Clinical trial NCT04846868: Clinical Trial of Iclepertin Effect on Cognition and Functional Capacity in Schizophrenia (CONNEX-1)
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-1)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Schizophrenia
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2021-04-15
Enrollment: 620
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: 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
timeFrame: at baseline and at week 26
Secondary outcomes:
measure: Change from baseline in the Schizophrenia Cognition Rating Scale (SCoRS) interviewer total score after 26 weeks of treatment
timeFrame: at baseline and at week 26
measure: Change from baseline to Week 26 in the adjusted total time T-score in the Virtual Reality Functional Capacity Assessment Tool (VRFCAT)
timeFrame: at baseline and at week 26
measure: Change from baseline to Week 26 in the T-score of the number of correct responses on Tower of London (ToL) test
timeFrame: at baseline and at week 26
measure: Change from screening visit 1a to Week 24 in Patient Reported Experience of Cognitive Impairment in Schizophrenia (PRECIS) total score
timeFrame: up to 24 weeks
Other outcomes:
Locations:
city: Garden Grove
country: United States
facility: Collaborative Neuroscience Network, LLC (CNS)
state: California
city: La Habra
country: United States
facility: Omega Clinical Trials,LLC
state: California
city: San Diego
country: United States
facility: Artemis Institute for Clinical Research, LLC
state: California
city: Santa Ana
country: United States
facility: Velocity Clinical Research-Santa Ana-68902
state: California
city: Hartford
country: United States
facility: Institute of Living
state: Connecticut
city: Miami
country: United States
facility: San Marcus Research Clinic, Inc.
state: Florida
city: Miami
country: United States
facility: CCM Clinical Research Group, LLC-Miami-68482
state: Florida
city: Atlanta
country: United States
facility: Atlanta Center
state: Georgia
city: Buffalo
country: United States
facility: University at Buffalo, The State University of New York
state: New York
city: Staten Island
country: United States
facility: Richmond Behavioral Associates-Staten Island-68636
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: North Canton
country: United States
facility: Neuro-Behavioral Clinical Research
state: Ohio
city: Eugene
country: United States
facility: PeaceHealth Medical Group
state: Oregon
city: Austin
country: United States
facility: Community Clinical Research, Inc.
state: Texas
city: DeSoto
country: United States
facility: InSite Clinical Research
state: Texas
city: Fort Worth
country: United States
facility: North Texas Clinical Trials
state: Texas
city: Houston
country: United States
facility: Houston Mind and Brain
state: Texas
city: Everett
country: United States
facility: Core Clinical Research
state: Washington
city: Melbourne
country: Australia
facility: Monash Alfred Psychiatry Research Centre
state: Victoria
city: Belo Horizonte,Minas Gerais
country: Brazil
facility: Hospital das Clinicas da Universidade Federal HC-UFMG
city: Belo Horizonte
country: Brazil
facility: CPN - Centro de Estudos em Neurociências
city: Criciuma
country: Brazil
facility: Hospital Sao Jose
city: Curitiba
country: Brazil
facility: Trial Tech- Tecnologia em pesquisa com medicamentos
city: Goiania
country: Brazil
facility: J A Serviços Médicos Ltda/ Instituto Goiano de Neuropisquiatria
city: Sao Jose do Rio Preto
country: Brazil
facility: Hospital de Base - Fac Med de Sao Jose do Rio Preto
city: Sao Paulo
country: Brazil
facility: BR Trials
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Kelowna
country: Canada
facility: OCT Research ULC
state: British Columbia
city: Toronto
country: Canada
facility: Centre for Addiction and Mental Health (CAMH)
state: Ontario
city: Baoding
country: China
facility: The sixth People's Hospital of Hebei Province
city: Beijing
country: China
facility: Peking University Sixth Hospital
city: Beijing
country: China
facility: Beijing HuiLongGuan Hospital
city: Changsha
country: China
facility: Brain hospital of Hunan province
city: Guangzhou
country: China
facility: The Affiliated Brain Hospital of Guangzhou Medical University
city: Guiyang
country: China
facility: The Affiliated Hospital of Guizhou Medical University
city: Jining
country: China
facility: Shandong Daizhuang Hospital
city: Kunming
country: China
facility: The First Affilliated Hospital Of Kunming of Medical College
city: Ningbo
country: China
facility: The Affilicated Kangning Hospital of Ningbo University
city: Shanghai
country: China
facility: Shanghai Mental Health Center
city: Shanghai
country: China
facility: Tongji Hospital, Tongji University
city: Wuxi
country: China
facility: Wuxi mental health center
city: Xinxiang
country: China
facility: The Second Affiliated Hospital of Xinxiang Medical Univ.
city: Barranquilla
country: Colombia
facility: Centro de Investigación y Proyectos en neurociencia CIPNA
city: Bello
country: Colombia
facility: E.S.E Hospital Mental de Antioquia
city: Bogota
country: Colombia
facility: Instituto Colombiano del Sistema Nervioso- Clínica Montserrat
city: Bogotá
country: Colombia
facility: Centro de Investigaciones del Sistema Nervioso SAS- Grupo Cisne SAS
city: Pereira
country: Colombia
facility: Psynapsis Salud Mental S.A.
city: Bad Homburg
country: Germany
facility: Zentrum für klinische Forschung Dr. med. I. Schöll GmbH
city: Berlin
country: Germany
facility: Praxis Dr. Hahn, Berlin
city: Mannheim
country: Germany
facility: Zentralinstitut für seelische Gesundheit
city: Westerstede
country: Germany
facility: Neurologie und Psychiatrie / Psychotherapie
city: Athens
country: Greece
facility: Eginition Hospital
city: Chaidari
country: Greece
facility: "Attikon" University General Hospital of Attica
city: Haidari
country: Greece
facility: Psychiatric Hospital of Attica
city: Heraclion
country: Greece
facility: AX Mental Health Clinic
city: Nea Kifisia
country: Greece
facility: General Oncology Hospital "Agioi Anargyri"
city: Thessaloniki
country: Greece
facility: University General Hospital of Thessaloniki AHEPA
city: Thessaloniki
country: Greece
facility: General Hospital of Thessaloniki "G. Papanikolaou"
city: Brescia
country: Italy
facility: ASST degli Spedali Civili di Brescia
city: Milano
country: Italy
facility: A.O. Fatebenefratelli
city: Milano
country: Italy
facility: Ist. San Raffaele Turro
city: Orbassano (to)
country: Italy
facility: Azienda Sanitaria Ospedale S. Luigi Gonzaga
city: Siena
country: Italy
facility: A.O.U. Senese Policlinico Santa Maria alle Scotte
city: Aichi, Konan
country: Japan
facility: Hotei Hospital
city: Chiba, Ichikawa
country: Japan
facility: National Center for Global Health and Medicine Kohnodai Hospital
city: Fukuoka, Fukuoka
country: Japan
facility: Mental Clinic Sakurazaka
city: Fukuoka, Fukuoka
country: Japan
facility: Fukuoka University Hospital
city: Fukuoka, Fukuoka
country: Japan
facility: Kuramitsu Hospital
city: Fukuoka, Omuta
country: Japan
facility: Shiranui Hospital
city: Hokkaido, Obihiro
country: Japan
facility: Obihiro-Kosei General Hospital
city: Hokkaido, Sapporo
country: Japan
facility: Hokkaido University Hospital
city: Kanagawa, Kawasaki
country: Japan
facility: St. Marianna University Hospital
city: Kanagawa, Sagamihara
country: Japan
facility: Kitasato University Hospital
city: Kanagawa, Yokohama
country: Japan
facility: Yokohama Onoecho Clinic
city: Kanagawa, Yokohama
country: Japan
facility: Hino Hospital
city: Kochi, Kochi
country: Japan
facility: Kochi Health Sciences Center
city: Kyoto, Maizuru
country: Japan
facility: National Hospital Organization Maizuru Medical Center
city: Miyagi, Sendai
country: Japan
facility: Tohoku University Hospital
city: Nagano, Matsumoto
country: Japan
facility: Shounan Hospital
city: Niigata, Niigata
country: Japan
facility: Niigata University Medical and Dental Hospital
city: Saga, Kanzaki-gun
country: Japan
facility: National Hospital Organization Hizen Psychiatric Medical Center
city: Saitama, Iruma-gun
country: Japan
facility: Saitama Medical University Hospital
city: Saitama, Kumagaya
country: Japan
facility: Nishi Kumagaya Hospital
city: Saitama, Saitama
country: Japan
facility: Sho Midori Hospital
city: Tochigi, Shimotsuga-gun
country: Japan
facility: Dokkyo Medical University Hospital
city: Tokushima, Tokushima
country: Japan
facility: Tokushima University Hospital
city: Tokyo, Kodaira
country: Japan
facility: National Center of Neurology and Psychiatry
city: Tokyo, Machida
country: Japan
facility: Asuka Hospital
city: Tokyo, Setagaya
country: Japan
facility: Showa University Karasuyama Hospital
city: Tokyo, Shinjuku-ku
country: Japan
facility: Shinjuku East Mental Clinic
city: Tokyo, Toshima-ku
country: Japan
facility: Ohwa Mental Clinic
city: Yamaguchi, Ube
country: Japan
facility: Yamaguchi University Hospital
city: Yamanashi, Chuo
country: Japan
facility: University of Yamanashi Hospital
city: Cdmx
country: Mexico
facility: GabiPros S.C.
city: Ciudad de Mexico
country: Mexico
facility: Instituto Nacional de Neurologia y Neurocirugia
city: Guadalajara
country: Mexico
facility: Clinica Cemelli
city: Merida
country: Mexico
facility: Medical Care & Research SA de CV
city: Monterrey
country: Mexico
facility: CIT-Neuropsique S.C
city: Monterrey
country: Mexico
facility: Instituto de Informacion e Investigacion en Salud Mental A.C. (INFOSAME).
city: Takpuna Auckland
country: New Zealand
facility: North Shore Hospital, Takapuna
city: Moss
country: Norway
facility: Sykehuset Østfold HF, avd. Moss
city: Oslo
country: Norway
facility: Akershus Universitetssykehus HF
city: Iloilo City
country: Philippines
facility: St. Paul's Hospital-Iloilo City-40765
city: Manila, Philippines
country: Philippines
facility: Philippine General Hospital
city: Bialystok
country: Poland
facility: Podlassian Center of Psychogeriatry, Bialystok
city: Lodz
country: Poland
facility: Central Teaching Hospital of the Medical University of Lodz
city: Poznan
country: Poland
facility: Individual Specialist Medical Practice Filip Rybakowski
city: Warsaw
country: Poland
facility: Institute of Psychiatry and Neurology in Warsaw
city: Zabrze
country: Poland
facility: Clinhouse
city: Helsingborg
country: Sweden
facility: Psykiatriska Kliniken
city: Uppsala
country: Sweden
facility: Akademiska sjukhuset
city: Ankara
country: Turkey
facility: Hacettepe Universitesi Tip Fakultesi
city: Ankara
country: Turkey
facility: Ankara University Medical School
city: Istanbul
country: Turkey
facility: Istanbul University
city: Izmir
country: Turkey
facility: Dokuz Eylul Universitesi Psikiyatri A.B.D.
city: Manisa
country: Turkey
facility: Celal Bayar Universitesi Tip Fakultesi
Study officials:
References: