ADVANCE-2: Efficacy and Safety of Pimavanserin as Adjunctive Treatment for the Negative Symptoms of Schizophrenia

Sponsor

ACADIA Pharmaceuticals Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04531982

Collaborator

(none)

426

Enrollment

Locations

Arms

30.8

Anticipated Duration (Months)

5.1

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To evaluate the efficacy and safety of adjunctive pimavanserin compared with adjunctive placebo in the treatment of negative symptoms of schizophrenia

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: Pimavanserin Drug: Placebo	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

426 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Pimavanserin as Adjunctive Treatment for the Negative Symptoms of Schizophrenia

Actual Study Start Date :

Aug 5, 2020

Anticipated Primary Completion Date :

Mar 1, 2023

Anticipated Study Completion Date :

Mar 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Drug - Pimavanserin Pimavanserin 34 mg taken as two tablets + background antipsychotic, once daily by mouth	Drug: Pimavanserin Pimavanserin 34 mg, taken as two blinded 17 mg tablets once daily by mouth
Placebo Comparator: Placebo Placebo + background antipsychotic, taken as two tablets, once daily by mouth	Drug: Placebo Placebo, taken as two blinded tablets once daily by mouth

Arm

Intervention/Treatment

Experimental: Drug - Pimavanserin

Pimavanserin 34 mg taken as two tablets + background antipsychotic, once daily by mouth

Drug: Pimavanserin

Pimavanserin 34 mg, taken as two blinded 17 mg tablets once daily by mouth

Placebo Comparator: Placebo

Placebo + background antipsychotic, taken as two tablets, once daily by mouth

Drug: Placebo

Placebo, taken as two blinded tablets once daily by mouth

Outcome Measures

Primary Outcome Measures

Negative Symptom Assessment-16 (NSA-16) total score - change from Baseline to Week 26 [26 Weeks Treatment Duration]
The NSA-16 is a 16-item scale that can be completed in approximately 15 to 20 minutes. The NSA-16 has been validated for the assessment of the negative symptoms of schizophrenia and assesses 5 domains of negative symptoms: (1) communication, (2) emotion/affect, (3) social involvement, (4) motivation, and (5) retardation.

Secondary Outcome Measures

Clinical Global Impression of Schizophrenia Scale-Severity (CGI-SCH-S) of negative symptoms score - change from Baseline to Week 26 [26 Weeks Treatment Duration]
The CGI-SCH-S is a clinician-rated, 7-point scale that is designed to evaluate positive, negative, depressive, cognitive symptoms, and overall severity in schizophrenia. For the purposes of this study, only the negative symptoms will be evaluated.
Clinical Global Impression of Schizophrenia Scale-Improvement (CGI-SCH-I) of negative symptoms score at Week 26 [26 Weeks Treatment Duration]
The CGI-SCH-I is a clinician-rated, 7-point scale that is designed to evaluate change in positive, negative, depressive, cognitive symptoms, and overall severity in schizophrenia. For the purposes of this study, only the negative symptoms will be evaluated.
Proportion of CGI-SCH-I of negative symptoms responders (CGI-SCH-I of negative symptoms score of 1 or 2) at Week 26 [26 Weeks Treatment Duration]
The CGI-SCH-I is a clinician-rated, 7-point scale that is designed to evaluate change in positive, negative, depressive, cognitive symptoms, and overall severity in schizophrenia. For the purposes of this study, only the negative symptoms will be evaluated.
Personal and Social Performance (PSP) scale score - change from Baseline to Week 26 [26 Weeks Treatment Duration]
The PSP is a validated, 100-point, single-item rating scale to assess the psychosocial functioning of subjects with schizophrenia. Ratings are based on the assessment of subject functioning across four domains of socially useful activities (e.g., work and study, personal and social relationships, self-care, and disturbing and aggressive behavior).
Proportion of NSA-16 responders (≥20%and ≥30% reduction in NSA-16 total score) at Week 26 [26 Weeks Treatment Duration]
The NSA-16 is a 16-item scale that can be completed in approximately 15 to 20 minutes. The NSA-16 has been validated for the assessment of the negative symptoms of schizophrenia and assesses 5 domains of negative symptoms: (1) communication, (2) emotion/affect, (3) social involvement, (4) motivation, and (5) retardation.
Positive and Negative Syndrome Scale (PANSS) total score - change from Baseline to Week 26 [26 Weeks Treatment Duration]
The PANSS is a 30-item scale used to evaluate the presence, absence, and severity of schizophrenia symptoms. The 30 items are arranged as 7 positive symptom items, 7 negative symptom items, and 16 general psychopathology symptom items. The PANSS total score can range from a minimum of 30 to a maximum of 210.
PANSS negative subscores - change from Baseline to Week 26 [26 Weeks Treatment Duration]
The PANSS is a 30-item scale used to evaluate the presence, absence, and severity of schizophrenia symptoms. The 30 items are arranged as 7 positive symptom items, 7 negative symptom items, and 16 general psychopathology symptom items. The PANSS total score can range from a minimum of 30 to a maximum of 210.
PANSS Marder factor (negative symptoms) score - change from Baseline to Week 26 [26 Weeks Treatment Duration]
The PANSS is a 30-item scale used to evaluate the presence, absence, and severity of schizophrenia symptoms. The 30 items are arranged as 7 positive symptom items, 7 negative symptom items, and 16 general psychopathology symptom items. The PANSS total score can range from a minimum of 30 to a maximum of 210.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female, ≥18 and ≤55 years of age at the time of Screening
Has a caregiver or some other identified responsible person (e.g., family member, social worker, caseworker, or nurse) considered reliable by the Investigator in providing support to the subject to help ensure compliance with study treatment, study visits, and protocol procedures, and who is also able to provide input helpful for completing study rating scales
Diagnosis of schizophrenia made ≥1 year prior to Screening
Is being treated must be one of the antipsychotics listed below:
Aripiprazole
Aripiprazole long-acting injectables
Abilify Maintena®
Aristada®
Asenapine
Brexpiprazole
Cariprazine
Lurasidone
Olanzapine
Paliperidone extended release (ER) (≤9 mg)
Paliperidone palmitate
Invega Sustenna® (≤156 mg)
Invega Trinza® (≤546 mg)
Trevicta® (≤350 mg)
Xeplion® (≤100 mg)
Risperidone
Risperidone long-acting injection
Must be medically stable and has been medically stable for at least 12 weeks prior to Screening, in the opinion of the Investigator

Exclusion Criteria:

Has a current comorbid psychiatric disorder other than schizophrenia or a disorder that would interfere with the ability to complete study assessments
Is at a significant risk of suicide, in the opinion of the Investigator
Has a significant risk of violent behavior in the opinion of the Investigator
A urine drug screen (UDS) result at Baseline that indicates the presence of any tested prohibited substance of potential abuse, including marijuana
Is taking a medication or drug or other substance that is prohibited according to this protocol, including medications that prolong the QT interval, strong cytochrome P450 (CYP) 3A4 enzyme (CYP3A4) inhibitors and inducers
Known family or personal history or symptoms of long QT syndrome or risk factors for torsade de pointes and/or sudden death, including symptomatic bradycardia, hypokalemia or hypomagnesemia, and the presence of congenital prolongation of the QT interval
Current evidence, or history within the previous 12 weeks prior to Screening, of a serious and/or unstable psychiatric, neurologic, cardiovascular, respiratory, gastrointestinal, renal, hepatic, hematologic, or other medical disorder, including cancer or malignancies that in the judgment of the Investigator would jeopardize the safe participation of the subject in the study
Has moderate to severe congestive heart failure
Has a history of myocardial infarction within 6 months prior to enrollment
Has a body mass index (BMI) <19 or ≥35 at Screening

Additional inclusion/exclusion criteria apply. Patients will be evaluated at screening to ensure that all criteria for study participation are met. Patients may be excluded from the study based on these assessments (and specifically, if it is determined that their baseline health and condition do not meet all prespecified entry criteria).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CENydET- Centro Neurobiologico y de Estres Traumatico-Biopsychomedical Research Group SRL	Ciudad Autonoma Buenos Aires		Argentina	1058 AAJ
2	FunDamoS	Ciudad Autonoma Buenos Aires		Argentina	C1405BOA
3	Fundación para el Estudio y Tratamiento de las Enfermedades Mentales - FETEM	Ciudad Autonoma de Buenos Aires		Argentina	C1133AAH
4	Resolution Psicopharmacology Research Institute	Ciudad de Mendoza		Argentina	5502
5	MHAT "Dr. Hristo Stambolski", EOOD	Kazanlak	Stara Zagora	Bulgaria	6100
6	Mental Health Center Prof. Dr. Ivan Temkov - Burgas EO Burgas; Department for Treatment of Emergency Psychiatric Conditions	Burgas		Bulgaria	8000
7	State Psychiatric Hospital - Kardzhali, EOOD	Kardzhali		Bulgaria	6600
8	State Psychiatric Hospital - Lovech	Lovech		Bulgaria	5500
9	UMHAT 'Dr. Georgi Stranski', EAD	Pleven		Bulgaria	5800
10	Medical Center Mentalcare OOD	Plovdiv		Bulgaria	4004
11	MC-Hipokrat-N E00D	Plovdiv		Bulgaria	4028
12	Medical Centre "Sveti Naum"	Sofia		Bulgaria	1113
13	DCC "Sv. Vrach and Sv. Sv. Kuzma and Damyan", OOD	Sofia		Bulgaria	1408
14	"UMHAT Alexandrovska EAD, Sofia; Clinic of Psychiatry, First Department of Psychiatry "	Sofia		Bulgaria	1431
15	Medical Center Hera EOOD	Sofia		Bulgaria	1510
16	Medical Center Intermedica, OOD	Sofia		Bulgaria	1680
17	DCC "Mladost M" - Varna, OOD	Varna		Bulgaria	9020
18	Mental Health Center - Veliko Tarnovo EOOD,	Veliko Tarnovo		Bulgaria	5000
19	Mental Health Center - Vratsa EOOD, Vratsa; Department of Psychiatry	Vratsa		Bulgaria	3000
20	Clinic for psychiatry Vrapce 536	Zagreb		Croatia	10090
21	Clinic for psychiatry Vrapce 537	Zagreb		Croatia	10090
22	Clinic for psychiatry Vrapce 550	Zagreb		Croatia	10090
23	Clinic for psychiatry Vrapce 557	Zagreb		Croatia	10090
24	NeuropsychiatrieHK s.r.o.	Hradec Králové		Czechia	503 41
25	Narodni ustav dusevniho zdravi	Klecany		Czechia	25067
26	A-SHINE s.r.o.	Plzen		Czechia	31200
27	CLINTRIAL s.r.o.	Praha 10		Czechia	100 00
28	MUDr. Tibor Miklos	Praha 10		Czechia	106 00
29	Mathe es Tarsa Bt.	Kalocsa	Bacs	Hungary	6300
30	Semmelweis University Department of Psychiatry and Psychotherapy	Budapest		Hungary	1083
31	Nyiro Gyula Korhaz - Orszagos Pszichiatriai es Addiktologiai Intezet	Budapest		Hungary	1135
32	PsychoTech Kft.	Pecs		Hungary	7633
33	"Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico U.O.C. Psichiatria - Padiglione Alfieri, primo piano"	Milano		Italy	20122
34	Ospedale San Raffaele (San Raffaele Turro)	Milano		Italy	20127
35	Neuromeda, JSC	Kaunas		Lithuania	50185
36	Romuvos klinika, UAB	Kaunas		Lithuania	LT-44279
37	Kaunas City Outpatient Clinic, Public Institution	Kaunas		Lithuania	LT-48259
38	Silutes Mental Health and Psychotherapy Center, JSC	Silute		Lithuania	99142
39	Podlaskie Centrum Psychogeriatrii	Bialystok		Poland	15-756
40	Przychodnia Srodmiescie Sp. z o. o.	Bydgoszcz		Poland	85-080
41	Centrum Badan Klinicznych P.I. House Sp. z o.o.	Gdańsk		Poland	80-546
42	Care Clinic centrum Medyczne	Katowice		Poland	40-568
43	Specjalistyczna Praktyka Lekarska Marek Domański	Lublin		Poland	20-582
44	MSCZ im. prof. J. Mazurkiewicza	Pruszków		Poland	05-802
45	Ośr. Badań Klin. CLINSANTE S.C.	Torun		Poland	87-100
46	State budget healthcare Institution of Stavropol region "Regional specialized psychiatric hospital #2".	Tonnel'nyy	Stavropol Region	Russian Federation	357034
47	GUZ Lipetsk Regional psychoneurological Hospital #1	Lipetsk		Russian Federation	398007
48	"SBIH of Moscow ""Psychiatric Clinical Hospital # 4 n.a. P.B. Gannushkin"" Short name: PCH N4 n.a. P.B.Gannushkin"	Moscow		Russian Federation	107076
49	SBIH of Moscow "Psych Clinical Hospital #1 N.A. Alekseev"	Moscow		Russian Federation	117152
50	Saint-Petersburg state healthcare institution "Saint Nicolas wonderworker psychiatric hospital"	Saint Petersburg		Russian Federation	190121
51	"FSBI "National medical scientific center of psychiatry and neurology n.a. V.M. Bekhterev" MoH Short name: NMSC of Psy&Neuro n.a. Bekhterev, 12 dep."	Saint Petersburg		Russian Federation	192019
52	"Saint-Petersburg Scientific Research Psychoneurological Institute n.a. V.M. Bekhterev"	Saint Petersburg		Russian Federation	192019
53	V. M. Bekhterev National Research Medical Center For Psychiatry and Neurology	Saint Petersburg		Russian Federation	192019
54	Saint Petersburg State Budget Healthcare Institution "City Psychiatric Hospital No. 6 (Inpatient Department with Treatment Center)	Saint Petersburg		Russian Federation	193167
55	Saint Petersburg State Public Institution of Healthcare "City Psychiatric Hospital #3 n.a. I. I. Skvortsov-Stepanov",	Saint Petersburg		Russian Federation	197341
56	St. Petersburg SHI "Psychoneurological Dispensary #10"	Saint-Petersburg		Russian Federation	190121
57	"Saint-Petersburg Scientific Research Psychoneurological Institute n.a. V.M. Bekhterev".	Saint-Petersburg		Russian Federation	192019
58	SPHI "City Mental Hospital #3 n.a. I.I.Skvortsov-Stepanov"	Saint-Petersburg		Russian Federation	197341
59	State Budget Healthcare Institution "Samara Psychiatric Hospital	Samara		Russian Federation	443016
60	FSBEI HE "Smolensk State Medical University" of the MoH of the RF (Clinical Research Centre of diagnostics and medicines)	Smolensk		Russian Federation	214019
61	Klinika StoLet" Ltd.	Tomsk		Russian Federation	634009
62	State Budget healthcare Institution of Yaroslavl region "Yaroslavl region clinical psychiatric hospital"	Yaroslavl		Russian Federation	150003
63	Clinical Hospital Center "Dr. Dragisa Misovic-Dedinje", Clinic of Psychiatry	Belgrade		Serbia	11000
64	Institute of Mental health	Belgrade		Serbia	11000
65	Clinical Center Kragujevac, Clinic of Psychiatry	Kragujevac		Serbia	34000
66	Psychiatric Clinic, Clinical Center Kragujevac	Kragujevac		Serbia	34000
67	Clinical Center Nis, Mental Health Protection Clinic	Nis		Serbia	18000
68	Hospital Clinic de Barcelona	Barcelona		Spain	08036
69	Hospital Universitari Vall d'Hebron	Barcelona		Spain	8035
70	Hospital Gregorio Marañon	Madrid		Spain	28007
71	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
72	CSM La Corredoria	Oviedo		Spain	33011
73	Centro de Salud Parquesol, 2ª planta - Servicio de Psiquiatria	Valladolid		Spain	47016
74	Hospital Provincial de Zamora	Zamora		Spain	49021
75	CI Cherkasy Regional Psychiatric Hospital of ChRC	Smila	Cherkas'ka Oblast	Ukraine	20708
76	Regional Clinical Psychiatric Hospital	Kropyvnytskyi	Kirovograd Region	Ukraine	25491
77	Kyiv City Psychoneurological Hospital #3 General Psychiatry Department No. 2	Kyiv	Vasylkiv District Kyiv Region	Ukraine	08631
78	"CIH Kharkiv Regional Clinical Psychiatric Hospital #3 Psychiatric Department of Primary Psychotic Episod Short Site name: CIH KRCPH #3 PD of PPE "	Kharkiv		Ukraine	61068
79	SI Institute of Neurology,Psychiatry&Narcology of NAMSU	Kharkiv		Ukraine	61068
80	State Institution "Institute of Neurology, Psychiatry and Narcology of NAMS of Ukraine", Department of Urgent Psychiatry and Narcology	Kharkiv		Ukraine	61068
81	Kyiv Regional Medical Incorporation "Psychiatry". Center of Novel Treatment and Rehabilitation of Psychotic disorders, build 5, Department #30	Kyiv		Ukraine	04080
82	"Kyiv CH on Railway Transport #2 of Branch Center of Healthcare Public Company Ukr Railway Short site name: Kyiv Railway Clinical Hospital № 2"	Kyiv		Ukraine	3049
83	CI Odesa Regional Medical Centre of Mental Health	Odesa		Ukraine	65014

Sponsors and Collaborators

ACADIA Pharmaceuticals Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

ACADIA Pharmaceuticals Inc.

ClinicalTrials.gov Identifier:

NCT04531982

Other Study ID Numbers:

ACP-103-064

First Posted:

Aug 31, 2020

Last Update Posted:

Oct 18, 2021

Last Verified:

Oct 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Schizophrenia

Pimavanserin

Study Results

No Results Posted as of Oct 18, 2021