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

NCT03859973 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 1346-00382018-002740-82
• Study Type: interventional
• Target: 200
• Locations: 6 countries
• Sites: 50

Brief Summary

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.

Conditions

Schizophrenia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Change From Baseline in Cognitive Function as Measured by the Overall MCCB Composite T Score (Including Social Cognition) After 12 Weeks of Treatment

  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

  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

  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)

  From first dose of study drug administration until four weeks after the last dose of study drug administration, up to 16 weeks.

Study Arms (2)

BI 425809 10 mg + Computerized Cognitive Training

EXPERIMENTAL

Drug: BI 425809

Placebo + Computerized Cognitive Training

PLACEBO COMPARATOR

Drug: Placebo

Interventions

BI 425809 DRUG

Tablet

Also known as: iclepertin

BI 425809 10 mg + Computerized Cognitive Training

Placebo DRUG

Tablet

Placebo + Computerized Cognitive Training

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (50)

Atria Clinical Research

Little Rock, Arkansas, 72209, United States

Location

Woodland Research Northwest

Rogers, Arkansas, 72758, United States

Location

Encino Hospital Medical Center

Encino, California, 91436, United States

Location

Collaborative Neuroscience Network, LLC (CNS)

Garden Grove, California, 92845, United States

Location

Synergy San Diego

Lemon Grove, California, 91945, United States

Location

Catalina Research Institute, LLC

Montclair, California, 91763, United States

Location

Pacific Research Partners, LLC

Oakland, California, 94607, United States

Location

NRC Research Institute

Orange, California, 92868, United States

Location

CNRI - Los Angeles

Pico Rivera, California, 90660, United States

Location

CNRI-San Diego, LLC

San Diego, California, 92102, United States

Location

Collaborative Neuroscience Network, LLC (CNS)

Torrance, California, 90502, United States

Location

Meridien Research

Maitland, Florida, 32751, United States

Location

Premier Clinical Research Institute

Miami, Florida, 33122, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Apalachee Center

Tallahassee, Florida, 32308, United States

Location

Jerome Golden Center for Behavioral Health

West Palm Beach, Florida, 33407, United States

Location

Synexus

Atlanta, Georgia, 30328, United States

Location

Uptown Research Institute

Chicago, Illinois, 60640, United States

Location

Lake Charles Clinical Trials LLC

Lake Charles, Louisiana, 70629, United States

Location

Cherry Health

Grand Rapids, Michigan, 49503, United States

Location

Center for Behavioral Medicine

Kansas City, Missouri, 64108, United States

Location

Synexus Clinical Research US, Inc.

New York, New York, 10017, United States

Location

UNC Center for Excellence in Community Mental Health, North Carolina Psychiatric Research Center

Raleigh, North Carolina, 27608, United States

Location

Midwest Clinical Research

Dayton, Ohio, 45417, United States

Location

FutureSearch Trials of Dallas, LP

Dallas, Texas, 75231, United States

Location

Pillar Clinical Research, LLC

Richardson, Texas, 75080, United States

Location

Office of Dr. Aqeel Hashmi, MD, PA

Richmond, Texas, 77407, United States

Location

Northwest Clinical Research Center

Bellevue, Washington, 98007, United States

Location

Lyell McEwin Hospital

Elizabeth Vale, South Australia, 5112, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

St Vincent's Hospital Melbourne

Fitzroy, Victoria, 3065, Australia

Location

Monash Alfred Psychiatry Research Centre

Melbourne, Victoria, 3004, Australia

Location

University of Calgary

Calgary, Alberta, T2N 4Z6, Canada

Location

BC Mental Health and Addictions Research Institute (University of British Columbia)

Vancouver, British Columbia, V5Z 4H4, Canada

Location

Centre for Addiction and Mental Health (CAMH)

Toronto, Ontario, M6J 1H4, Canada

Location

IUSMM Institut Universitaire en Sante Mentale de Montreal

Montreal, Quebec, H1N 3M5, Canada

Location

CTR Esquirol

Caen, 14033, France

Location

HOP Dijon-Bourgogne

Dijon, 21079, France

Location

CAB Médical Psyché

Douai, 59500, France

Location

HOP la Colombière

Montpellier, 34295, France

Location

HOP Saint-Jacques

Nantes, 44093, France

Location

HOP Pasteur

Nice, 06000, France

Location

GHU Paris Psychiatrie et Neurosciences

Paris, 75674, France

Location

HOP Nord

Saint-Priest-en-Jarez, 42270, France

Location

North Shore Hospital, Takapuna

Takpuna Auckland, 0622, New Zealand

Location

The Fritchie Centre

Cheltenham, GL53 9DZ, United Kingdom

Location

Royal Edinburgh Hospital

Edinburgh, EH10 5HF, United Kingdom

Location

Queen Elizabeth University Hospital

Glasgow, G51 4TF, United Kingdom

Location

Maudsley Hospital

London, SE5 8AZ, United Kingdom

Location

Warneford Hospital

Oxford, OX3 7JX, United Kingdom

Location

Related Publications (2)

• Harvey PD, McDonald S, Fu E, Reuteman-Fowler C. Efficacy and safety of iclepertin (BI 425809) with adjunctive computerized cognitive training in patients with schizophrenia. Schizophr Res Cogn. 2024 Dec 14;40:100340. doi: 10.1016/j.scog.2024.100340. eCollection 2025 Jun.

  PMID: 39759424 DERIVED

• 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.

  PMID: 32036587 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Schizophrenia

Interventions

BI 425809

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2019
• First Posted: March 1, 2019
• Study Start: April 15, 2019
• Primary Completion: September 30, 2022
• Study Completion: November 4, 2022
• Last Updated: November 18, 2023
• Results First Posted: November 18, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• 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.
• 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'.

Locations

CA (4); FR (8); US (28); AU (4); NZ (1); GB (5)