Prostatic Neoplasms, Castration-Resistant
Conditions
Brief summary
The purpose of this study is to: a) establish the recommended phase 2 dose (RP2D) and to evaluate the antitumor activity and safety of niraparib combination therapies (Combinations 1 and 2) and b) to determine the relative bioavailability of niraparib and abiraterone acetate (AA) in combination (Combination 3) in participants with metastatic castration-resistant prostate cancer (mCRPC).
Detailed description
This multicenter study will evaluate safety and efficacy of niraparib in combination with other anti-cancer agents. Combination 1 will combine niraparib with the anti-programmed cell death protein (PD)-1 monoclonal antibody cetrelimab, in participants with mCRPC. Combination 1 has 2 parts: in Part 1 (dose selection), participants will be enrolled to establish RP2D doses of niraparib and cetrelimab; and Part 2 (dose expansion) will evaluate the combination therapy in an expanded number of participants into 2 cohorts (biomarker positive or biomarker negative). Combination 2 will combine niraparib with abiraterone acetate plus prednisone (AA-P) in mCRPC participants with DNA-repair gene defects (DRD). Combination 3 will evaluate the relative bioavailability (BA) of niraparib and AA in combination. In a pharmacokinetics (PK) assessment phase, niraparib and AA will be administered, and in an extension phase, niraparib and AA-P will be administered. Combinations 1 and 2 will have 5 phases: A Pre-screening Phase, a Screening Phase, a Treatment Phase, a Follow-up Phase, and a Long-term Extension (LTE) Phase; Combination 3 has 3 phases: A Screening Phase, A PK Assessment Phase, an Extension Phase (including LTE phase). Study evaluations will include efficacy, PK, PK/pharmacodynamics, biomarkers, safety and tolerability.
Interventions
DRUGNiraparib 200 mg
Participants will receive niraparib 200 mg orally.
DRUGCetrelimab 240 mg
Participants will receive cetrelimab 240 mg IV every 2 weeks.
Participants will receive cetrelimab 480 mg IV every 4 weeks.
Participants will receive AA 1000 mg orally.
DRUGPrednisone 5 mg
Participants will receive prednisone 5 mg orally.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
for Combination 3: * Diagnosed with mCRPC, who in the opinion of the investigator may benefit from treatment in Combination 3 of this study * Able to continue gonadotropin releasing hormone analogue (GnRHa) therapy during the study if not surgically castrate (that is, subjects who has not undergone bilateral orchiectomy). * Eastern Cooperative Oncology Group Performance Status (ECOG PS) of less than or equal to (\<=) 1 * Toxicity associated with prior chemotherapy or radiotherapy has resolved to Grade \<= 1 (except alopecia or Grade \<= 2 neuropathy) at screening * Participant must agree not to donate sperm while on study treatment, and for 3 months following the last dose of study treatment
Exclusion criteria
* History or current diagnosis of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) * Active malignancies (that is, progressing or requiring treatment change in the last 24 months) other than the disease being treated under study. The only allowed exceptions are: non-muscle invasive bladder cancer; skin cancer (non-melanoma or melanoma); breast cancer; malignancy that is considered cured with minimal risk of recurrence * Active infection requiring systemic therapy * Allergies, hypersensitivity, or intolerance to niraparib or the corresponding excipients Combination 3: * Symptomatic brain metastases * Prior disease progression during combination treatment with AA and poly (adenosine diphosphate \[ADP\]-ribose) polymerase inhibitor (PARPi). Prior discontinuation of treatment with AA or PARPi due to AA- or PARPi-related toxicity
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Combination 1: Part 1: Number of Participants With Specified Toxicity | Cycle 1 (28 days) | Number of participants with specified toxicity during Cycle 1 was reported. Only toxicities that occurred during safety evaluation period(defined as first 28 days of treatment-Cycle 1 of Part 1) was used for analysis of specified toxicities and for dose reduction decisions. Toxicities were graded for severity as per NCI-CTCAE, version 4.03. Safety evaluation criteria were: Any Grade(G) \>=3 non-hematological toxicity without anorexia, or constipation, fatigue improved to G\<=2 in \<7 days, vomiting and diarrhea resolved in \<=3 days, laboratory abnormalities with hospitalization, tumor flare improved to G\<=2 in \<=7 days, elevation in AST/ALT for \<=7 days and G3 hypertension controlled by medical therapy; any treatment-related(TR)G4 or G\>=3 thrombocytopenia required platelet transfusion; Any TR G4 neutropenia \>=7 days or G3 or 4 neutropenia with infection/fever \>38.5 degrees Celsius; Any TR SAE or intolerable toxicity. |
| Combination 1: Part 2: Objective Response Rate (ORR) | Up to 37 months | ORR of soft tissue (visceral or nodal disease) was defined as percentage of participants with measurable disease who achieved a best response of either complete response (CR) or partial response (PR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with no evidence of bone progression according to prostate cancer working group 3 (PCWG3) criteria. |
| Combination 2: Composite Response Rate (RR) | Up to 31 months | Composite response rate was defined as the percentage of participants who had a composite response which is defined as one of the following PCWG3 criteria: Objective response (percentage of participants with measurable disease who achieved a best response of either CR or PR as assessed by RECIST 1.1 with no evidence of bone progression according to PCWG3 criteria) (confirmed per RECIST 1.1), or; circulating tumor cells (CTC) response: defined as CTC=0 per 7.5 milliliters (mL) of blood at 8 weeks for participants who had CTC greater than or equal to (\>=) 1 at baseline or CTC less than (\<) 5 per 7.5 mL with CTC \>=5 at baseline, confirmed by a second consecutive value obtained 4 or more weeks later, or prostate-specific antigen (PSA) declined of \>=50 percentage (%), measured twice 3 to 4 weeks apart. This outcome measure was analyzed for specified arms only as pre-planned in the protocol. |
| Combination 1: Part 2: Number of Participants With Adverse Events (AEs) | Up to 37 months | AE was defined as an any untoward medical occurrence in a clinical study subject administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. |
| Combination 2: Number of Participants With Adverse Events (AEs) | Up to 31 months | AE was defined as an any untoward medical occurrence in a clinical study subject administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. |
| Combination 1: Part 2: Number of Participants With Adverse Events (AEs) of Grade >=3 Severity | Up to 37 months | AE was defined as an any untoward medical occurrence in a clinical study subject administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. An assessment of severity grade was made using the National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) as Grade 1 (mild): awareness of symptoms that are easily tolerated, causing minimal discomfort and not interfering with everyday activities; Grade 2 (moderate): sufficient discomfort is present to cause interference with normal activity; Grade 3 (severe): extreme distress, causing significant impairment of functioning or incapacitation, prevents normal everyday activities; Grade 4 (Life-threatening): urgent intervention indicated; and Grade 5 (death). |
| Combination 2: Number of Participants With Adverse Events (AEs) of Grade >=3 Severity | Up to 31 months | AE was defined as an any untoward medical occurrence in a clinical study subject administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. An assessment of severity grade was made using the NCI-CTCAE as Grade 1 (mild): awareness of symptoms that are easily tolerated, causing minimal discomfort and not interfering with everyday activities; Grade 2 (moderate): sufficient discomfort is present to cause interference with normal activity; Grade 3 (severe): extreme distress, causing significant impairment of functioning or incapacitation, prevents normal everyday activities; Grade 4 (Life-threatening): urgent intervention indicated; and Grade 5 (death). |
| Combination 3: Maximum Observed Plasma Concentration (Cmax) of Niraparib and Abiraterone Acetate After a Single Dose | Pre-dose, 30 min, 1 hour (hr), 1.5 hr, 2hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 24 hr, 48 hr, 72 hr, and 168 hr post dose on Day 1 | Cmax is defined as maximum observed plasma concentration of niraparib and abiraterone acetate (AA) after a single dose. |
| Combination 3: Maximum Observed Plasma Concentration (Cmax) of Niraparib Normalized by the Dose(Niraparib) (Cmax/Dose) of Niraparib Administered With AA After a Single Dose | Pre-dose, 30 min, 1 hour (hr), 1.5 hr, 2hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 24 hr, 48 hr, 72 hr, and 168 hr post dose on Day 1 | Cmax/dose of niraparib was defined as maximum observed plasma concentration of niraparib Cmax normalized by the dose of niraparib administered with AA after a single dose. |
| Combination 3: Area Under the Plasma Concentration-Time Curve From Time Zero to 168 Hours (AUC [0-168hr]) of Niraparib Administered With AA After a Single Dose | Pre-dose, 30 min, 1 hour (hr), 1.5 hr, 2hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 24 hr, 48 hr, 72 hr, and 168 hr post dose on Day 1 | AUC(0-168 hours) was defined as area under the plasma concentration-time curve from time zero to 168 hours of Niraparib administered with AA After a single dose. |
| Combination 3: Area Under the Plasma Concentration-Time Curve for Niraparib From Time Zero to 168 Hours (AUC [0-168 Hours]/Dose) of Niraparib Administered With AA After a Single Dose | Pre-dose, 30 min, 1 hour (hr), 1.5 hr, 2hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 24 hr, 48 hr, 72 hr, and 168 hr post dose on Day 1 | AUC0(168 hours)/dose was defined as area under the plasma concentration-time curve for niraparib from time 0 to 168 hours of niraparib administered with AA after a single dose. |
Secondary
| Measure | Time frame |
|---|---|
| Combination 1: Parts 1 and 2: Plasma Concentrations of Niraparib | Day 1 |
| Combination 1: Parts 1 and 2: Maximum Observed Plasma Concentration (Cmax) of Niraparib | Day 1 |
| Combination 1: Parts 1 and 2: Time to Reach the Maximum Plasma Concentration (Tmax) of Niraparib | Day 1 |
| Combination 1: Parts 1 and 2: Minimum Observed (Predose) Concentration Following Multiple Dosing (Ctrough) of Niraparib | Day 1 |
| Combination 1: Parts 1 and 2: Number of Participants With Anti-drug Antibodies of Niraparib | From baseline up to end of study (6 years 10 months) |
| Combination 1: Part 2 and Combination 2: Circulating Tumor Cells (CTC) Response | From baseline up to end of study (6 years 10 months) |
| Combination 1: Part 2: Composite Response Rate | From baseline up to end of study (6 years 10 months) |
| Combination 2: Objective Response Rate (ORR) | From baseline up to end of study (6 years 10 months) |
| Combination 1: Part 2 and Combination 2: Duration of Objective Response | From baseline up to end of study (6 years 10 months) |
| Combination 1: Part 2 and Combination 2: Overall Survival | From baseline up to end of study (6 years 10 months) |
| Combination 3: Cmax of Niraparib and Abiraterone Acetate After a Single Dose For Low-strength FDC | Pre-dose, 30 min, 1 hour (hr), 1.5 hr, 2hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 24 hr, 48 hr, 72 hr, and 168 hr post dose on Day 1 |
| Combination 3: Maximum Observed Plasma Concentration (Cmax) of Niraparib Normalized by the Dose(Niraparib) (Cmax/Dose) of Niraparib Administered With AA After a Single Dose for Low-strength FDC | Pre-dose, 30 min, 1 hour (hr), 1.5 hr, 2hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 24 hr, 48 hr, 72 hr, and 168 hr post dose on Day 1 |
| Combination 3: Area Under the Plasma Concentration-Time Curve From Time Zero to 168 Hours (AUC [0-168hr]) of Niraparib Administered With AA After a Single Dose For Low-strength FDC | Pre-dose, 30 min, 1 hour (hr), 1.5 hr, 2hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 24 hr, 48 hr, 72 hr, and 168 hr post dose on Day 1 |
| Combination 3: Area Under the Plasma Concentration-Time Curve for Niraparib From Time Zero to 168 Hours (AUC [0-168 Hours]/Dose) of Niraparib Administered With AA After a Single Dose For Low-strength FDC | Pre-dose, 30 min, 1 hour (hr), 1.5 hr, 2hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 24 hr, 48 hr, 72 hr, and 168 hr post dose on Day 1 |
| Combination 3: Number of Participants With Adverse Events | From baseline up to end of study (6 years 10 months) |
| Combination 3: Number of Participants With Clinical Laboratory Parameters | From baseline up to end of study (6 years 10 months) |
Countries
Belgium, Canada, Israel, Italy, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Participant flow
Pre-assignment details
In Combination 2, one participant who was homologous recombination repair (HRR) negative was erroneously enrolled to Cohort 2C (BRCA monoallelic loss) and thus was not included in the Intent-to-Treat (ITT) Population for the efficacy analysis. but was included in the safety analysis. This participant data were presented in participant flow, baseline characteristics and adverse events section. Data reported based on primary completion date, i.e., August 31, 2021.
Participants by arm
| Arm | Count |
|---|---|
| Combination 1: Part 1 (Dose Seletion): Niraparib 200 mg + Cetrelimab 240 mg Participants with metastatic castration-resistant prostate cancer (mCRPC) who were either biomarker positive (BM+) or BM negative (BM-) for deoxyribonucleic acid (DNA)-repair gene defects (DRD) or BM+ for cyclin-dependent kinase 12 (CDK12) pathogenic alterations received niraparib 200 milligrams (mg) orally once daily in combination with cetrelimab 240 mg intravenous (IV) once every 4 weeks (i.e., on Day 1 of each cycle) in each 28-day treatment cycle until disease progression, unacceptable toxicity, death, or the sponsor terminated the study. | 6 |
| Combination 1: Part 1 (Dose Selection): Niraparib 200 mg + Cetrelimab 480 mg Participants with mCRPC who were either BM+ or BM- for DRD or BM+ for CDK12 pathogenic alterations received niraparib 200 mg orally once daily in combination with cetrelimab 480 mg IV infusion once every 4 weeks (i.e., on Day 1 of each cycle) in each 28-day treatment cycle until disease progression, unacceptable toxicity, death, or the sponsor terminated the study. | 6 |
| Combination 1: Part 2 (Dose Expansion): Cohort 1A: BM+: Niraparib 200 mg + Cetrelimab 480 mg Participants with mCRPC and were BM+ received established recommended Phase 2 dose (RP2D) of niraparib 200 mg once daily in combination with cetrelimab 480 mg IV infusion every 4 weeks i.e., on Day 1 of each cycle) in each 28-day treatment cycle until disease progression, unacceptable toxicity, death, or the sponsor terminated the study. | 21 |
| Combination 1: Part 2 (Dose Expansion): Cohort 1B: BM-: Niraparib 200 mg + Cetrelimab 480 mg Participants with mCRPC and were BM- received established RP2D of niraparib 200 mg once daily in combination with cetrelimab 480 mg IV infusion every 4 weeks i.e., on Day 1 of each cycle) in each 28-day treatment cycle until disease progression, unacceptable toxicity, death, or the sponsor terminated the study. | 11 |
| Combination 2: Cohort 2A: Niraparib+Abiraterone Acetate+Prednisone Participants with mCRPC and HRR gene alterations (breast cancer gene \[BRCA\] biallelic loss \[2A\]) received niraparib 200 mg orally once daily in combination with abiraterone acetate 1000 mg orally once daily plus prednisone (P) 10 mg (2\*5 mg) orally twice daily in each 28-day treatment cycle until disease progression, unacceptable toxicity, death, or the sponsor terminated the study. | 8 |
| Combination 2: Cohort 2C: Niraparib+Abiraterone Acetate+Prednisone Participants with mCRPC and HRR gene alterations (BRCA monoallelic loss \[2C\]) received niraparib 200 mg orally once daily in combination with abiraterone acetate 1000 mg orally once daily plus prednisone 10 mg (2\*5 mg) orally twice daily in each 28-day treatment cycle until disease progression, unacceptable toxicity, death, or the sponsor terminated the study. | 9 |
| Combination 2: Cohort 2D: Niraparib+Abiraterone Acetate+Prednisone Participants with mCRPC and HRR gene alterations (other DRD monoallelic loss \[2D\]) received niraparib 200 mg orally once daily in combination with abiraterone acetate 1000 mg orally once daily plus prednisone 10 mg (2\*5 mg) orally twice daily in each 28-day treatment cycle until disease progression, unacceptable toxicity, death, or the sponsor terminated the study. | 6 |
| Combination 2: Cohort 2C: HRR Negative: Niraparib + Abiraterone Acetate + Prednisone Participants with mCRPC and HRR gene alteration negative received niraparib 200 mg orally once daily in combination with abiraterone acetate 1000 mg orally once daily plus prednisone 10 mg (2\*5 mg) orally twice daily in each 28-day treatment cycle until disease progression, unacceptable toxicity, death, or the sponsor terminated the study. | 1 |
| Combination 3: Cohort 1A: Niraparib + Abiraterone Acetate, SA Participants with mCRPC (regardless of HRR BM status) received a single dose of niraparib 200 mg in combination with single oral dose of abiraterone acetate 1000 mg as single agent (SA) orally from Cycle 1 Day 1 to Day 8. After completion of Cycle 1 Day 8 (Pharmacokinetic \[PK\] Assessment Phase), Participants had the option to enter the Long-term Extension Phase of the study and received protocol defined treatment until study discontinuation. | 17 |
| Combination 3: Cohort 1B: Niraparib + Abiraterone Acetate, FDC1-RS (G010) Participants with mCRPC received a single dose of niraparib 200 mg in combination with single oral dose of abiraterone acetate 1000 as fixed-dose combination 1 (FDC1) regular-strength (RS) tablets orally from Cycle 2 1 Day 1 to Day 8. After completion of Cycle 1 Day 8 (PK Assessment Phase), participants had an option to enter the Long-term Extension Phase of the study and received protocol defined treatment until study discontinuation. | 17 |
| Combination 3: Cohort 2: Niraparib + Abiraterone Acetate, FDC2-RS (G012) Participants with mCRPC received a single dose of niraparib 200 mg in combination with single oral dose of abiraterone acetate 1000 mg as FDC2 RS tablets orally from Cycle 2 1 Day 1 to Day 8. After completion of Cycle 1 Day 8 (PK Assessment Phase), participants had an option to enter the Long-term Extension Phase of the study and received protocol defined treatment until study discontinuation. | 17 |
| Combination 3: Cohort 3: Niraparib + Abiraterone Acetate, FDC1-LS Participants with mCRPC received a single oral dose of niraparib 100 mg in combination with single oral dose of abiraterone acetate 1000 mg as FDC1 low strength (LS) tablets orally from Cycle 2 1 Day 1 to Day 8. After completion of Cycle 1 Day 8 (PK Assessment Phase), participants had an option to enter the Long-term Extension Phase of the study and received protocol defined treatment until study discontinuation. | 17 |
| Total | 136 |
Baseline characteristics
| Characteristic | Combination 1: Part 2 (Dose Expansion): Cohort 1B: BM-: Niraparib 200 mg + Cetrelimab 480 mg | Combination 1: Part 1 (Dose Seletion): Niraparib 200 mg + Cetrelimab 240 mg | Combination 1: Part 1 (Dose Selection): Niraparib 200 mg + Cetrelimab 480 mg | Combination 1: Part 2 (Dose Expansion): Cohort 1A: BM+: Niraparib 200 mg + Cetrelimab 480 mg | Total | Combination 3: Cohort 3: Niraparib + Abiraterone Acetate, FDC1-LS | Combination 3: Cohort 2: Niraparib + Abiraterone Acetate, FDC2-RS (G012) | Combination 3: Cohort 1B: Niraparib + Abiraterone Acetate, FDC1-RS (G010) | Combination 3: Cohort 1A: Niraparib + Abiraterone Acetate, SA | Combination 2: Cohort 2C: HRR Negative: Niraparib + Abiraterone Acetate + Prednisone | Combination 2: Cohort 2D: Niraparib+Abiraterone Acetate+Prednisone | Combination 2: Cohort 2C: Niraparib+Abiraterone Acetate+Prednisone | Combination 2: Cohort 2A: Niraparib+Abiraterone Acetate+Prednisone |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 66.6 years STANDARD_DEVIATION 3.91 | 65.3 years STANDARD_DEVIATION 7.15 | 66.7 years STANDARD_DEVIATION 12.56 | 68.1 years STANDARD_DEVIATION 6.6 | 70.4 years STANDARD_DEVIATION 7.61 | 72.9 years STANDARD_DEVIATION 7.36 | 71.2 years STANDARD_DEVIATION 7.85 | 71.1 years STANDARD_DEVIATION 7.96 | 72.3 years STANDARD_DEVIATION 7.19 | 80 years | 72.8 years STANDARD_DEVIATION 9.75 | 71.3 years STANDARD_DEVIATION 5.89 | 71.4 years STANDARD_DEVIATION 8.23 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 7 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 8 Participants | 5 Participants | 6 Participants | 21 Participants | 121 Participants | 16 Participants | 16 Participants | 14 Participants | 14 Participants | 0 Participants | 5 Participants | 9 Participants | 7 Participants |
| Region of Enrollment BELGIUM | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 16 Participants | 3 Participants | 4 Participants | 2 Participants | 4 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment CANADA | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 16 Participants | 0 Participants | 2 Participants | 2 Participants | 2 Participants | 0 Participants | 2 Participants | 4 Participants | 1 Participants |
| Region of Enrollment ISRAEL | 2 Participants | 0 Participants | 0 Participants | 3 Participants | 27 Participants | 8 Participants | 2 Participants | 5 Participants | 7 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment ITALY | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Region of Enrollment SPAIN | 1 Participants | 2 Participants | 4 Participants | 2 Participants | 13 Participants | 0 Participants | 4 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment UNITED KINGDOM | 0 Participants | 3 Participants | 0 Participants | 4 Participants | 8 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment UNITED STATES | 8 Participants | 1 Participants | 2 Participants | 8 Participants | 53 Participants | 6 Participants | 4 Participants | 8 Participants | 4 Participants | 1 Participants | 3 Participants | 4 Participants | 4 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 11 Participants | 6 Participants | 6 Participants | 21 Participants | 136 Participants | 17 Participants | 17 Participants | 17 Participants | 17 Participants | 1 Participants | 6 Participants | 9 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 6 / 6 | 5 / 6 | 18 / 21 | 7 / 11 | 5 / 8 | 4 / 9 | 2 / 6 | 0 / 1 | 3 / 17 | 1 / 17 | 4 / 17 | 2 / 17 |
| other Total, other adverse events | 6 / 6 | 6 / 6 | 21 / 21 | 11 / 11 | 8 / 8 | 9 / 9 | 5 / 6 | 1 / 1 | 10 / 17 | 10 / 17 | 6 / 17 | 5 / 17 |
| serious Total, serious adverse events | 2 / 6 | 3 / 6 | 12 / 21 | 6 / 11 | 4 / 8 | 5 / 9 | 1 / 6 | 1 / 1 | 4 / 17 | 4 / 17 | 7 / 17 | 3 / 17 |
Outcome results
Primary
Combination 1: Part 1: Number of Participants With Specified Toxicity
Number of participants with specified toxicity during Cycle 1 was reported. Only toxicities that occurred during safety evaluation period(defined as first 28 days of treatment-Cycle 1 of Part 1) was used for analysis of specified toxicities and for dose reduction decisions. Toxicities were graded for severity as per NCI-CTCAE, version 4.03. Safety evaluation criteria were: Any Grade(G) \>=3 non-hematological toxicity without anorexia, or constipation, fatigue improved to G\<=2 in \<7 days, vomiting and diarrhea resolved in \<=3 days, laboratory abnormalities with hospitalization, tumor flare improved to G\<=2 in \<=7 days, elevation in AST/ALT for \<=7 days and G3 hypertension controlled by medical therapy; any treatment-related(TR)G4 or G\>=3 thrombocytopenia required platelet transfusion; Any TR G4 neutropenia \>=7 days or G3 or 4 neutropenia with infection/fever \>38.5 degrees Celsius; Any TR SAE or intolerable toxicity.
Time frame: Cycle 1 (28 days)
Population: The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. This outcome measure was analyzed for specified arms only as pre-planned in the protocol.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combination 1: Part 1 (Dose Seletion): Niraparib 200 mg + Cetrelimab 240 mg | Combination 1: Part 1: Number of Participants With Specified Toxicity | 0 Participants |
| Combination 1: Part 1 (Dose Selection): Niraparib 200 mg + Cetrelimab 480 mg | Combination 1: Part 1: Number of Participants With Specified Toxicity | 0 Participants |
Primary
Combination 1: Part 2: Number of Participants With Adverse Events (AEs)
AE was defined as an any untoward medical occurrence in a clinical study subject administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment.
Time frame: Up to 37 months
Population: The safety analysis set included all randomized participants who received at least 1 dose of study drug. This outcome measure was analyzed for specified arms only as pre-planned in the protocol.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combination 1: Part 1 (Dose Seletion): Niraparib 200 mg + Cetrelimab 240 mg | Combination 1: Part 2: Number of Participants With Adverse Events (AEs) | 21 Participants |
| Combination 1: Part 1 (Dose Selection): Niraparib 200 mg + Cetrelimab 480 mg | Combination 1: Part 2: Number of Participants With Adverse Events (AEs) | 11 Participants |
Primary
Combination 1: Part 2: Number of Participants With Adverse Events (AEs) of Grade >=3 Severity
AE was defined as an any untoward medical occurrence in a clinical study subject administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. An assessment of severity grade was made using the National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) as Grade 1 (mild): awareness of symptoms that are easily tolerated, causing minimal discomfort and not interfering with everyday activities; Grade 2 (moderate): sufficient discomfort is present to cause interference with normal activity; Grade 3 (severe): extreme distress, causing significant impairment of functioning or incapacitation, prevents normal everyday activities; Grade 4 (Life-threatening): urgent intervention indicated; and Grade 5 (death).
Time frame: Up to 37 months
Population: The safety analysis set included all randomized participants who received at least 1 dose of study drug. This outcome measure was analyzed for specified arms only as pre-planned in the protocol.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combination 1: Part 1 (Dose Seletion): Niraparib 200 mg + Cetrelimab 240 mg | Combination 1: Part 2: Number of Participants With Adverse Events (AEs) of Grade >=3 Severity | 14 Participants |
| Combination 1: Part 1 (Dose Selection): Niraparib 200 mg + Cetrelimab 480 mg | Combination 1: Part 2: Number of Participants With Adverse Events (AEs) of Grade >=3 Severity | 8 Participants |
Primary
Combination 1: Part 2: Objective Response Rate (ORR)
ORR of soft tissue (visceral or nodal disease) was defined as percentage of participants with measurable disease who achieved a best response of either complete response (CR) or partial response (PR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with no evidence of bone progression according to prostate cancer working group 3 (PCWG3) criteria.
Time frame: Up to 37 months
Population: Intent-to-Treat (ITT) analysis set included all participants who had at least 1 dose of both study drugs at the selected RP2D in Combination 1: Part 2 of study. This outcome measure was analyzed for specified arms only as pre-planned in the protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combination 1: Part 1 (Dose Seletion): Niraparib 200 mg + Cetrelimab 240 mg | Combination 1: Part 2: Objective Response Rate (ORR) | 23.8 Percentage of participants |
| Combination 1: Part 1 (Dose Selection): Niraparib 200 mg + Cetrelimab 480 mg | Combination 1: Part 2: Objective Response Rate (ORR) | 9.1 Percentage of participants |
Primary
Combination 2: Composite Response Rate (RR)
Composite response rate was defined as the percentage of participants who had a composite response which is defined as one of the following PCWG3 criteria: Objective response (percentage of participants with measurable disease who achieved a best response of either CR or PR as assessed by RECIST 1.1 with no evidence of bone progression according to PCWG3 criteria) (confirmed per RECIST 1.1), or; circulating tumor cells (CTC) response: defined as CTC=0 per 7.5 milliliters (mL) of blood at 8 weeks for participants who had CTC greater than or equal to (\>=) 1 at baseline or CTC less than (\<) 5 per 7.5 mL with CTC \>=5 at baseline, confirmed by a second consecutive value obtained 4 or more weeks later, or prostate-specific antigen (PSA) declined of \>=50 percentage (%), measured twice 3 to 4 weeks apart. This outcome measure was analyzed for specified arms only as pre-planned in the protocol.
Time frame: Up to 31 months
Population: ITT analysis set included all participants who had at least 1 dose of both study drugs at the selected RP2D in Part 2 of study. In Combination 2, one participant who was HRR negative was erroneously enrolled to Cohort 2C (BRCA monoallelic loss) and was presented under arm named Combination 2: Cohort 2C: HRR negative: Niraparib + Abiraterone Acetate + Prednisone. Due to erroneous enrollment, this participant was not included in the ITT population for the efficacy analysis of this endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combination 1: Part 1 (Dose Seletion): Niraparib 200 mg + Cetrelimab 240 mg | Combination 2: Composite Response Rate (RR) | 75.0 Percentage of participants |
| Combination 1: Part 1 (Dose Selection): Niraparib 200 mg + Cetrelimab 480 mg | Combination 2: Composite Response Rate (RR) | 55.6 Percentage of participants |
| Combination 2: Cohort 2D: Niraparib+Abiraterone Acetate+Prednisone | Combination 2: Composite Response Rate (RR) | 33.3 Percentage of participants |
Primary
Combination 2: Number of Participants With Adverse Events (AEs)
AE was defined as an any untoward medical occurrence in a clinical study subject administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment.
Time frame: Up to 31 months
Population: The safety analysis set included all randomized participants who received at least 1 dose of study drug. This outcome measure was analyzed for specified arms only as pre-planned in the protocol.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combination 1: Part 1 (Dose Seletion): Niraparib 200 mg + Cetrelimab 240 mg | Combination 2: Number of Participants With Adverse Events (AEs) | 8 Participants |
| Combination 1: Part 1 (Dose Selection): Niraparib 200 mg + Cetrelimab 480 mg | Combination 2: Number of Participants With Adverse Events (AEs) | 9 Participants |
| Combination 2: Cohort 2D: Niraparib+Abiraterone Acetate+Prednisone | Combination 2: Number of Participants With Adverse Events (AEs) | 5 Participants |
| Combination 2: Cohort 2C: HRR Negative: Niraparib + Abiraterone Acetate + Prednisone | Combination 2: Number of Participants With Adverse Events (AEs) | 1 Participants |
Primary
Combination 2: Number of Participants With Adverse Events (AEs) of Grade >=3 Severity
AE was defined as an any untoward medical occurrence in a clinical study subject administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. An assessment of severity grade was made using the NCI-CTCAE as Grade 1 (mild): awareness of symptoms that are easily tolerated, causing minimal discomfort and not interfering with everyday activities; Grade 2 (moderate): sufficient discomfort is present to cause interference with normal activity; Grade 3 (severe): extreme distress, causing significant impairment of functioning or incapacitation, prevents normal everyday activities; Grade 4 (Life-threatening): urgent intervention indicated; and Grade 5 (death).
Time frame: Up to 31 months
Population: The safety analysis set included all randomized participants who received at least 1 dose of study drug. This outcome measure was analyzed for specified arms only as pre-planned in the protocol.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combination 1: Part 1 (Dose Seletion): Niraparib 200 mg + Cetrelimab 240 mg | Combination 2: Number of Participants With Adverse Events (AEs) of Grade >=3 Severity | 6 Participants |
| Combination 1: Part 1 (Dose Selection): Niraparib 200 mg + Cetrelimab 480 mg | Combination 2: Number of Participants With Adverse Events (AEs) of Grade >=3 Severity | 7 Participants |
| Combination 2: Cohort 2D: Niraparib+Abiraterone Acetate+Prednisone | Combination 2: Number of Participants With Adverse Events (AEs) of Grade >=3 Severity | 4 Participants |
| Combination 2: Cohort 2C: HRR Negative: Niraparib + Abiraterone Acetate + Prednisone | Combination 2: Number of Participants With Adverse Events (AEs) of Grade >=3 Severity | 1 Participants |
Primary
Combination 3: Area Under the Plasma Concentration-Time Curve for Niraparib From Time Zero to 168 Hours (AUC [0-168 Hours]/Dose) of Niraparib Administered With AA After a Single Dose
AUC0(168 hours)/dose was defined as area under the plasma concentration-time curve for niraparib from time 0 to 168 hours of niraparib administered with AA after a single dose.
Time frame: Pre-dose, 30 min, 1 hour (hr), 1.5 hr, 2hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 24 hr, 48 hr, 72 hr, and 168 hr post dose on Day 1
Population: PK analysis set included all participants who received at least 1 dose of both study agents (either as a FDC or SAC) and had at least 1 concentration value. Here, 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. This outcome measure was analyzed for specified arms only as pre-planned in the protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Combination 1: Part 1 (Dose Seletion): Niraparib 200 mg + Cetrelimab 240 mg | Combination 3: Area Under the Plasma Concentration-Time Curve for Niraparib From Time Zero to 168 Hours (AUC [0-168 Hours]/Dose) of Niraparib Administered With AA After a Single Dose | 73.36 nanogram*hour/milliliter/milligram | Standard Deviation 36.73 |
| Combination 1: Part 1 (Dose Selection): Niraparib 200 mg + Cetrelimab 480 mg | Combination 3: Area Under the Plasma Concentration-Time Curve for Niraparib From Time Zero to 168 Hours (AUC [0-168 Hours]/Dose) of Niraparib Administered With AA After a Single Dose | 59.31 nanogram*hour/milliliter/milligram | Standard Deviation 24.87 |
| Combination 2: Cohort 2D: Niraparib+Abiraterone Acetate+Prednisone | Combination 3: Area Under the Plasma Concentration-Time Curve for Niraparib From Time Zero to 168 Hours (AUC [0-168 Hours]/Dose) of Niraparib Administered With AA After a Single Dose | 66.61 nanogram*hour/milliliter/milligram | Standard Deviation 29.22 |
Primary
Combination 3: Area Under the Plasma Concentration-Time Curve From Time Zero to 168 Hours (AUC [0-168hr]) of Niraparib Administered With AA After a Single Dose
AUC(0-168 hours) was defined as area under the plasma concentration-time curve from time zero to 168 hours of Niraparib administered with AA After a single dose.
Time frame: Pre-dose, 30 min, 1 hour (hr), 1.5 hr, 2hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 24 hr, 48 hr, 72 hr, and 168 hr post dose on Day 1
Population: PK analysis set included all participants who received at least 1 dose of both study agents (either as a FDC or SAC) and had at least 1 concentration value. Here, 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. This outcome measure was analyzed for specified arms only as pre-planned in the protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Combination 1: Part 1 (Dose Seletion): Niraparib 200 mg + Cetrelimab 240 mg | Combination 3: Area Under the Plasma Concentration-Time Curve From Time Zero to 168 Hours (AUC [0-168hr]) of Niraparib Administered With AA After a Single Dose | 14672 Nanograms*hour per milliliter (ng*h/mL) | Standard Deviation 7346 |
| Combination 1: Part 1 (Dose Selection): Niraparib 200 mg + Cetrelimab 480 mg | Combination 3: Area Under the Plasma Concentration-Time Curve From Time Zero to 168 Hours (AUC [0-168hr]) of Niraparib Administered With AA After a Single Dose | 11862 Nanograms*hour per milliliter (ng*h/mL) | Standard Deviation 4973 |
| Combination 2: Cohort 2D: Niraparib+Abiraterone Acetate+Prednisone | Combination 3: Area Under the Plasma Concentration-Time Curve From Time Zero to 168 Hours (AUC [0-168hr]) of Niraparib Administered With AA After a Single Dose | 13321 Nanograms*hour per milliliter (ng*h/mL) | Standard Deviation 5843 |
Primary
Combination 3: Maximum Observed Plasma Concentration (Cmax) of Niraparib and Abiraterone Acetate After a Single Dose
Cmax is defined as maximum observed plasma concentration of niraparib and abiraterone acetate (AA) after a single dose.
Time frame: Pre-dose, 30 min, 1 hour (hr), 1.5 hr, 2hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 24 hr, 48 hr, 72 hr, and 168 hr post dose on Day 1
Population: Pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of both study agents (either as a fixed dose combination \[FDC\] or single agent combination \[SAC\]) and had at least 1 concentration value. Here, 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. This outcome measure was analyzed for specified arms only as pre-planned in the protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Combination 1: Part 1 (Dose Seletion): Niraparib 200 mg + Cetrelimab 240 mg | Combination 3: Maximum Observed Plasma Concentration (Cmax) of Niraparib and Abiraterone Acetate After a Single Dose | 428 Nanograms per milliliter (ng/mL) | Standard Deviation 189 |
| Combination 1: Part 1 (Dose Selection): Niraparib 200 mg + Cetrelimab 480 mg | Combination 3: Maximum Observed Plasma Concentration (Cmax) of Niraparib and Abiraterone Acetate After a Single Dose | 398 Nanograms per milliliter (ng/mL) | Standard Deviation 160 |
| Combination 2: Cohort 2D: Niraparib+Abiraterone Acetate+Prednisone | Combination 3: Maximum Observed Plasma Concentration (Cmax) of Niraparib and Abiraterone Acetate After a Single Dose | 417 Nanograms per milliliter (ng/mL) | Standard Deviation 176 |
Primary
Combination 3: Maximum Observed Plasma Concentration (Cmax) of Niraparib Normalized by the Dose(Niraparib) (Cmax/Dose) of Niraparib Administered With AA After a Single Dose
Cmax/dose of niraparib was defined as maximum observed plasma concentration of niraparib Cmax normalized by the dose of niraparib administered with AA after a single dose.
Time frame: Pre-dose, 30 min, 1 hour (hr), 1.5 hr, 2hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 24 hr, 48 hr, 72 hr, and 168 hr post dose on Day 1
Population: PK analysis set included all participants who received at least 1 dose of both study agents (either as a FDC or SAC) and had at least 1 concentration value. Here, 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. This outcome measure was analyzed for specified arms only as pre-planned in the protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Combination 1: Part 1 (Dose Seletion): Niraparib 200 mg + Cetrelimab 240 mg | Combination 3: Maximum Observed Plasma Concentration (Cmax) of Niraparib Normalized by the Dose(Niraparib) (Cmax/Dose) of Niraparib Administered With AA After a Single Dose | 2.14 nanograms per milliliter per milligram | Standard Deviation 0.95 |
| Combination 1: Part 1 (Dose Selection): Niraparib 200 mg + Cetrelimab 480 mg | Combination 3: Maximum Observed Plasma Concentration (Cmax) of Niraparib Normalized by the Dose(Niraparib) (Cmax/Dose) of Niraparib Administered With AA After a Single Dose | 1.99 nanograms per milliliter per milligram | Standard Deviation 0.8 |
| Combination 2: Cohort 2D: Niraparib+Abiraterone Acetate+Prednisone | Combination 3: Maximum Observed Plasma Concentration (Cmax) of Niraparib Normalized by the Dose(Niraparib) (Cmax/Dose) of Niraparib Administered With AA After a Single Dose | 2.09 nanograms per milliliter per milligram | Standard Deviation 0.88 |
Secondary
Combination 1: Part 2 and Combination 2: Circulating Tumor Cells (CTC) Response
Time frame: From baseline up to end of study (6 years 10 months)
Secondary
Combination 1: Part 2 and Combination 2: Duration of Objective Response
Time frame: From baseline up to end of study (6 years 10 months)
Secondary
Combination 1: Part 2 and Combination 2: Overall Survival
Time frame: From baseline up to end of study (6 years 10 months)
Secondary
Combination 1: Part 2: Composite Response Rate
Time frame: From baseline up to end of study (6 years 10 months)
Secondary
Combination 1: Parts 1 and 2: Maximum Observed Plasma Concentration (Cmax) of Niraparib
Time frame: Day 1
Secondary
Combination 1: Parts 1 and 2: Minimum Observed (Predose) Concentration Following Multiple Dosing (Ctrough) of Niraparib
Time frame: Day 1
Secondary
Combination 1: Parts 1 and 2: Number of Participants With Anti-drug Antibodies of Niraparib
Time frame: From baseline up to end of study (6 years 10 months)
Secondary
Combination 1: Parts 1 and 2: Plasma Concentrations of Niraparib
Time frame: Day 1
Secondary
Combination 1: Parts 1 and 2: Time to Reach the Maximum Plasma Concentration (Tmax) of Niraparib
Time frame: Day 1
Secondary
Combination 2: Objective Response Rate (ORR)
Time frame: From baseline up to end of study (6 years 10 months)
Secondary
Combination 3: Area Under the Plasma Concentration-Time Curve for Niraparib From Time Zero to 168 Hours (AUC [0-168 Hours]/Dose) of Niraparib Administered With AA After a Single Dose For Low-strength FDC
Time frame: Pre-dose, 30 min, 1 hour (hr), 1.5 hr, 2hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 24 hr, 48 hr, 72 hr, and 168 hr post dose on Day 1
Secondary
Combination 3: Area Under the Plasma Concentration-Time Curve From Time Zero to 168 Hours (AUC [0-168hr]) of Niraparib Administered With AA After a Single Dose For Low-strength FDC
Time frame: Pre-dose, 30 min, 1 hour (hr), 1.5 hr, 2hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 24 hr, 48 hr, 72 hr, and 168 hr post dose on Day 1
Secondary
Combination 3: Cmax of Niraparib and Abiraterone Acetate After a Single Dose For Low-strength FDC
Time frame: Pre-dose, 30 min, 1 hour (hr), 1.5 hr, 2hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 24 hr, 48 hr, 72 hr, and 168 hr post dose on Day 1
Secondary
Combination 3: Maximum Observed Plasma Concentration (Cmax) of Niraparib Normalized by the Dose(Niraparib) (Cmax/Dose) of Niraparib Administered With AA After a Single Dose for Low-strength FDC
Time frame: Pre-dose, 30 min, 1 hour (hr), 1.5 hr, 2hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 24 hr, 48 hr, 72 hr, and 168 hr post dose on Day 1
Secondary
Combination 3: Number of Participants With Adverse Events
Time frame: From baseline up to end of study (6 years 10 months)
Secondary
Combination 3: Number of Participants With Clinical Laboratory Parameters
Time frame: From baseline up to end of study (6 years 10 months)