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    Summary
    EudraCT Number:2020-002820-35
    Sponsor's Protocol Code Number:KRT-232-103
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2020-08-11
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedGermany - BfArM
    A.2EudraCT number2020-002820-35
    A.3Full title of the trial
    A Phase 1b/2, Open-Label Study Evaluating the Safety and Efficacy of KRT-232 in Patients with p53 Wild Type (p53WT) Merkel Cell Carcinoma (MCC) Who Have Failed Anti-PD-1 or Anti-PD-L1 Immunotherapy, or in Combination with Avelumab in MCC Patients who are Anti-PD-1 or Anti-PD-L1 Treatment Naïve
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study Evaluating the Safety and Efficacy of KRT-232 in Patients with p53 Wild-Type (p53WT) Merkel Cell Carcinoma (MCC) Who Have Failed Anti-PD-1 or Anti-PD-L1 Immunotherapy, or in Combination with Avelumab in MCC Patients who are Anti-PD-1 or Anti-PD-L1 Treatment Naïve
    A.4.1Sponsor's protocol code numberKRT-232-103
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03787602
    A.5.4Other Identifiers
    Name:IND NumberNumber:115894
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorKartos Therapeutics, Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportKartos Therapeutics, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationKartos Therapeutics, Inc.
    B.5.2Functional name of contact pointEmily Houlihan
    B.5.3 Address:
    B.5.3.1Street Address275 Shoreline Drive, Suite 300
    B.5.3.2Town/ cityRedwood City
    B.5.3.3Post codeCA 94065
    B.5.3.4CountryUnited States
    B.5.4Telephone number+14019548042
    B.5.6E-mailehoulihan@kartosthera.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameNavtemadlin (KRT-232)
    D.3.2Product code KRT-232 with active ingredient content of 10%
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNNavtemadlin
    D.3.9.1CAS number 1352066-68-2
    D.3.9.2Current sponsor codeKRT-232
    D.3.9.3Other descriptive nameAMG 232
    D.3.9.4EV Substance CodeSUB123933
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number15
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameNavtemadlin (KRT-232)
    D.3.2Product code KRT-232 with active ingredient content of 10%
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNNavtemadlin
    D.3.9.1CAS number 1352066-68-2
    D.3.9.2Current sponsor codeKRT-232
    D.3.9.3Other descriptive nameAMG 232
    D.3.9.4EV Substance CodeSUB123933
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number60
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 3
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Bavencio
    D.2.1.1.2Name of the Marketing Authorisation holderMerck Europe B.V.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameBavencio (Avelumab)
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNAVELUMAB
    D.3.9.1CAS number 1537032-82-8
    D.3.9.4EV Substance CodeSUB180078
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 4
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameNavtemadlin (KRT-232)
    D.3.2Product code KRT-232 with active ingredient content of 25%
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNNavtemadlin
    D.3.9.1CAS number 1352066-68-2
    D.3.9.2Current sponsor codeKRT-232
    D.3.9.3Other descriptive nameAMG 232
    D.3.9.4EV Substance CodeSUB123933
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number60
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 5
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameNavtemadlin (KRT-232)
    D.3.2Product code KRT-232 with active ingredient content of 25%
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNNavtemadlin
    D.3.9.1CAS number 1352066-68-2
    D.3.9.2Current sponsor codeKRT-232
    D.3.9.3Other descriptive nameAMG 232
    D.3.9.4EV Substance CodeSUB123933
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number60
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    p53 Wild-Type (p53WT) Merkel Cell Carcinoma (MCC)
    E.1.1.1Medical condition in easily understood language
    Merkel Cell Carcinoma (MCC)
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10064025
    E.1.2Term Merkel cell carcinoma
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    - Cohort 1 Part 1: To determine the KRT-232 recommended phase 2 dose (RP2D)
    - Cohort 1 Part 2: To determine the objective response rate (ORR) in subjects with p53WT MCC who have failed anti-PD-1 or anti-PD-L1 immunotherapy
    - Cohort 2 Part 1: To determine the KRT-232 RP2D in combination with avelumab
    - Cohort 2 Part 2: To determine the objective response rate (ORR) in treatment-naïve subjects with p53WT MCC}- Cohort 3: To determine the confirmed objective response rate (ORR) in subjects with p53WT MCC who are chemotherapy naïve and who have failed anti-PD-1 or anti-PDL-1 immunotherapy
    - Cohort 4: To determine the confirmed objective response rate (ORR) in subjects with p53WT MCC who have failed anti-PD-1 or anti-PDL-1 immunotherapy and who have received at least 1 line of prior chemotherapy
    E.2.2Secondary objectives of the trial
    Cohort 3: To determine the objective response rate (ORR) in subjects with p53WT MCC who are chemotherapy naïve and who have failed anti-PD-1 or anti-PDL-1 immunotherapy- Cohort 4: To determine the objective response rate (ORR) in subjects with p53WT MCC who have failed anti-PD-1 or anti-PDL-1 immunotherapy and who have received at least 1 line of prior chemotherapy
    - To determine duration of response (DoR)
    - To determine progression-free survival (PFS)
    - To determine overall survival (OS)
    - To determine the clinical benefit rate (CBR)
    - To determine KRT-232 safety and tolerability
    - To determine the pharmacokinetic/pharmacodynamic (PK/PD) profile of KRT-232
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. For Cohorts 1, 3 and 4, subjects must have failed treatment with at least one PD-1 inhibitor or PD-L1 inhibitor for metastatic MCC
    2. For Cohort 2, subjects must not have received any anti-PD-1 or anti-PD-L1 treatments for metastatic MCC
    3. For Cohort 3, subjects must not have received any prior chemotherapy.
    4. For Cohort 4, subjects must have received at least 1 line of prior chemotherapy
    5. Adults ≥ 18 years of age and willing to provide written informed consent
    6. ECOG performance status of 0 to 1
    7. Histologically confirmed MCC. Disease must be measurable, with at least 1 measurable lesion by RECIST criteria, version 1.1
    8. For Cohorts 1 and 2: MCC expressing p53WT based on any CLIA or FDA approved sequencing test or by a test approved by the local health authority or, if not available, by a validated test. For Cohort 2, subjects may be enrolled and treated with avelumab monotherapy before p53WT status is known
    9. For Cohorts 3 and 4: MCC expressing p53WT based on Central Laboratory testing
    10. Fresh or archival tumor tissue must be submitted for biomarker assessment.
    11. Adequate hematological, hepatic, and renal function within 14 days prior to the first dose of KRT-232 as defined in more detail in the protocol
    12. Agree to comply with contraception requirements as defined in more detail in the protocol
    E.4Principal exclusion criteria
    1. For Cohort 2, subjects must not have autoimmune disease, medical conditions requiring systemic immunosuppression, prior stem cell transplant, or active infection with HBV or HCV
    2. Concurrent anticancer treatment such as chemotherapy, cytoreductive therapy, immune therapy, or cytokine therapy within 28 days or approximately 5 half-lives, whichever is shorter, prior to the first dose of KRT-232
    3. Radiation therapy within 2 weeks prior to the first dose of KRT-232
    4. Toxicity from prior radiation therapy that has not resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade 0 or Grade 1 (with the exception of Grade 2 alopecia)
    5. Participation in another interventional clinical trial within the past 4 weeks of the first dose of KRT 232 (participation in observational studies is permitted)
    6. Patients previously treated with MDM2 antagonist therapies or p53-directed therapies
    7. Women who are pregnant or breastfeeding
    8. History of major organ transplant
    9. Subjects with known central nervous system (CNS) metastases that are previously untreated
    10. Uncontrolled intercurrent illness including, but not limited to, acute hepatitis A; known history of human immunodeficiency virus (HIV)-positive; clinically significant cardiac disease (New York Heart Association Class III or IV); symptomatic congestive heart failure; unstable angina pectoris; ventricular arrhythmia; or psychiatric illness/social situations that would limit compliance with study requirements
    11. Subjects with clinically significant bacterial, fungal, parasitic, or viral infection that requires therapy. Subjects with acute bacterial infections requiring antibiotic use should delay screening/ enrollment until the course of antibiotic therapy has been completed.
    12. Other malignancy within the last 3 years, other than chronic lymphocytic leukemia (CLL), curatively
    treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, organ-confined or
    treated nonmetastatic prostate cancer with normal prostate-specific antigen, in situ breast carcinoma after complete surgical resection, or superficial transitional cell bladder carcinoma. Patients with CLL must not in the opinion of the investigator require or be receiving any treatment for their CLL in order to be eligible.
    13. Grade 2 or higher QTc prolongation (>480 milliseconds per NCI-CTCAE criteria, version 5.0)
    14. Known hypersensitivity or contraindications to any of the study drugs, required prophylaxes or their excipients
    E.5 End points
    E.5.1Primary end point(s)
    - Cohort 1 Part 1: Safety Review Committee (SRC) will determine recommended phase 2 dose (RP2D) for expansion based on safety and tolerability of each arm.
    - Cohort 1 Part 2: Objective Response Rate (ORR) as assessed per RECIST criteria version 1.1
    - Cohort 2 Part 1: Dose Limiting toxicity (DLT) will be used to establish the Maximum Tolerated Dose (MTD) of KRT-232 in combination with avelumab. SRC will determine the RP2D based on the safety of combination of KRT-232 with avelumab.
    - Cohort 2 Part 2: ORR will be assessed per RECIST criteria version 1.1
    - Cohort 3: ORR as assessed per RECIST criteria version 1.1 based on independent review committee (IRC) review of tumor assessments.
    - Cohort 4: ORR as assessed per RECIST criteria version 1.1 based on IRC review of tumor assessments.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Response Assessment: Response to KRT-232 treatment will be determined by the investigator according to RECIST criteria version 1.1. Target and non-target lesions will be assessed at Screening and followed throughout the study at protocol-specified time points. Response assessments will be performed at Week 5, Week 10, Week 15, Week 20, Week 25, Week 30 and thereafter every 12 weeks until disease progression. Response assessments should be performed at the specified time points independent of cycle visit or treatment modifications. For Cohorts 3 and 4, suspected progression must be confirmed by the IRC prior to treatment discontinuation.
    E.5.2Secondary end point(s)
    - Cohort 3: ORR as assessed per RECIST criteria version 1.1 based on investigator assessment.
    - Cohort 4: ORR as assessed per RECIST criteria version 1.1 based on investigator assessment.
    - Median DoR (Kaplan-Meier estimate) among subjects who achieve a response from the first observation of response to disease progression per IRC or investigator assessment, or death.
    - Median time from the first study dose to disease progression per IRC or investigator assessment, or death and landmark PFS rate (%)(Kaplan-Meier estimate)
    - Median time from the first study dose to death (Kaplan-Meier estimate) and landmark survival rate (%)
    - CBR is defined among subjects who achieve PR, CR or stable disease that lasts at least 10 weeks, per IRC or investigator assessment.
    - Analyses of the safety endpoints will include the following measurements or assessments: physical
    examinations, laboratory tests, and AEs that led to KRT-232 dose reductions, interruptions or discontinuations, AEs, serious AEs (SAEs), ECGs, vital signs
    - KRT-232 and acyl glucuronide metabolite (M1) PK parameters, including but not limited to, maximum
    observed concentration (Cmax), minimum observed concentration (Cmin), area under the plasma concentration-time curve (AUC), and terminal elimination half-life (t1/2z)
    E.5.2.1Timepoint(s) of evaluation of this end point
    DoR: Time from documentation of response until disease progression per IRC or investigator assessment, or death.
    PFS: Time from initial treatment until disease progression per IRC or investigator assessment, or death.
    OS: Time from initial treatment until death
    Vital signs: Day 1 of each cycle
    ECOG performance status: Day 1 of each cycle as per ECOG performance status scale
    ECG Triplicate: Cycle 1 Day 1, Cycle 3 Day 1, Cycle 6 Day 1, Cycle 9 Day 1, and every 3rd cycle thereafter (21 D Cycle)
    ECG Triplicate: Cycle 1 Day 1, Cycle 3 Day 1, Cycle 6 Day 1, and every 3rd cycle thereafter (28 D Cycle)
    Hematology: Cycle 1, 2, and 3: Days 1, 8, 15, 22 (for 28 D Cycle); Cycle 4 and beyond on Day 1 of each cycle
    AEs: Every visit
    Blood for PK: At time points specified in Appendix I of protocol
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    Phase 1b/2, Open-Label Study
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial4
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned11
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA12
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    United States
    France
    Germany
    Italy
    Spain
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The study will be considered complete 1 year after the last subject is enrolled in the study, at which time subjects who remain on study treatment will be evaluated for eligibility to enroll in a rollover study.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 87
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 88
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state15
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 125
    F.4.2.2In the whole clinical trial 175
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Subjects who achieve a response (CR or PR by RECIST criteria version 1.1) will be followed until disease progression, regardless of whether they are on study drug treatment or not. Subjects who stop KRT-232 and start on a new anti-MCC therapy will no longer be followed for efficacy outcomes and will enter long-term follow-up for survival only.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2021-01-05
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-12-30
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2023-09-28
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