Evaluating Safety and Efficacy of VV119 in Acute Schizophrenia Adults

Официальное название

A Phase 2,Multicenter, Randomized, Double-blind, Placebo and Active Comparator Parallel-controlled Study to Evaluate the Safety and Efficacy of VV119 in Adults With Acute Schizophrenia

Обзор

This will be a multicenter, randomized, double-blind, placebo and active comparator parallel-controlled study designed to assess the safety and efficacy of VV119 (2.0 to 6.0 mg) for the treatment of adult participants diagnosed with DSM-5 schizophrenia who are in an acute exacerbation phase.

Подробное описание

Aripiprazole (20 mg) is included as a positive control to confirm the assay sensitivity of the study. The primary objective of the study is to assess the efficacy of VV119 in adult inpatients with a Diagnostic and Statistical Manual-Fifth Edition (DSM-5) diagnosis of schizophrenia. The secondary objective of the study is to assess overall safety of VV119 in adult inpatients diagnosed with DSM-5 schizophrenia.The exploratory objective is to characterize the population PK and quantify PK/PD relationship of VV119 in schizophrenia patients.

Вмешательства

• Препарат VV119 2mg
  VV119 capsules 1 capsule (2mg/capsule) + VV119 capsules placebo 2 capsules + aripiprazole tablet placebo 2 tablets
• Препарат VV119 4mg
  VV119 capsules 2 capsules (2mg/capsule) + VV119 capsules placebo 1 capsules + aripiprazole tablet placebo 2 tablets
• Препарат VV119 6mg
  VV119 capsule 3 capsules (2mg/capsule) + aripiprazole tablet placebo 2 tablets
• Препарат Aripiprazole tablet
  VV119 capsule placebo 3 capsules (2mg/capsule) + aripiprazole tablet 2 tablets
• Препарат Placebo
  VV119 capsule placebo 3 capsules (2mg/capsule) + aripiprazole tablet placebo 2 tablets

Первичные конечные точки

• Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6 [Срок оценки: Baseline and Week 6]

Вторичные конечные точки (6)

• Change From Baseline in PANSS Positive Score at Week 6 [Срок оценки: Baseline and Week 6]
• Change From Baseline in PANSS Negative Score at Week 6 [Срок оценки: Baseline and Week 6]
• Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 6 [Срок оценки: Baseline and Week 6]
• Clinical Global Impression - Improvement (CGI-I) Score at Week 6 [Срок оценки: Week 6]
• Response Rate at Week 6 [Срок оценки: Week 6]
• Change From Baseline in Calgary Depression Scale for Schizophrenia (CDSS) Score at Week 6 [Срок оценки: Baseline and Week 6]

Критерии участия

Критерии включения

• Male or female participants, 18-65 years,inclusive, at screening.
• Body Mass Index of 18.5 to 35.0kg/m2 , and body weight no less than 50.0kg (males), body weight no less than 45.0kg (females).
• Participant has a primary diagnosis of schizophrenia established by a comprehensive psychiatric evaluation based on the DSM-5 criteria and confirmed by Mini International Neuropsychiatric Interview for Schizophrenia and Psychotic Disorder Studies (MINI).
• Participant is experiencing an acute exacerbation or relapse of symptoms, with onset less than 2 months before screening:a.Participans who have been recently hospitalized or who would benefit from hospitalization for an acute exacerbation or relapse of schizophrenia;b.If hospitalized at screening, the participant's current admission for acute exacerbation shall be ≤2 weeks.
• Positive and Negative Syndrome Scale total score between 80 and 120, inclusive, at screening,Score of ≥ 4 (moderate or greater) for ≥ 2 of the following Positive Scale (P) items at screening:

Item 1 (P1; delusions) Item 2 (P2; conceptual disorganization) Item 3 (P3; hallucinatory behavior) Item 6 (P6; suspiciousness/persecution).

• WOCBP and male participants and their partners shall use medically approved effective contraception throughout treatment and for 3 months after the final study drug dose, such as intrauterine devices, contraceptive pills, or condoms.
• Participants who are able to understand and follow study plans and instructions; Participants who have voluntarily decided to participate in this study and signed the informed consent form.

Критерии исключения

• Any primary DSM-5 disorder other than schizophrenia.
• Investigator-assessed treatment-resistant schizophrenia: participants who failed adequate sequential monotherapy with ≥2 structurally distinct, potent antipsychotics for positive symptoms,Each drug was given at ≥600 mg/day chlorpromazine equivalents for ≥6 consecutive weeks with poor efficacy.
• Subjects with a >20% reduction in total PANSS score from screening to baseline. Reduction rate = (Screening total PANSS score - Baseline total PANSS score) / (Screening total PANSS score - 30).
• Per investigator assessment via the Columbia-Suicide Severity Rating Scale (C-SSRS), participants with suicidal risk/intent in the 6 months before screening (answered "Yes" to C-SSRS Ideation Item 4 or 5) or any actual suicidal behavior within 12 months prior are excluded. Non-suicidal self-injury in the past year is not exclusionary, though participants with substantial current self-harm risk per clinical judgment will still be excluded.
• Electroconvulsive therapy (ECT) within 3 months before screening.
• Chronic clozapine use prior to screening.
• Discontinuation of short/intermediate-acting antipsychotics or other psychoactive agents (antidepressants, mood stabilizers, antiepileptics, etc.) for less than 5 half-lives or less than 1 week at randomization.
• Long-acting injectable antipsychotics (risperidone paliperidone palmitate, aripiprazole long-acting injectable, etc.) discontinued for less than 5 half-lives at randomization.
• Discontinuation of QT-prolonging and torsades de pointes (TdP)-inducing medications (levofloxacin, fluconazole, ondansetron, amiodarone, metronidazole, erythromycin, haloperidol, etc.) for less than 5 half-lives at randomization.
• Discontinuation of moderate/potent CYP3A or CYP2D6 inhibitors/inducers for less than 5 half-lives at randomization, or planned use of such agents throughout the study.
• Prior inadequate response to aripiprazole (≥20 mg/day for minimum 6 weeks).
• History or active epilepsy (febrile convulsions excluded).
• History or current presence of neuroleptic malignant syndrome (NMS).
• History or active malignancy of any type.
• History or active ocular disease: open/closed-angle glaucoma, or acute bacterial/viral eye infection within 1 week pre-screening.
• History or active tardive dyskinesia.
• History of conditions/surgeries altering drug ADME or conferring safety risks (gastrectomy, gastrointestinal anastomosis, bowel resection, urinary obstruction, dysuria, etc.).
• History of drug/food allergies, or hypersensitivity to study drug, its components, or aripiprazole analogs.
• Pregnant or lactating female at screening/baseline.
• History of alcohol/psychoactive substance abuse/dependence (excluding caffeine, nicotine) within 1 year pre-screening, or positive urine drug/alcohol screen at screening.
• Clinically significant abnormal vital signs/physical exam findings at screening/baseline per investigator judgment that may interfere with study participation.
• Orthostatic drop ≥20 mmHg systolic or ≥10 mmHg diastolic within 3 minutes of standing at screening.
• QTcF >450 ms (male) / >470 ms (female) at screening/baseline (Fridericia formula); or other clinically significant 12-lead ECG abnormalities interfering with study participation per investigator.
• Severe unstable medical illness (cardiac, hepatic, renal, hematologic, endocrine, neurologic, etc.) deemed ineligible by investigator.
• Elevated ALT/AST >1.5×ULN, Cr >1.2×ULN, TBIL >1.5×ULN, or other clinically significant lab abnormalities at screening/baseline per investigator assessment.
• Positive HBsAg, HCV-Ab, HIV-Ab or TP-Ab at screening.
• Participation in another interventional trial with investigational product/device within 3 months pre-screening, or ongoing trial enrollment.
• Other exclusion criteria per investigator discretion .

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Beijing Anding Hospital of Capital Medical University — Пекин

Идентификаторы

NCT: NCT07703956 · VV119-SCH-II-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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