The primary objective of this trial in CIAS is to assess the efficacy in improving cognitive impairment using MCCB in patients with schizophrenia treated for 26 weeks with Iclepertin 10mg as compared with placebo.
ID
Source
Brief title
Condition
- Schizophrenia and other psychotic disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint include:
- 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.
Secondary outcome
The key secondary efficacy endpoints include:
- Change from baseline in the SCoRS interviewer total score after 26 weeks of
treatment.
- Change from baseline to Week 26 in the adjusted total time T-score in the
VRFCAT
The secondary efficacy endpoints include:
- Change from baseline to week 26 in the T-score of number of correct responses
on Tower of London (ToL).
- Change in Patient Reported Experience of Cognitive Impairment in
Schizophrenia (PRECIS) total score from screening visit 1a to Week 24
Background summary
Schizophrenia is a serious and chronic mental illness leading to poor quality
of life and disability.
Schizophrenia is typically defined by three clusters of symptoms: positive
symptoms, negative symptoms and cognitive impairments.
Cognitive impairments are a core feature of schizophrenia and a major
determinant of poor functional outcome.
Antipsychotics are the primary medication for schizophrenia, with major effects
on the reduction of *psychotic* symptoms and prevention of relapses but
demonstrate virtually no beneficial effects on cognition in schizophrenia.
A potential treatment for the cognitive impairment associated with
schizophrenia is therefore a significant unmet need.
For more information regarding the background, please refer to the protocol
version 3.0 / 18 Sep 2023, page 17.
Study objective
The primary objective of this trial in CIAS is to assess the efficacy in
improving cognitive impairment using MCCB in patients with schizophrenia
treated for 26 weeks with Iclepertin 10mg as compared with placebo.
Study design
A phase III randomized, double-blind, placebo-controlled, parallel group trial,
with a treatment duration of 26 weeks.
Intervention
There are two treatment groups:
- Iclepertin once daily
- Placebo once daily
The treatment period is 26 weeks.
Study burden and risks
The amount of visits to the hospital is likely more often than the patient is
used to. Additionally, the visits are longer and additional tests are being
performed/additional blood is being drawn. Study-specific questionnaires and
assessments are also done.
These can be experienced as intensive and long. The patient will also have to
film him- or herself every day while taking the study drug. This is done with
an application on the phone of the participant, to monitor adherence to the
therapy.
For detailed information on the assessments and tests, please refer to pages
6-7 of the protocol, version 3.0 / 18 Sep 2023.
Earlier trials show that the study drug is generally safe and well tolerated.
No serious adverse events have been seen. However, this remains an experimental
drug, and there is always a chance of adverse effects we have not seen yet, or
worse than we have seen until now.
Furthermore, from earlier trials it seems that Iclepertin has a positive effect
on cognition, which should lead to an improvement in day-to-day functioning.
Basisweg 10
Amsterdam 1043 AP
NL
Basisweg 10
Amsterdam 1043 AP
NL
Listed location countries
Age
Inclusion criteria
1. Patient must be capable of providing a signed and dated written informed
consent by visit 1 in accordance with International Council on Harmonisation
for Good Clinical Practice (ICH-GCP) and local legislation prior to admission
to the trial.
2. Male or female patients who are 18-50 years (inclusive) of age at time of
consent.
3. Diagnosis of schizophrenia utilizing DSM-5 with the following clinical
features:
-- Outpatient, clinically stable and in the residual (non-acute) phase of their
illness.
-- No hospitalization or increase in level of psychiatric care due to worsening
of schizophrenia within 12 weeks prior to randomization.
-- PANSS score: items P1, P3-P6 <= 5 and item P2 and P7 <= 4 at Visit 1, and
confirmed at Visit 2.
4. Patients should have functional impairment in day-to-day activities such as
difficulties following conversation or expressing themselves, difficulties
staying focused, difficulties remembering instructions, what to say or how to
get to places, per investigator judgement.
5. Patients maintained on current antipsychotic treatment (minimum 1 and
maximum 2 antipsychotics, but clozapine is not allowed) for at least 12 weeks
and on current dose for at least 35 days prior to randomization.
-- For patients on two antipsychotics, at least one antipsychotic must be
within the approved label dose range. The second antipsychotic must not exceed
the maximum daily dose per local label. Note: If the total dose is stable,
different dosage forms of the same antipsychotic treatment will be considered
as one antipsychotic.
6. 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. Maximum
daily benzodiazepine load of up to 1 mg lorazepam-equivalent as needed (pro re
nata, prn). Table of relevant medications and their equivalencies will be
provided as a part of ISF
-- For any other psychoactive medications cannot exceed the maximum daily dose
per local label of the country where the study is being conducted.
Further criteria apply.
Exclusion criteria
1. Participant with current DSM-5 diagnosis other than Schizophrenia, including
but not limited to bipolar, schizoaffective, major depressive disorder etc.
M.I.N.I. for Psychotic disorders should be used for guidance.
2. Cognitive impairment due to developmental, neurological (e.g., stroke) or
other disorders including head trauma, or patients with dementia or epilepsy.
3. Severe movement disorders
-- Leading to cognitive impairment (e.g. Parkinson dementia), or
-- Interfering with the efficacy assessments, or
-- Due to antipsychotic treatment that cannot be controlled with low dose
anticholinergic treatment (equal to maximum 1 mg benztropine twice daily).
Table of relevant medications and their equivalencies will be provided as a
part of ISF
4. Any suicidal behavior in the past 1-year prior to screening and during the
screening period.
5. Suicidal ideation of type 5 in the C-SSRS (ie. active suicidal thought with
plan and intent) in the past 3 months prior to screening and up to and
including Visit 2.
-- Patients with Suicidal Ideation type 4 in the C-SSRS (i.e. active suicidal
thought with intent but without specific plan), within 3 months prior to
screening and up to and including visit 2, can be randomized in the study, if
assessed and documented by a licensed mental health professional that there is
no immediate risk of suicide.
6. History of moderate or severe substance use disorder (other than caffeine
and nicotine), as defined in DSM-5 within the last 12 months prior to informed
consent.
7. Positive urine drug screen at Visit 1 based on central lab test. For a list
of drugs assessed in the urine drug screen, please refer to Table 5.2.3:1.
8. Patients who were treated with any of the following within 6 months prior to
randomization:
-- Clozapine
-- Stimulants (e.g. methylphenidate, dextroamphetamine, modafinil)
-- Ketamine or esketamine
-- Electroconvulsive therapy (ECT) or modified ECT
Further criteria apply.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2020-003744-84-NL |
| ClinicalTrials.gov | NCT04846881 |
| CCMO | NL77197.100.21 |