A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase III Study of Fuzuloparib Combined With Abiraterone Acetate and Prednisone (AA-P) Versus Placebo Combined With AA-P as First-Line Treatment in Patients With Metastatic Castration-Resistant Prostate Cancer

Study Overview
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Brief Summary
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To evaluate whether Fuzuloparib plus AA-P is superior to placebo plus AA-P as first-line treatment by assessment of radiographic progression-free survival (rPFS) in mCRPC subjects unselected for deoxyribonucleic acid (DNA) damage repair deficiencies (DRD) status (Cohort 1) to evaluate whether Fuzuloparib plus AA-P is superior to placebo plus AA-P as first-line treatment by assessment of rPFS in mCRPC subjects harboring DRD (Cohort 2).

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase III Study of Fuzuloparib Combined With Abiraterone Acetate and Prednisone (AA-P) Versus Placebo Combined With AA-P as First-Line Treatment in Patients With Metastatic Castration-Resistant Prostate Cancer

Conditions
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Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Intervention / Treatment
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* Drug: Fuzuloparib , Abiraterone acetate and Prednisone
* Drug: Fuzuloparib Placebo， Abiraterone acetate and Prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Able and willing to provide a written informed consent A score of 0 to 1 for ECOG performance status Age of ≥ 18 years old Prostate adenocarcinoma confirmed Disease progression of metastatic prostate cancer while the subject was on androgen deprivation therapy. The functional level of the organs must meet the requirements Blood and tumor tissue samples are provided during screening to determine the DRD status Exclusion Criteria Prior treatment with any PARP inhibitor Have received any systemic anti-tumor treatment during the mCRPC stage or non-metastatic CRPC stage Have used any CYP3A4 inducers or inhibitors within 14 days prior to the first dose Plan to receive any other anti-tumor treatment Presence of radiologically confirmed tumor lesions in the brain Contraindications to the use of Prednisone History of uncontrolled pituitary or adrenal dysfunction Uncontrolled hypertension Presence of active heart diseases Human immunodeficiency virus-positive Presence of dysphagia, chronic diarrhea, intestinal obstruction, or other factors affecting drug intake and absorption Active HBV or HCV infection Presence of concomitant diseases

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Fuzuloparib Combined with Abiraterone Acetate and Prednisone (AA-P) versus Placebo Combined with AA-P
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group A<br>Fuzuloparib plus AA-P | Drug: Fuzuloparib , Abiraterone acetate and Prednisone<br>* Fuzuloparib capsules (strength: 50 mg),150mg, Bid,po Abiraterone acetate tablets (strength: 250 mg) 1000mg Qd,po Prednisone tablets (strength: 5 mg) 5mg, Bid po<br>* Other names: SHR3162;|
| Placebo Comparator: Treatment group B<br>Fuzuloparib Placebo plus AA-P | Drug: Fuzuloparib Placebo， Abiraterone acetate and Prednisone<br>* Fuzuloparib capsules Placebo (strength: 50 mg),150mg, Bid,po Abiraterone acetate tablets (strength: 250 mg)1000mg Qd,po Prednisone tablets (strength: 5 mg)5mg, Bid po<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rPFS by blinded independent central review (BICR) using RESIST1.1 and PCWG3 | progression-free survival | up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OS | time from randomization to death due to any cause | up to 4 years | 
| ORR | The percentage of subjects with measureable disease at baseline who achieved a complete or partial response in their soft tissue disease using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria | up to 3 years | 
| Time to PSA progression | Time from randomisation to the first time of PSA progression according to the criterion of PCGW3 | up to 3 years | 
| Time to skeletal-related events | Time from randomisation to the first occurrence of a fracture or treatment for the fracture. The skeletal-related event is defined as the occurrence of either pathological or clinical fracture, spinal cord compression, bone-related radiotherapy or surgery. | up to 4 years |