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

• ClinicalTrials.gov Identifier: NCT04531982
• Recruitment Status: Active, not recruiting
• First Posted: August 31, 2020
• Last Update Posted: August 16, 2023
• Sponsor: ACADIA Pharmaceuticals Inc.
• Information provided by (Responsible Party): ACADIA Pharmaceuticals Inc.

Tracking Information

• First Submitted Date: August 26, 2020
• First Posted Date: August 31, 2020
• Last Update Posted Date: August 16, 2023
• Actual Study Start Date: August 5, 2020
• Estimated Primary Completion Date: January 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 26, 2020)

Negative Symptom Assessment-16 (NSA-16) total score - change from Baseline to Week 26 [ Time Frame: 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 26, 2020)

• Clinical Global Impression of Schizophrenia Scale-Severity (CGI-SCH-S) of negative symptoms score - change from Baseline to Week 26 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy and Safety of Pimavanserin as Adjunctive Treatment for the Negative Symptoms of Schizophrenia
• 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
• Brief Summary: To evaluate the efficacy and safety of adjunctive pimavanserin compared with adjunctive placebo in the treatment of negative symptoms of schizophrenia
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Schizophrenia

Intervention

• Drug: Pimavanserin
  Pimavanserin 34 mg, taken as two blinded 17 mg tablets once daily by mouth
• Drug: Placebo
  Placebo, taken as two blinded tablets once daily by mouth

Study Arms

• Experimental: Drug - Pimavanserin
  Pimavanserin 34 mg taken as two tablets + background antipsychotic, once daily by mouth
  Intervention: Drug: Pimavanserin
• Placebo Comparator: Placebo
  Placebo + background antipsychotic, taken as two tablets, once daily by mouth
  Intervention: Drug: Placebo

• Publications *: Darwish M, Bugarski-Kirola D, Passarell J, Owen J, Jaworowicz D, DeKarske D, Stankovic S. Pimavanserin Exposure-Response Analyses in Patients With Schizophrenia: Results From the Phase 2 ADVANCE Study. J Clin Psychopharmacol. 2022 Nov-Dec 01;42(6):544-551. doi: 10.1097/JCP.0000000000001611. Epub 2022 Oct 3.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: August 15, 2023): 454
• Original Estimated Enrollment (submitted: August 26, 2020): 386
• Estimated Study Completion Date: January 2024
• Estimated Primary Completion Date: January 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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 (including no recent hospitalization for exacerbation of psychiatric disorder) 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 confirmed 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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Bulgaria, Croatia, Czechia, Hungary, Italy, Lithuania, Poland, Russian Federation, Serbia, Spain, Ukraine

Administrative Information

• NCT Number: NCT04531982
• Other Study ID Numbers: ACP-103-064
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: ACADIA Pharmaceuticals Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: ACADIA Pharmaceuticals Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: ACADIA Pharmaceuticals Inc.
• Verification Date: August 2023