Clinical trial NCT04846881: Clinical Trial of Iclepertin Effect on Cognition and Functional Capacity in Schizophrenia (CONNEX-2)
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-2)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Schizophrenia
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2021-04-15
Enrollment: 611
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. During this time, they visit the study site about 15 times and get about 3 phone calls from the study team. The doctors also regularly check participants' health and take note of any unwanted effects.


Eligibility criteria: Inclusion criteria

1. Patient must be capable of providing a signed and dated written informed consent by visit 1 in accordance with International Council on Harmonisation for Good Clinical Practice (ICH-GCP) and local legislation prior to 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 hospitalization3 or increase in level of psychiatric care4 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 staying focused, difficulties remembering 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 as needed.
   * For any other psychoactive medications cannot exceed the maximum daily dose per local label of the country where the study is being conducted.
7. Women of childbearing potential (WOCBP)5 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 patient at a minimum one 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. Patient with current DSM-5 diagnosis other than Schizophrenia, including but not limited to bipolar, schizoaffective, major depressive disorder etc. The 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. stroke) or other disorders including head trauma, or patients with dementia or epilepsy.
3. Severe movement disorders

   * Leading to cognitive impairment (e.g. Parkinson's 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 Suicidality 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: Bellflower
country: United States
facility: Clinical Innovations, Inc
state: California
city: Costa Mesa
country: United States
facility: ATP Clinical Research, Inc.
state: California
city: Long Beach
country: United States
facility: ASCLEPES Research Centers, P.C. dba Alliance Research
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: Orange
country: United States
facility: NRC Research Institute
state: California
city: Torrance
country: United States
facility: Collaborative Neuroscience Research, LLC-Torrance-69527
state: California
city: New Haven
country: United States
facility: Connecticut Mental Health Center
state: Connecticut
city: Hialeah
country: United States
facility: Research in Miami Inc
state: Florida
city: Miami
country: United States
facility: Optimus U Corporation-Miami-69452
state: Florida
city: West Palm Beach
country: United States
facility: Health Synergy Clinical Research, LLC
state: Florida
city: Chicago
country: United States
facility: American Medical Research
state: Illinois
city: Baltimore
country: United States
facility: Sheppard Pratt Physicians's Practice Association, Inc.
state: Maryland
city: Saint Louis
country: United States
facility: PsychCare Consultants Research
state: Missouri
city: Cedarhurst
country: United States
facility: Neurobehavioral Research, Inc.
state: New York
city: New York
country: United States
facility: New York State Psychiatric Institute
state: New York
city: Beachwood
country: United States
facility: Insight Clinical Trials
state: Ohio
city: Dallas
country: United States
facility: Relaro Medical Trials, LLC
state: Texas
city: Fort Worth
country: United States
facility: John Peter Smith Health Network
state: Texas
city: Salem
country: United States
facility: Salem VA Medical Center
state: Virginia
city: Bellevue
country: United States
facility: Northwest Clinical Research Center
state: Washington
city: Caba
country: Argentina
facility: CENYDET-Centro Neurobiologico y de Estres Traumatico (Biopsychomedical Research Group S.R.L.)
city: Caba
country: Argentina
facility: SERES Neurociencia Cognitiva Aplicada
city: Caba
country: Argentina
facility: Fundación FunDaMos para la asistencia e investigación en psiquiatría
city: Cordoba
country: Argentina
facility: CEN (Centro Especializado Neurociencias)
city: Córdoba
country: Argentina
facility: Sanatorio Morra S.A.
city: La Plata
country: Argentina
facility: Clinica Privada de Salud Mental Santa Teresa de Avila
city: Mendoza
country: Argentina
facility: Resolution Psychopharmacology Research Institute
city: Rosario
country: Argentina
facility: Centro de Investigacion y Asistencia en Psiquiatria (CIAP)
city: Rio de Janeiro
country: Brazil
facility: Ruschel Medicina e Pesquisa Clínica
city: Sao Paulo
country: Brazil
facility: Clínica Viver - Centro de Desospitalização Humana
city: Sao Paulo
country: Brazil
facility: Hospital das Clinicas da FMUSP
city: São Bernardo do Campo
country: Brazil
facility: CEMEC - Centro Multidisciplinar de Estudos Clínicos
city: São Paulo
country: Brazil
facility: Cpquali Pesquisa Clinica Ltda
city: Santiago
country: Chile
facility: Biomedica Research Group
city: Segunda Región
country: Chile
facility: Psicomed Estudios Clínicos
city: Rijeka
country: Croatia
facility: Clincal Hospital Centre Rijeka
city: Zagreb
country: Croatia
facility: Clinical Hospital Centre Zagreb
city: Zagreb
country: Croatia
facility: Solmed Polyclinic
city: Zagreb
country: Croatia
facility: Psychiatric Hospital 'Sveti Ivan'
city: Zagreb
country: Croatia
facility: University Psychiatric Hospital Vrapce
city: Bordeaux
country: France
facility: HOP Charles Perrens
city: Clermont-Ferrand
country: France
facility: HOP Gabriel-Montpied
city: Créteil
country: France
facility: HOP Albert Chenevier
city: Le Chesnay-Rocquencourt
country: France
facility: HOP André Mignot
city: Lille
country: France
facility: HOP Fontan
city: Montpellier
country: France
facility: HOP la Colombière
city: Nantes
country: France
facility: HOP Hôtel-Dieu
city: Nice
country: France
facility: HOP Pasteur
city: Nîmes
country: France
facility: HOP Carémeau
city: Rennes
country: France
facility: HOP Guillaume Régnier
city: Rouffach
country: France
facility: HOP Rouffach
city: Saint Priest en Jarez
country: France
facility: HOP Nord-Saint-Priest-en-Jarez-53664
city: Budapest
country: Hungary
facility: Obuda Health Center
city: Budapest
country: Hungary
facility: Semmelweis University
city: Debrecen
country: Hungary
facility: University of Debrecen, Gyula Kenezi University Hospital
city: Pecs
country: Hungary
facility: PsychoTech Ltd.
city: Aichi, Toyoake
country: Japan
facility: Okehazama Hospital Fujita Kokoro Care Center
city: Aichi, Toyota
country: Japan
facility: Toyota Memorial Hospital
city: Chiba, Chiba
country: Japan
facility: National Hospital Organization Shimofusa Psychiatric Medical Center
city: Fukuoka, Chikugo
country: Japan
facility: Uematsu Mental Clinic
city: Fukuoka, Fukuoka
country: Japan
facility: AK Clinic
city: Fukuoka, Kurume
country: Japan
facility: Hirota Clinic
city: Gumma, Kiryu
country: Japan
facility: Kishi Hospital
city: Hokkaido, Sapporo
country: Japan
facility: Hokudai-dori Mental Health Clinic
city: Hyogo, Kobe
country: Japan
facility: Tatsuta Clinic
city: Ishikwa, Kahoku-gun
country: Japan
facility: Kanazawa Medical University Hospital
city: Kanagawa, Kawasaki
country: Japan
facility: Kishiro Mental Clinic
city: Kanagawa, Yokohama
country: Japan
facility: Links Mental Clinic
city: Kanagawa, Yokohama
country: Japan
facility: Yokohama City University Hospital
city: Kumamoto, Kumamoto
country: Japan
facility: Yuge Neuropsychiatric Hospital
city: Kumamoto, Yatsushiro
country: Japan
facility: Medical Corporation Yamadakai Yatsushiro Welfare Hospital
city: Nagano, Suwa
country: Japan
facility: Suwa Red Cross Hospital
city: Nara, Kashihara
country: Japan
facility: Nara Medical University Hospital
city: Okinawa, Nakagami-gun
country: Japan
facility: University of the Ryukyus Hospital
city: Osaka, Osaka
country: Japan
facility: Osaka City Hospital Organization Osaka City General Hospital
city: Saga, Karatsu
country: Japan
facility: Rainbow and Sea Hospital
city: Saga, Tosu
country: Japan
facility: Inuo Hospital
city: Tokyo, Adachi-ku
country: Japan
facility: Medical Corporation Seijin Hospital
city: Tokyo, Bunkyo-ku
country: Japan
facility: Institute of Science Tokyo Hospital
city: Tokyo, Kita-ku
country: Japan
facility: Nishigahara Hospital
city: Tokyo, Minato-ku
country: Japan
facility: Minami-Aoyama Antique Street Clinic
city: Tokyo, Ota-ku
country: Japan
facility: Toho University Omori Medical Center
city: Tokyo, Shibuya-ku
country: Japan
facility: Maynds Tower Mental Clinic
city: Tokyo, Shinjuku-ku
country: Japan
facility: Shinjuku East Mental Clinic
city: Toyama, Nanto
country: Japan
facility: Hokuriku Hospital
city: Busan
country: Korea, Republic of
facility: Inje University Haeundae Paik Hospital
city: Daegu
country: Korea, Republic of
facility: Daegu Catholic University Medical Center
city: Incheon
country: Korea, Republic of
facility: Inha University Hospital
city: Jeonju
country: Korea, Republic of
facility: Chonbuk National University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Ipoh
country: Malaysia
facility: Hospital Raja Permaisuri Bainun
city: Kuala Lumpur
country: Malaysia
facility: University of Malaya Medical Centre
city: Kuching
country: Malaysia
facility: Hospital Sentosa
city: Seremban, Negeri Sembilan
country: Malaysia
facility: Hospital Tuanku Ja'afar
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Maastricht
country: Netherlands
facility: Maastricht University
city: Bełchatow
country: Poland
facility: Psychiatric Doctor's Office Ireneusz Kaczorowski
city: Bialystok
country: Poland
facility: Podlassian Center of Psychogeriatry, Bialystok
city: Gdansk
country: Poland
facility: Health Center Alcea
city: Gliwice
country: Poland
facility: MentalMEDIC
city: Swiecie
country: Poland
facility: Provincial Hospital for Nervous and Mentally Ill in Swiecie
city: Szczecin
country: Poland
facility: EUROMEDIS Sp. z o.o., Szczecin
city: Zabrze
country: Poland
facility: Clinhouse
city: Bucharest
country: Romania
facility: Mental Health Center Sector 4
city: Sibiu
country: Romania
facility: SC Carpe Diem SRL
city: Belgrade
country: Serbia
facility: Institute for Mental Health
city: Novi Knezevac
country: Serbia
facility: Special Hospital for Psychiatric Diseases Sveti Vračevi
city: Novi Sad
country: Serbia
facility: Clinical Center of Vojvodina
city: Singapore
country: Singapore
facility: Changi General Hospital
city: Singapore
country: Singapore
facility: Institute of Mental Health
city: Bojnice
country: Slovakia
facility: Psychiatria, Nemocnica s poliklinikou Prievidza so sidlom v Bojniciach
city: Kosice
country: Slovakia
facility: EPAMED s.r.o.
city: Rimavska Sobota
country: Slovakia
facility: Psychiatricka Ambulancia Psycholine s.r.o.
city: Barcelona
country: Spain
facility: Hestia Palau
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: Collado De Villalba
country: Spain
facility: Hospital Universitario General de Villalba
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofía-Córdoba-40500
city: Getafe
country: Spain
facility: Centro de Salud mental de Getafe
city: Majadahonda
country: Spain
facility: Hospital Puerta de Hierro
city: Palma
country: Spain
facility: Hospital de Son Llàtzer
city: Salamanca
country: Spain
facility: Centro de Salud de San Juan
city: Sant Boi de Llobregat
country: Spain
facility: Benito Menni Complejo Asistencial en Salud Mental
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocío
city: Valencia
country: Spain
facility: Hospital Clínico de Valencia
city: Vigo
country: Spain
facility: Hospital Nicolás Peña
city: Zamora
country: Spain
facility: Hospital Provincial. Complejo Asistencial de Zamora
city: Nove
country: Ukraine
facility: Communal Non-Profit Enterprise "Regional Clinical Psychiatric Hospital" of Kirovohrad Regional Council
Study officials:
References: