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Safety of RUTI® Vaccination in MDR-TB Patients

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ClinicalTrials.gov Identifier: NCT02711735
Recruitment Status : Not yet recruiting
First Posted : March 17, 2016
Last Update Posted : July 3, 2018
Sponsor:
Collaborator:
London School of Hygiene and Tropical Medicine
Information provided by (Responsible Party):
Tjip S van der Werf, University Medical Center Groningen

February 25, 2016
March 17, 2016
July 3, 2018
January 1, 2019
January 2020   (Final data collection date for primary outcome measure)
Clinical safety parameters related to vaccination [ Time Frame: 8 weeks ]
Safety Evaluation: Physical examination, SAEs, routine laboratory, chest radiography, between the intervention and control group within 8 weeks after vaccination.
Same as current
Complete list of historical versions of study NCT02711735 on ClinicalTrials.gov Archive Site
  • IFN-y release of PBMCs in response to antigen stimulation [ Time Frame: 8 weeks ]
    Immunogenicity Evaluation: Immunogenic properties of RUTI® vaccine (before vaccination and at week 2 and 8 after vaccination) compared to placebo assessed by i) IFN-γ production of ex vivo stimulated peripheral blood mononuclear cells (PBMC)
  • Mycobacterial Growth Inhibition Assay [ Time Frame: 8 weeks ]
    Immunogenicity Evaluation: Immunogenic properties of RUTI® vaccine (before vaccination and at week 2 and 8 after vaccination) compared to placebo assessed by the summative ability of PBMCs to control mycobacterial growth in an ex vivo system.
Same as current
Not Provided
Not Provided
 
Safety of RUTI® Vaccination in MDR-TB Patients
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.
Prospective, randomized, double-blind, multicentre, placebo-controlled clinical phase IIa trial to evaluate safety and immunogenicity of RUTI® vaccine in Multidrug-resistant Tuberculosis (MDR-TB) patients favourably responding to standard MDR-TB treatment. Time point of vaccination starts at 16 weeks upon start of standard MDR-TB treatment (cohort A), and if clinically safe as evaluated by an independent panel of experts (DSMB), another cohort of patients will be vaccinated at 12 weeks upon start of standard MDR-TB treatment (cohort B). All the patients will be followed up 8 weeks after vaccination.
Not Provided
Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Tuberculosis, Multidrug Resistant
  • Biological: RUTI® Therapeutic vaccine
    Participants randomised to this arm will receive one single dose of RUTI® vaccine in the right/left deltoid muscle.
  • Biological: Matching RUTI® Placebo
    Participants randomised to this arm will receive aone single dose of matching RUTI® placebo in the right / left deltoid
  • Active Comparator: RUTI® vaccine
    Intervention: Patients randomized to receive RUTI® vaccine will receive one injection of RUTI® vaccine in their right or left deltoid muscle.
    Intervention: Biological: RUTI® Therapeutic vaccine
  • Placebo Comparator: Matching RUTI® Placebo
    Intervention: Patients randomized to receive Placebo will receive one injection of Placebo in their right or left deltoid muscle.
    Intervention: Biological: Matching RUTI® Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
27
Same as current
July 2020
January 2020   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • 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 enrollment 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,
  • MDR-TB patients with Mycobacterium tuberculosis (or Mycobacterium africanum) by culture, at least also present in sputum;
  • Diagnosed with active MDR-TB, and therefore managed with second line TB drugs;
  • Having successfully completed 16 or 12 weeks (depending on the cohort) of MDR-TB treatment, fully supervised, and
  • with beneficial initial response to therapy, evidenced by

    • 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 Data Safety Monitoring Board; evidence of improvement on chest x-ray.
    • Microbiological response criteria: as evidenced by improvement in at least 2 measurements at least 4 weeks apart, using Mycobacterial Growth Indicator Tube (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 New York Heart Association class 2; a diagnosis of metastasized malignancy; renal failure in excess of creatinine clearance < 30 mls/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 (Body Mass Index >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 bilirubin > 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 < 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.
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
Contact: Tjip S van der Werf, MD PhD +31503612350 t.s.van.der.werf@umcg.nl
Not Provided
 
 
NCT02711735
201600136
Yes
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Plan to Share IPD: Yes
Tjip S van der Werf, University Medical Center Groningen
Archivel Farma S.L.
London School of Hygiene and Tropical Medicine
Principal Investigator: Tjip S van der Werf, MD PhD University Medical Center Groningen, The Netherlands
Archivel Farma S.L.
June 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP