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

Schizophrenia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03859973
• Other study ID #: 1346-0038
• Secondary ID: 2018-002740-82
• Status: Completed
• Phase: Phase 2
• Start date: April 15, 2019
• Est. completion date: November 4, 2022

Study information

• Verified date: October 2023
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: November 4, 2022
• Est. primary completion date: September 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• BI 425809
Tablet
• Placebo
Tablet

Locations

Country	Name	City	State
Australia	Monash Medical Centre	Clayton	Victoria
Australia	Lyell McEwin Hospital	Elizabeth Vale	South Australia
Australia	St Vincent's Hospital Melbourne	Fitzroy	Victoria
Australia	Monash Alfred Psychiatry Research Centre	Melbourne	Victoria
Canada	University of Calgary	Calgary	Alberta
Canada	IUSMM Institut Universitaire en Sante Mentale de Montreal	Montreal	Quebec
Canada	Centre for Addiction and Mental Health (CAMH)	Toronto	Ontario
Canada	BC Mental Health and Addictions Research Institute (University of British Columbia)	Vancouver	British Columbia
France	CTR Esquirol	Caen
France	HOP Dijon-Bourgogne	Dijon
France	CAB Médical Psyché	Douai
France	HOP la Colombière	Montpellier
France	HOP Saint-Jacques	Nantes
France	HOP Pasteur	Nice
France	GHU Paris Psychiatrie et Neurosciences	Paris
France	HOP Nord	Saint Priest en Jarez
New Zealand	North Shore Hospital, Takapuna	Takpuna Auckland
United Kingdom	The Fritchie Centre	Cheltenham
United Kingdom	Royal Edinburgh Hospital	Edinburgh
United Kingdom	Queen Elizabeth University Hospital	Glasgow
United Kingdom	Maudsley Hospital	London
United Kingdom	Warneford Hospital	Oxford
United States	Synexus	Atlanta	Georgia
United States	Northwest Clinical Research Center	Bellevue	Washington
United States	Uptown Research Institute	Chicago	Illinois
United States	FutureSearch Trials of Dallas, LP	Dallas	Texas
United States	Midwest Clinical Research	Dayton	Ohio
United States	Encino Hospital Medical Center	Encino	California
United States	Collaborative Neuroscience Network, LLC (CNS)	Garden Grove	California
United States	Cherry Health	Grand Rapids	Michigan
United States	Center for Behavioral Medicine	Kansas City	Missouri
United States	Lake Charles Clinical Trials LLC	Lake Charles	Louisiana
United States	Synergy San Diego	Lemon Grove	California
United States	Atria Clinical Research	Little Rock	Arkansas
United States	Meridien Research	Maitland	Florida
United States	Premier Clinical Research Institute	Miami	Florida
United States	University of Miami	Miami	Florida
United States	Catalina Research Institute, LLC	Montclair	California
United States	Synexus Clinical Research US, Inc.	New York	New York
United States	Pacific Research Partners, LLC	Oakland	California
United States	NRC Research Institute	Orange	California
United States	CNRI - Los Angeles	Pico Rivera	California
United States	UNC Center for Excellence in Community Mental Health, North Carolina Psychiatric Research Center	Raleigh	North Carolina
United States	Pillar Clinical Research, LLC	Richardson	Texas
United States	Office of Dr. Aqeel Hashmi, MD, PA	Richmond	Texas
United States	Woodland Research Northwest	Rogers	Arkansas
United States	CNRI-San Diego, LLC	San Diego	California
United States	Apalachee Center	Tallahassee	Florida
United States	Collaborative Neuroscience Network, LLC (CNS)	Torrance	California
United States	Jerome Golden Center for Behavioral Health	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  New Zealand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	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.
Secondary	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.
Secondary	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.

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