CONNEX-3: A Study to Test Whether Iclepertin Improves Learning and Memory in People With Schizophrenia

NCT04860830 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: 1346-00132020-003726-23
• Study Type: interventional
• Target: 609
• Locations: 18 countries
• Sites: 110

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

  The MCCB assesses 7 cognitive domains, including speed of processing, attention vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. T-scores in the general population have a mean of 50 and standard deviation of 10, and a higher score indicates better cognition. The primary analysis was a restricted maximum likelihood (REML) based approach using a mixed-effects model for repeated measurements (MMRM), which included the fixed categorical effects of treatment at each visit, fixed categorical effect of the stratification factor using the screening MCCB overall composite T-score, and a fixed effect for the continuous covariate of baseline at each visit. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-subject dependencies. Intercurrent events were addressed using different pre-defined strategies.

  The MMRM model incorporates values from baseline (Week 0), Week 12 and Week 26. The data represent the Least Squares Means at Week 26.

Secondary Outcomes (6)

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

  The MMRM model incorporates values from baseline (Week 0), Week 12 and Week 26. The data represent the Least Squares Means at Week 26.

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

  The MMRM model incorporates values from baseline (Week 0), Week 12 and Week 26. The data represent the Least Squares Means at Week 26.

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

  At baseline (Week 0) and at Week 26.

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

  The MMRM model incorporates values from baseline (screening), Week 15 and Week 24. The data represent the Least Squares Means at Week 24.

• Ocular Safety Sub-study: Change From Baseline in Humphrey Visual Field 24-2 Swedish Interactive Thresholding Algorithm (SITA) Standard at Week 24

  Measurements were performed at baseline (screening) and at Week 24.

Study Arms (2)

Iclepertin 10 mg

EXPERIMENTAL

Patients with schizophrenia took one tablet of 10 milligram (mg) iclepertin orally once daily for 26 weeks. Patients were permitted to remain on other antipsychotic and psychotropic medications, as specified in the eligibility criteria.

Drug: Iclepertin

Placebo

PLACEBO COMPARATOR

Patients with schizophrenia took one tablet of placebo matching iclepertin orally once daily for 26 weeks. Patients were permitted to remain on other antipsychotic and psychotropic medications, as specified in the eligibility criteria.

Drug: Placebo

Interventions

Iclepertin DRUG

One tablet of 10 mg once daily for 26 weeks.

Also known as: BI 425809

Iclepertin 10 mg

Placebo DRUG

One tablet once daily for 26 weeks.

Placebo

Eligibility Criteria

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

You may qualify if:

• Signed and dated written informed consent.
• 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).
• \-- Patients must be clinically stable and in the residual (non-acute) phase of their illness with no hospitalization or increase level of care due to worsening of schizophrenia in the past 12 weeks or no uncontrolled positive symptoms.
• Patients should have functional impairment in day-to-day activities per investigator judgement.
• Patients maintained on current antipsychotic treatment for at least 12 weeks and on current dose for at least 35 days prior to randomization.
• 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.
• Women of childbearing potential must use highly effective methods of birth control.

You may not qualify if:

• Patient with current DSM-5 diagnosis other than Schizophrenia.
• Cognitive impairment due to other causes, or patients with dementia or epilepsy.
• Severe movement disorders.
• Any suicidal behavior in past year or suicidal ideation in the past 3 months.
• History of moderate or severe substance use disorder within the last 12 months prior to informed consent.
• Positive urine drug screen.
• Patients who were treated with Clozapine, stimulants, ketamine or electroconvulsive therapy within 6 months prior to randomization.
• Current participation in any investigational drug trial.
• Cognitive Remediation Therapy within 12 weeks prior to screening.
• Initiation or change in any type or frequency of psychotherapy within 12 weeks prior to randomization.
• Any clinically significant finding or condition that would jeopardize the patient´s safety while participating in the trial or their capability to participate in the trial.
• Haemoglobin (Hb) below lower limit of normal .
• History of haemolytic anaemia, red blood cell (RBC) membrane diseases, known Glucose-6-phosphate dehydrogenase deficiency, anaemia of any cause or patients planning to donate blood.
• Severe renal impairment.
• Indication of liver disease.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (110)

Advanced Research Center, Inc.

Anaheim, California, 92805, United States

Location

ProScience Research Group

Culver City, California, 90230, United States

Location

University of California Los Angeles

Los Angeles, California, 90095, United States

Location

CNRI - Los Angeles

Pico Rivera, California, 90660, United States

Location

Stanford University Medical Center

Stanford, California, 94304, United States

Location

Sunwise Clinical Research-Walnut Creek-70166

Walnut Creek, California, 94596, United States

Location

Advanced Medical Research Group Inc

Hollywood, Florida, 33021, United States

Location

Accel Research Sites Network

Maitland, Florida, 32751, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Ivetmar Medical Group, LLC

Miami, Florida, 33155, United States

Location

Nova Psychiatry Inc.

Orlando, Florida, 32803, United States

Location

Synexus Clinical Research-Atlanta-67262

Atlanta, Georgia, 30328, United States

Location

Augusta University

Augusta, Georgia, 30912, United States

Location

Center for Behavioral Health, LLC

Gaithersburg, Maryland, 20877, United States

Location

Arch Clinical Trials, LLC

St Louis, Missouri, 63141, United States

Location

Omaha Insomnia and Psychiatric Services

Omaha, Nebraska, 68144, United States

Location

Hassman Research Institute-Berlin-60540

Berlin, New Jersey, 08009, United States

Location

UNC Center for Excellence in Community Mental Health, North Carolina Psychiatric Research Center

Raleigh, North Carolina, 27608, United States

Location

Midwest Clinical Research

Dayton, Ohio, 45417, United States

Location

Rivus Wellness and Research Institute

Oklahoma City, Oklahoma, 73112, United States

Location

Cutting Edge Research Group

Oklahoma City, Oklahoma, 73116, United States

Location

Oasis Life Care

State College, Pennsylvania, 16801, United States

Location

Ben Taub General Hospital

Houston, Texas, 77030, United States

Location

LinQ Research, LLC-Richmond-70076

Richmond, Texas, 77407, United States

Location

Clínica Privada Banfield

Banfield, B1828CKR, Argentina

Location

Fundación para el Estudio y Tratamiento de las Enfermedades Mentales (FETEM)

CABA, C1133AAH, Argentina

Location

Fundación FunDaMos para la asistencia e investigación en psiquiatría

CABA, C1405BOA, Argentina

Location

CEN (Centro Especializado Neurociencias)

Córdoba, 5004, Argentina

Location

Instituto Modelo de Neurología Lennox

Córdoba, X5000FAL, Argentina

Location

Instituto Médico DAMIC S.R.L.

Córdoba, X5003DCE, Argentina

Location

Instituto de Neurociencias San Agustín

La Plata, 1900, Argentina

Location

Instituto Médico de la Fundación Estudios Clínicos

Rosario, 2000, Argentina

Location

Centro Medico Luquez

San Vicente, X5006CBI, Argentina

Location

AKH - Medical University of Vienna

Vienna, 1090, Austria

Location

CUP Vivalia -La Clairière

Bertix, 6880, Belgium

Location

Sint-Kamillus

Bierbeek, 3360, Belgium

Location

Universitair Psychiatrisch Centrum Duffel (UPC Duffel)

Duffel, 2570, Belgium

Location

Meclinas

Mechelen, 2800, Belgium

Location

Ruschel Medicina e Pesquisa Clínica

Rio de Janeiro, 22270-060, Brazil

Location

Clínica Viver - Centro de Desospitalização Humana

São Paulo, 04020-060, Brazil

Location

Filipopolis Ambulatory for Group Practice for Specialized Care in Psychiatry

Plovdiv, 4000, Bulgaria

Location

Medical Center "Spectar"

Plovdiv, 4000, Bulgaria

Location

Medical Center Hera EOOD

Sofia, 1510, Bulgaria

Location

Beijing Anding Hospital

Beijing, 100088, China

Location

The Second Xiangya Hospital Of Central South University

Changsha, 410011, China

Location

The third affiliated hospital of Sun Yat-Sen University

Guangzhou, 510630, China

Location

Huzhou Third Municipal Hospital

Huzhou, 313000, China

Location

Nanjing Brain Hospital

Nanjing, 210029, China

Location

Shenzhen Kangning Hospital

Shenzhen, 518003, China

Location

The First Hospital of Hebei Medical University

Shijiazhuang, 050030, China

Location

Tianjin Anding Hospital

Tianjin, 300222, China

Location

First Affiliated Hospital of Xi'an JiaoTong University

Xi'an, 710061, China

Location

Xi'an Mental Health Center

Xi'an, 710101, China

Location

Zhumadian Psychiatric Hospital

Zhumadian, 463000, China

Location

National Institute of Mental Health

Klecany, 25067, Czechia

Location

MP Meditrine s.r.o.

Ostrava, 708 00, Czechia

Location

A-SHINE s.r.o

Pilsen, 30100, Czechia

Location

PRAGTIS s.r.o.

Prague, 120 00, Czechia

Location

INEP medical s.r.o.

Prague, 18600, Czechia

Location

Psychiatrie Ricany s.r.o.

Říčany, 251 01, Czechia

Location

Aalborg Universitetsshospital

Aalborg, 9000, Denmark

Location

Aarhus University Hospital

Aarhus, 8200, Denmark

Location

Psykiatrisk Center Glostrup

Glostrup Municipality, 2600, Denmark

Location

HUS Jorvi Hospital

Espoo, 2740, Finland

Location

Aurora hospital

Helsinki, 00250, Finland

Location

CRST - Clinical Research Services Turku

Turku, 20520, Finland

Location

Studienzentrum für Neurologie und Psychiatrie

Böblingen, 71034, Germany

Location

LWL-Klinik Dortmund

Dortmund, 44287, Germany

Location

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, 55131, Germany

Location

Klinikum der Universität München - Campus Innenstadt

München, 80336, Germany

Location

Universitätsklinikum Tübingen

Tübingen, 72076, Germany

Location

JSC Romuvos Clinic

Kaunas, LT-44279, Lithuania

Location

LUHS KH Psichiatric Clinic Mariu Division

Kaunas, LT-53137, Lithuania

Location

JSC Medical center "Puriena"

Šilutė, LT-99142, Lithuania

Location

Vilnius City Mental Health Center

Vilnius, LT-10309, Lithuania

Location

Centro de Investigacion Integral MEDIVEST S.C

Chihuahua City, 31203, Mexico

Location

Centro para el Desarrollo de la Medicina y de Asistencia Medica Especializada S.C.

Culiacán, 80230, Mexico

Location

Hospital Aranda de la Parra

León, 37000, Mexico

Location

Centro de Investigación Clinica Acelerada, S.C.

Mexico City, 07369, Mexico

Location

Iecsi S.C.

Monterrey, 64310, Mexico

Location

Hospital Universitario Dr Jose Eleuterio Gonzalez

Monterrey, 64460, Mexico

Location

BIND Investigaciones S.C.

San Luis Potosí City, 78213, Mexico

Location

ULS da Região de Leiria, E.P.E.

Leiria, 2410-197, Portugal

Location

ULS de Santa Maria, E.P.E

Lisbon, 1649-035, Portugal

Location

ULS de Loures-Odivelas, E.P.E

Loures, 2674-514, Portugal

Location

Clinical Hospital Center Dr. Dragisa Misovic

Belgrade, 11000, Serbia

Location

General Hospital Euromedik

Belgrade, 11000, Serbia

Location

Special Hospital for Psychiatric Diseases Gornja Toponica

Gornja Toponica, 18202, Serbia

Location

Inje University Busan Paik Hospital

Busan, 47392, South Korea

Location

Yeungnam University Medical Center

Daegu, 705-717, South Korea

Location

Chonnam National University Hospital

Gwangju, 61453, South Korea

Location

Seoul National University Bundang Hospital

Seongnam, 13620, South Korea

Location

CHA Bundang Medical Center

Seongnam-si, 13496, South Korea

Location

Pusan National University Yangsan Hospital

Yangsan, 50612, South Korea

Location

Kai-Syuan Psychiatric Hospital

Kaohsiung City, 802, Taiwan

Location

Chang Gung Memorial Hospital-Keelung

Keelung, 204, Taiwan

Location

Chung Shan Medical University Hospital

Taichung, 40201, Taiwan

Location

NCKUH

Tainan, 704, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Chang Gung Memorial Hospital, Linkou

Taoyuan, 333, Taiwan

Location

Taoyuan Psychiatric Center

Taoyuan District, 33058, Taiwan

Location

Bodmin Community Hospital

Bodmin, PL31 2QT, United Kingdom

Location

The Fritchie Centre

Cheltenham, GL53 9DZ, United Kingdom

Location

Redesmere

Chester, CH2 1BQ, United Kingdom

Location

Western General Hospital

Edinburgh, EH4 2XU, United Kingdom

Location

Queen Elizabeth University Hospital

Glasgow, G51 4TF, United Kingdom

Location

Maudsley Hospital

London, SE5 8AZ, United Kingdom

Location

Warneford Hospital

Oxford, OX3 7JX, United Kingdom

Location

Moorgreen Hospital

Southampton, SO30 3JB, United Kingdom

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

Interventions

BI 425809

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 26, 2021
• First Posted: April 27, 2021
• Study Start: August 9, 2021
• Primary Completion: October 28, 2024
• Study Completion: November 20, 2024
• Last Updated: February 6, 2026
• Results First Posted: February 6, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: One year after the approval has been granted by major Regulatory Authorities and after the primary manuscript has been accepted for publication, or after termination of the development program.
• 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 the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.

Locations

CN (11); AU (1); BU (3); TW (8); US (24); SE (3); FI (3); ME (7); DK (3); BE (4); GB (8); AR (9); LI (4); KR (6); BR (2); CZ (6); DE (5); PT (3)