Ignite Creation Date:
2025-12-24 @ 5:05 PM
Ignite Modification Date:
2025-12-29 @ 2:50 AM
Study NCT ID:
NCT04046250
Status:
COMPLETED
Last Update Posted:
2023-08-25
First Post:
2019-08-01
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Phase 2a Study to Evaluate Suppression of Methotrexate-induced Mucositis by TK112690
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'submissionTracking': {'firstMcpInfo': {'postDateStruct': {'date': '2021-05-10', 'type': 'ACTUAL'}}}}, 'conditionBrowseModule': {'meshes': [{'id': 'D052016', 'term': 'Mucositis'}, {'id': 'D006258', 'term': 'Head and Neck Neoplasms'}], 'ancestors': [{'id': 'D005759', 'term': 'Gastroenteritis'}, {'id': 'D005767', 'term': 'Gastrointestinal Diseases'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}, {'id': 'D009059', 'term': 'Mouth Diseases'}, {'id': 'D009057', 'term': 'Stomatognathic Diseases'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D009369', 'term': 'Neoplasms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D013812', 'term': 'Therapeutics'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'eyoussef@tosk.com', 'phone': '312.244.0068', 'title': 'Emile Youssef, MD, PhD', 'organization': 'Tosk, Inc.'}, 'certainAgreement': {'otherDetails': 'Each of the three clinical sites has a PI. Each PI is bound by a CDA covering the clinical data.\n\nTosk intends to prepare a manuscript reporting results from this trial combined with the results from the Phase 1b clinical trial. All the PIs will have a chance to review and approve the findings reported in the manuscript. Tosk expects to submit the manuscript for publication in early 2022.', 'restrictionType': 'OTHER', 'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'timeFrame': '6 Weeks', 'eventGroups': [{'id': 'EG000', 'title': 'TK112690', 'description': 'TK112690 treatment\n\nTK-112690: TK112690 treatment pre-methotrexate treatment', 'otherNumAtRisk': 11, 'deathsNumAtRisk': 11, 'otherNumAffected': 1, 'seriousNumAtRisk': 11, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Placebo', 'description': 'TK112690 formulation\n\nPlacebo TK-112690: Placebo', 'otherNumAtRisk': 11, 'deathsNumAtRisk': 11, 'otherNumAffected': 7, 'seriousNumAtRisk': 11, 'deathsNumAffected': 1, 'seriousNumAffected': 2}], 'otherEvents': [{'term': 'GI Disorders', 'stats': [{'groupId': 'EG000', 'numAtRisk': 11, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 11, 'numAffected': 7}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Medra'}], 'seriousEvents': [{'term': 'Neutropenia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 11, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 11, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Medra'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Mucositis', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'TK112690', 'description': 'TK112690 treatment\n\nTK-112690: TK112690 treatment pre-methotrexate treatment'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'TK112690 formulation\n\nPlacebo TK-112690: Placebo'}], 'classes': [{'title': 'NCI/CTCAE at 4 WKs', 'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'OG000'}, {'value': '7', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '0.37', 'spread': '0.19', 'groupId': 'OG000'}, {'value': '2.84', 'spread': '0.29', 'groupId': 'OG001'}]}]}, {'title': 'WHO at 4 WKs', 'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'OG000'}, {'value': '7', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '0.34', 'spread': '0.17', 'groupId': 'OG000'}, {'value': '2.87', 'spread': '0.31', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'up to 4 Weeks', 'description': "Mucositis Evaluation Using Established Scoring Systems: NCI/CTCAE at 4 WKs (Primary) and WHO at 4 WKs (Primary).\n\nNCI/CTCAE=National Cancer Institute/Common Terminology Criteria for Adverse Events and WHO=World Health Organization\n\nNCI Grades- 0= No mucositis, 1=Mild mucositis (Painless ulcers, erythema, or mild soreness in the absence of lesions), 2=Moderate mucositis (Painful erythema, edema, or ulcers but eating or swallowing possible), 3= Severe mucositis (Painful erythema, edema, or ulcers requiring IV hydration), 4=Life threatening, 5=Death WHO Grades- 0=No mucositis, 1= Mild (Oral soreness, erythema), 2=Moderate (Oral erythema, ulcers, solid diet tolerated), 3=Severe (Oral ulcers, liquid diet only), 4=Life-threatening (Oral alimentation impossible).\n\nFor both the scales above, a higher score implies greater mucositis.\n\nScale specific mean values for patients in each group (placebo or treated) are calculated and compared by Student's t-test.", 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Patients with SCCHN who have failed at least one prior treatment of chemotherapy and/or radiation'}, {'type': 'SECONDARY', 'title': 'Incidence Adverse Events That Are Related to Treatment', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'TK112690', 'description': 'TK112690 treatment\n\nTK-112690: TK112690 treatment pre-methotrexate treatment'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'TK112690 formulation\n\nPlacebo TK-112690: Placebo'}], 'classes': [{'title': 'SAEs', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}]}]}, {'title': 'Deaths', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'TEAE GI and Related', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Measured Weekly Over 4 Weeks of Study', 'description': 'Tolerance', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'TK112690', 'description': 'TK112690 treatment\n\nTK-112690: TK112690 treatment pre-methotrexate treatment'}, {'id': 'FG001', 'title': 'Placebo', 'description': 'TK112690 formulation\n\nPlacebo TK-112690: Placebo'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '11'}, {'groupId': 'FG001', 'numSubjects': '11'}]}, {'type': 'COMPLETED', 'achievements': [{'comment': 'Four Methotrexate + TK-112690 Treatments', 'groupId': 'FG000', 'numSubjects': '8'}, {'comment': 'Four Methotrexate + TK-12260 Placebo Treatments', 'groupId': 'FG001', 'numSubjects': '7'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '3'}, {'groupId': 'FG001', 'numSubjects': '4'}]}], 'dropWithdraws': [{'type': 'Death', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}]}, {'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '3'}, {'groupId': 'FG001', 'numSubjects': '3'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'BG000'}, {'value': '11', 'groupId': 'BG001'}, {'value': '22', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'TK112690', 'description': 'TK112690 treatment\n\nTK-112690: TK112690 treatment pre-methotrexate treatment'}, {'id': 'BG001', 'title': 'Placebo', 'description': 'TK112690 formulation\n\nPlacebo TK-112690: Placebo'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '54', 'spread': '11', 'groupId': 'BG000'}, {'value': '49', 'spread': '13', 'groupId': 'BG001'}, {'value': '52', 'spread': '12', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '7', 'groupId': 'BG000'}, {'value': '8', 'groupId': 'BG001'}, {'value': '15', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '4', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '7', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Ethnicity (NIH/OMB)', 'classes': [{'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '11', 'groupId': 'BG000'}, {'value': '11', 'groupId': 'BG001'}, {'value': '22', 'groupId': 'BG002'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'India', 'categories': [{'measurements': [{'value': '11', 'groupId': 'BG000'}, {'value': '11', 'groupId': 'BG001'}, {'value': '22', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2019-02-25', 'size': 2668429, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_000.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2021-04-10T18:18', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR'], 'maskingDescription': 'The study will be partially blinded. The patient and investigator will be blinded as to whether TK112690 or placebo is administered. The clinical research organization, sponsor, and site pharmacist will know whether the patient was administered active drug or placebo.'}, 'primaryPurpose': 'PREVENTION', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'A total of 22 patients will be enrolled into one of 2 different: TK112690 treated or placebo treated.'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 22}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2019-05-15', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-08', 'completionDateStruct': {'date': '2020-03-31', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2023-08-11', 'studyFirstSubmitDate': '2019-08-01', 'resultsFirstSubmitDate': '2021-04-14', 'studyFirstSubmitQcDate': '2019-08-05', 'lastUpdatePostDateStruct': {'date': '2023-08-25', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2021-05-08', 'studyFirstPostDateStruct': {'date': '2019-08-06', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2021-06-03', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2019-10-10', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Mucositis', 'timeFrame': 'up to 4 Weeks', 'description': "Mucositis Evaluation Using Established Scoring Systems: NCI/CTCAE at 4 WKs (Primary) and WHO at 4 WKs (Primary).\n\nNCI/CTCAE=National Cancer Institute/Common Terminology Criteria for Adverse Events and WHO=World Health Organization\n\nNCI Grades- 0= No mucositis, 1=Mild mucositis (Painless ulcers, erythema, or mild soreness in the absence of lesions), 2=Moderate mucositis (Painful erythema, edema, or ulcers but eating or swallowing possible), 3= Severe mucositis (Painful erythema, edema, or ulcers requiring IV hydration), 4=Life threatening, 5=Death WHO Grades- 0=No mucositis, 1= Mild (Oral soreness, erythema), 2=Moderate (Oral erythema, ulcers, solid diet tolerated), 3=Severe (Oral ulcers, liquid diet only), 4=Life-threatening (Oral alimentation impossible).\n\nFor both the scales above, a higher score implies greater mucositis.\n\nScale specific mean values for patients in each group (placebo or treated) are calculated and compared by Student's t-test."}], 'secondaryOutcomes': [{'measure': 'Incidence Adverse Events That Are Related to Treatment', 'timeFrame': 'Measured Weekly Over 4 Weeks of Study', 'description': 'Tolerance'}]}, 'oversightModule': {'isUsExport': True, 'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Mucositis', 'Methotrexate', 'Uridine Phosphorylase Inhibitor', 'Head and Neck Cancer'], 'conditions': ['Mucositis']}, 'descriptionModule': {'briefSummary': 'Patients will receive methotrexate at a dose of 45 mg/m2 administered weekly for 4 consecutive weeks as an iv infusion along with a nutritional supplement administered two hours before the methotrexate. One hour before the methotrexate treatment the patients will be administered the first infusion of the day of either TK112690 or placebo depending on randomization. Five hours after the methotrexate treatment the patients will be administered the second treatment of either TK112690 or placebo depending on randomization. The TK112690 dose will be 45 mg/kg.', 'detailedDescription': 'Patients will receive methotrexate at a dose of 45 mg/m2 administered weekly for 4 consecutive weeks as an iv infusion along with a nutritional supplement administered two hours before the methotrexate. One hour before the methotrexate treatment the patients will be administered the first infusion of the day of either TK112690 or placebo depending on randomization infusion. Five hours after the methotrexate treatment the patients will be administered the second treatment of either TK112690 or placebo depending on randomization. The TK112690 dose will be 45 mg/kg.\n\n* A total of 22 patients will be enrolled into one of 2 different dose groups: TK-112690 treated or placebo treated.\n* Screening must be within 15 days of subject enrollment.\n* Patients will remain for observation at the clinical site for a minimum of 25 hours post initial TK112690 or placebo dose.\n* Study follow-up will occur on Week 6, two weeks after the last dosing of methotrexate.\n* Blinding: The study will be partially blinded. The patient and investigator will be blinded as to whether TK112690 or placebo is administered. The CRO, sponsor, and site pharmacist will know whether the patient was administered active drug or placebo.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '80 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria\n\n* Male and female subjects over 18 years old with a histologically or cytological confirmed diagnosis of locally residual, recurrent or metastatic SCCHN.\n* Subject must have failed at least one courses of non-MTX chemotherapy, or one course of non-MTX chemotherapy and chemo radiation for treating their SCCHN.\n* No prior systemic treatments for cancer (chemotherapy and/or radiotherapy) 4 weeks prior to screening.\n* No other concurrent, active, invasive malignancies.\n* An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.\n* Must have a life expectancy of at least 6 months.\n* History of brain metastases allowed if disease has stabilized or improved after radiation and/or craniotomy.\n* No active angina or uncontrolled arrhythmia.\n* No detectable infection including hepatitis B/C and HIV.\n* Not pregnant or nursing. Women of childbearing potential must have a negative urine pregnancy test at screening and on the day before dosing and must use medically acceptable methods of birth control. Acceptable methods of birth control include oral or transdermal contraceptives, condoms, spermicidal foam, IUD, progestin implant or injection, abstinence, vaginal ring, or sterilization of partner. The reason for non-childbearing potential, such as bilateral tubal ligation, bilateral oophorectomy, hysterectomy, or post-menopausal for ≥ 1 year, must be specified in the patient's medical history file and CRF.\n* Must have adequate organ and immune function as indicated by the following laboratory values:\n\nParameter Laboratory Values Serum creatinine ≤1.5 x ULN Est. creatinine clearance ≥45 mL/min Total bilirubin ≤2.0 mg/dL (≤34.2 μmol/L) AST \\& ALT ≤3 x ULN Absolute granulocytes ≥1.5 x 109 cells/L Platelets ≥100,000/µL\n\n● Be able to read and understand, and provide a signature or thumb impression on the Informed Consent Form (ICF) before entering the study.\n\nExclusion Criteria:\n\n* Subject has not failed at least one courses of non-MTX chemotherapy or one course of non-MTX chemotherapy and chemo radiation for treating their SCCHN.\n* Uncontrolled active infection.\n* Current mucositis (\\>Grade 1).\n* Pregnant or nursing mother.\n* Prior history of a cerebrovascular accident or hemorrhage.\n* Congestive heart failure, as defined by New York Heart Association class III or IV.\n* Uncontrolled hypertension.\n* Active psychiatric/mental illness making informed consent or useful clinical follow-up unlikely.\n* Subjects who have previously been enrolled into this study and subsequently withdrew.\n* Subject receiving other investigational agent(s).\n* Any systemic immunosuppressive medication/therapy (eg, other chemotherapy, steroids).\n* Any significant systemic illness, unstable or severe medical condition(s) that could put the subject at risk during the study, interfere with outcome measures, or affect compliance with the protocol procedures such as intercurrent infection and/or autoimmune disease, ie, any condition that compromises the immune system.\n* Known or suspected intolerance or hypersensitivity to the study materials (TK-112690 and/or excipients or closely related compounds).\n* Subjects, who have received, or plan to receive, radiation or chemotherapy within 4 weeks of screening.\n* Subjects that have a history of poor compliance in clinical research studies.\n* Subjects that have participated in any other investigative clinical trial in the past 4 weeks."}, 'identificationModule': {'nctId': 'NCT04046250', 'acronym': 'TK112690', 'briefTitle': 'Phase 2a Study to Evaluate Suppression of Methotrexate-induced Mucositis by TK112690', 'organization': {'class': 'INDUSTRY', 'fullName': 'Tosk, Inc.'}, 'officialTitle': 'Phase 2a, Multi-center, Placebo-controlled, Randomized, Partially Blinded, Study Infused TK112690 or or Placebo Administered Along With Methotrexate Weekly for Four Consecutive Weeks to Patients With Recurrent or Residual SCCHN', 'orgStudyIdInfo': {'id': 'CLP-2690-0003'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'TK112690', 'description': 'TK112690 treatment', 'interventionNames': ['Drug: TK-112690']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'description': 'TK112690 formulation', 'interventionNames': ['Drug: Placebo TK-112690']}], 'interventions': [{'name': 'TK-112690', 'type': 'DRUG', 'otherNames': ['Treatment'], 'description': 'TK112690 treatment pre-methotrexate treatment', 'armGroupLabels': ['TK112690']}, {'name': 'Placebo TK-112690', 'type': 'DRUG', 'description': 'Placebo', 'armGroupLabels': ['Placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '560091', 'city': 'Bangalore', 'state': 'Karnataka', 'country': 'India', 'facility': 'Bangalore Cancer', 'geoPoint': {'lat': 12.97194, 'lon': 77.59369}}, {'zip': '580025', 'city': 'Navanagar', 'state': 'Karnataka', 'country': 'India', 'facility': 'Karnatak Cancer Therapy and Research Institute'}, {'zip': '700094', 'city': 'Kolkata', 'state': 'West Bengal', 'country': 'India', 'facility': 'Netaji Subhash Chandra Bose Cancer Hospital', 'geoPoint': {'lat': 22.56263, 'lon': 88.36304}}], 'overallOfficials': [{'name': 'Emile Youssef, MD, PhD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Tosk, Inc.'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Tosk, Inc.', 'class': 'INDUSTRY'}, 'collaborators': [{'name': 'Crystal Life Sciences', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'SPONSOR'}}}}