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

Recruitment Status
COMPLETED - HAS RESULTS
(See Contacts and Locations)Verified September 2025 by Boehringer Ingelheim
Sponsor
Boehringer Ingelheim
Information Provided by (Responsible Party)
Boehringer Ingelheim
Clinicaltrials.gov Identifier
NCT04846868
Other Study ID Numbers:
1346-0011
First Submitted
April 12, 2021
First Posted
April 14, 2021
Results First Posted
September 15, 2025
Last Update Posted
November 4, 2025
Last Verified
September 2025

ClinicalTrials.gov processed this data on October 2025. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Condition or DiseaseIntervention/Treatment
Schizophrenia
Drug: IclepertinDrug: Placebo

Study Design

Study TypeInterventional
Actual Enrollment620 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingQuadruple
Primary PurposeTreatment
Official TitleA 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)
Study Start DateSeptember 7, 2021
Actual Primary Completion DateSeptember 16, 2024
Actual Study Completion DateSeptember 30, 2024

Groups and Cohorts

Group/CohortIntervention/Treatment
Iclepertin 10 mg
Patients with schizophrenia took orally once a day one 10 milligram (mg) tablet of iclepertin.
Drug: Iclepertin
One 10 milligram (mg) tablet once a day.
Placebo-matching Iclepertin 10 mg
Patients with schizophrenia took orally once a day one tablet of placebo-matching iclepertin.
Drug: Placebo
One tablet once a day.

Outcome Measures

Primary Outcome Measures
  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.
Secondary Outcome Measures
  1. Key Secondary Endpoint: Change From Baseline in the Schizophrenia Cognition Rating Scale (SCoRS) Interviewer Total Score After 26 Weeks of Treatment
    The SCoRS is an interview based- assessment tool to evaluate the cognitive function of individuals with schizophrenia that incorporates the input of the patient, the caregiver and the interviewer. It is composed of 20 items on a 7-point Likert scale, ranging from 20 to 140 points, where a higher score indicates a greater cognitive impairment. The estimated treatment effect included the effect of any concomitant therapies and partner change in SCoR assessment for all randomized patients on-treatment. On-treatment is defined as the period of 1st drug administration/1st resumed dose after interruption until last drug administration + REP. The change from baseline was analyzed with mixed-effects model for repeated measures (MMRM) 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 treated as the repeated measure.
  2. 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)
    The VRFCAT is a computerized assessment measuring the functional capacity of an individual to perform everyday tasks. It generates a composite score based on the amount of time taken to complete the tasks. The lower the VRFCAT T-score, the better patient's functional capacity. A mean T-score of 50 and a standard deviation of 10 reflects the T-score in a general population. The estimated treatment effect included the effect of any concomitant therapies for all randomized patients on-treatment. On-treatment is defined as the period of 1st drug administration/1st resumed dose after interruption until last drug administration + REP. The change from baseline was analyzed with MMRM 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 treated as the repeated measure.
  3. Change From Screening Visit 1a in Patient Reported Experience of Cognitive Impairment in Schizophrenia (PRECIS) Total Score at Week 24
    The Patient Reported Experience of Cognitive Impairment in Schizophrenia (PRECIS) score evaluates how cognitive difficulties impact the daily life of individuals with schizophrenia. It is composed of 28 items on a 5-category Likert scale (1=not at all/not at all hard, 5=very much/very hard), and the total score was derived by calculating the average score of the first 26 items, where higher scores mean a worse patient experience. The estimated treatment effect included the effect of any concomitant therapies for all randomized patients on-treatment. On-treatment is defined as the period of 1st drug administration/1st resumed dose after interruption until last drug administration + REP. The change from baseline was analyzed with MMRM 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 treated as the repeated measure.
  4. Change From Baseline in the T-score of the Number of Correct Responses on Tower of London at Week 26
    The Tower of London (ToL) evaluates executive functioning, reasoning, problem-solving, and goal-directed behavior. It measures the number of correct responses in solving an exercise that consists on moving colored balls to match a target configuration. The higher the ToL T-score, the better patient's cognitive function. A mean T-score of 50 and a standard deviation of 10 reflects the T-score in a general population. The estimated treatment effect included the effect of any concomitant therapies for all randomized patients on-treatment. On-treatment is defined as the period of 1st drug administration/1st resumed dose after interruption until last drug administration + REP. The change from baseline comparing the groups was analyzed using analysis of covariance (ANCOVA) model including treatment, stratification factor of screening MCCB overall composite T-score, and baseline number of correct responses on Tower of London T-score.
  5. Ocular Safety Sub-study: Humphrey Visual Field 24-2 Swedish Interactive Thresholding Algorithm (SITA) Standard
    The Humphrey Visual Field 24-2 SITA Standard is a diagnostic test to measure visual fields, or perimetry. The Humphrey visual field test measures the entire area of peripheral vision that can be seen while the eye is focused on a central point. During this test, lights of varying intensities appear in different parts of the visual field while the patient's eye is focused on a central spot. The perception of these lights is charted and then compared to results of a healthy eye at the same age of the patient to determine if any damage has occurred. The tests ranks from 0 to 100%, where 0 means no vision and 100 means perfect vision.
  6. Ocular Safety Sub-study: Central Retinal Thickness as Measured by Spectral Domain Optical Coherence Tomography (SD-OCT)
    The central retinal thickness for both eyes was measured by high-definition optical coherence tomography (spectral domain OCT), which evaluates the retinal and sub-retinal structures of both eyes.

Eligibility Criteria

Ages Eligible for Study(Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
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
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.

Contacts and Locations

Sponsors and CollaboratorsBoehringer Ingelheim
Locations
Collaborative Neuroscience Network, LLC (CNS) | Garden Grove California, United States, 92845Omega Clinical Trials,LLC | La Habra California, United States, 90631Artemis Institute for Clinical Research, LLC | San Diego California, United States, 92103Velocity Clinical Research-Santa Ana-68902 | Santa Ana California, United States, 92704Institute of Living | Hartford Connecticut, United States, 06106San Marcus Research Clinic, Inc. | Miami Florida, United States, 33014CCM Clinical Research Group, LLC-Miami-68482 | Miami Florida, United States, 33133Atlanta Center | Atlanta Georgia, United States, 30331University at Buffalo, The State University of New York | Buffalo New York, United States, 14215Richmond Behavioral Associates-Staten Island-68636 | Staten Island New York, United States, 10314University of Cincinnati | Cincinnati Ohio, United States, 45219Neuro-Behavioral Clinical Research | North Canton Ohio, United States, 44720PeaceHealth Medical Group | Eugene Oregon, United States, 97401Community Clinical Research, Inc. | Austin Texas, United States, 78754InSite Clinical Research | DeSoto Texas, United States, 75115North Texas Clinical Trials | Fort Worth Texas, United States, 76104Houston Mind and Brain | Houston Texas, United States, 77055Core Clinical Research | Everett Washington, United States, 98201Monash Alfred Psychiatry Research Centre | Melbourne Victoria, Australia, 3004CPN - Centro de Estudos em Neurociências | Belo Horizonte , Brazil, 30150-270Hospital das Clinicas da Universidade Federal de Minas Gerais (HCUFMG) | Belo Horizonte,Minas Gerais , Brazil, 31270901Hospital Sao Jose | Criciúma , Brazil, 88811-000Trial Tech- Tecnologia em pesquisa com medicamentos | Curitiba , Brazil, 80.240-280J A Serviços Médicos Ltda/ Instituto Goiano de Neuropisquiatria | Goiânia , Brazil, 74093-040Hospital de Base - Fac Med de Sao Jose do Rio Preto | São José do Rio Preto , Brazil, 15090-000BR Trials | São Paulo , Brazil, 01236-030University of Calgary | Calgary Alberta, Canada, T2N 4Z6OCT Research ULC | Kelowna British Columbia, Canada, V1Y 1Z9Centre for Addiction and Mental Health (CAMH) | Toronto Ontario, Canada, M6J 1H3The sixth People's Hospital of Hebei Province | Baoding , China, 71000Peking University Sixth Hospital | Beijing , China, 100089Beijing HuiLongGuan Hospital | Beijing , China, 100096The Second People's Hospital of Hunan Province (Brain Hospital of Hunan Province) | Changsha , China, 410007The Affiliated Brain Hospital of Guangzhou Medical University | Guangzhou , China, 510370The Affiliated Hospital of Guizhou Medical University | Guiyang , China, 550004Shandong Daizhuang Hospital | Jining , China, 272051The First Affilliated Hospital Of Kunming of Medical College | Kunming , China, 650032The Affilicated Kangning Hospital of Ningbo University | Ningbo , China, 315201Shanghai Mental Health Center | Shanghai , China, 200030Tongji Hospital, Tongji University | Shanghai , China, 200065Wuxi mental health center | Wuxi , China, 214151The Second Affiliated Hospital of Xinxiang Medical Univ. | Xinxiang , China, 453002Centro de Investigación y Proyectos en neurociencia CIPNA | Barranquilla , Colombia, 80020E.S.E Hospital Mental de Antioquia | Bello , Colombia, 51053Instituto Colombiano del Sistema Nervioso- Clínica Montserrat | Bogotá , Colombia, 110121Centro de Investigaciones del Sistema Nervioso SAS- Grupo Cisne SAS | Bogotá , Colombia, 111166Psynapsis Salud Mental S.A. | Pereira , Colombia, 660003Zentrum für klinische Forschung Dr. med. I. Schöll GmbH | Bad Homburg , Germany, 61348Praxis Dr. Hahn, Berlin | Berlin , Germany, 13187Zentralinstitut für seelische Gesundheit | Mannheim , Germany, 68159Neurologie und Psychiatrie / Psychotherapie | Westerstede , Germany, 26655Eginition Hospital | Athens , Greece, 11528"Attikon" University General Hospital of Attica | Chaïdári , Greece, 12462Psychiatric Hospital of Attica | Haidari , Greece, 12462AX Mental Health Clinic | Heraklion , Greece, 71305General Oncology Hospital "Agioi Anargyri" | Nea Kifissia , Greece, 14564University General Hospital of Thessaloniki AHEPA | Thessaloniki , Greece, 54636General Hospital of Thessaloniki "G. Papanikolaou" | Thessaloniki , Greece, 57 010ASST degli Spedali Civili di Brescia | Brescia , Italy, 25123A.O. Fatebenefratelli | Milan , Italy, 20121Ist. San Raffaele Turro | Milan , Italy, 20127Azienda Sanitaria Ospedale S. Luigi Gonzaga | Orbassano (TO) , Italy, 10043A.O.U. Senese | Siena , Italy, 53100Hotei Hospital | Aichi, Konan , Japan, 483-8248Japan Institute for Health Security National Kohnodai Medical Center | Chiba, Ichikawa , Japan, 272-8516Mental Clinic Sakurazaka | Fukuoka, Fukuoka , Japan, 810-0023Fukuoka University Hospital | Fukuoka, Fukuoka , Japan, 814-0180Kuramitsu Hospital | Fukuoka, Fukuoka , Japan, 819-0037Shiranui Hospital | Fukuoka, Omuta , Japan, 836-0004Obihiro-Kosei General Hospital | Hokkaido, Obihiro , Japan, 080-0024Hokkaido University Hospital | Hokkaido, Sapporo , Japan, 060-8648St. Marianna University Hospital | Kanagawa, Kawasaki , Japan, 216-8511Kitasato University Hospital | Kanagawa, Sagamihara , Japan, 252-0375Yokohama Onoecho Clinic | Kanagawa, Yokohama , Japan, 231-0015Hino Hospital | Kanagawa, Yokohama , Japan, 234-0051Kochi Health Sciences Center | Kochi, Kochi , Japan, 781-8555National Hospital Organization Maizuru Medical Center | Kyoto, Maizuru , Japan, 625-8502Tohoku University Hospital | Miyagi, Sendai , Japan, 980-8574Shounan Hospital | Nagano, Matsumoto , Japan, 390-0847Niigata University Medical and Dental Hospital | Niigata, Niigata , Japan, 951-8520National Hospital Organization Hizen Psychiatric Medical Center | Saga, Kanzaki-gun , Japan, 842-0192Saitama Medical University Hospital | Saitama, Iruma-gun , Japan, 350-0495Nishi Kumagaya Hospital | Saitama, Kumagaya , Japan, 360-0816Sho Midori Hospital | Saitama, Saitama , Japan, 336-0022Dokkyo Medical University Hospital | Tochigi, Shimotsuga-gun , Japan, 321-0293Tokushima University Hospital | Tokushima, Tokushima , Japan, 770-8503National Center of Neurology and Psychiatry | Tokyo, Kodaira , Japan, 187-8851Asuka Hospital | Tokyo, Machida , Japan, 194-0005Showa University Karasuyama Hospital | Tokyo, Setagaya , Japan, 157-8577Shinjuku East Mental Clinic | Tokyo, Shinjuku-ku , Japan, 160-0021Ohwa Mental Clinic | Tokyo, Toshima-ku , Japan, 170-0002Yamaguchi University Hospital | Yamaguchi, Ube , Japan, 755-8505University of Yamanashi Hospital | Yamanashi, Chuo , Japan, 409-3898Clinica Cemelli | Guadalajara , Mexico, 44660GabiPros S.C. | Mexico City , Mexico, 07000Instituto Nacional de Neurologia y Neurocirugia | Mexico City , Mexico, 14269Medical Care & Research SA de CV | Mérida , Mexico, 97070CIT-Neuropsique S.C | Monterrey , Mexico, 64610Instituto de Informacion e Investigacion en Salud Mental A.C. (INFOSAME). | Monterrey , Mexico, 64710North Shore Hospital | Takpuna Auckland , New Zealand, 0622Sykehuset Østfold HF, avd. Moss | Moss , Norway, N-1535Akershus Universitetssykehus HF | Oslo , Norway, N-0963St. Paul's Hospital-Iloilo City-40765 | Iloilo City , Philippines, 5000Philippine General Hospital | Manila, Philippines , Philippines, 1000Podlassian Center of Psychogeriatry, Bialystok | Bialystok , Poland, 15-756Central Teaching Hospital of the Medical University of Lodz | Lodz , Poland, 92-216Individual Specialist Medical Practice Filip Rybakowski | Poznan , Poland, 60-744Institute of Psychiatry and Neurology in Warsaw | Warsaw , Poland, 02-957Clinhouse | Zabrze , Poland, 41-807Psykiatriska Kliniken | Helsingborg , Sweden, 201 53Akademiska sjukhuset | Uppsala , Sweden, 751 85Hacettepe Universitesi Tip Fakultesi | Ankara , Turkey (Türkiye), 06230Ankara University Medical School | Ankara , Turkey (Türkiye), 06590Istanbul University | Istanbul , Turkey (Türkiye), 34093Dokuz Eylul Universitesi Psikiyatri A.B.D. | Izmir , Turkey (Türkiye), 35340Celal Bayar Universitesi Tip Fakultesi | Manisa , Turkey (Türkiye), 45030
Study Documents (Full Text)
Documents provided by Boehringer Ingelheim: Study Protocol  June 24, 2024Documents provided by Boehringer Ingelheim: Statistical Analysis Plan  October 24, 2024