CONNEX-3: A Study to Test Whether Iclepertin Improves Learning and Memory in People With Schizophrenia

Study Overview
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Brief Summary
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This study is open to adults with schizophrenia. Schizophrenia can affect the way a person thinks, their memory and their mental functioning. Examples include struggling to remember things, or to read a book or pay attention to a movie. Some people have difficulty calculating the right change or planning a trip so that they arrive on time. The purpose of this study is to find out whether a medicine called iclepertin improves learning and memory in people with schizophrenia. Participants are put into two groups randomly, which means by chance. One group takes iclepertin tablets and the other group takes placebo tablets. Placebo tablets look like iclepertin tablets but do not contain any medicine. Participants take a tablet once a day for 26 weeks. In addition, all participants take their normal medication for schizophrenia. During this time, doctors regularly test learning and memory of the participants by use of questionnaires, interviews, and computer tests. The results of the mental ability tests are compared between the groups. Participants are in the study for about 8 months and visit the study site about 14 times. During this time, doctors regularly check participants' health and take note of any unwanted effects.

Official Title
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A Phase III Randomized, Double-blind, Placebo-controlled Parallel Group Trial to Examine the Efficacy and Safety of Iclepertin Once Daily Over 26 Week Treatment Period in Patients With Schizophrenia (CONNEX-3)

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: iclepertin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Signed and dated written informed consent. Male or female patients who are 18-50 years (inclusive) of age at time of consent. Diagnosis of schizophrenia utilizing Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-5). -- Patients must be clinically stable and in the residual (non-acute) phase of their illness with no hospitalization or increase level of care due to worsening of schizophrenia in the past 12 weeks or no uncontrolled positive symptoms. Patients should have functional impairment in day-to-day activities per investigator judgement. Patients maintained on current antipsychotic treatment for at least 12 weeks and on current dose for at least 35 days prior to randomization. Patients with any other concomitant psychoactive medications (except for anticholinergics) need to be maintained on same drug for at least 12 weeks and on current dose/ regimen for at least 35 days prior to randomization. Women of childbearing potential must use highly effective methods of birth control. Have a study partner who interacts with the patient on a regular basis. Further inclusion criteria apply. Exclusion criteria Patient with current DSM-5 diagnosis other than Schizophrenia. Cognitive impairment due to other causes, or patients with dementia or epilepsy. Severe movement disorders. Any suicidal behavior in past year or suicidal ideation in the past 3 months. History of moderate or severe substance use disorder within the last 12 months prior to informed consent. Positive urine drug screen. Patients who were treated with Clozapine, stimulants, ketamine or electroconvulsive therapy within 6 months prior to randomization. Current participation in any investigational drug trial. Cognitive Remediation Therapy within 12 weeks prior to screening. Initiation or change in any type or frequency of psychotherapy within 12 weeks prior to randomization. Any clinically significant finding or condition that would jeopardize the patient´s safety while participating in the trial or their capability to participate in the trial. Haemoglobin (Hb) below lower limit of normal . History of haemolytic anaemia, red blood cell (RBC) membrane diseases, known Glucose-6-phosphate dehydrogenase deficiency, anaemia of any cause or patients planning to donate blood. Severe renal impairment. Indication of liver disease. Any documented active or suspected malignancy or history of malignancy within 5 years. Women who are pregnant, nursing, or who plan to become pregnant while in the trial. Further exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Iclepertin treatment group<br> | Drug: iclepertin<br>* iclepertin<br>|
| Placebo Comparator: Placebo group<br> | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in overall composite T-score of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) consensus cognitive battery (MCCB) | MCCB 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 | After 26 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in the Schizophrenia Cognition Rating Scale (SCoRS) interviewer total score | 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. Higher ratings reflect a greater degree of impairment. | After 26 weeks of treatment | 
| Change from baseline to Week 26 in the adjusted total time in the Virtual Reality Functional Capacity Assessment Tool (VRFCAT) |  | Up to week 26 | 
| Change from baseline to Week 26 in the T-score of the number of correct responses on Tower of London |  | Up to week 26 | 
| Change from screening visit 1a to Week 24 in Patient Reported Experience of Cognitive Impairment in Schizophrenia (PRECIS) total score | PRECIS is a patient reported outcome (PRO) for recording patients' subjective experience of Cognitive Impairment Associated with Schizophrenia (CIAS). The questionnaire contains 28 items covering 6 domains: Memory (6 items), communication (4 items), self-control (3 items), executive function (4 items), attention (6 items), and sharp thinking (3 items). Two additional items assess the overall degree of bother associated with all domains. Questions are answered via a 5-category Likert scale, with higher scores corresponding to worse patient experience. The Total Score is derived by calculating the simple average score of the first 26 items. | Up to week 24 |