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

NCT04846868 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: 1346-00112020-003760-11
• Study Type: interventional
• Target: 620
• Locations: 17 countries
• Sites: 116

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.

Conditions

Schizophrenia

Outcome Measures

Primary Outcomes (1)

• 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. The larger the MCCB overall composite T-score, the better patient cognition. A mean T-score of 50 and a standard deviation of 10 reflects the general population. The estimated treatment effect included the effect of any concomitant therapies for all randomized patients on on-treatment periods. On-treatment is defined as the period of first drug administration/first resumed dose after interruption until last drug administration + REP (residual effect period). The change from baseline was analyzed with a MMRM (mixed-effects model for repeated measures) with the fixed effects: treatment at each visit, stratification factor using the screening MCCB overall composite T-score, and baseline MCCB overall composite T-score at each visit. Visit was the repeated measure.

  MMRM included measurements at baseline, Week 12, and Week 26. Change from baseline values at Week 26 is reported.

Secondary Outcomes (6)

• Key Secondary Endpoint: Change From Baseline in the Schizophrenia Cognition Rating Scale (SCoRS) Interviewer Total Score After 26 Weeks of Treatment

  MMRM included measurements at baseline, Week 12, and Week 26. Change from baseline values at Week 26 is reported.

• Key Secondary Endpoint: Change From Baseline to Week 26 in the Adjusted Total Time T-score in the Virtual Reality Functional Capacity Assessment Tool (VRFCAT)

  MMRM included measurements at baseline, Week 12, and Week 26. Change from baseline values at Week 26 is reported.

• Change From Screening Visit 1a in Patient Reported Experience of Cognitive Impairment in Schizophrenia (PRECIS) Total Score at Week 24

  MMRM included measurements at Visit 1a (Week -2/Week -1), Week 15, and Week 24. Change from Visit 1a values at Week 24 is reported.

• Change From Baseline in the T-score of the Number of Correct Responses on Tower of London at Week 26

  At baseline and at Week 26.

• Ocular Safety Sub-study: Humphrey Visual Field 24-2 Swedish Interactive Thresholding Algorithm (SITA) Standard

  At baseline and at Week 24.

Study Arms (2)

Iclepertin 10 mg

EXPERIMENTAL

Patients with schizophrenia took orally once a day one 10 milligram (mg) tablet of iclepertin.

Drug: Iclepertin

Placebo-matching Iclepertin 10 mg

PLACEBO COMPARATOR

Patients with schizophrenia took orally once a day one tablet of placebo-matching iclepertin.

Drug: Placebo

Interventions

Iclepertin DRUG

One 10 milligram (mg) tablet once a day.

Iclepertin 10 mg

Placebo DRUG

One tablet once a day.

Placebo-matching Iclepertin 10 mg

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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) 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.
• 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.
• 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.
• 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.
• 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.
• 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.

You may not qualify if:

• 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.
• Cognitive impairment due to developmental, neurological (e.g., epilepsy, stroke) or other disorders including head trauma, or patients with dementia or epilepsy.
• 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).
• Any suicidal behavior in the past 1-year prior to screening and during the screening period.
• 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.
• 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.
• Positive urine drug screen at Visit 1 based on central lab test.
• 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (116)

Collaborative Neuroscience Network, LLC (CNS)

Garden Grove, California, 92845, United States

Location

Omega Clinical Trials,LLC

La Habra, California, 90631, United States

Location

Artemis Institute for Clinical Research, LLC

San Diego, California, 92103, United States

Location

Velocity Clinical Research-Santa Ana-68902

Santa Ana, California, 92704, United States

Location

Institute of Living

Hartford, Connecticut, 06106, United States

Location

San Marcus Research Clinic, Inc.

Miami, Florida, 33014, United States

Location

CCM Clinical Research Group, LLC-Miami-68482

Miami, Florida, 33133, United States

Location

Atlanta Center

Atlanta, Georgia, 30331, United States

Location

University at Buffalo, The State University of New York

Buffalo, New York, 14215, United States

Location

Richmond Behavioral Associates-Staten Island-68636

Staten Island, New York, 10314, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45219, United States

Location

Neuro-Behavioral Clinical Research

North Canton, Ohio, 44720, United States

Location

PeaceHealth Medical Group

Eugene, Oregon, 97401, United States

Location

Community Clinical Research, Inc.

Austin, Texas, 78754, United States

Location

InSite Clinical Research

DeSoto, Texas, 75115, United States

Location

North Texas Clinical Trials

Fort Worth, Texas, 76104, United States

Location

Houston Mind and Brain

Houston, Texas, 77055, United States

Location

Core Clinical Research

Everett, Washington, 98201, United States

Location

Monash Alfred Psychiatry Research Centre

Melbourne, Victoria, 3004, Australia

Location

CPN - Centro de Estudos em Neurociências

Belo Horizonte, 30150-270, Brazil

Location

Hospital das Clinicas da Universidade Federal de Minas Gerais (HCUFMG)

Belo Horizonte,Minas Gerais, 31270901, Brazil

Location

Hospital Sao Jose

Criciúma, 88811-000, Brazil

Location

Trial Tech- Tecnologia em pesquisa com medicamentos

Curitiba, 80.240-280, Brazil

Location

J A Serviços Médicos Ltda/ Instituto Goiano de Neuropisquiatria

Goiânia, 74093-040, Brazil

Location

Hospital de Base - Fac Med de Sao Jose do Rio Preto

São José do Rio Preto, 15090-000, Brazil

Location

BR Trials

São Paulo, 01236-030, Brazil

Location

University of Calgary

Calgary, Alberta, T2N 4Z6, Canada

Location

OCT Research ULC

Kelowna, British Columbia, V1Y 1Z9, Canada

Location

Centre for Addiction and Mental Health (CAMH)

Toronto, Ontario, M6J 1H3, Canada

Location

The sixth People's Hospital of Hebei Province

Baoding, 71000, China

Location

Peking University Sixth Hospital

Beijing, 100089, China

Location

Beijing HuiLongGuan Hospital

Beijing, 100096, China

Location

The Second People's Hospital of Hunan Province (Brain Hospital of Hunan Province)

Changsha, 410007, China

Location

The Affiliated Brain Hospital of Guangzhou Medical University

Guangzhou, 510370, China

Location

The Affiliated Hospital of Guizhou Medical University

Guiyang, 550004, China

Location

Shandong Daizhuang Hospital

Jining, 272051, China

Location

The First Affilliated Hospital Of Kunming of Medical College

Kunming, 650032, China

Location

The Affilicated Kangning Hospital of Ningbo University

Ningbo, 315201, China

Location

Shanghai Mental Health Center

Shanghai, 200030, China

Location

Tongji Hospital, Tongji University

Shanghai, 200065, China

Location

Wuxi mental health center

Wuxi, 214151, China

Location

The Second Affiliated Hospital of Xinxiang Medical Univ.

Xinxiang, 453002, China

Location

Centro de Investigación y Proyectos en neurociencia CIPNA

Barranquilla, 80020, Colombia

Location

E.S.E Hospital Mental de Antioquia

Bello, 51053, Colombia

Location

Instituto Colombiano del Sistema Nervioso- Clínica Montserrat

Bogotá, 110121, Colombia

Location

Centro de Investigaciones del Sistema Nervioso SAS- Grupo Cisne SAS

Bogotá, 111166, Colombia

Location

Psynapsis Salud Mental S.A.

Pereira, 660003, Colombia

Location

Zentrum für klinische Forschung Dr. med. I. Schöll GmbH

Bad Homburg, 61348, Germany

Location

Praxis Dr. Hahn, Berlin

Berlin, 13187, Germany

Location

Zentralinstitut für seelische Gesundheit

Mannheim, 68159, Germany

Location

Neurologie und Psychiatrie / Psychotherapie

Westerstede, 26655, Germany

Location

Eginition Hospital

Athens, 11528, Greece

Location

"Attikon" University General Hospital of Attica

Chaïdári, 12462, Greece

Location

Psychiatric Hospital of Attica

Haidari, 12462, Greece

Location

AX Mental Health Clinic

Heraklion, 71305, Greece

Location

General Oncology Hospital "Agioi Anargyri"

Nea Kifissia, 14564, Greece

Location

University General Hospital of Thessaloniki AHEPA

Thessaloniki, 54636, Greece

Location

General Hospital of Thessaloniki "G. Papanikolaou"

Thessaloniki, 57 010, Greece

Location

ASST degli Spedali Civili di Brescia

Brescia, 25123, Italy

Location

A.O. Fatebenefratelli

Milan, 20121, Italy

Location

Ist. San Raffaele Turro

Milan, 20127, Italy

Location

Azienda Sanitaria Ospedale S. Luigi Gonzaga

Orbassano (TO), 10043, Italy

Location

A.O.U. Senese

Siena, 53100, Italy

Location

Hotei Hospital

Aichi, Konan, 483-8248, Japan

Location

Japan Institute for Health Security National Kohnodai Medical Center

Chiba, Ichikawa, 272-8516, Japan

Location

Mental Clinic Sakurazaka

Fukuoka, Fukuoka, 810-0023, Japan

Location

Fukuoka University Hospital

Fukuoka, Fukuoka, 814-0180, Japan

Location

Kuramitsu Hospital

Fukuoka, Fukuoka, 819-0037, Japan

Location

Shiranui Hospital

Fukuoka, Omuta, 836-0004, Japan

Location

Obihiro-Kosei General Hospital

Hokkaido, Obihiro, 080-0024, Japan

Location

Hokkaido University Hospital

Hokkaido, Sapporo, 060-8648, Japan

Location

St. Marianna University Hospital

Kanagawa, Kawasaki, 216-8511, Japan

Location

Kitasato University Hospital

Kanagawa, Sagamihara, 252-0375, Japan

Location

Yokohama Onoecho Clinic

Kanagawa, Yokohama, 231-0015, Japan

Location

Hino Hospital

Kanagawa, Yokohama, 234-0051, Japan

Location

Kochi Health Sciences Center

Kochi, Kochi, 781-8555, Japan

Location

National Hospital Organization Maizuru Medical Center

Kyoto, Maizuru, 625-8502, Japan

Location

Tohoku University Hospital

Miyagi, Sendai, 980-8574, Japan

Location

Shounan Hospital

Nagano, Matsumoto, 390-0847, Japan

Location

Niigata University Medical and Dental Hospital

Niigata, Niigata, 951-8520, Japan

Location

National Hospital Organization Hizen Psychiatric Medical Center

Saga, Kanzaki-gun, 842-0192, Japan

Location

Saitama Medical University Hospital

Saitama, Iruma-gun, 350-0495, Japan

Location

Nishi Kumagaya Hospital

Saitama, Kumagaya, 360-0816, Japan

Location

Sho Midori Hospital

Saitama, Saitama, 336-0022, Japan

Location

Dokkyo Medical University Hospital

Tochigi, Shimotsuga-gun, 321-0293, Japan

Location

Tokushima University Hospital

Tokushima, Tokushima, 770-8503, Japan

Location

National Center of Neurology and Psychiatry

Tokyo, Kodaira, 187-8851, Japan

Location

Asuka Hospital

Tokyo, Machida, 194-0005, Japan

Location

Showa University Karasuyama Hospital

Tokyo, Setagaya, 157-8577, Japan

Location

Shinjuku East Mental Clinic

Tokyo, Shinjuku-ku, 160-0021, Japan

Location

Ohwa Mental Clinic

Tokyo, Toshima-ku, 170-0002, Japan

Location

Yamaguchi University Hospital

Yamaguchi, Ube, 755-8505, Japan

Location

University of Yamanashi Hospital

Yamanashi, Chuo, 409-3898, Japan

Location

Clinica Cemelli

Guadalajara, 44660, Mexico

Location

GabiPros S.C.

Mexico City, 07000, Mexico

Location

Instituto Nacional de Neurologia y Neurocirugia

Mexico City, 14269, Mexico

Location

Medical Care & Research SA de CV

Mérida, 97070, Mexico

Location

CIT-Neuropsique S.C

Monterrey, 64610, Mexico

Location

Instituto de Informacion e Investigacion en Salud Mental A.C. (INFOSAME).

Monterrey, 64710, Mexico

Location

North Shore Hospital

Takpuna Auckland, 0622, New Zealand

Location

Sykehuset Østfold HF, avd. Moss

Moss, N-1535, Norway

Location

Akershus Universitetssykehus HF

Oslo, N-0963, Norway

Location

St. Paul's Hospital-Iloilo City-40765

Iloilo City, 5000, Philippines

Location

Philippine General Hospital

Manila, Philippines, 1000, Philippines

Location

Podlassian Center of Psychogeriatry, Bialystok

Bialystok, 15-756, Poland

Location

Central Teaching Hospital of the Medical University of Lodz

Lodz, 92-216, Poland

Location

Individual Specialist Medical Practice Filip Rybakowski

Poznan, 60-744, Poland

Location

Institute of Psychiatry and Neurology in Warsaw

Warsaw, 02-957, Poland

Location

Clinhouse

Zabrze, 41-807, Poland

Location

Psykiatriska Kliniken

Helsingborg, 201 53, Sweden

Location

Akademiska sjukhuset

Uppsala, 751 85, Sweden

Location

Hacettepe Universitesi Tip Fakultesi

Ankara, 06230, Turkey (Türkiye)

Location

Ankara University Medical School

Ankara, 06590, Turkey (Türkiye)

Location

Istanbul University

Istanbul, 34093, Turkey (Türkiye)

Location

Dokuz Eylul Universitesi Psikiyatri A.B.D.

Izmir, 35340, Turkey (Türkiye)

Location

Celal Bayar Universitesi Tip Fakultesi

Manisa, 45030, Turkey (Türkiye)

Location

Related Publications (1)

• Keefe RSE, Harvey PD, Correll CU, Falkai P, Hashimoto N, Klein H, Krystal JH, Marder S, Medalia A, Sumiyoshi T, Wang G, Zhang H, Blahova Z, Bichard-Sall I, English BA, Fu E, Gruenenfelder F, Groeschl M, Kimura K, Tang W, von der Goltz C, Fowler C. Efficacy and safety of iclepertin for cognitive impairment associated with schizophrenia (CONNEX programme): results from three phase 3 randomised controlled trials. Lancet Psychiatry. 2025 Dec;12(12):906-920. doi: 10.1016/S2215-0366(25)00296-2.

  PMID: 41233083 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Schizophrenia

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2021
• First Posted: April 15, 2021
• Study Start: September 8, 2021
• Primary Completion: September 17, 2024
• Study Completion: October 1, 2024
• Last Updated: November 5, 2025
• Results First Posted: November 5, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• 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.
• 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'.

Locations

PL (5); AU (1); NO (2); ME (6); IT (5); NZ (1); CA (3); CO (5); US (18); PH (2); BR (7); GR (7); CN (13); SE (2); TU (5); DE (4); JP (30)