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

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-2)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04846881
• Other study ID #: 1346-0012
• Secondary ID: 2020-003744-84
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 7, 2021
• Est. completion date: November 13, 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. During this time, they visit the study site about 15 times and get about 3 phone calls from the study team. The doctors also regularly check participants' health and take note of any unwanted effects.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 611
• Est. completion date: November 13, 2024
• Est. primary completion date: October 21, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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 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 hospitalization3 or increase in level of psychiatric care4 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 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.

• For any other psychoactive medications cannot exceed the maximum daily dose per local label of the country where the study is being conducted.

7. Women of childbearing potential (WOCBP)5 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 patient at a minimum one 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. Patient with current DSM-5 diagnosis other than Schizophrenia, including but not limited to bipolar, schizoaffective, major depressive disorder etc. The 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. stroke) or other disorders including head trauma, or patients with dementia or epilepsy.

3. Severe movement disorders

• Leading to cognitive impairment (e.g. Parkinson's 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 Suicidality 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
Argentina	CENYDET-Centro Neurobiológico y de Estres Traumático (Biopsychomedical Research Group S.R.L.)	Caba
Argentina	Fundación FunDaMos para la asistencia e investigación en psiquiatría	Caba
Argentina	SERES Neurociencia Cognitiva Aplicada	Caba
Argentina	CEN (Centro Especializado Neurociencias)	Cordoba
Argentina	Sanatorio Morra S.A.	Córdoba
Argentina	Clinica Privada de Salud Mental Santa Teresa de Avila	La Plata
Argentina	Resolution Psychopharmacology Research Institute	Mendoza
Argentina	Centro de Investigacion y Asistencia en Psiquiatria (CIAP)	Rosario
Brazil	Ruschel Medicina e Pesquisa Clínica	Rio de Janeiro
Brazil	CEMEC - Centro Multidisciplinar de Estudos Clínicos	São Bernardo do Campo
Brazil	Clínica Viver - Centro de Desospitalização Humana	Sao Paulo
Brazil	Hospital das Clinicas da FMUSP	Sao Paulo
Brazil	Cpquali Pesquisa Clinica Ltda	São Paulo
Chile	Biomedica Research Group	Santiago
Chile	Psicomed Estudios Clínicos	Segunda Región
Croatia	Clincal Hospital Centre Rijeka	Rijeka
Croatia	Clinical Hospital Centre Zagreb	Zagreb
Croatia	Psychiatric Hospital 'Sveti Ivan'	Zagreb
Croatia	Solmed Clinic	Zagreb
Croatia	University Psychiatric Hospital Vrapce	Zagreb
France	HOP Charles Perrens	Bordeaux
France	HOP Gabriel-Montpied	Clermont-Ferrand
France	HOP Albert Chenevier	Créteil
France	HOP Fontan	Lille
France	HOP la Colombière	Montpellier
France	HOP Hôtel-Dieu	Nantes
France	HOP Pasteur	Nice
France	HOP Carémeau	Nîmes
France	HOP Guillaume Régnier	Rennes
France	HOP Rouffach	Rouffach
France	HOP Nord	Saint Priest en Jarez
Hungary	Obuda Health Center	Budapest
Hungary	Semmelweis University	Budapest
Hungary	University of Debrecen, Gyula Kenezi University Hospital	Debrecen
Hungary	PsychoTech Ltd.	Pecs
Japan	Okehazama Hospital Fujita Kokoro Care Center	Aichi, Toyoake
Japan	Toyota Memorial Hospital	Aichi, Toyota
Japan	National Hospital Organization Shimofusa Psychiatric Medical Center	Chiba, Chiba
Japan	Uematsu Mental Clinic	Fukuoka, Chikugo
Japan	AK Clinic	Fukuoka, Fukuoka
Japan	Hirota Clinic	Fukuoka, Kurume
Japan	Kishi Hospital	Gumma, Kiryu
Japan	Hokudai-dori Mental Health Clinic	Hokkaido, Sapporo
Japan	Tatsuta Clinic	Hyogo, Kobe
Japan	Kanazawa Medical University Hospital	Ishikwa, Kahoku-gun
Japan	Kishiro Mental Clinic	Kanagawa, Kawasaki
Japan	Links Mental Clinic	Kanagawa, Yokohama
Japan	Yokohama City University Hospital	Kanagawa, Yokohama
Japan	Yuge Neuropsychiatric Hospital	Kumamoto, Kumamoto
Japan	Medical Corporation Yamadakai Yatsushiro Welfare Hospital	Kumamoto, Yatsushiro
Japan	Suwa Red Cross Hospital	Nagano, Suwa
Japan	Nara Medical University Hospital	Nara, Kashihara
Japan	University of the Ryukyus Hospital	Okinawa, Nakagami-gun
Japan	Osaka City Hospital Organization Osaka City General Hospital	Osaka, Osaka
Japan	Rainbow and Sea Hospital	Saga, Karatsu
Japan	Inuo Hospital	Saga, Tosu
Japan	Medical Corporation Seijin Hospital	Tokyo, Adachi-ku
Japan	Tokyo Medical and Dental University Hospital	Tokyo, Bunkyo-ku
Japan	Nishigahara Hospital	Tokyo, Kita-ku
Japan	Minami-Aoyama Antique Street Clinic	Tokyo, Minato-ku
Japan	Toho University Omori Medical Center	Tokyo, Ota-ku
Japan	Maynds Tower Mental Clinic	Tokyo, Shibuya-ku
Japan	Shinjuku East Mental Clinic	Tokyo, Shinjuku-ku
Japan	Hokuriku Hospital	Toyama, Nanto
Korea, Republic of	Inje University Haeundae Paik Hospital	Busan
Korea, Republic of	Daegu Catholic University Medical Center	Daegu
Korea, Republic of	Inha University Hospital	Incheon
Korea, Republic of	Chonbuk National University Hospital	Jeonju
Korea, Republic of	Seoul National University Hospital	Seoul
Malaysia	Hospital Raja Permaisuri Bainun	Ipoh
Malaysia	University of Malaya Medical Centre	Kuala Lumpur
Malaysia	Hospital Sentosa	Kuching
Malaysia	Hospital Tuanku Ja'afar	Seremban, Negeri Sembilan
Netherlands	Universitair Medisch Centrum Groningen	Groningen
Netherlands	Maastricht University	Maastricht
Poland	Psychiatric Doctor's Office Ireneusz Kaczorowski	Belchatow
Poland	Podlassian Center of Psychogeriatry, Bialystok	Bialystok
Poland	Health Center Alcea	Gdansk
Poland	MentalMEDIC	Gliwice
Poland	Provincial Hospital for Nervous and Mentally Ill in Swiecie	Swiecie
Poland	EUROMEDIS Sp. z o.o., Szczecin	Szczecin
Poland	Clinhouse	Zabrze
Romania	Mental Health Center Sector 4	Bucharest
Romania	SC Carpe Diem SRL	Sibiu
Serbia	Institute for Mental Health	Belgrade
Serbia	Special Hospital for Psychiatric Diseases Sveti Vracevi	Novi Knezevac
Serbia	Clinical Center of Vojvodina	Novi Sad
Singapore	Changi General Hospital	Singapore
Singapore	Institute of Mental Health	Singapore
Slovakia	Psychiatria, Nemocnica s poliklinikou Prievidza so sidlom v Bojniciach	Bojnice
Slovakia	EPAMED s.r.o.	Kosice
Slovakia	Psychiatricka Ambulancia Psycholine s.r.o.	Rimavska Sobota
Spain	Hestia Palau	Barcelona
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospital Universitario General de Villalba	Collado De Villalba
Spain	Hospital Universitario Reina Sofía	Córdoba
Spain	Centro de Salud mental de Getafe	Getafe
Spain	Hospital Puerta de Hierro	Majadahonda
Spain	Hospital de Son Llàtzer	Palma
Spain	Centro de Salud de San Juan	Salamanca
Spain	Benito Menni Complejo Asistencial en Salud Mental	Sant Boi de Llobregat
Spain	Hospital Virgen del Rocío	Sevilla
Spain	Hospital Clínico de Valencia	Valencia
Spain	Hospital Nicolás Peña	Vigo
Spain	Hospital Provincial. Complejo Asistencial de Zamora	Zamora
Ukraine	Communal Non-Profit Enterprise "Regional Clinical Psychiatric Hospital" of Kirovohrad Regional Council	Nove
United States	Sheppard Pratt Physicians's Practice Association, Inc.	Baltimore	Maryland
United States	Insight Clinical Trials	Beachwood	Ohio
United States	Northwest Clinical Research Center	Bellevue	Washington
United States	Clinical Innovations, Inc	Bellflower	California
United States	Neurobehavioral Research, Inc.	Cedarhurst	New York
United States	American Medical Research	Chicago	Illinois
United States	ATP Clinical Research, Inc.	Costa Mesa	California
United States	Relaro Medical Trials, LLC	Dallas	Texas
United States	John Peter Smith Health Network	Fort Worth	Texas
United States	Research in Miami Inc	Hialeah	Florida
United States	ASCLEPES Research Centers, P.C. dba Alliance Research	Long Beach	California
United States	University of California Los Angeles	Los Angeles	California
United States	Optimus U Corporation	Miami	Florida
United States	Connecticut Mental Health Center	New Haven	Connecticut
United States	New York State Psychiatric Institute	New York	New York
United States	NRC Research Institute	Orange	California
United States	PsychCare Consultants Research	Saint Louis	Missouri
United States	Salem VA Medical Center	Salem	Virginia
United States	Collaborative Neuroscience Research, LLC	Torrance	California
United States	Health Synergy Clinical Research, LLC	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Chile,  Croatia,  France,  Hungary,  Japan,  Korea, Republic of,  Malaysia,  Netherlands,  Poland,  Romania,  Serbia,  Singapore,  Slovakia,  Spain,  Ukraine, 

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

External Links

•   Related Info