Clinical trial NCT03793712: Study With Lu AF11167 for the Treatment of Negative Symptoms in Patients With Schizophrenia
Official title: Interventional, Randomized, Double-blind, Parallel-group, Placebo-controlled, Fixed-flexible-dose Study of Lu AF11167 for the Treatment of Persistent Prominent Negative Symptoms in Patients With Schizophrenia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Schizophrenia
Lead sponsor: H. Lundbeck A/S
Sponsor class: INDUSTRY
First posted: 2019-01-04
Enrollment: 168
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A study to evaluate the efficacy of 2 fixed-flexible doses of Lu AF11167 on negative symptoms in patients with schizophrenia


Eligibility criteria: Inclusion Criteria

* The patient has schizophrenia, diagnosed according to DSM-5® as confirmed by the Mini-International Neuropsychiatric Interview for Schizophrenia and Psychotic Disorders Studies (MINI-Schz).
* The patient has been known to the site or investigator and treated by the site or investigator for at least the last 6 months prior to Screening Visit 1.
* The patient has suffered from persistent prominent negative symptoms for the last 6 months prior to the Screening Visit 1, in the opinion of the investigator and recorded in medical records.
* The patient has been treated for schizophrenia with stable doses of an oral antipsychotic within the approved dose range and without any dose increase during the last 6 months prior to Screening Visit 1 (dose reductions are acceptable). Combination therapy of two antipsychotics is only allowed with the written approval of the Medical Monitor in cases where the second antipsychotic is a low-potency first generation antipsychotic drug (e.g., chlorpromazine, promazine or chlorprothixene at low doses) or quetiapine at a dose of ≤150 mg, given in the evening for sleep problems and where both can be discontinued during the washout phase without endangering the patient's safety. Both antipsychotics will be withdrawn during the washout phase and need to be discontinued before Screening Visit 2. Combination therapy of more than 2 antipsychotic medications is not allowed during the previous 6 months prior to Screening Visit 1.
* The patient has had no psychiatric admissions/hospitalization due to a clinical deterioration during the last 6 months prior to Screening Visit 1, this excludes ambulatory visits to ask for advice from the psychiatry team.Patients hospitalized during the last 6 months for social reasons only or patients who are currently hospitalized for social reasons can be included with the Medical Monitor's approval.
* The patient is in a clinically stable phase of schizophrenia and has not more than moderate severity on relevant positive symptoms, that is a score of ≤4 (moderate) out of score of 7 on each of the following PANSS items: Delusions (P1), Hallucinatory behaviour (P3), Suspiciousness / persecution (P6), Uncooperativeness (G8), Unusual thought content (G9) at Screening Visit 1, Washout Visit(s), Screening Visit 2, and Baseline Visit and a score ≤5 on Conceptual disorganization (P2).
* The patient currently has no clinically significant acute extrapyramidal side effects (acute EPS) or tardive dyskinesia (TD) based upon the protocol-specified clinical examination.
* The patient has prominent negative symptoms as demonstrated by a PANSS Marder Negative Symptom Factor Score (NSFS) ≥20 at Screening Visit 1, Washout Visit(s) and Screening Visit 2. NSFS is the sum of scores of the following PANSS items: Blunted affect (N1), Emotional withdrawal (N2), Poor rapport (N3), Passive/apathetic social withdrawal (N4), Lack of spontaneity \& flow of conversation (N6), Motor retardation (G7) and Active social avoidance (G16).
* The patient has a Clinical Global Impression-Schizophrenia Severity of Illness (CGI-SCH-S) overall severity score ≤4 at Screening Visit 1.
* The patient does not currently have a diagnosis of Major Depressive Disorder or have depressive symptoms rated with a total score ≥5 on the Calgary Depression Scale for Schizophrenia (CDSS).
* The patient has no history of violent behaviour for the last 12 months prior to Screening Visit 1.
* The patient has a caregiver or an identified responsible person (for example, partner, family member, social worker, case worker, or nurse) considered reliable by the investigator in providing support to the patient to ensure compliance with study treatment, outpatient visits, and protocol procedures.

Exclusion criteria

* The patient has had an acute exacerbation requiring hospitalization within the last 6 months prior to Screening Visit 1.
* The patient has had an acute exacerbation requiring change in antipsychotic medication (with reference to drug or dose) within the last 6 months prior to Screening Visit 1.
* The patient has a current diagnosis or a history of substance use disorder according to DSM-5® criteria within 6 months prior to Screening Visit 1 with the exception of tobacco, or mild cannabis or mild alcohol use disorder (occasional - but not weekly recreational cannabis use is acceptable). Patients with a positive drug screen test for opiates, methadone, cocaine, amphetamines \[including ecstasy\], barbiturates, verified by repeated testing, are excluded from the study.
* The patient is at significant risk of harming himself/herself or others in the investigator's opinion.
* The patient has tested positive for hepatitis A virus antibody (anti-HAV IgM), hepatitis B surface antigen (HBsAg), or hepatitis C virus antibody (anti-HCV). If the anti-HCV test result is positive, but acute/chronic infection is excluded with a negative HCV RNA test patient can be included in the study.
* The patient has tested positive for human immunodeficiency virus (HIV).
* The patient has a present condition that might compromise liver function (for example, alcohol abuse, hepatitis, hepatic insufficiency, cholestasis, haemachromatosis, deficit in alpha 1 antitrypsine, Wilson's Disease, autoimmune diseases, cirrhosis).
* The patient has any other disorder for which the treatment takes priority over treatment of schizophrenia or is likely to interfere with the study treatment or impair treatment compliance.

Other in- and exclusion criteria may apply.

Primary outcomes:
measure: Change in Negative Symptom Scale (BNSS) total score
timeFrame: from baseline to Week 12
Secondary outcomes:
measure: Change in Personal and Social Performance (PSP) score
timeFrame: from baseline to Week 12
measure: Change in Positive and Negative Syndrome Scale (PANSS) total score
timeFrame: from baseline to Week 12
measure: Change in PANSS Marder Negative Symptom Factor score: negative symptoms
timeFrame: from baseline to Week 12
measure: Change in PANSS Negative subscale score
timeFrame: from baseline to Week 12
measure: Change in Clinical Global Impression - Schizophrenia (CGI-SCH-S) negative symptoms score
timeFrame: from baseline to Week 12
measure: Clinical Global Impression - Schizophrenia (CGI-SCH-DC) negative symptoms score
timeFrame: at Week 12
measure: CGI-SCH-DC negative symptoms response
timeFrame: at Week 12
measure: BNSS response
timeFrame: at Week 12
measure: Change in PANSS -Positive subscale score
timeFrame: from baseline to Week 12
measure: Change in Clinical Global Impression - Schizophrenia (CGI-SCH-S) severity of illness overall severity score
timeFrame: from baseline to Week 12
measure: Clinical Global Impression - Schizophrenia (CGI-SCH-DC) degree of change in overall severity score
timeFrame: at Week 12
measure: Change in Calgary Depression Scale for Schizophrenia (CDSS) total score
timeFrame: from baseline to Week 12
Other outcomes:
Locations:
city: Bourgas
country: Bulgaria
facility: Mental Health Center Prof. Dr. Ivan Temkov EOOD (BG0001)
city: Kazanlak
country: Bulgaria
facility: MHAT Dr. Hristo Stambolski (BG0007)
city: Lovech
country: Bulgaria
facility: State Psychiatric Hospital Lovech (BG0012)
city: Novi Iskar
country: Bulgaria
facility: First Department for men with acute mental diseases-NPH Sv. Ivan Rilski (BG0010)
city: Pleven
country: Bulgaria
facility: UMHAT Dr.Georgi Stranski EAD (BG0006)
city: Plovdiv
country: Bulgaria
facility: Dr.Svetlozar Georgiev MD, Office of Office of Ambulatory for Group Practice for Specialized Psychiartic Help ¿ PHILIPOPOLIS OOD (BG0014)
city: Sevlievo
country: Bulgaria
facility: State Psychiatric Hospital - Sevlievo (BG009)
city: Sofia
country: Bulgaria
facility: Medical Center INTERMEDICA (BG0003)
city: Varna
country: Bulgaria
facility: DCC Mladost-M (BG0004)
city: Varna
country: Bulgaria
facility: DCC Mladost-M Varna OOD (BG0005)
city: Varna
country: Bulgaria
facility: Med Centre Medical plus (BG008)
city: Veliko Tarnovo
country: Bulgaria
facility: Center for Mental Health Veliko Tarnovo (BG0013)
city: Vratsa
country: Bulgaria
facility: Mental Health Center-Vratsa EOOD (BG0002)
city: Brno
country: Czechia
facility: Dr.Jan Holan MD, Office of (CZ0003)
city: Havířov
country: Czechia
facility: Meditrine s.r.o. - Psychiatricka Ambulance, Lecebne Centrum (CZ0005)
city: Hostivice
country: Czechia
facility: Clinline services s.r.o. (CZ0006)
city: Hradec Králové
country: Czechia
facility: Neuropsychiatrie HK, s.r.o. (CZ0004)
city: Plzen
country: Czechia
facility: A-Shine s.r.o. (CZ0001)
city: Praha 8
country: Czechia
facility: Institute of Neuropsychiatric Care (INEP) (CZ0007)
city: Tallinn
country: Estonia
facility: Marienthali Kliinik (EE0001)
city: Tartu
country: Estonia
facility: OU Jaanson & Laane (EE0002)
city: Berlin
country: Germany
facility: Medical Pratice For Neurology/Psychiatry (DE0003)
city: Berlin
country: Germany
facility: Office of Dr.Kirsten Hahn (DE0002)
city: Mannheim
country: Germany
facility: Zentralinstitut fur Seelische Gesundheit (ZI)-Leitung Abteilung Molekulares Neuroimaging (DE0004)
city: Oranienburg
country: Germany
facility: Dr. Frank Kuehn MD, Office Of (DE001)
city: Tuebingen
country: Germany
facility: Klinikum der Eberhard-Karls-Universitaet Tuebingen (DE0007)
city: Budapest
country: Hungary
facility: Nyiro Gyula Hospital - OPAI (HU0006)
city: Budapest
country: Hungary
facility: Semmelweis Egyetem-Neurologiai Klinika (HU0005)
city: Gyöngyös
country: Hungary
facility: Bugat Pal Hospital (HU0008)
city: Kalocsa
country: Hungary
facility: Dr Mathe es Tarsa Bt (HU0001)
city: Kaposvár
country: Hungary
facility: Somogy Megyei Kaposi Mor Oktato Korhaz (HU0003)
city: Nyíregyháza
country: Hungary
facility: Szabolcs-Szatmar-Bereg megyei Korhazak es Egyetemi Oktatokorhaz, Josa Andras Oktatokorhaz, Pszichiatriai es Pszichoterapias Osztaly (HU0002)
city: Vác
country: Hungary
facility: Javorszky Odon Hospital (HU0004)
city: Daugavpils
country: Latvia
facility: Daugavpils Psychoneurological Hospital (LV0005)
city: Jelgava
country: Latvia
facility: Hospital Gintermuiza (LV0001)
city: Liepāja
country: Latvia
facility: Jsc Piejuras Slimnica Psychiatry Clinic (LV0003)
city: Riga
country: Latvia
facility: Riga Centre Of Psychiatry And Addiction Disorders (LV0002)
city: Sigulda
country: Latvia
facility: Sigulda Hospital Outpatient Clinic (LV0006)
city: Bełchatów
country: Poland
facility: Gabinet Lekarski Psychiatryczny Ireneusz Kaczorowski (PL0012)
city: Białystok
country: Poland
facility: Wlokiennicza Med Specjalistyczna Praktyka Lekarska dr n. med. Tomasz Markowski (PL0005)
city: Bydgoszcz
country: Poland
facility: Med-Ars (Pl0010)
city: Kielce
country: Poland
facility: Centrum Zdrowia Psychicznego Biomed - Jan Latala (PL0006)
city: Kielce
country: Poland
facility: Przychodnia Syntonia Izabela Chojnowska-Cwiakala (PL0011)
city: Pruszcz Gdański
country: Poland
facility: Syntonia Sp. z o.o. (PL0002)
city: Kharkiv
country: Ukraine
facility: Si Inpn Namsu (Ua0003)
city: Kharkiv
country: Ukraine
facility: Si Inpn Namsu (Ua0008)
city: Kherson
country: Ukraine
facility: Kherson Regional Psychiatric Hospital (UA0009)
city: Kiev
country: Ukraine
facility: Kiev Regional Specialized Psycho-Narcological Medical Care (UA0005)
city: Kropyvnytskyi
country: Ukraine
facility: Communal Institution Kirovograd Regional Psychiatric Hospital. Donetsk National Medical University, Chair of psychiatry, psychotherapy, narcology and medical psychology (UA0004)
city: Kyiv
country: Ukraine
facility: Railway Clinical Hospital #1, Ukr Research Institute, Social And Forensic Psychatriy And Drug Abuse (UA0007)
city: Odessa
country: Ukraine
facility: Odessa Regional Medical Centre of Mental Health (UA0006)
city: Poltava
country: Ukraine
facility: Ukrainian Medical Stomatological Academy, Chair Of Psychiatry, Narcology And Medical Psychology Based On O.F. Maltsev Poltava Regional Clinical Psychiatric Hospital (UA0001)
city: Vinnitsa
country: Ukraine
facility: Vinnitsa National Medical University (UA0002)
Study officials:
affiliation: LundbeckClinicalTrials@Lundbeck.com
name: Email contact via H. Lundbeck A/S
role: STUDY_DIRECTOR
References:
citation: Meyer-Lindenberg A, Nielsen J, Such P, Lemming OM, Zambori J, Buller R, der Goltz CV. A double-blind, randomized, placebo-controlled proof of concept study of the efficacy and safety of Lu AF11167 for persistent negative symptoms in people with schizophrenia. Eur Neuropsychopharmacol. 2022 Aug;61:4-14. doi: 10.1016/j.euroneuro.2022.05.009. Epub 2022 Jun 12.