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    Summary
    EudraCT Number:2018-000060-29
    Sponsor's Protocol Code Number:RAP-MD-30
    National Competent Authority:Slovakia - SIDC (Slovak)
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2018-10-24
    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 ConcernedSlovakia - SIDC (Slovak)
    A.2EudraCT number2018-000060-29
    A.3Full title of the trial
    A Randomized, Double-blind, Placebo-controlled, Multicenter Study of Rapastinel as Monotherapy in Patients with Major Depressive Disorder
    Randomizované, dvojito zaslepené, placebom kontrolované, multicentrické klinické skúšanie rapastinelu ako monoterapie u pacientov s veľkou depresívnou poruchou
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Randomized, Double-blind, Placebo-controlled, Multicenter Study of Rapastinel as Monotherapy in Patients with Major Depressive Disorder
    A.4.1Sponsor's protocol code numberRAP-MD-30
    A.5.4Other Identifiers
    Name:INDNumber:136,870
    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 SponsorAllergan Ltd.
    B.1.3.4CountryUnited Kingdom
    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 supportAllergan Sales LLC
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAllergan Ltd.
    B.5.2Functional name of contact pointEU Global Clinical Trial Management
    B.5.3 Address:
    B.5.3.1Street AddressMarlow International, The Parkway
    B.5.3.2Town/ cityMarlow, Buckinghamshire
    B.5.3.3Post codeSL7 1YL
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number441628494444
    B.5.6E-mailML-RAP-MD-30@allergan.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 namerapastinel
    D.3.2Product code AGN-241659 (previously GLYX-13)
    D.3.4Pharmaceutical form Solution for injection in pre-filled syringe
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous bolus use (Noncurrent)
    Intravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNRAPASTINEL
    D.3.9.2Current sponsor codeAGN-241659
    D.3.9.4EV Substance CodeSUB192215
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number75 to 150
    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 namerapastinel
    D.3.2Product code AGN-241659 (previously GLYX-13)
    D.3.4Pharmaceutical form Solution for injection in pre-filled syringe
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous bolus use (Noncurrent)
    Intravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNRAPASTINEL
    D.3.9.2Current sponsor codeAGN-241659
    D.3.9.4EV Substance CodeSUB192215
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number75 to 150
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for injection in pre-filled syringe
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Major depressive disorder
    E.1.1.1Medical condition in easily understood language
    Severe depression
    E.1.1.2Therapeutic area Psychiatry and Psychology [F] - Mental Disorders [F03]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10057840
    E.1.2Term Major depression
    E.1.2System Organ Class 10037175 - Psychiatric disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the efficacy of rapastinel (450 mg IV) versus placebo and rapastinel (225 mg IV) versus placebo in the treatment of MDD, as measured by the change from baseline Montgomery-Asberg Depression Rating Scale (MADRS) total score at end of treatment (end of week 6)
    E.2.2Secondary objectives of the trial
    To evaluate the efficacy of rapastinel (450 mg IV) versus placebo and rapastinel (225 mg IV) versus placebo in the treatment of MDD, as measured by the change from baseline MADRS total score at 1 day post-first dose of treatment

    To evaluate the safety and tolerability of rapastinel (450 mg IV) versus placebo and rapastinel (225 mg IV) versus placebo in the treatment of MDD, as evaluated by adverse events (AEs), clinical laboratory measures, electrocardiograms (ECGs), vital signs, and Columbia-Suicide Severity Rating Scale (C-SSRS)
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Pharmacogenetic
    Blood samples will be collected at any time between Visits 2 and 9, inclusive, to determine individual genotype status and for pharmacogenetic biobanking. Participation is optional.

    Pharmacokinetic
    Sparse pharmacokinetic (PK) samples will be taken from patients consenting to optional PK sampling to determine plasma concentrations of rapastinel using a validated bioanalytical method.
    E.3Principal inclusion criteria
    Criteria to be assessed at Visit 1 (Screening)
    1. Written informed consent, obtained from the patient before the initiation of any study-specific procedures
    2. Male or female outpatients, 18 to 75 (inclusive) years of age at Visit 1
    3. Meet DSM-5 criteria for MDD (based on confirmation from the MINI), with a current major depressive episode of at least 8 weeks and not exceeding 18 months in duration at Visit 1
    4. Have a minimum score of 26 on the rater-administered MADRS and a minimum score of 24 on the computer-administered MADRS at Visit 1
    5. Have a difference of no greater than 7 points between the rater-administered MADRS and computer-administered MADRS at Visit 1
    6. Have a CGI-S score ≥ 4 at Visit 1
    7. Treatment naive in the present episode or have failed to respond (< 50% reduction in depressive symptoms as documented using the ATRQ) to 1 to 3 ADTs given at adequate doses (as defined by the ADT package insert) and duration of > 8 weeks during the present episode
    8. Normal physical-examination findings, clinical-laboratory test results, and ECG results from Screening (Visit 1) or abnormal results that are determined to be not clinically significant by the investigator and documented as such in the eCRF
    9. If female of childbearing potential, have a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test at Visit 1
    10. Ability to follow study instructions and likely to complete all required visits

    Criteria to be assessed at Visit 2 (Baseline)
    11. Have a minimum score of 26 on the rater-administered MADRS and a minimum score of 24 on the computer-administered MADRS at Visit 2
    12. Have a difference of no greater than 7 points between the rater-administered MADRS and computer-administered MADRS at Visit 2
    13. Have a CGI-S score ≥ 4 at Visit 2
    E.4Principal exclusion criteria
    1. DSM-5–based diagnosis of any disorder other than MDD that was the primary focus of treatment within 6 months before Visit 1.
    2. Lifetime history of meeting DSM-5 criteria for:
    a. Schizophrenia spectrum or other psychotic disorder
    b. Bipolar or related disorder
    c. Major neurocognitive disorder
    d. Neurodevelopmental disorder of greater than mild severity or of a severity that impacts the patient’s ability to consent, follow study directions, or otherwise safely participate in the study
    e. Dissociative disorder
    f. Posttraumatic stress disorder
    g. MDD with psychotic features
    3. History of meeting DSM-5 criteria for alcohol or substance use disorder (other than nicotine or caffeine) within the 6 months before Visit 1
    4. DSM-5–based diagnosis of any personality disorder of sufficient severity to interfere with participation in this study in the opinion of the investigator
    5. History of:
    a. Inadequate response to electroconvulsive therapy (ECT), a monoamine oxidase inhibitor, ketamine, or adjunctive treatment with an antipsychotic
    b. Treatment with clozapine or any depot antipsychotic
    c. ECT, vagus nerve stimulation, transcranial magnetic stimulation, or any experimental central nervous system treatment during the current episode or in the 6 months before Visit 1 (whichever is longer)
    d. Tardive dyskinesia, serotonin syndrome, or neuroleptic malignant syndrome
    e. Intolerance or hypersensitivity to rapastinel
    6. Having received:
    a. Anticonvulsant/mood stabilizer, within 1 year prior to Visit 1
    b. Antipsychotic in the current episode, with the exception of quetiapine given for insomnia ≤ 50 mg/day provided it can be safely discontinued prior to Visit 2
    c. Combination therapy of 2 or more ADTs in the current episode if given for depression at adequate dose and duration
    d. ADT augmentation agent in the current episode
    7. Positive result at Visit 1 from the urine drug screen (UDS) test for any prohibited medication. Exception: patients with a positive UDS at Visit 1 for opiates, cannabinoids or episodic use of benzodiazepines may be allowed as described more detailed in the protocol
    8. Suicide risk, as determined by meeting any of the following criteria:
    a. A suicide attempt within the past year
    b. Significant risk, as judged by the investigator, based on the psychiatric interview or information collected in the C-SSRS at Visit 1 or Visit 2
    c. MADRS Item 10 score ≥ 5 at Visit 1 or Visit 2 on the MADRS
    9. At imminent risk of injuring self or others or causing significant damage to property, as judged by the investigator
    10. Requiring concomitant treatment with any of the prohibited medications, supplements, or herbal products listed in Appendix III
    11. Prior participation in any investigational study of rapastinel/GLYX-13
    12. Initiation or termination of psychotherapy for depression within the 3 months preceding Visit 1, or plans to initiate, terminate, or change such therapy during the course of the study
    13. Ongoing treatment with phototherapy, or termination of phototherapy within 1 month of Visit 1
    14. Weight < 40 kg or > 125 kg at screening
    15. Females who are pregnant, breastfeeding, or planning to become pregnant or breastfeed during the study
    16. Females of childbearing potential and male partners of females of childbearing potential, not using a reliable means of contraception
    17. Any cardiovascular disease that is clinically significant, unstable, or decompensated
    18. Heart rate (supine) of ≤ 45 bpm or ≥ 120 bpm, or any heart rate that is clinically symptomatic at Visit 1 or Visit 2 based upon vital signs
    19. Any systolic and/or diastolic blood pressure (BP) that is symptomatic or clinically significant in the opinion of the investigator
    20. History of congenital QTc prolongation or QTc prolongation (screening ECG with QTcF ≥ 450 msec for men and QTcF ≥ 470 msec for women)
    21. Hypo- or hyperthyroidism, unless stabilized on appropriate pharmacotherapy with no change in dosage for at least 1 month before Visit 1
    22. History of seizure disorder, stroke, significant head injury, tumor of the central nervous system, or any other condition that predisposes to seizure
    23. Known human immunodeficiency virus (HIV) infection
    24. Positive hepatitis C antibody on screening, with the exception of patients for whom the reflex HCV RNA test is negative
    25. Positive test for hepatitis B surface antigen and/or hepatitis B core antibody immunoglobulin M
    26. Screening liver enzyme test (aspartate aminotransferase [AST] and/or alanine aminotransferase [ALT]) results > 2 times the upper limit of normal (ULN)
    27. Current enrollment in an investigational drug or device study or participation in such a study within 6 months of entry into this study
    28. Inability to speak, read, and understand the local language sufficiently to understand the nature of the study, to provide written informed consent, or to allow the completion of all study assessments
    E.5 End points
    E.5.1Primary end point(s)
    Change from baseline in MADRS total score at the end of the double-blind treatment period (end of Week 6)
    E.5.1.1Timepoint(s) of evaluation of this end point
    After 6 weeks of treatment
    E.5.2Secondary end point(s)
    Key secondary endpoint:
    Change from baseline in MADRS total score at 1 day after first dose of investigational product (IP)

    Other:
    • Change from baseline in MADRS at 7 days after first dose of treatment
    • Change from baseline in CGI-S at 1 and 7 days after first dose of treatment, and end of treatment
    • Rate of sustained responders during treatment
    • Rate of responders at 1 and 7 days after first dose of treatment, and end of treatment (end of Week 6)
    • Rate of sustained remitters during treatment
    • Rate of remitters at 1 and 7 days after first dose of treatment, and end of treatment (end of Week 6)
    • Time to first response
    • Time to first sustained response
    • Time to first remission
    • Time to first sustained remission
    • Change from baseline in Sheehan Disability Scale (SDS) at end of treatment
    E.5.2.1Timepoint(s) of evaluation of this end point
    Key secondary endpoint:
    Change from baseline in MADRS total score at 1 day after first dose of
    investigational product (IP)

    Additional endpoints:
    At each visit and the final analysis will be done at the end of the study
    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 No
    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) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    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 Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial3
    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 concerned6
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA24
    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
    Hungary
    Japan
    Poland
    Russian Federation
    Slovakia
    Ukraine
    E.8.7Trial has a data monitoring committee Yes
    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 years2
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months6
    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: 620
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 70
    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 state60
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 196
    F.4.2.2In the whole clinical trial 690
    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)
    After completing this study, all participants may have the option of continuing into the extension study with continued access to study drug provided the study is still open to enrollment. The study will be limited to a certain number of participants, so participation is not guaranteed.
    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 Decision2018-12-31
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-12-31
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2019-06-20
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