Clinical Trial of Iclepertin Effect on Cognition and Functional Capacity in Schizophrenia (CONNEX-2)

The change from baseline in MCCB (MATRICS Consensus Cognitive Battery) overall composite T-score at Week 26 is reported. This was analyzed using a mixed-effects model for repeated measurements (MMRM) comparing the change from baseline in MCCB overall composite T-score at Week 26 between iclepertin 10 mg daily and placebo. The MCCB comprises 10 tests to measure cognitive performance in 7 cognitive domains: speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. The composite T-score is derived from the 7 cognitive domain T-scores. The T-score is standardized to the normative population with a mean of 50 and standard deviation of 10. A higher MCCB overall composite T-score indicates better cognition.

Time frame: The MMRM model is a longitudinal analysis which incorporated values at screening, baseline and at Week 12 and Week 26. The data presented here represent the Least Squares Mean at Week 26.

Population: Randomized Set (RS): included all patients who signed informed consent and were randomized into the trial, regardless of whether a patient was treated with trial medication. Patients randomized in error and discontinued from the study before the start of trial medication were excluded from the RS. Patients in the RS were analyzed under the randomized trial medication.

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, ranging from No impairment to Severe Impairment, with higher ratings reflecting a greater degree of impairment. The SCoRS rater integrates information from separate patient and study partner interviews to generate a total score. 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 total score was the sum of the 20 item scores. If six or more of the 20 items were missing, the total score was not derived and treated as missing for that participant at the visit, otherwise, missing items were imputed with the mean of the observed items for the purpose of total score calculation.

Time frame: The MMRM model is a longitudinal analysis which incorporated values at screening, baseline and at Week 12 and Week 26. The data presented here represent the Least Squares Mean at Week 26.

Population: Randomized Set (RS): included all patients who signed informed consent and were randomized into the trial, regardless of whether a patient was treated with trial medication. Patients randomized in error and discontinued from the study before the start of trial medication were excluded from the RS. Patients in the RS were analyzed under the randomized trial medication.

Change from baseline in the T-score of the number of correct responses on Tower of London at Week 26, using an analysis of covariance (ANCOVA) model, is reported. The Tower of London evaluates executive functions such as reasoning and problem-solving ability. It measures the number of correct responses in solving an exercise that involves moving colored balls to match a target configuration. The higher the ToL T-score, the better is the patient's cognitive function. A mean T-score of 50 and a standard deviation of 10 reflects the T-score in the normative population. The administration time was about 7 minutes.

Time frame: Baseline and at Week 26

Population: Randomized Set (RS): included all patients who signed informed consent and were randomized into the trial, regardless of whether a patient was treated with trial medication. Patients randomized in error and discontinued from the study before the start of trial medication were excluded from the RS. Patients in the RS were analyzed under the randomized trial medication.

The VRFCAT is a virtual reality shopping trip performed on a tablet. The task has several linked and sequential scenarios, including matching a recipe to the content of kitchen cabinets, preparing a shopping list, taking the correct bus, shopping efficiently, and catching the correct return bus. These tasks are performed in a fixed sequence. The tool records the total amount of time taken to complete the sequence of tasks, adjusting for number of errors and forced progressions. A T-score is generated from this adjusted total time. The lower the adjusted total time T-score, the better is the patient's functional capacity. The T-score has a mean of 50 and a standard deviation of 10 in the normative population.

Time frame: The MMRM model is a longitudinal analysis which incorporated values at screening, baseline and at Week 12 and Week 26. The data presented here represent the Least Squares Mean at Week 26.

Population: Randomized Set (RS): included all patients who signed informed consent and were randomized into the trial, regardless of whether a patient was treated with trial medication. Patients randomized in error and discontinued from the study before the start of trial medication were excluded from the RS. Patients in the RS were analyzed under the randomized trial medication.

The Patient Reported Experience of Cognitive Impairment in Schizophrenia (PRECIS) score evaluates how cognitive difficulties impact the daily life of individuals with schizophrenia. It is composed of 28 items on a 5-category Likert scale (1=not at all/not at all hard, 5=very much/very hard), and the total score was derived by calculating the average score of the first 26 items, where higher scores indicate a worse patient experience. The questionnaire takes 5-15 minutes to complete and provides insights into cognitive impairment associated with schizophrenia (CIAS) impact.

Time frame: The MMRM model is a longitudinal analysis which incorporated values at screening, and at Week 15 and Week 24. The data presented here represent the Least Squares Mean at Week 24.

Population: Randomized Set (RS): included all patients who signed informed consent and were randomized into the trial, regardless of whether a patient was treated with trial medication. Patients randomized in error and discontinued from the study before the start of trial medication were excluded from the RS. Patients in the RS were analyzed under the randomized trial medication.