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

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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Placebo; Drug: Iclepertin

• Study Type: Interventional
• Enrollment (Actual): 620
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Boehringer Ingelheim; Phone Number: 1-800-243-0127; Email: clintriage.rdg@boehringer-ingelheim.com

Study Locations

• Australia
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Medical Centre
    • Melbourne, Victoria, Australia, 3004
      • Monash Alfred Psychiatry Research Centre
• Brazil
  • Belo Horizonte, Brazil, 30150-270
    • CPN - Centro de Estudos em Neurociências
  • Belo Horizonte,Minas Gerais, Brazil, 31270901
    • Hospital das Clinicas da Universidade Federal HC-UFMG
  • Criciuma, Brazil, 88811-000
    • Hospital Sao Jose
  • Curitiba, Brazil, 80.240-280
    • Trial Tech- Tecnologia em pesquisa com medicamentos
  • Goiania, Brazil, 74093-040
    • J A Serviços Médicos Ltda/ Instituto Goiano de Neuropisquiatria
  • Sao Jose do Rio Preto, Brazil, 15090-000
    • Hospital de Base - Fac Med de Sao Jose do Rio Preto
  • Sao Paulo, Brazil, 01236-030
    • BR Trials
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • University of Calgary
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 1Z9
      • OCT Research ULC
  • Ontario
    • Toronto, Ontario, Canada, M6J 1H3
      • Centre for Addiction and Mental Health (CAMH)
• China
  • Baoding, China, 71000
    • The sixth People's Hospital of Hebei Province
  • Beijing, China, 100096
    • Beijing HuiLongGuan Hospital
  • Beijing, China, 100089
    • Peking University Sixth Hospital
  • Changsha, China, 410007
    • Brain Hospital of Hunan Province
  • Guangzhou, China, 510370
    • The Affiliated Brain Hospital of Guangzhou Medical University
  • Guiyang, China, 550004
    • The Affiliated Hospital Of GuiZhou Medical University
  • Jining, China, 272051
    • Shandong Daizhuang Hospital
  • Kunming, China, 650032
    • The First Affilliated Hospital Of Kunming of Medical College
  • Ningbo, China, 315201
    • NingBo KangNing Hospital
  • Shanghai, China, 200065
    • Tongji Hospital, Tongji University
  • Shanghai, China, 200030
    • Shanghai Mental Health Center
  • Wuxi, China, 214151
    • Wuxi mental health center
  • Xinxiang, China, 453002
    • The Second Affiliated Hospital of Xinxiang Medical Univ.
• Colombia
  • Barranquilla, Colombia, 80020
    • Centro de Investigación y Proyectos en neurociencia CIPNA
  • Bello, Colombia, 51053
    • E.S.E Hospital Mental de Antioquia
  • Bogota, Colombia, 110121
    • Instituto Colombiano del Sistema Nervioso- Clínica Montserrat
  • Bogotá, Colombia, 111166
    • Centro de Investigaciones del Sistema Nervioso SAS- Grupo Cisne SAS
  • Pereira, Colombia, 660003
    • Psynapsis Salud Mental S.A.
• Germany
  • Bad Homburg, Germany, 61350
    • Zentrum für klinische Forschung Dr. med. I. Schöll
  • Berlin, Germany, 13187
    • Praxis Dr. Hahn, Berlin
  • Mannheim, Germany, 68159
    • Zentralinstitut für seelische Gesundheit
  • Westerstede, Germany, 26655
    • Neurologie und Psychiatrie / Psychotherapie
• Greece
  • Athens, Greece, 11528
    • Eginition Hospital
  • Chaidari, Greece, 12462
    • "Attikon" University General Hospital of Attica
  • Haidari, Greece, 12462
    • Psychiatric Hospital of Attica
  • Heraclion, Greece, 71305
    • AX Mental Health Clinic
  • Nea Kifisia, Greece, 14564
    • General Oncology Hospital "Agioi Anargyri"
  • Thessaloniki, Greece, 54636
    • University General Hospital of Thessaloniki AHEPA
  • Thessaloniki, Greece, 57 010
    • General Hospital of Thessaloniki "G. Papanikolaou"
• Italy
  • Brescia, Italy, 25123
    • Asst Degli Spedali Civili Di Brescia
  • Lecce, Italy, 73100
    • USL5 di Lecce
  • Milano, Italy, 20121
    • A.O. Fatebenefratelli
  • Milano, Italy, 20127
    • Ist. San Raffaele Turro
  • Orbassano (to), Italy, 10043
    • Azienda Sanitaria Ospedale S. Luigi Gonzaga
  • Roma, Italy, 00179
    • IRCCS Fondazione Santa Lucia
  • Siena, Italy, 53100
    • A.O.U. Senese Policlinico Santa Maria alle Scotte
• Japan
  • Aichi, Konan, Japan, 483-8248
    • Hotei Hospital
  • Chiba, Ichikawa, Japan, 272-8516
    • National Center for Global Health and Medicine Kohnodai Hospital
  • Fukuoka, Fukuoka, Japan, 814-0180
    • Fukuoka University Hospital
  • Fukuoka, Fukuoka, Japan, 819-0037
    • Kuramitsu Hospital
  • Fukuoka, Fukuoka, Japan, 810-0023
    • Mental Clinic Sakurazaka
  • Fukuoka, Omuta, Japan, 836-0004
    • Shiranui Hospital
  • Hokkaido, Obihiro, Japan, 080-0024
    • Obihiro-Kosei General Hospital
  • Hokkaido, Sapporo, Japan, 060-8648
    • Hokkaido University Hospital
  • Kanagawa, Kawasaki, Japan, 216-8511
    • St. Marianna University Hospital
  • Kanagawa, Sagamihara, Japan, 252-0375
    • Kitasato University Hospital
  • Kanagawa, Yokohama, Japan, 231-0015
    • Yokohama Onoecho Clinic
  • Kanagawa, Yokohama, Japan, 234-0051
    • Hino Hospital
  • Kochi, Kochi, Japan, 781-8555
    • Kochi Health Sciences Center
  • Kyoto, Maizuru, Japan, 625-8502
    • National Hospital Organization Maizuru Medical Center
  • Miyagi, Sendai, Japan, 980-8574
    • Tohoku University Hospital
  • Nagano, Matsumoto, Japan, 390-0847
    • Shounan Hospital
  • Niigata, Niigata, Japan, 951-8520
    • Niigata University Medical and Dental Hospital
  • Saga, Kanzaki-gun, Japan, 842-0192
    • National Hospital Organization Hizen Psychiatric Medical Center
  • Saitama, Iruma-gun, Japan, 350-0495
    • Saitama Medical University Hospital
  • Saitama, Kumagaya, Japan, 360-0816
    • Nishi Kumagaya Hospital
  • Saitama, Saitama, Japan, 336-0022
    • Sho Midori Hospital
  • Tochigi, Shimotsuga-gun, Japan, 321-0293
    • Dokkyo Medical University Hospital
  • Tokushima, Tokushima, Japan, 770-8503
    • Tokushima University Hospital
  • Tokyo, Kodaira, Japan, 187-8851
    • National Center of Neurology and Psychiatry
  • Tokyo, Machida, Japan, 194-0005
    • Asuka Hospital
  • Tokyo, Setagaya, Japan, 157-8577
    • Showa University Karasuyama Hospital
  • Tokyo, Shinjuku-ku, Japan, 160-0022
    • Shinjuku East Mental Clinic
  • Tokyo, Toshima-ku, Japan, 170-0002
    • Ohwa Mental Clinic
  • Yamaguchi, Ube, Japan, 755-8505
    • Yamaguchi University Hospital
  • Yamanashi, Chuo, Japan, 409-3898
    • University of Yamanashi Hospital
• Mexico
  • Cdmx, Mexico, 07810
    • GabiPros S.C.
  • Ciudad de Mexico, Mexico, 14269
    • Instituto Nacional de Neurologia y Neurocirugia
  • Guadalajara, Mexico, 44660
    • Clinica Cemelli
  • Merida, Mexico, 97070
    • Medical Care & Research SA de CV
  • Monterrey, Mexico, 64610
    • CIT-Neuropsique S.C
  • Monterrey, Mexico, 64710
    • Instituto de Informacion e Investigacion en Salud Mental A.C. (INFOSAME).
• New Zealand
  • Takpuna Auckland, New Zealand, 0622
    • North Shore Hospital, Takapuna
• Norway
  • Moss, Norway, N-1535
    • Sykehuset Østfold HF, avd. Moss
  • Oslo, Norway, N-0963
    • Akershus universitetssykehus HF
• Philippines
  • Iloilo City, Philippines, 5000
    • St. Paul's Hospital
  • Makati City, Philippines, 1229
    • Makati Medical Center
  • Manila, Philippines, Philippines, 1000
    • Philippine General Hospital
• Poland
  • Bialystok, Poland, 15-756
    • Podlassian Center of Psychogeriatry, Bialystok
  • Lodz, Poland, 92-216
    • Central Teaching Hospital of the Medical University of Lodz
  • Poznan, Poland, 60-744
    • Individual Specialist Medical Practice Filip Rybakowski
  • Warsaw, Poland, 02-957
    • Institute of Psychiatry and Neurology in Warsaw
  • Zabrze, Poland, 41-807
    • Clinhouse
• Sweden
  • Helsingborg, Sweden, 201 53
    • Psykiatriska Kliniken
  • Uppsala, Sweden, 751 85
    • Akademiska sjukhuset
• Turkey
  • Ankara, Turkey, 06230
    • Hacettepe Universitesi Tip Fakultesi
  • Ankara, Turkey, 06590
    • Ankara University Medical School
  • Istanbul, Turkey, 34093
    • Istanbul University
  • Izmir, Turkey, 35340
    • Dokuz Eylul Universitesi Psikiyatri A.B.D.
  • Manisa, Turkey, 45030
    • Celal Bayar Universitesi Tip Fakultesi
• United States
  • California
    • Garden Grove, California, United States, 92845
      • Collaborative Neuroscience Network, LLC (CNS)
    • La Habra, California, United States, 90631
      • Omega Clinical Trials,LLC
    • San Diego, California, United States, 92103
      • Artemis Institute for Clinical Research, LLC
    • Santa Ana, California, United States, 92704
      • Velocity Clinical Research
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Institute of Living
  • Florida
    • Miami, Florida, United States, 33014
      • San Marcus Research Clinic, Inc.
    • Miami, Florida, United States, 33133
      • CCM Clinical Research Group, LLC
  • Georgia
    • Atlanta, Georgia, United States, 30331
      • Atlanta Center
  • New York
    • Buffalo, New York, United States, 14215
      • University at Buffalo, The State University of New York
    • Staten Island, New York, United States, 10314
      • Richmond Behavioral Associates
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati
    • North Canton, Ohio, United States, 44720
      • Neuro-Behavioral Clinical Research
  • Oregon
    • Eugene, Oregon, United States, 97401
      • PeaceHealth Medical Group
  • Texas
    • Austin, Texas, United States, 78754
      • Community Clinical Research, Inc.
    • DeSoto, Texas, United States, 75115
      • InSite Clinical Research
    • Fort Worth, Texas, United States, 76104
      • North Texas Clinical Trials
    • Houston, Texas, United States, 77055
      • Houston Mind and Brain
  • Washington
    • Everett, Washington, United States, 98201
      • Core Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo
Experimental: Iclepertin	Drug: Iclepertin; Iclepertin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): June 16, 2021
• Primary Completion (Estimated): September 13, 2024
• Study Completion (Estimated): October 11, 2024

Study Registration Dates

• First Submitted: April 13, 2021
• First Submitted That Met QC Criteria: April 13, 2021
• First Posted (Actual): April 15, 2021

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: 1346-0011; 2020-003760-11 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement".

Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.

The data shared are the raw clinical study data sets.

• IPD Sharing Time Frame: After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• IPD Sharing Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing Agreement'.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No