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

• ClinicalTrials.gov Identifier: NCT03859973
• Recruitment Status: Recruiting
• First Posted: March 1, 2019
• Last Update Posted: July 28, 2020
• Sponsor: Boehringer Ingelheim
• Information provided by (Responsible Party): Boehringer Ingelheim

Tracking Information

• First Submitted Date: February 25, 2019
• First Posted Date: March 1, 2019
• Last Update Posted Date: July 28, 2020
• Actual Study Start Date: April 15, 2019
• Estimated Primary Completion Date: May 7, 2021 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: February 28, 2019): 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) [ Time Frame: Up to 12 weeks ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 28, 2019)

• Change from baseline in cognitive function as measured by the overall MCCB composite score (including social cognition) [ Time Frame: Up to 12 weeks ]
• Change from baseline in the effect of cognitive deficit on day-to-day functioning as measured by SCoRS total score [ Time Frame: Up to 12 weeks ]
  Schizophrenia Cognition Rating Scale (SCoRS)
• Change from baseline in Positive and Negative Syndrome Scale (PANSS) total score [ Time Frame: Up to 12 weeks ]
  Positive and Negative Syndrome Scale (PANSS)
• Percentage of patients with (S)AEs [ Time Frame: Up to 12 weeks ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: This Study Tests Whether BI 425809 Together With Brain Training Using a Computer Improves Mental Functioning in Patients With Schizophrenia
• 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
• Brief Summary: The primary objective of this Phase II exploratory trial is to provide Proof of Concept (PoC) data to assess the effect on cognition of oral once daily administration of BI 425809 given for 12 weeks in patients with schizophrenia on stable antipsychotic treatment and adjunctive Computerized Cognitive Training (CCT).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Schizophrenia

Intervention

• Drug: BI 425809
  Tablet
• Drug: Placebo
  Tablet

Study Arms

• Experimental: BI 425809
  Active drug treatment arm
  Intervention: Drug: BI 425809
• Experimental: Placebo
  Placebo drug arm
  Intervention: Drug: Placebo

• 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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 28, 2019): 200
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 4, 2021
• Estimated Primary Completion Date: May 7, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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, and current antipsychotic and concomitant psychotropic medications must meet the criteria below:

  • Patients may take up to 2 antipsychotics (typical and/or atypical), except for clozapine
  • Patients must be stable on current antipsychotics and concomitant psychotropic medications (e.g. 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 ---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. 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 computerized cognitive training (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).
• Patients must be able to comply with all protocol procedures including the at-home CCT exercises, 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.
• Use of systemic steroids within 30 days prior to randomization.
• Patients taking strong or moderate CYP3A4 inhibitors or inducers within the last 30 days prior to randomization. A list of strong or moderate CYP3A4 inhibitors and inducers will be provided in the ISF.
• Patients who must or wish to continue the intake of restricted medications or herbal remedies
• Patients who received treatment with medical devices (e.g. TMS, neurofeedback) for any psychiatric condition within the last 3 months prior to randomization.
• Patients who have received electroconvulsive therapy (ECT) within 6 months prior to randomization or repeated courses of ECT within the past 2 years.
• Any suicidal behavior in the past 2 years (i.e. actual attempt, interrupted attempt, aborted attempt, or preparatory acts or behavior) prior to randomization.
• Any suicidal ideation of type 4 or 5 in the C-SSRS in the past 3 months (i.e. active suicidal thought with intent but without specific plan, or active suicidal thought with plan and intent) prior to randomization.

• Any of the following, in the judgment of the investigator:

  • Clinically significant finding of the physical examination, vital signs (including blood pressure (BP) and pulse rate (PR)), ECG or laboratory value (as measured by the central laboratory) that would jeopardize the patient's safety while participating in the trial or their capability to participate in the trial.
  • Symptomatic/unstable/uncontrolled or clinically relevant concomitant disease or any other clinical condition that would jeopardize the patient's safety while participating in the trial or capability to participate in the trial.
  • Significant or unstable physical condition that may require change in medication or hospitalization that would impact cognitive function, or planned elective surgery requiring general anesthesia during the study period.
  • Patients for which cognitive or other impairment (including severe hearing impairment) or symptom severity compromises the ability to perform the CCT or assessments related to cognitive outcome measures.
• Severe renal impairment defined as an eGFR < 30mL/min/1.73m² in the Visit 1 central lab report.
• Indication of liver disease, defined by serum levels of either ALT (SGPT), AST (SGOT), or alkaline phosphatase above 3 times upper limit of normal as determined in the Visit 1 central lab report.
• Known history of HIV infection based on review of medical history and/or a positive result for ongoing Hepatitis B or C infection on the Visit 1 central lab report.
• Any documented active or suspected malignancy or history of malignancy within 5 years prior to screening, except appropriately treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin or in situ carcinoma of uterine cervix.
• Hb less than 120 g/L (12g/dL) in men or 115 g/L (11.5g/dL) in women at Visit 1.
• History of hemoglobinopathy such as thalassemia major or sickle-cell anemia.
• Women who are pregnant, nursing, or who plan to become pregnant while in the trial.
• Significant history of drug abuse disorder within the last 6 months prior to informed consent (including alcohol, as defined in DSM-5-substance use disorder or in the opinion of the investigator), or a positive urine drug screen at Visit 1. Note: Patients testing positive for cannabis on urine drug screen at Visit 1 may be re-tested once if there is a reasonable explanation and expectation that the patient will not test positive again on re-test, and at the discretion of the investigator.
• Patients who are not fluent in the language of the batteries/questionnaires which will be used in the country.
• Patient who did not make an effortful attempt to complete the cognition battery at Visit 1 in the clinical judgement of the investigator.
• Patients that previously received treatment in any study with BI 425809.
• Patients with an allergy to BI 425809 and/or any of the excipients (including lactose) or placebo ingredients. A list of BI 425809 and placebo ingredients will be provided in the ISF.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 50 Years (Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Boehringer Ingelheim; 1-800-243-0127; clintriage.rdg@boehringer-ingelheim.com

• Listed Location Countries: Australia, Canada, France, New Zealand, United Kingdom, United States

Administrative Information

• NCT Number: NCT03859973
• Other Study ID Numbers: 1346-0038; 2018-002740-82 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

Plan Description

Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions:

1. Studies in products where Boehringer Ingelheim is not the license holder;
2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials;
3. Studies conducted in a single center or targeting rare diseases (because of limitations with anonymization).

Requestors can use the following link http:// trials.boehringer-ingelheim.com/ to:

1. find information in order to request access to clinical study data, for listed studies.
2. request access to clinical study documents that meet criteria, and upon a signed 'Document Sharing Agreement.

• Responsible Party: Boehringer Ingelheim
• Study Sponsor: Boehringer Ingelheim
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Boehringer Ingelheim
• Verification Date: July 2020