Clinical Trial of Iclepertin Effect on Cognition and Functional Capacity in Schizophrenia (CONNEX-1)

Schizophrenia Clinical Trial

Official title:

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-1)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04846868
• Other study ID #: 1346-0011
• Secondary ID: 2020-003760-11
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 16, 2021
• Est. completion date: October 11, 2024

Study information

• Verified date: June 2024
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 620
• Est. completion date: October 11, 2024
• Est. primary completion date: September 13, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

Inclusion criteria

1. Patients must be capable of providing signed and dated written informed consent by date of Visit 1 in accordance with ICH Harmonized Tripartite Guideline for Good Clinical Practice (ICH-GCP) and the local legislation prior to the 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 Diagnostic and Statistical Manual of Mental Disorders 5th Edition (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.

• Positive and Negative Syndrome Scale (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 to stay focused, difficulties to remember 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.

• For any other psychoactive medications, doses cannot exceed the maximum daily dose per local label.

7. Women of childbearing potential (WOCBP) 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. A list of contraception methods meeting these criteria is provided in the protocol. 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.

8. Have a study partner, defined as any person either private or professional who knows the patient well, has been capable of interacting with the patient on regular basis, and preferably consistent throughout the study.

• The study partner must interact with the subject a minimum 1 hour per week and, preferably, at least 2 times a week. At least one interaction per week should be in person.

• The study partner must have educational achievement of minimum 8th grade.

• Professional study partners (e.g. study nurse, social worker etc.) are allowed if not involved in administration of any of the protocol assessments.

Further inclusion 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. Mini International Neuropsychiatric Interview (M.I.N.I.) for Psychotic disorders should be used for guidance.

2. Cognitive impairment due to developmental, neurological (e.g., epilepsy, 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).

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 Columbia Suicide Severity Rating Scale (C-SSRS) (i.e. 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.

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 exclusion criteria apply.

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• Iclepertin
Iclepertin
• Placebo
Placebo

Locations

Country	Name	City	State
Australia	Monash Alfred Psychiatry Research Centre	Melbourne	Victoria
Brazil	CPN - Centro de Estudos em Neurociências	Belo Horizonte
Brazil	Hospital das Clinicas da Universidade Federal HC-UFMG	Belo Horizonte,Minas Gerais
Brazil	Hospital Sao Jose	Criciuma
Brazil	Trial Tech- Tecnologia em pesquisa com medicamentos	Curitiba
Brazil	J A Serviços Médicos Ltda/ Instituto Goiano de Neuropisquiatria	Goiania
Brazil	Hospital de Base - Fac Med de Sao Jose do Rio Preto	Sao Jose do Rio Preto
Brazil	BR Trials	Sao Paulo
Canada	University of Calgary	Calgary	Alberta
Canada	OCT Research ULC	Kelowna	British Columbia
Canada	Centre for Addiction and Mental Health (CAMH)	Toronto	Ontario
China	The sixth People's Hospital of Hebei Province	Baoding
China	Beijing HuiLongGuan Hospital	Beijing
China	Peking University Sixth Hospital	Beijing
China	Brain hospital of Hunan province	Changsha
China	The Affiliated Brain Hospital of Guangzhou Medical University	Guangzhou
China	The Affiliated Hospital of Guizhou Medical University	Guiyang
China	Shandong Daizhuang Hospital	Jining
China	The First Affilliated Hospital Of Kunming of Medical College	Kunming
China	Ningbo Kangning Hospital	Ningbo
China	Shanghai Mental Health Center	Shanghai
China	Tongji Hospital, Tongji University	Shanghai
China	Wuxi mental health center	Wuxi
China	The Second Affiliated Hospital of Xinxiang Medical Univ.	Xinxiang
Colombia	Centro de Investigación y Proyectos en neurociencia CIPNA	Barranquilla
Colombia	E.S.E Hospital Mental de Antioquia	Bello
Colombia	Instituto Colombiano del Sistema Nervioso- Clínica Montserrat	Bogota
Colombia	Centro de Investigaciones del Sistema Nervioso SAS- Grupo Cisne SAS	Bogotá
Colombia	Psynapsis Salud Mental S.A.	Pereira
Germany	Zentrum für klinische Forschung Dr. med. I. Schöll	Bad Homburg
Germany	Praxis Dr. Hahn, Berlin	Berlin
Germany	Zentralinstitut für seelische Gesundheit	Mannheim
Germany	Neurologie und Psychiatrie / Psychotherapie	Westerstede
Greece	Eginition Hospital	Athens
Greece	"Attikon" University General Hospital of Attica	Chaidari
Greece	Psychiatric Hospital of Attica	Haidari
Greece	AX Mental Health Clinic	Heraclion
Greece	General Oncology Hospital "Agioi Anargyri"	Nea Kifisia
Greece	General Hospital of Thessaloniki "G. Papanikolaou"	Thessaloniki
Greece	University General Hospital of Thessaloniki AHEPA	Thessaloniki
Italy	ASST degli Spedali Civili di Brescia	Brescia
Italy	A.O. Fatebenefratelli	Milano
Italy	Ist. San Raffaele Turro	Milano
Italy	Azienda Sanitaria Ospedale S. Luigi Gonzaga	Orbassano (to)
Italy	A.O.U. Senese Policlinico Santa Maria alle Scotte	Siena
Japan	Hotei Hospital	Aichi, Konan
Japan	National Center for Global Health and Medicine Kohnodai Hospital	Chiba, Ichikawa
Japan	Fukuoka University Hospital	Fukuoka, Fukuoka
Japan	Kuramitsu Hospital	Fukuoka, Fukuoka
Japan	Mental Clinic Sakurazaka	Fukuoka, Fukuoka
Japan	Shiranui Hospital	Fukuoka, Omuta
Japan	Obihiro-Kosei General Hospital	Hokkaido, Obihiro
Japan	Hokkaido University Hospital	Hokkaido, Sapporo
Japan	St. Marianna University Hospital	Kanagawa, Kawasaki
Japan	Kitasato University Hospital	Kanagawa, Sagamihara
Japan	Hino Hospital	Kanagawa, Yokohama
Japan	Yokohama Onoecho Clinic	Kanagawa, Yokohama
Japan	Kochi Health Sciences Center	Kochi, Kochi
Japan	National Hospital Organization Maizuru Medical Center	Kyoto, Maizuru
Japan	Tohoku University Hospital	Miyagi, Sendai
Japan	Shounan Hospital	Nagano, Matsumoto
Japan	Niigata University Medical and Dental Hospital	Niigata, Niigata
Japan	National Hospital Organization Hizen Psychiatric Medical Center	Saga, Kanzaki-gun
Japan	Saitama Medical University Hospital	Saitama, Iruma-gun
Japan	Nishi Kumagaya Hospital	Saitama, Kumagaya
Japan	Sho Midori Hospital	Saitama, Saitama
Japan	Dokkyo Medical University Hospital	Tochigi, Shimotsuga-gun
Japan	Tokushima University Hospital	Tokushima, Tokushima
Japan	National Center of Neurology and Psychiatry	Tokyo, Kodaira
Japan	Asuka Hospital	Tokyo, Machida
Japan	Showa University Karasuyama Hospital	Tokyo, Setagaya
Japan	Shinjuku East Mental Clinic	Tokyo, Shinjuku-ku
Japan	Ohwa Mental Clinic	Tokyo, Toshima-ku
Japan	Yamaguchi University Hospital	Yamaguchi, Ube
Japan	University of Yamanashi Hospital	Yamanashi, Chuo
Mexico	GabiPros S.C.	Cdmx
Mexico	Instituto Nacional de Neurologia y Neurocirugia	Ciudad de Mexico
Mexico	Clinica Cemelli	Guadalajara
Mexico	Medical Care & Research SA de CV	Merida
Mexico	CIT-Neuropsique S.C	Monterrey
Mexico	Instituto de Informacion e Investigacion en Salud Mental A.C. (INFOSAME).	Monterrey
New Zealand	North Shore Hospital, Takapuna	Takpuna Auckland
Norway	Sykehuset Østfold HF, avd. Moss	Moss
Norway	Akershus Universitetssykehus HF	Oslo
Philippines	St. Paul's Hospital	Iloilo City
Philippines	Makati Medical Center	Makati City
Philippines	Philippine General Hospital	Manila, Philippines
Poland	Podlassian Center of Psychogeriatry, Bialystok	Bialystok
Poland	Central Teaching Hospital of the Medical University of Lodz	Lodz
Poland	Individual Specialist Medical Practice Filip Rybakowski	Poznan
Poland	Institute of Psychiatry and Neurology in Warsaw	Warsaw
Poland	Clinhouse	Zabrze
Sweden	Psykiatriska Kliniken	Helsingborg
Sweden	Akademiska sjukhuset	Uppsala
Turkey	Ankara University Medical School	Ankara
Turkey	Hacettepe Universitesi Tip Fakultesi	Ankara
Turkey	Istanbul University	Istanbul
Turkey	Dokuz Eylul Universitesi Psikiyatri A.B.D.	Izmir
Turkey	Celal Bayar Universitesi Tip Fakultesi	Manisa
United States	Atlanta Center	Atlanta	Georgia
United States	Community Clinical Research, Inc.	Austin	Texas
United States	University at Buffalo, The State University of New York	Buffalo	New York
United States	University of Cincinnati	Cincinnati	Ohio
United States	InSite Clinical Research	DeSoto	Texas
United States	PeaceHealth Medical Group	Eugene	Oregon
United States	Core Clinical Research	Everett	Washington
United States	North Texas Clinical Trials	Fort Worth	Texas
United States	Collaborative Neuroscience Network, LLC (CNS)	Garden Grove	California
United States	Institute of Living	Hartford	Connecticut
United States	Houston Mind and Brain	Houston	Texas
United States	Omega Clinical Trials,LLC	La Habra	California
United States	CCM Clinical Research Group, LLC	Miami	Florida
United States	San Marcus Research Clinic, Inc.	Miami	Florida
United States	Neuro-Behavioral Clinical Research	North Canton	Ohio
United States	Artemis Institute for Clinical Research, LLC	San Diego	California
United States	Velocity Clinical Research	Santa Ana	California
United States	Richmond Behavioral Associates	Staten Island	New York

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Canada,  China,  Colombia,  Germany,  Greece,  Italy,  Japan,  Mexico,  New Zealand,  Norway,  Philippines,  Poland,  Sweden,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	at baseline and at week 26
Secondary	Change from baseline in the Schizophrenia Cognition Rating Scale (SCoRS) interviewer total score after 26 weeks of treatment	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.	at baseline and at week 26
Secondary	Change from baseline to Week 26 in the adjusted total time T-score in the Virtual Reality Functional Capacity Assessment Tool (VRFCAT)		at baseline and at week 26
Secondary	Change from baseline to Week 26 in the T-score of the number of correct responses on Tower of London (ToL) test		at baseline and at week 26
Secondary	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 24 weeks

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