Schizophrenia
Conditions
Brief summary
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.
Interventions
DRUGIclepertin
One tablet of 10 mg once daily for 26 weeks.
DRUGPlacebo
One tablet once daily for 26 weeks.
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Overall Composite T-score of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) After 26 Weeks of Treatment | The MMRM model incorporates values from baseline (Week 0), Week 12 and Week 26. The data represent the Least Squares Means at Week 26. | The MCCB assesses 7 cognitive domains, including speed of processing, attention vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. T-scores in the general population have a mean of 50 and standard deviation of 10, and a higher score indicates better cognition. The primary analysis was a restricted maximum likelihood (REML) based approach using a mixed-effects model for repeated measurements (MMRM), which included the fixed categorical effects of treatment at each visit, fixed categorical effect of the stratification factor using the screening MCCB overall composite T-score, and a fixed effect for the continuous covariate of baseline at each visit. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-subject dependencies. Intercurrent events were addressed using different pre-defined strategies. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Schizophrenia Cognition Rating Scale (SCoRS) Interviewer Total Score After 26 Weeks of Treatment | The MMRM model incorporates values from baseline (Week 0), Week 12 and Week 26. The data represent the Least Squares Means at Week 26. | 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. The interviewer integrates information from separate patient and study partner interviews to generate a total score, which ranges from 20 to 80. The analysis was a REML-based approach using a MMRM model, which included the discrete fixed effects of treatment at each visit, fixed categorical covariate of the stratification factor using the screening MCCB overall composite T-score, a fixed effect for the continuous covariate of baseline at each visit. Visit was treated as the repeated measure with an unstructured covariance structure to model the within-subject measurements. Subjects were considered as a random effect. Intercurrent events were addressed using different pre-defined strategies. |
| Change From Baseline to Week 26 in the Adjusted Total Time T-score in Virtual Reality Functional Capacity Assessment Tool (VRFCAT) | The MMRM model incorporates values from baseline (Week 0), Week 12 and Week 26. The data represent the Least Squares Means at Week 26. | The VRFCAT is a virtual reality shopping trip performed on a tablet, and was used as an electronic Functional Capacity measure by measuring the total time adjusting for the number of errors. T-scores in the general population have a mean of 50 and standard deviation of 10, and a higher score indicates a better functional outcome. The analysis was a REML-based approach using a MMRM model, which included the discrete fixed effects of treatment at each visit, fixed categorical covariate of the stratification factor using the screening MCCB overall composite T-score, a fixed effect for the continuous covariate of baseline at each visit. Visit was treated as the repeated measure with an unstructured covariance structure to model the within-subject measurements. Subjects were considered as a random effect. Intercurrent events were addressed using different pre-defined strategies. |
| Change From Baseline to Week 26 in the T-score of the Number of Correct Responses on Tower of London | At baseline (Week 0) and at Week 26. | This is an Executive Functions/Reasoning and Problem Solving test where patients were shown two images on opposite sides of a tablet screen. Each image showed a different configuration of 3 colored balls arranged on 3 pegs. Patients were required to accurately determine the total number of times the balls in one picture would have to be moved in order to make the arrangement of balls identical to that of the other opposing picture, while employing the standard rules employed in tower tests. T-scores in the general population have a mean of 50 and standard deviation of 10, and a higher score indicates a better outcome. The analysis was performed with an analysis of covariance (ANCOVA) model, which included treatment, stratification factor of screening MCCB overall composite T-score (\< 30, ≥ 30), and baseline number of correct responses on Tower of London T-score. |
| Change From Screening Visit 1a to Week 24 in Patient Reported Experience of Cognitive Impairment in Schizophrenia (PRECIS) Total Score | The MMRM model incorporates values from baseline (screening), Week 15 and Week 24. The data represent the Least Squares Means at Week 24. | PRECIS consists of 26 items covering 6 domains (memory, communication, self-control, executive function, attention, and sharp thinking), and 2 additional items assessing the overall degree of bother associated with all domains. Questions are answered via a 5-category Likert scale, with higher scores indicating a worse patient experience. The total score, ranging from 26 to 130, is the average score of the first 26 items. The analysis was a REML-based approach using a MMRM model, which included the discrete fixed effects of treatment at each visit, fixed categorical covariate of the stratification factor using the screening MCCB overall composite T-score, and continuous fixed effects for the corresponding baseline endpoint value at each visit. Visit was treated as the repeated measure with an unstructured covariance structure to model the within-subject measurements. Subjects were considered as a random effect. Intercurrent events were addressed using different pre-defined strategies. |
| Ocular Safety Sub-study: Change From Baseline in Humphrey Visual Field 24-2 Swedish Interactive Thresholding Algorithm (SITA) Standard at Week 24 | Measurements were performed at baseline (screening) and at Week 24. | The Humphrey visual field is a diagnostic test to measure visual fields, or perimetry. The Humphrey visual field test measures the entire area of peripheral vision that can be seen while the eye is focused on a central point. During this test, lights of varying intensities appear in different parts of the visual field while the patient's eye is focused on a central spot. The perception of these lights is charted and then compared to results of a healthy eye at the same age of the patient to determine if any damage has occurred. Visual field Index goes from 100%= perfect to 0= no vision. |
| Ocular Safety Sub-study: Change From Baseline in Spectral Domain Ocular Coherence Tomography (OCT) | Measurements were performed at baseline (screening) and at Week 24. | The central retinal thickness measurements were recorded for each eye via high definition optical coherence tomography (spectral domain OCT) to evaluate the retinal and sub-retinal structures. |
Countries
Argentina, Austria, Belgium, Brazil, Bulgaria, China, Czechia, Denmark, Finland, Germany, Lithuania, Mexico, Portugal, Serbia, South Korea, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
Multi-center, multi-national, randomized, double-blind, placebo controlled, parallel group, 26-week trial in patients with schizophrenia on stable antipsychotic treatment randomized with equal ratio to iclepertin or placebo. Patients who completed the trial could directly enroll into a open-label extension trial to assess the long-term safety and tolerability of iclepertin (1346-0014). A dedicated ocular sub-study was conducted in several countries to investigate the ocular safety of iclepertin.
Pre-assignment details
Patients and study partners signed informed consent forms and were informed that they were free to withdraw consent at any time without penalty or prejudice. All patients were screened for eligibility prior to participation and attended a specialist site which ensured that they strictly met all inclusion and no exclusion criteria. Study partners were not enrolled nor assigned a study ID, and other than the endpoints related to patients, no other data was collected from them.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 33.8 Years STANDARD_DEVIATION 8.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 83 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 231 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Overall composite T-score of the MATRICS consensus cognitive battery (MCCB) | 29.6 T-score STANDARD_DEVIATION 13.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 17 Participants |
| Race (NIH/OMB) Asian | 228 Participants |
| Race (NIH/OMB) Black or African American | 27 Participants |
| Race (NIH/OMB) More than one race | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 304 Participants |
| Sex: Female, Male Female | 130 Participants |
| Sex: Female, Male Male | 208 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 301 | 0 / 305 |
| other Total, other adverse events | 68 / 301 | 65 / 305 |
| serious Total, serious adverse events | 13 / 301 | 14 / 305 |
Outcome results
None listed