Ignite Creation Date:
2025-12-24 @ 10:03 PM
Ignite Modification Date:
2026-02-28 @ 9:31 AM
Study NCT ID:
NCT02711735
Status:
TERMINATED
Last Update Posted:
2022-07-05
First Post:
2016-02-25
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Safety of RUTI® Vaccination in MDR-TB Patients
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D018088', 'term': 'Tuberculosis, Multidrug-Resistant'}], 'ancestors': [{'id': 'D014376', 'term': 'Tuberculosis'}, {'id': 'D009164', 'term': 'Mycobacterium Infections'}, {'id': 'D000193', 'term': 'Actinomycetales Infections'}, {'id': 'D016908', 'term': 'Gram-Positive Bacterial Infections'}, {'id': 'D001424', 'term': 'Bacterial Infections'}, {'id': 'D001423', 'term': 'Bacterial Infections and Mycoses'}, {'id': 'D007239', 'term': 'Infections'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 9}}, 'statusModule': {'whyStopped': 'Lack of recruitment', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2020-03-18', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2022-06', 'completionDateStruct': {'date': '2020-09-09', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2022-06-30', 'studyFirstSubmitDate': '2016-02-25', 'studyFirstSubmitQcDate': '2016-03-16', 'lastUpdatePostDateStruct': {'date': '2022-07-05', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2016-03-17', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2020-09-09', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Clinical safety parameters related to vaccination', 'timeFrame': '8 weeks', 'description': 'Safety Evaluation: Physical examination, SAEs, routine laboratory, chest radiography, between the intervention and control group within 8 weeks after vaccination.'}], 'secondaryOutcomes': [{'measure': 'IFN-y release of PBMCs in response to antigen stimulation', 'timeFrame': '8 weeks', 'description': '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)'}, {'measure': 'Mycobacterial Growth Inhibition Assay', 'timeFrame': '8 weeks', 'description': '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.'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Tuberculosis, Multidrug Resistant']}, 'referencesModule': {'references': [{'pmid': '19853680', 'type': 'BACKGROUND', 'citation': 'Vilaplana C, Montane E, Pinto S, Barriocanal AM, Domenech G, Torres F, Cardona PJ, Costa J. Double-blind, randomized, placebo-controlled Phase I Clinical Trial of the therapeutical antituberculous vaccine RUTI. Vaccine. 2010 Jan 22;28(4):1106-16. doi: 10.1016/j.vaccine.2009.09.134. Epub 2009 Oct 22.'}, {'pmid': '24586912', 'type': 'BACKGROUND', 'citation': "Nell AS, D'lom E, Bouic P, Sabate M, Bosser R, Picas J, Amat M, Churchyard G, Cardona PJ. Safety, tolerability, and immunogenicity of the novel antituberculous vaccine RUTI: randomized, placebo-controlled phase II clinical trial in patients with latent tuberculosis infection. PLoS One. 2014 Feb 26;9(2):e89612. doi: 10.1371/journal.pone.0089612. eCollection 2014."}]}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': '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)'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion criteria\n\nIn order to be eligible to participate in this study, a subject must meet all of the following criteria:\n\n* Diagnosed with pulmonary MDR-TB, and therefore managed with second line TB drugs;\n* 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;\n* 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;\n* The patient must provide written informed consent;\n* The patient must be willing and able to attend all study visits and comply with all study procedures.\n\nInclusion criteria for vaccination\n\n* Having successfully completed 16, 8 or 4 weeks (depending on the cohort) of MDR-TB treatment, fully supervised, and\n* With beneficial initial response to therapy, evidenced by:\n\nClinical 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).\n\nTransient 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.\n\n• 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.\n\nExclusion criteria\n\nA potential subject who meets any of the following criteria will be excluded from participation in this study:\n\n* Inability to provide written informed consent;\n* Women reported, or detected, or willing to be pregnant during the trial period;\n* 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;\n* 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;\n* Any of the following laboratory parameters:\n\nAspartate 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\n\n* 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;\n* Cytotoxic chemotherapy or radiation therapy within the previous 3 months;\n* 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;\n* Blood transfusion in the last three weeks prior to the trial;\n* Documented allergy to TB vaccines, notably, to the RUTI® vaccine.'}, 'identificationModule': {'nctId': 'NCT02711735', 'briefTitle': 'Safety of RUTI® Vaccination in MDR-TB Patients', 'organization': {'class': 'INDUSTRY', 'fullName': 'Archivel Farma S.L.'}, 'officialTitle': '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.', 'orgStudyIdInfo': {'id': '201600136'}, 'secondaryIdInfos': [{'id': '2016-000850-36', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'RUTI® vaccine', 'description': 'Intervention: Patients randomized to receive RUTI® vaccine will receive one injection of RUTI® vaccine in their right or left deltoid muscle.', 'interventionNames': ['Biological: RUTI® Therapeutic vaccine']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Matching RUTI® Placebo', 'description': 'Intervention: Patients randomized to receive Placebo will receive one injection of Placebo in their right or left deltoid muscle.', 'interventionNames': ['Biological: Matching RUTI® Placebo']}], 'interventions': [{'name': 'RUTI® Therapeutic vaccine', 'type': 'BIOLOGICAL', 'description': 'Participants randomised to this arm will receive one single dose of RUTI® vaccine in the right/left deltoid muscle.', 'armGroupLabels': ['RUTI® vaccine']}, {'name': 'Matching RUTI® Placebo', 'type': 'BIOLOGICAL', 'description': 'Participants randomised to this arm will receive aone single dose of matching RUTI® placebo in the right / left deltoid', 'armGroupLabels': ['Matching RUTI® Placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '58000', 'city': 'Chernivtsi', 'country': 'Ukraine', 'facility': '"Chernivtsi Regional Clinical TB Dispensary", II tuberculosis department of multidrug-resistant tuberculosis', 'geoPoint': {'lat': 48.29045, 'lon': 25.93241}}, {'zip': '76018', 'city': 'Ivano-Frankivsk', 'country': 'Ukraine', 'facility': '"Ivano-Frankivsk Regional Phthisiopulmonology Center of Ivano-Frankivsk Regional Council", Center for Pulmonary Diseases', 'geoPoint': {'lat': 48.92312, 'lon': 24.71248}}, {'zip': '61096', 'city': 'Kharkiv', 'country': 'Ukraine', 'facility': 'Medical Department #2 (resistant tuberculosis) of Kharkiv Regional Antituberculosis Dispensary No1', 'geoPoint': {'lat': 49.98177, 'lon': 36.25475}}], 'overallOfficials': [{'name': 'Tjip S van der Werf, MD PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University Medical Center Groningen, The Netherlands'}]}, 'ipdSharingStatementModule': {'infoTypes': ['STUDY_PROTOCOL'], 'ipdSharing': 'YES'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Archivel Farma S.L.', 'class': 'INDUSTRY'}, 'collaborators': [{'name': 'London School of Hygiene and Tropical Medicine', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR'}}}}