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Safety of RUTI® Vaccination in MDR-TB Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02711735
Recruitment Status : Terminated (Lack of recruitment)
First Posted : March 17, 2016
Last Update Posted : July 5, 2022
Sponsor:
Collaborator:
London School of Hygiene and Tropical Medicine
Information provided by (Responsible Party):
Archivel Farma S.L.

Tracking Information
First Submitted Date  ICMJE February 25, 2016
First Posted Date  ICMJE March 17, 2016
Last Update Posted Date July 5, 2022
Actual Study Start Date  ICMJE March 18, 2020
Actual Primary Completion Date September 9, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 16, 2016)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 16, 2016)
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety of RUTI® Vaccination in MDR-TB Patients
Official Title  ICMJE Double-Blind, Randomized, Placebo-Controlled Phase IIa Clinical Trial to Investigate the Safety and Immunogenicity of RUTI® Therapeutic Vaccination in Patients With MDR-TB After Successful Intensive-phase Treatment.
Brief Summary 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 2 weeks upon start of standard MDR-TB treatment (cohort B), All the patients will be followed up 8 weeks after vaccination.
Detailed Description 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 2 weeks upon start of standard MDR-TB treatment (cohort B)
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Tuberculosis, Multidrug Resistant
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: June 30, 2022)
9
Original Estimated Enrollment  ICMJE
 (submitted: March 16, 2016)
27
Actual Study Completion Date  ICMJE September 9, 2020
Actual Primary Completion Date September 9, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Ukraine
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02711735
Other Study ID Numbers  ICMJE 201600136
2016-000850-36 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Supporting Materials: Study Protocol
Current Responsible Party Archivel Farma S.L.
Original Responsible Party Tjip van der Werf, University Medical Center Groningen, Prof dr Tjip S van der Werf
Current Study Sponsor  ICMJE Archivel Farma S.L.
Original Study Sponsor  ICMJE University Medical Center Groningen
Collaborators  ICMJE London School of Hygiene and Tropical Medicine
Investigators  ICMJE
Principal Investigator: Tjip S van der Werf, MD PhD University Medical Center Groningen, The Netherlands
PRS Account Archivel Farma S.L.
Verification Date June 2022

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