This Study Tests Whether BI 425809 Together With Brain Training Using a Computer Improves Mental Functioning in Patients With Schizophrenia

A Phase II Randomized, Double-blinded, Placebo-controlled Parallel Group Trial to Examine the Efficacy and Safety of BI 425809 Once Daily With Adjunctive Computerized Cognitive Training Over 12 Week Treatment Period in Patients With Schizophrenia

This is a study in adults with schizophrenia. The study tests whether a medicine called BI 425809 together with brain training improves mental abilities.

Participants take study medication once a day for 12 weeks. At the start of the study, the participants are put into 2 groups. It is decided by chance who gets into which group. One group gets BI 425809 tablets every day. The other group gets placebo tablets every day. Placebo tablets look like the BI 425809 tablets, but contain no medicine. During the study, all participants do brain training using a computer.

The doctors regularly test mental abilities of the participants. The results of the mental ability tests are compared between the groups. The doctors also check the general health of the patients.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Placebo; Drug: BI 425809

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Elizabeth Vale, South Australia, Australia, 5112
      • Lyell McEwin Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Medical Centre
    • Fitzroy, Victoria, Australia, 3065
      • St Vincent's Hospital Melbourne
    • Melbourne, Victoria, Australia, 3004
      • Monash Alfred Psychiatry Research Centre
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • University of Calgary
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4H4
      • BC Mental Health and Addictions Research Institute (University of British Columbia)
  • Ontario
    • Toronto, Ontario, Canada, M6J 1H4
      • Centre for Addiction and Mental Health (CAMH)
  • Quebec
    • Montreal, Quebec, Canada, H1N 3M5
      • IUSMM Institut Universitaire en Sante Mentale de Montreal
• France
  • Caen, France, 14033
    • CTR Esquirol
  • Dijon, France, 21079
    • HOP Dijon-Bourgogne
  • Douai, France, 59500
    • CAB Médical Psyché
  • Montpellier, France, 34295
    • HOP la Colombière
  • Nantes, France, 44093
    • HOP Saint-Jacques
  • Nice, France, 06000
    • HOP Pasteur
  • Paris, France, 75674
    • GHU Paris Psychiatrie et Neurosciences
  • Saint Priest en Jarez, France, 42270
    • HOP Nord
• New Zealand
  • Takpuna Auckland, New Zealand, 0622
    • North Shore Hospital, Takapuna
• United Kingdom
  • Cheltenham, United Kingdom, GL53 9DZ
    • The Fritchie Centre
  • Edinburgh, United Kingdom, EH10 5HF
    • Royal Edinburgh Hospital
  • Glasgow, United Kingdom, G51 4TF
    • Queen Elizabeth University Hospital
  • London, United Kingdom, SE5 8AZ
    • Maudsley Hospital
  • Oxford, United Kingdom, OX3 7JX
    • Warneford Hospital
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72209
      • Atria Clinical Research
    • Rogers, Arkansas, United States, 72758
      • Woodland Research Northwest
  • California
    • Encino, California, United States, 91436
      • Encino Hospital Medical Center
    • Garden Grove, California, United States, 92845
      • Collaborative Neuroscience Network, LLC (CNS)
    • Lemon Grove, California, United States, 91945
      • Synergy San Diego
    • Montclair, California, United States, 91763
      • Catalina Research Institute, LLC
    • Oakland, California, United States, 94607
      • Pacific Research Partners, LLC
    • Orange, California, United States, 92868
      • NRC Research Institute
    • Pico Rivera, California, United States, 90660
      • CNRI - Los Angeles
    • San Diego, California, United States, 92102
      • CNRI-San Diego, LLC
    • Torrance, California, United States, 90502
      • Collaborative Neuroscience Network, LLC (CNS)
  • Florida
    • Maitland, Florida, United States, 32751
      • Meridien Research
    • Miami, Florida, United States, 33136
      • University of Miami
    • Miami, Florida, United States, 33122
      • Premier Clinical Research Institute
    • Tallahassee, Florida, United States, 32308
      • Apalachee Center
    • West Palm Beach, Florida, United States, 33407
      • Jerome Golden Center for Behavioral Health
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Synexus
  • Illinois
    • Chicago, Illinois, United States, 60640
      • Uptown Research Institute
  • Louisiana
    • Lake Charles, Louisiana, United States, 70629
      • Lake Charles Clinical Trials LLC
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Cherry Health
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Center for Behavioral Medicine
  • New York
    • New York, New York, United States, 10017
      • Synexus Clinical Research US, Inc.
  • North Carolina
    • Raleigh, North Carolina, United States, 27608
      • UNC Center for Excellence in Community Mental Health, North Carolina Psychiatric Research Center
  • Ohio
    • Dayton, Ohio, United States, 45417
      • Midwest Clinical Research
  • Texas
    • Dallas, Texas, United States, 75231
      • FutureSearch Trials of Dallas, LP
    • Richardson, Texas, United States, 75080
      • Pillar Clinical Research, LLC
    • Richmond, Texas, United States, 77407
      • Office of Dr. Aqeel Hashmi, MD, PA
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Signed and dated written informed consent in accordance with ICH Harmonized Tripartite Guideline for Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial.
• Male or female patients who are 18-50 years (inclusive) of age at time of consent.

• Established schizophrenia (as per DSM-5) with the following clinical features:

  • Outpatient, with no hospitalization for worsening of schizophrenia within 3 months prior to randomization
  • Psychiatrically stable without symptom exacerbation within 3 months prior to randomization
  • PANSS score ≤ 5 on positive items P1, P3-P7 and ≤ 4 on positive item P2 at Visit 1, and confirmed at Visit 2

• Patients must be on stable antipsychotic treatment; also, current antipsychotic medications and concomitant anticholinergics, antiepileptics, lithium and allowed antidepressants must meet the criteria below:

  • Patients must take 1 and may take up to 2 antipsychotics (typical and/or atypical), except for clozapine
  • Patients must be stable on current antipsychotics, anticholinergics, antiepileptics, lithium and allowed antidepressants for at least 3 months prior to randomization and be on current dose for at least 30 days prior to randomization o Patients on Long-Acting Injectable (LAI) antipsychotics should be on the same medication and dose for at least 3 months prior to randomization
• Women of childbearing potential (WOCBP)2 must be ready and able to use highly effective methods of birth control per Non-Clinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals (ICH M3 (R2)) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in Section 4.2.2.3. Such methods should be used throughout the trial, and for a period of at least 35 days after last trial drug intake, and the patient must agree to periodic pregnancy testing during participation in the trial.
• Patients must demonstrate their ability to properly use the CCT device and program, as well as be compliant with CCT run-in (defined as completing at least 2 hours per week for two weeks, totalling 4 hours CCT, during the screening period)3.
• Patients must be able to comply with all protocol procedures, in the investigator's opinion.
• Patients must have a study partner who will preferably be consistent throughout the study. It is recommended that the study partner should interact (in-person or telephone) with the subject at least 2 times a week.

Exclusion Criteria:

• Patients who have a categorical diagnosis of another current major psychiatric disorder on the Mini-International Neuropsychiatric Interview (M.I.N.I.).
• Diseases of the central nervous system (CNS) that may impact the assessment of the cognitive tests as per investigator's opinion. A movement disorder due to antipsychotic treatment not currently controlled with anti- EPS treatment or another movement disorder (e.g. Parkinson´s disease).
• Patients with a history of participating in any formal cognitive remediation program for 10 or more training sessions.

• Patients who were treated with any of the following medications within the last 6 months prior to randomization:

  • Bitopertin, BI 409306, encenicline or other investigational drug testing effects on cognition in schizophrenia
  • Clozapine (atypical antipsychotic medication)
  • Sarcosine, cycloserine, serine and glycine
  • Stimulants (e.g. methylphenidate, dextroamphetamine, modafinil)
  • Tricyclic antidepressants
• Patients receiving any other investigational drug (other than a potential cognitive enhancing drug) within 30 days or 6 half-lives (whichever is longer) prior to randomization. For investigational LAI antipsychotics, the last injection must be at least 3 months or two administration cycles (i.e. 6 months if administration is every 3 months) prior to randomization, whichever is longer.
• Patients who have participated in a clinical trial with repeated assessments (i.e. a single assessment is not exclusionary) with the MATRICS Consensus Cognitive Battery (MCCB) within the last 6 months prior to randomization.
• Patients who required a change in ongoing benzodiazepine or sleep medication dose or regimen within the last 30 days prior to randomization.
• Patients with known active infection with SARS-CoV-2 within the last 30 days prior to randomization.
• Other exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BI 425809 10 mg + Computerized Cognitive Training	Drug: BI 425809; Tablet; Other Names: iclepertin
Placebo Comparator: Placebo + Computerized Cognitive Training	Drug: Placebo; Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Neurocognitive Function as Measured by the Neurocognitive Composite Score of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) After 12 Weeks of Treatment	MCCB neurocognitive composite T-score assesses 6 cognitive domains, including speed of processing, attention vigilance, working memory, verbal learning, visual learning, reasoning and problem solving. MCCB neurocognitive T-scores in the general population have a mean of 50 and standard deviation of 10. A higher T-score indicates better cognition. Change from baseline in MCCB neurocognitive composite T-score at Week 12 was modelled based on a restricted maximum likelihood (REML) based approach using a mixed model with repeated measurements (MMRM) which included the following fixed effects: categorical factor of planned treatment, visit (screening, baseline, week 6 and Week 12), planned treatment by visit interaction, continuous covariate of baseline value, baseline by visit interaction, categorical factor of age group, and continuous covariate of change from screening to baseline value. The Least Squares Mean (95 % Confidence Interval) at Week 12 is reported.	At screening (28 days prior to first drug drug administration), at baseline and at Weeks 6 and 12 after first drug administration.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Cognitive Function as Measured by the Overall MCCB Composite T Score (Including Social Cognition) After 12 Weeks of Treatment	MCCB cognitive score comprises 10 tests, which assess 7 cognitive domains, including speed of processing, attention vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. MCCB cognitive T-scores in the general population have a mean of 50 and standard deviation of 10. A higher T-score indicates better cognition. Change from baseline in MCCB overall composite T-score was modelled using a restricted maximum likelihood (REML) based approach using a mixed model with repeated measurements (MMRM) which included the following fixed effects: categorical factor of planned treatment, visit (screening, baseline, week 6 and Week 12), planned treatment by visit interaction, continuous covariate of baseline value, baseline by visit interaction, categorical factor of age group, and continuous covariate of change from screening to baseline value. The Least Squares Mean (95 % Confidence Interval) at Week 12 is reported.	At screening (28 days prior to first drug drug administration), at baseline and at Weeks 6 and 12 after first drug administration.
Change From Baseline in the Effect of Cognitive Deficit on Day-to-day Functioning as Measured by SCoRS Total Score After 12 Weeks of Treatment	Schizophrenia Cognition Rating Scale (SCoRS) is a 20-item interview-based assessment of cognitive deficits and the degree to which they affect day-to-day functioning. Each item is rated on a 4-point scale. SCoRS total score is between 20 and 80 where higher score values represent greater degree of impairment in day-to-day functions due to cognitive deficits. The composite score was the average of non-missing responses. If five or more of the 20 items were missing, the composite score was missing for that participant at the visit. Change from baseline in SCoRS total score after 12 weeks of treatment was modelled using an Analysis of Covariance (ANCOVA) which included the following fixed effects: categorical factor of planned treatment, continuous covariate of baseline value, categorical factor of age group.	At baseline and at 12 weeks after first drug administration.
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score After 12 Weeks of Treatment	PANSS was used to evaluate broad psychopathology associated with schizophrenia disease state. The PANSS has 30 items. Each is rated from 1 to 7 points. The total factor score is the summation of the actual points for each item, leading the total score ranging from 30 to 210; a higher score indicates a worse disease condition. Change from baseline in PANNS total score after 12 weeks of treatment was modelled based on a restricted maximum likelihood (REML) based approach using a mixed model with repeated measurements (MMRM) which included the following fixed effects: categorical factor of planned treatment, visit (baseline, Week 6 and Week 12), planned treatment by visit interaction, continuous covariate of baseline value, baseline by visit interaction, categorical factor of age group. The Least Squares Mean (95 % Confidence Interval) at Week 12 is reported.	At baseline and at Weeks 6 and 12 after first drug administration.
Percentage of Patients With Any Adverse Event (AE) and With Serious Adverse Events (SAEs)	Percentage of patients with any Adverse Event (AE) and with serious adverse events (SAEs) is reported. Percentages were rounded to one decimal place.	From first dose of study drug administration until four weeks after the last dose of study drug administration, up to 16 weeks.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General Publications

• Harvey PD, Bowie CR, McDonald S, Podhorna J. Evaluation of the Efficacy of BI 425809 Pharmacotherapy in Patients with Schizophrenia Receiving Computerized Cognitive Training: Methodology for a Double-blind, Randomized, Parallel-group Trial. Clin Drug Investig. 2020 Apr;40(4):377-385. doi: 10.1007/s40261-020-00893-8.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2019
• Primary Completion (Actual): September 30, 2022
• Study Completion (Actual): November 4, 2022

Study Registration Dates

• First Submitted: February 25, 2019
• First Submitted That Met QC Criteria: February 28, 2019
• First Posted (Actual): March 1, 2019

Study Record Updates

• Last Update Posted (Estimated): November 20, 2023
• Last Update Submitted That Met QC Criteria: October 30, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Nootropic Agents; BI 425809
• Other Study ID Numbers: 1346-0038; 2018-002740-82 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement".

Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.

The data shared are the raw clinical study data sets.

• IPD Sharing Time Frame: After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• IPD Sharing Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing Agreement'.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No