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    Summary
    EudraCT Number:2011-004103-20
    Sponsor's Protocol Code Number:INO-VT-464-CL-001
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2011-08-31
    Trial results View 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 ConcernedUK - MHRA
    A.2EudraCT number2011-004103-20
    A.3Full title of the trial
    A Phase 1/2 Open-Label Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Seviteronel in Subjects with Castration-Resistant Prostate Cancer
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study of the safety, pharmacokinetics and effects of seviteronel in men with prostate cancer that does not respond to hormone treatment
    A.4.1Sponsor's protocol code numberINO-VT-464-CL-001
    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 SponsorInnocrin Pharmaceuticals, 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 supportInnocrin Pharmaceuticals, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationDLRC Ltd
    B.5.2Functional name of contact pointPhilippe Huchon
    B.5.3 Address:
    B.5.3.1Street AddressExeter House, 1 Amor Way, Dunham's Lane
    B.5.3.2Town/ cityLetchworth Garden City
    B.5.3.3Post codeSG6 1UG
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number00441462372330
    B.5.5Fax number00441462372227
    B.5.6E-mailphilippe.huchon@dlrc.co.uk
    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 nameINO-464
    D.3.2Product code INO-464
    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 INNSeviteronel
    D.3.9.1CAS number 1375603-40-9
    D.3.9.2Current sponsor codeINO-464
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number75
    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 nameINO-464
    D.3.2Product code INO-464
    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 INNSeviteronel
    D.3.9.1CAS number 1375603-40-9
    D.3.9.2Current sponsor codeINO-464
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    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
    Castration-resistant prostate cancer (CRPC)
    E.1.1.1Medical condition in easily understood language
    Cancer of the prostate gland that has become hormone resistant
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10060862
    E.1.2Term Prostate cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objectives of the Phase 1 portion of the study are:
    To determine the safety and tolerability of seviteronel in “treatment naïve” (not treated with previous abiraterone or enzalutamide) subjects with CRPC.

    The primary objectives of the Phase 2 portion of the study are:
    •Proportion of subjects who have ≥50% PSA decline at any time on study from the start of treatment with seviteronel
    •Median time to radiographic disease progression evaluated by computerized tomography (CT scan) or magnetic resonance imaging (MRI) and radionuclide bone scans by RECIST 1.1 or Prostate Cancer Clinical Trials Working Group 3 (PCWG3; Scher et al, 2016)
    E.2.2Secondary objectives of the trial
    The secondary objectives of the Phase 1 portion of the study are:
    •Pharmacokinetics (PK) of seviteronel
    •Pharmacodynamics (PD) of seviteronel based on changes in prostate-specific antigen (PSA) levels from baseline
    •PD of seviteronel based on radiographic and clinical tumor responses using Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as modified in the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) (Scher et al, 2008) in subjects with evaluable and/or measurable metastases
    •PD of seviteronel based on adrenal, pituitary, and testicular hormone level responses.

    The secondary objectives of the Phase 2 portion of the study are:
    •Radiographic response rate by RECIST 1.1 & PCWG3
    •Safety of seviteronel with or without concurrent glucocorticoid administration
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1.≥18 years of age
    2.Able to provide written informed consent or have their legal representatives provide written informed consent
    3.Documented histological or cytological evidence of adenocarcinoma of the prostate. Subjects whose pathology reports are no longer available may be enrolled if, in the opinion of the investigator, the subject has a clinical course consistent with prostatic adenocarcinoma
    4.ECOG Performance Status of 0 or 1
    5.Undergone orchiectomy, or have ongoing LHRH analogue therapy prior to C1D1. Subjects on LHRH analogues should remain on these agents for the duration of the study
    6.Castrate levels of testosterone ≤50 ng/dl (or 1.7 nmol/L) and have progressive disease at Screening defined as PSA rise determined by a minimum of 2 rising PSA values ≥ 1 week between each assessment. The PSA value at the Screening visit must be ≥ 2ng/mL with or without:
    •Soft tissue disease progression defined by RECIST 1.1 at Screening or ≤ 28 days of C1D1. Measurable disease is not required for entry. Lymph nodes ≥ 1.5cm (short axis) are considered measurable disease (PCWG3, Scher 2016)
    •Bone disease progression defined by ≥2 new lesions on bone scan at Screening, or ≤ 28 days of C1D1
    7.Have received abiraterone and/or enzalutamide. Subject must have received either abiraterone or enzalutamide for ≥12 weeks. Other second generation CYP17 inhibitors/androgen receptor antagonists including but not limited to TAK-700 (orteronel), TOK-001 (galeterone) may have been taken in place of abiraterone and ARN-509 (apalutamide) may have been taken in place of enzalutamide.
    8.Adequate hematopoietic function as evidenced by:
    •WBC ≥ 3,000/μl
    •ANC ≥ 1,500/μl
    •Platelet count ≥ 100,000/μl
    •HGB ≥ 10 g/dl and not transfusion dependent
    9.Adequate liver function, including all the following:
    •Total serum bilirubin ≤2.0 x ULN unless the subject has documented Gilbert syndrome;
    •Aspartate and alanine aminotransferase (AST & ALT) ≤3.0 x ULN or ≤5.0 x ULN if subject has liver metastasis;
    •Alkaline phosphatase ≤3.0 x ULN or ≤5 x ULN in case of bone metastasis and/or hepatic metastasis
    10.Subjects must have adequate renal function as evidenced by a serum creatinine of ≤2.0 mg/dl
    11.Potassium (K+) ≥3.5 mEq/l
    12.Subject and his female partner who is of childbearing potential must use 2 acceptable methods of birth control (one of which must include a condom as a barrier method of contraception) starting at Screening and continuing throughout the study period and for 3 months after final study drug administration
    13.Able to swallow study medication
    14.Able to comply with study requirements
    E.4Principal exclusion criteria
    1.Received sipuleucel-T (Provenge ®) treatment within 28 days of C1D1
    2.Received 5-alpha reductase inhibitors such as finasteride (PROSCAR®, PROPECIA®), or dutasteride (AVODART®) within 28 days of C1D1
    3.Received any investigational agent ≤ 28 days of C1D1
    4.Received palliative radiotherapy ≤ 2 weeks of C1D1
    5.Symptomatic CNS metastases
    6.History of another invasive malignancy ≤ 3 years of C1D1
    7.A QTcF interval of > 470 msec; if the Screening ECG QTcF interval is > 470 msec, it may be repeated, and if repeat < 470 msec, the subject may be enrolled
    8.Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes, second degree or third degree atrioventricular heart block without a permanent pacemaker in place)
    9.Started a bone modifying agent (e.g. bisphosphonates, denosumab) ≤ 28 days of C1D1 (note: ongoing bone modifying agents administered > 28 days are allowed)
    10.Any medical condition that could preclude subject participation in the study, pose an undue medical hazard, or which could interfere with study results
    11.Class III or IV Congestive Heart Failure (CHF) as defined by the New York Heart Association (NYHA) functional classification system within the previous 6 months
    12.A history of loss of consciousness or transient ischemic attack ≤ 12 months of C1D1
    13.Known active HIV, Hepatitis B, or Hepatitis C infections
    14.Known or suspected hypersensitivity to seviteronel, or any components of the formulation
    15.Any other condition which in the opinion of the investigator would preclude participation in the study
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint of the study is the maximum tolerated dose (MTD) of INO-464 when administered orally to patients with castration-resistant prostate cancer. The MTD is defined as the highest dose-level of VT-464 in Phase 1 at which the incidence of dose-limiting toxicity (DLT) was less than 33% within the Single-Dose stage of the study or the first continuous 28-day dosing cycle.
    E.5.1.1Timepoint(s) of evaluation of this end point
    A dose-limiting toxicity (DLT) is defined as any Grade 3 or greater adverse event possibly/probably/definitely related to INO-464 from the first dose of VT-464 through the first continuous, 28-day dosing cycle (Cycle 1). The occurrence of DLTs in each cohort of Phase 1 will be used to determine the MTD. DLTs will be reported by the study investigators to the sponsor as they occur.
    E.5.2Secondary end point(s)
    Secondary Objectives Phase 1
    To describe the:
    • Pharmacokinetics (PK) of seviteronel
    • Pharmacodynamics (PD) of seviteronel based on changes in prostate-specific antigen (PSA) levels from baseline
    • PD of seviteronel based on radiographic and clinical tumor responses using Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as modified in the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) (Scher et al, 2008) in subjects with evaluable and/or measurable metastases
    • PD of seviteronel based on adrenal, pituitary, and testicular hormone level responses
    Secondary Objectives Phase 2
    To determine the:
    • Radiographic response rate by RECIST 1.1 & PCWG3
    • Safety of seviteronel with or without concurrent glucocorticoid administration
    E.5.2.1Timepoint(s) of evaluation of this end point
    PK: Plasma samples on Single-dose stage (Phase 1 only) Day 1 Predose, .5, 1, 2, 4, 6, 8, and 24 hours postdose; Cycle 1, Day 1 Predose, .5, 1, 2, 4, 6, and 8 hours postdose; Cycle 1, Day 14 predose; Cycle 2, Day 1 Predose, .5, 1, 2, 4, 6, and 8 hours postdose; and Day 1 of all subsequent cycles.
    PD: PSA will be obtained at Screening, on Cycle 1, Days 1 and 14 and at all subsequent study visits. Extent of metastatic disease will be evaluated at Screening and on Day 1 of all 28-day cycles.
    An endocrine panel will be obtained on Single-dose stage Day 1 (Phase 1 only) Pre-dose and 2, 4, and 24 hours postdose; Cycle 1, Day 1 Pre-dose; Cycle 2, Day 1 Pre-dose and 2, 4, and 8 hours postdose; all subsequent 28-day cycles Day 1 Pre-dose and 2, 4, and 8 hours postdose; and at the final visit.
    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 No
    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 No
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans Yes
    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 No
    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 No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA2
    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
    Greece
    Switzerland
    United States
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months8
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months8
    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: 31
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 123
    F.2 Gender
    F.2.1Female No
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    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 state35
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 40
    F.4.2.2In the whole clinical trial 154
    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)
    The study protocol does not indicate any provisions for post-treatment care or therapy.
    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 Decision2011-10-05
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2011-10-13
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2019-01-23
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