Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43874   clinical trials with a EudraCT protocol, of which   7293   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2020-004752-16
    Sponsor's Protocol Code Number:BP40283
    National Competent Authority:Croatia - MIZ
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2023-04-06
    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 ConcernedCroatia - MIZ
    A.2EudraCT number2020-004752-16
    A.3Full title of the trial
    PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO ASSESS THE EFFECTS OF RO6889450 (RALMITARONT) IN PATIENTS WITH SCHIZOPHRENIA OR SCHIZOAFFECTIVE DISORDER AND NEGATIVE SYMPTOMS
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase II Study to Evaluate the Effects of RO6889450 (Ralmitaront) in Patients with Schizophrenia or Schizoaffective Disorder and Negative Symptoms
    A.4.1Sponsor's protocol code numberBP40283
    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 SponsorF. Hoffmann-La Roche Ltd
    B.1.3.4CountrySwitzerland
    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 supportF. Hoffmann-La Roche Ltd
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationF. Hoffmann-La Roche Ltd
    B.5.2Functional name of contact pointTrial Information Support Line-TISL
    B.5.3 Address:
    B.5.3.1Street AddressGrenzacherstrasse 124
    B.5.3.2Town/ cityBasel
    B.5.3.3Post code4070
    B.5.3.4CountrySwitzerland
    B.5.6E-mailglobal.rochegenentechtrials@roche.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 nameralmitaront
    D.3.2Product code RO6889450
    D.3.4Pharmaceutical form Capsule, hard
    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 INNRalmitaront
    D.3.9.2Current sponsor codeRO6889450
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    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 placeboCapsule, hard
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Schizophrenia or schizoaffective disorder
    E.1.1.1Medical condition in easily understood language
    Schizophrenia is a serious mental disorder in which people interpret reality abnormally. Schizophrenia may result in hallucinations, delusions, and disordered behavior that impairs daily functioning
    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 21.1
    E.1.2Level PT
    E.1.2Classification code 10039621
    E.1.2Term Schizoaffective disorder
    E.1.2System Organ Class 10037175 - Psychiatric disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10039626
    E.1.2Term Schizophrenia
    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
    • Part A: To compare the efficacy of 150 milligram (mg) once daily (QD) of RO6889450 as monotherapy with placebo on negative symptoms in patients with schizophrenia or schizoaffective disorder
    • Part B: To compare the efficacy of 150 mg or 300 mg QD of RO6889450 as add-on therapy with placebo on negative symptoms in patients with schizophrenia or schizoaffective disorder
    E.2.2Secondary objectives of the trial
    • To compare the effect of RO6889450 with placebo on clinical global impression severity (CGI-S) and clinical global impression change (CGI-I) (overall and negative symptoms)
    • To compare the effect of RO6889450 with placebo on symptoms of schizophrenia or schizoaffective disorder as assessed with the positive and negative syndrome scale (PANSS), brief negative symptom scale (BNSS) and defeatist performance attitude scale (DPAS)
    • To compare the safety and tolerability of 12 weeks of treatment with RO6889450 as monotherapy (Part A) or add-on therapy with placebo (Part B)
    • To evaluate the pharmacokinetics (PK) of RO6889450 and RO6889450-derived metabolite(s)
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • Male or female participants aged 18-55 years (inclusive)
    • Patients with a diagnostic and statistical manual of mental disorders, fifth edition (DSM-5) diagnosis of schizophrenia or schizoaffective disorder as confirmed by the mini international neuropsychiatric interview (MINI)
    • Part B only: Stable treatment with a dopamine 2 receptor (D2)/serotonin 2A receptor (5HT2A) antagonists or pure D2 antagonist(s), or a D2 partial agonist for a minimum of six months and receiving no more than two antipsychotics. Antipsychotic regimen: participants must be on a "primary" antipsychotic and may be on a secondary antipsychotic. The secondary antipsychotic dose must be equal to or less than the equivalent dose of the primary antipsychotic. The sum of the primary and secondary antipsychotics must be <=6 mg of risperidone equivalents
    • Medically stable during the prior three months. Medication changes (other than antipsychotics) in the three months prior to screening may be acceptable if, in the opinion of the Investigator, the change of medication does not affect the participant's medical stability throughout the duration of the study
    • Participant is outpatient with no psychiatric hospitalizations within the prior six months (hospitalization for social management within this time is acceptable)
    • PANSS-negative symptom factor score (PANSS-NSFS) score of 18 or higher
    • Rating on items of the PANSS: less than 5 on G8 (uncooperativeness), P1 (delusions), P3 (hallucinations), P4 (excitement/hyperactivity), and P6 (suspiciousness/persecution); and less than 4 on P7 (hostility) and G14 (poor impulse control)
    • Has an informant who is considered reliable by the Investigator to provide support to the participant and to help ensure compliance with study visits and protocol procedures; who preferably is also able to provide input helpful for completing study rating scales and is in regular contact with the participant in order to be able to alert the Investigator of worsening signs and symptoms for the participant
    • Body mass index (BMI) between 18 and 40 kilograms per square metre (kg/m^2) inclusive
    • A woman is eligible to participate if she is not pregnant (negative serum pregnancy test at screening and negative urine pregnancy test at baseline), not breastfeeding, not a woman of childbearing potential (WOCBP), or WOCBP who agrees to remain abstinent or use acceptable contraceptive methods during the treatment period and for at least 28 days after the last dose of study drug
    E.4Principal exclusion criteria
    • Part A only: Confirmed suicidal behavior based on Investigator judgment or violent behavior resulting in injury or property damage in the prior five years. A history prior to the last five years requires approval by the patient review committee (PRC) on a case-by-case basis
    • Part A only: Lifetime history of homicidal behavior
    • Moderate to severe substance use disorder within six months (excluding nicotine) as defined by DSM-5
    • Any Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) CGI subscore greater or equal to 3
    • Other current DSM-5 diagnosis (e.g., bipolar disorder, major depressive disorder)
    • PANSS item G6 (depression) greater than or equal to 5
    • Significant risk of suicide or harming him- or herself or others according to the Investigator’s judgment
    • A prior or current general medical condition that might be impairing cognition or other psychiatric functioning (e.g., migraine headaches requiring prophylactic treatment, head trauma, dementia, seizure disorder, stroke; or neurodegenerative, inflammatory, infectious, neoplastic, toxic, metabolic, endocrine conditions)
    • Positive result at screening for hepatitis B surface antigen (HBsAg), hepatitis C (hepatitis C antibody), or human immunodeficiency virus (HIV)-1 and -2. hepatitis C (HCV) antibody positive patients are eligible if HCV ribonucleic acid (RNA) is negative
    • Tardive dyskinesia that is moderate to severe or requires treatment
    • History of neuroleptic malignant syndrome
    • Average triplicate QTcF interval greater than 450 millisecond (msec) for males and 470 msec for females or other clinically significant abnormality on screening electrocardiogram (ECG) based on centralized reading
    • Clinically significant abnormalities in laboratory safety test results (including hepatic and renal panels, complete blood count, chemistry panel, coagulation, and urinalysis)
    o Aspartate transaminase (AST), alanine transaminase (ALT) >2 X upper limit of normal (ULN)
    o Total bilirubin >1.5 ULN with the exception of Gilbert syndrome
    o Serum creatinine >1.5 ULN
    • Significant or unstable physical condition that in the Investigator’s judgment might require a change in medication or hospitalization during the study
    • On more than one antidepressant (trazodone used at a dose up to and including 50 mg at bedtime is considered a hypnotic agent), or if on one antidepressant, a change in dose within 28 days prior to screening
    • History of clozapine treatment: Clozapine treatment for schizophrenia within 5 years prior to screening is prohibited. Low dose (< 200 mg/day) usage is permitted for insomnia or dyskinesia only, but not within 12 months prior to screening
    • History of treatment with electroconvulsive therapy (ECT)
    • Concomitant use of prohibited medications
    • Positive urine drug screen for amphetamines, methamphetamines, opiates, buprenorphine, methadone, cannabinoids, cocaine and barbiturates. In case of uncertain or questionable results, the urine drug screen may be repeated once during the screening period to confirm eligibility
    • Receipt of an investigational drug within 28 days or five times the half-life of the investigational drug (whichever is longer) before the first study drug administration
    • Donation of blood over 400 milliliter (mL) within three months prior to screening
    • Diagnosis of corona virus (COVID-19) infection (confirmed or presumptive) 4 weeks prior to Screening or during Screening. Participants can be re-screened after 4 weeks of full recovery in addition to Investigator and/or institutional approval to enroll
    • Part A only: Participant will be excluded if unable to taper off an antipsychotic in the one week prior to baseline (e.g., in the case of symptom exacerbation or antipsychotics with a longer half-life)
    • Female participants who are of childbearing potential must have a negative pregnancy test result at baseline
    E.5 End points
    E.5.1Primary end point(s)
    1. Change from baseline at Week 12 in the BNSS avolition/apathy sub-score (sum of items “behavior” and “internal experience”)
    E.5.1.1Timepoint(s) of evaluation of this end point
    1. Baseline and Week 12
    E.5.2Secondary end point(s)
    1. Change from baseline in CGI-S overall scores
    2. Change from baseline in CGI-S negative symptoms scores
    3. Change from baseline in CGI-I overall scores
    4. Change from baseline in CGI-I negative symptoms scores
    5. Change from baseline in PANSS total scores
    6. Change from baseline in PANSS symptom factor scores
    7. Change from baseline in BNSS total scores
    8. Change from baseline in BNSS Symptom Factor scores
    9. Change from baseline in DPAS scores
    10. Incidence, nature, and severity of adverse events (AEs), serious AEs (SAEs), and of treatment discontinuations due to AEs
    11. Change from baseline in vital signs
    12. Change from baseline in ECG intervals
    13. Incidence of laboratory abnormalities, based on hematology, clinical chemistry, coagulation and urinalysis test results
    14. Change from baseline in Columbia-suicide severity rating scale (C-SSRS)
    15. Change from baseline in extrapyramidal symptom rating scale, abbreviated (ESRS-A)
    16. Steady state area under the curve (AUCss) and Maximum concentration (Cmax) of RO6889450, and, if feasible, of RO6889450-derived metabolite(s) at indicated time points
    17. Concentration of RO6889450 and RO6889450-derived metabolite per time point
    E.5.2.1Timepoint(s) of evaluation of this end point
    1-15. Baseline to Week 12
    16-17. Day 7, 14, 28, 42, 56, 84, and 112
    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 No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Tolerability
    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 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 concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA10
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA Yes
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Japan
    United States
    Ukraine
    Serbia
    Bulgaria
    Croatia
    Poland
    Spain
    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
    Last participant last observation (LPLO) expected to occur approximately 28 days after the last participant’s last dose.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years5
    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: 220
    F.1.3Elderly (>=65 years) No
    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 state50
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 50
    F.4.2.2In the whole clinical trial 220
    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 Sponsor does not intend to provide RO6889450 or other study interventions to participants after conclusion of the study or any earlier participant withdrawal.
    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 Decision2023-03-28
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-11-24
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2023-05-08
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Wed May 08 21:48:25 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA