Evaluating Safety and Efficacy of VV119 in Acute Schizophrenia Adults

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

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.

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.

Inclusion Criteria:

1. Male or female participants, 18-65 years,inclusive, at screening.

2. 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).

3. 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).

4. 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.

5. 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).

6. 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.

7. 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.

Exclusion Criteria:

1. Any primary DSM-5 disorder other than schizophrenia.
2. 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.
3. 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).
4. 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.
5. Electroconvulsive therapy (ECT) within 3 months before screening.
6. Chronic clozapine use prior to screening.
7. 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.
8. Long-acting injectable antipsychotics (risperidone paliperidone palmitate, aripiprazole long-acting injectable, etc.) discontinued for less than 5 half-lives at randomization.
9. 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.
10. 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.
11. Prior inadequate response to aripiprazole (≥20 mg/day for minimum 6 weeks).
12. History or active epilepsy (febrile convulsions excluded).
13. History or current presence of neuroleptic malignant syndrome (NMS).
14. History or active malignancy of any type.
15. History or active ocular disease: open/closed-angle glaucoma, or acute bacterial/viral eye infection within 1 week pre-screening.
16. History or active tardive dyskinesia.
17. History of conditions/surgeries altering drug ADME or conferring safety risks (gastrectomy, gastrointestinal anastomosis, bowel resection, urinary obstruction, dysuria, etc.).
18. History of drug/food allergies, or hypersensitivity to study drug, its components, or aripiprazole analogs.
19. Pregnant or lactating female at screening/baseline.
20. History of alcohol/psychoactive substance abuse/dependence (excluding caffeine, nicotine) within 1 year pre-screening, or positive urine drug/alcohol screen at screening.
21. Clinically significant abnormal vital signs/physical exam findings at screening/baseline per investigator judgment that may interfere with study participation.
22. Orthostatic drop ≥20 mmHg systolic or ≥10 mmHg diastolic within 3 minutes of standing at screening.
23. 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.
24. Severe unstable medical illness (cardiac, hepatic, renal, hematologic, endocrine, neurologic, etc.) deemed ineligible by investigator.
25. 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.
26. Positive HBsAg, HCV-Ab, HIV-Ab or TP-Ab at screening.
27. Participation in another interventional trial with investigational product/device within 3 months pre-screening, or ongoing trial enrollment.
28. Other exclusion criteria per investigator discretion .