Clinical Trials Register

Summary
EudraCT Number:	2017-003364-12
Sponsor's Protocol Code Number:	64091742PCR3001
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2018-11-20
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2017-003364-12

A.3

Full title of the trial

A Phase 3 Randomized, Placebo-controlled, Double-blind Study of Niraparib in Combination with Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for Treatment of Subjects with Metastatic Prostate Cancer

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A Phase 3 Study of Niraparib in Combination with Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for Treatment of Patients with Metastatic Prostate Cancer

A.4.1

Sponsor's protocol code number

64091742PCR3001

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Janssen-Cilag International N.V.
B.1.3.4	Country	Belgium
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Janssen Research & Development, LLC
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Janssen-Cilag International N.V.
B.5.2	Functional name of contact point	Clinical Registry group
B.5.3	Address:
B.5.3.1	Street Address	Archimedesweg 29
B.5.3.2	Town/ city	Leiden
B.5.3.3	Post code	2333 CM
B.5.3.4	Country	Netherlands
B.5.6	E-mail	ClinicalTrialsEU@its.jnj.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Niraparib 100 mg capsules
D.3.2	Product code	JNJ-64091742
D.3.4	Pharmaceutical form	Capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NIRAPARIB
D.3.9.1	CAS number	1038915-60-4
D.3.9.2	Current sponsor code	JNJ-64091742
D.3.9.3	Other descriptive name	niraparib tosylate monohydrate
D.3.9.4	EV Substance Code	SUB177208
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	niraparib/abiraterone 100/500mg (G010)
D.3.2	Product code	CJNJ-67652000-G010
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NIRAPARIB
D.3.9.1	CAS number	1038915-60-4
D.3.9.2	Current sponsor code	JNJ-64091742
D.3.9.4	EV Substance Code	SUB177208
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ABIRATERONE ACETATE
D.3.9.1	CAS number	154229-18-2
D.3.9.3	Other descriptive name	ABIRATERONE ACETATE
D.3.9.4	EV Substance Code	SUB31647
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	500
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	niraparib/abiraterone 50/500mg (G009)
D.3.2	Product code	CJNJ-67652000-G009
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NIRAPARIB
D.3.9.1	CAS number	1038915-60-4
D.3.9.2	Current sponsor code	JNJ-64091742
D.3.9.4	EV Substance Code	SUB177208
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ABIRATERONE ACETATE
D.3.9.1	CAS number	154229-18-2
D.3.9.3	Other descriptive name	ABIRATERONE ACETATE
D.3.9.4	EV Substance Code	SUB31647
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	500
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Metastatic Prostate Cancer

E.1.1.1

Medical condition in easily understood language

Metastatic Prostate Cancer

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10036909
E.1.2	Term	Prostate cancer metastatic
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the effectiveness of niraparib plus AA-P compared to AA-P plus placebo.

E.2.2

Secondary objectives of the trial

* To assess the clinical benefit of niraparib plus AA-P compared to AA-P plus placebo
* To characterize the safety profile of niraparib when given with AA-P compared to AA-P with placebo

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Criterion modified per Amendment 3
1.1 Criterion modified per Amendment 4
1.2 HRR gene alteration status (as identified by the sponsor's required assays or local testing for HRR gene alteration) as follows:
a. Cohort 1: positive for HRR gene alteration
b. Cohort 2: not positive for HRR gene alteration (ie, no HRR gene alteration)
c. Cohort 3
2. Metastatic disease documented by positive bone scan or metastatic lesions on computed tomography (CT) or magnetic resonance imaging (MRI).
3. Criterion modified per Amendment 2
3.1 Metastatic prostate cancer in the setting of castrate levels of testosterone ≤50 ng/dL on a GnRHa or bilateral orchiectomy as evidenced by prostate-specific antigen (PSA) progression or radiographic progression
4. Able to continue GnRHa during the study if not surgically castrate
5. ECOG PS Grade of 0 or 1
6. Score of ≤3 on the Brief Pain Inventory-Short Form (BPI-SF) Question #3 (worst pain in last 24 hours).
7. Criterion modified per Amendment 2
7.1 Clinical laboratory values at Screening:
a .Absolute neutrophil count (ANC) ≥1.5 x 10^9/L.
b. Hemoglobin ≥9.0 g/dL, independent of transfusions for at least 30 days.
c. Platelet count ≥100 x 10^9/L.
d. Serum albumin ≥3.0 g/dL.
e. Creatinine clearance ≥30 mL/min either calculated or directly measured via 24-hour urine collection.
f. Serum potassium ≥3.5 mmol/L.
g. Serum total bilirubin ≤1.5 x upper limit of normal (ULN) or direct bilirubin ≤1 x ULN (Note: in subjects with Gilbert's syndrome, if total bilirubin is >1.5 x ULN, measure direct and indirect bilirubin, and if direct bilirubin is ≤1.5 x ULN, subject may be eligible as determined by the medical monitor).
h. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 x ULN.
8. Able to swallow the study drug tablets and capsules whole.
9. To avoid risk of drug exposure through the ejaculate (even men with vasectomies), subjects must agree while on study drug and for 3 months following the last dose of study drug to:
a. Use a condom during sexual activity.
b. Not donate sperm.
10. Willing and able to adhere to the prohibitions and restrictions specified in the protocol

E.4

Principal exclusion criteria

1. Prior treatment with a PARP inhibitor
2. Criterion modified per Amendment 2
2.1 Systemic therapy (ie, novel second-generation AR-targeted therapy such as enzalutamide, apalutamide, or darolutamide; taxane-based chemotherapy, or more than 4 months of AA-P prior to randomization) in the mCRPC setting; or AA-P outside of the mCRPC setting.
3. Criterion modified per Amendment 2
3.1 For subjects who received 2 to 4 months of AA-P prior to randomization for the treatment of mCRPC, evidence of progression by PSA (per PCWG3) during screening. These potential subjects are required to have 2 PSA values during the Prescreening and Screening Phases. The second PSA value should be within 2 weeks of randomization. If PSA rise is thought to be due to flare, the investigator
should confirm that there is no radiographic progression.
4. Symptomatic brain metastases
5. History or current diagnosis of myelodysplastic syndrome (MDS)/acute
myeloid leukemia (AML)
6. Other prior malignancy ≤2 years prior to randomization, or malignancy that currently requires active systemic therapy
7. Severe or unstable angina, myocardial infarction or ischemia requiring coronary artery bypass graft or stent within the previous 6 months, symptomatic congestive heart failure, arterial or venous thromboembolic events (e.g. adequate cardiac function), or clinically significant ventricular arrhythmias within 6 months prior to randomization or New York Heart Association (NYHA) Class II to IV heart disease
8. Presence of uncontrolled hypertension. Subjects with a history of hypertension are allowed, if BP is controlled to within these limits by anti-hypertensive treatment.
9. Current evidence of any of the following:
a. Any medical condition that would make prednisone use contraindicated
b. Any chronic medical condition requiring a higher equivalent dose of corticosteroid than 10 mg prednisone (or equivalent) once daily.
10. Active or symptomatic viral hepatitis or chronic liver disease (as evidenced by ascites or bleeding disorders secondary to hepatic dysfunction).
11. History of adrenal dysfunction
12. Known allergies, hypersensitivity, or intolerance to AA or niraparib or the corresponding excipients
13. Subjects who are receiving opioid analgesics at the time of screening
14. Human immunodeficiency virus (HIV) positive subjects with 1 or more of the following:
a. Not receiving highly active antiretroviral therapy.
b. Receiving antiretroviral therapy that may interfere with the study drug
c. A change in antiretroviral therapy within 6 months of the start of screening
d. CD4 count <350 at screening.
e. An acquired immunodeficiency syndrome-defining opportunistic infection within 6 months of the start of screening.
15. Subjects who have had the following ≤28 days prior to randomization:
a. A transfusion (platelets or red blood cells).
b. Hematopoietic growth factors.
c. An investigational agent for prostate cancer.
d. Major surgery (sponsor should be consulted regarding what constitutes major surgery).
e. Radiation therapy

E.5 End points

E.5.1

Primary end point(s)

Radiographic progression-free survival (rPFS)

E.5.1.1

Timepoint(s) of evaluation of this end point

While on study treatment, radiographic imaging will be performed at Cycle 3 Day 1, Cycle 5 Day 1, Cycle 7 Day 1, and then every 12 weeks

E.5.2

Secondary end point(s)

* OS
* Time-to-symptomatic progression
* Time-to-initiation of cytotoxic chemotherapy
* Observed plasma concentrations of niraparib and abiraterone and estimated population PK and exposure parameters for niraparib
* Incidence and severity of AEs
* Clinical laboratory test results

E.5.2.1

Timepoint(s) of evaluation of this end point

Assessments of the secondary endpoints are variable but carried out on a regular basis from C1D1 through the follow up as described in the endpoint requirements

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Biomarker evaluations, PRO

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

105

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Belgium

Brazil

Bulgaria

Canada

China

Czech Republic

France

Germany

Hungary

Israel

Italy

Korea, Republic of

Malaysia

Netherlands

Poland

Portugal

Russian Federation

South Africa

Spain

Sweden

Taiwan

Turkey

Ukraine

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

260

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

840

F.2 Gender

F.2.1

Female

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

339

F.4.2.2

In the whole clinical trial

1100

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Protocol section 3.1: in the event of early completion or study termination by sponsor, the sponsor will continue to provide study treatments until unequivocal disease progression, unacceptable toxicity, or an alternate method is in place to avoid treatment interruption. In the event of positive study result at the final rPFS analysis for each cohort, sponsor may decide to allow the study to proceed into an Open-label Extension.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2018-12-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-04-17

P. End of Trial
P.	End of Trial Status	GB - no longer in EU/EEA

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