An International, Randomized, Double-Blind, 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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Jiangsu Hengrui Pharmaceuticals Co. Ltd.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

8 Nov 2021 → ongoing

Decision date (initial)

2024-03-21

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

External identifiers

EU CT number

2023-509396-16-00

EudraCT number

2020-006063-28

ClinicalTrials.gov

NCT04691804

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy, Pharmacokinetic

- To evaluate whether fuzuloparib plus AA-P is superior to placebo plus AA-P as first-line treatment by assessment of rPFS in metastatic castration-resistant prostate cancer (mCRPC) subjects unselected for 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)

Secondary objectives 1

1. To evaluate the OS in unselected mCRPC subjects (Cohort 1) and in mCRPC subjects harboring DRD (Cohort 2), respectively.

Conditions and MedDRA coding

Metastatic Castration-Resistant Prostate Cancer

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Age of ≥ 18 years old.
2. A score of 0 to 1 for ECOG performance status.
3. Expected survival of ≥ 6 months.
4. Prostate adenocarcinoma confirmed by histology or cytology examinations, with no indication of neuroendocrine differentiation or small cell characteristics.
5. Metastatic lesions with imaging evidence.
6. Disease progression of metastatic prostate cancer while the subject was on androgen deprivation therapy. See the disease progression at study entry definition in the protocol.
7. Continuous treatment with luteinizing hormone-releasing hormone analogue (LHRHa) (drug-induced castration) or previous bilateral orchidectomy (surgical castration); subjects who have not undergone bilateral orchidectomy must plan to maintain effective LHRHa treatment within 4 weeks prior to the randomization of this study and throughout the entire study.
8. Testosterone is at the castration level (≤ 50 ng/dL or 1.73 nmol/L) during screening.
9. Blood and tumor tissue samples (tumor sample is optional) are provided during screening to determine the DRD status; subjects in Cohort 2 must be DRD positive.
10. The functional level of the organs must meet the requirements (no blood transfusion or treatment with hematopoietic growth factor within 2 weeks prior to routine blood screening) as detailed in the protocol.
11. For patients who are judged by the investigator as having the ability to ejaculate and who are sexually active must agree to take effective contraceptive measures and not to donate sperm from the first dose to 3 months after the last dose of study treatment.
12. Participate in this clinical trial voluntarily, understand and have signed the informed consent.

Exclusion criteria 21

1. Prior treatment with any PARP inhibitor.
2. Have received any systemic anti-tumor treatment during the mCRPC stage or non-metastatic CRPC (nmCRPC) stage, including chemotherapy, immunotherapy, abiraterone acetate or other CYP17 inhibitors, novel AR antagonists (such as enzalutamide, apalutamide, darolutamide, SHR3680, and proxalutamide) and other molecular targeted therapies. See protocol for the allowed exceptions.
3. Prior treatment with abiraterone acetate, other CYP17 inhibitors, novel AR antagonists, or chemotherapy during HSPC stage, with PSA elevation, radiographic progression or other clinical progressions during the treatment and 6 months after the end of this treatment (as determined by the investigator).
4. With severe bone injury caused by bone metastasis of prostate cancer as judged by the investigator, including poorly controlled severe bone pain, and pathological fractures and spinal cord compressions that have occurred in the last 6 months before the first dose or are expected to occur soon.
5. Radiotherapy or major surgery within 4 weeks before the first dose, or participation in other drug clinical trials within 4 weeks or 5 half-lives, whichever is longer, prior to start of this study drug at day 1 (C1D1).
6. Have used any strong/moderate CYP3A4 inducers or inhibitors within 14 days prior to the first dose.
7. The use of drugs that may affect P-gp cannot be interrupted during the study.
8. Plan to receive any other anti-tumor treatment during the study treatment of this study.
9. Presence of radiologically confirmed tumor lesions in the brain.
10. Contraindications to the use of prednisone (corticosteroids), such as active infections or other medical conditions.
11. Any chronic medical conditions that require a dose of corticosteroid ≥ 5 mg prednisone BID.
12. History of uncontrolled pituitary or adrenal dysfunction.
13. Uncontrolled hypertension (persistent systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg). Subjects with a history of hypertension are allowed to participate in the study if their blood pressure can be effectively controlled by antihypertensive therapy.
14. Presence of active heart diseases (including severe/unstable angina pectoris, symptomatic congestive heart failure of NYHA Class III or IV, left ventricular ejection fraction < 50%, and ventricular arrhythmia requiring drug therapy) or a history of arterial or venous thrombosis (including pulmonary embolism and cerebrovascular accident) within 6 months, or myocardial infarction within 12 months prior to the first dose.
15. History of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML), or a history of other malignant tumors within 5 years prior to the first dose (except carcinoma in situ that has been completely relieved and the malignant tumor that is judged by investigators as slowly progressive).
16. Active HBV or HCV infection (HBsAg positive with virus copy ≥ 500 IU/mL, HCV antibody positive with HCV RNA higher than the lower limit of detection of the analytical method).
17. Human immunodeficiency virus-positive subjects with 1 or more of the following: - Not receiving highly active antiretroviral therapy. - Had a change in antiretroviral therapy within 6 months of the start of screening. - Receiving antiretroviral therapy that may interfere with study drug (consult sponsor for review of medication prior to enrollment). - CD4 count < 350/mm3 or CD4/CD8 ratio value lower than the minimum of the normal range at screening. - AIDS-defining opportunistic infection within 12 months of start of screening.
18. Presence of dysphagia, chronic diarrhea, intestinal obstruction, or other factors affecting drug intake and absorption.
19. With known allergy or intolerance to fuzuloparib, abiraterone acetate, prednisone, or their excipients.
20. Confirmed SARS-CoV-2 (COVID-19) infection (validated test positive), or suspected COVID-19 infection (clinical symptoms without documented test results), or close contact with a person with known or suspected COVID-19 infection, within 4 weeks before the first dose. The subject may be included with a documented negative result for a validated COVID-19 test.
21. Presence of concomitant diseases (such as severe diabetes mellitus, psychiatric disorders, and pneumonitis or interstitial lung disease) or any other situation that may pose serious risks to the safety of the subjects or may affect their ability to complete the study as judged by the investigator.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. -Cohort 1: rPFS (assessed by Blinded Independent Central Review [BICR] according to RECIST 1.1 and PCWG3 criteria) in unselected mCRPC subjects. - Cohort 2: rPFS (assessed by Blinded Independent Central Review [BICR] according to RECIST 1.1 and PCWG3 criteria) in mCRPC subjects harboring DRD.

Secondary endpoints 1

1. OS in unselected mCRPC subjects (Cohort 1) and in mCRPC subjects harboring DRD (Cohort 2), respectively.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Jiangsu Hengrui Pharmaceuticals Co. Ltd.

Sponsor organisation

Jiangsu Hengrui Pharmaceuticals Co. Ltd.

Address

7 Kunlunshan Road, Economic and Technological Development Zone Economic and Technological Development Zone

City

Lianyungang

Postcode

222047

Country

China

Scientific contact point

Organisation

Jiangsu Hengrui Pharmaceuticals Co. Ltd.

Contact name

Wenliang Wang

Public contact point

Organisation

Jiangsu Hengrui Pharmaceuticals Co. Ltd.

Contact name

Wenliang Wang

Third parties 8

Locations

6 EU/EEA countries · 31 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 73 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

12 submissions — initial application plus substantial / non-substantial modifications