobacterium africanum) confirmed by sputum culture;- having successfully completed 16 (Cohort A) or 12 weeks (Cohort B) of MDR-TB treatment, fully supervised, with beneficial initial response to therapy, evidenced by:;1) Clinical response criteria: in patients initially presenting with three classical symptoms (weight loss, chronic cough, fever or night sweats), clinical improvement should be recorded in at least two of three symptoms at least 4 weeks apart; ;in patients with only two of these symptoms present initially, patients should show improvement in at least one symptom, at least 4 weeks apart; and in addition, patients should not develop clinical deterioration * i.e., on-going weight loss, or increased cough, or new-onset fever or night sweats. ;In addition, the attending physician should ascertain an overall clinical beneficial response to treatment. 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. ;2) Microbiological response criteria: as evidenced by improvement in at least 2 measurements at least 4 weeks apart, using MGIT (liquid culture microbiological assay read at 10 days)

Exclusion Criteria

- 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; ;- 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 <350 copies/mL; those with 350 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.;-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