Trial Outcomes & Findings for A Safety and Efficacy Extension Study of a Recombinant Fusion Protein Linking Coagulation Factor IX With Albumin (rIX-FP) in Patients With Hemophilia B (NCT NCT02053792)

NCT ID: NCT02053792

Last Updated: 2022-07-14

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

97 participants

Primary outcome timeframe

For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it takes to achieve 50 EDs.

Results posted on

2022-07-14

Participant Flow

Approximately 115 male previously treated patients (PTPs) and previously untreated patients (PUPs) with hemophilia B were planned to be enrolled, including all eligible PTPs from CSLB-sponsored rIX-FP lead-in studies, approximately 10 PTPs who required major, nonemergency surgery, and approximately 20 PUPs.

Participant milestones

Participant milestones
Measure	CSL654 (PTPs) Previously treated patients (PTPs) will administer CSL654 (rIX-FP) by intravenous infusion as routine prophylaxis, prevention, and on-demand treatment during a treatment period of approximately 5 years or the time it takes to reach 100 exposure days (EDs). The dose of rIX-FP administered will be based on the subject's previous rIX-FP use and/or pharmacokinetic data.	CSL654 (PUPs) Previously untreated patients (PUPs) will administer CSL654 (rIX-FP) by intravenous infusion as weekly prophylaxis and/or on-demand treatment during the first 12 months, and as weekly routine prophylaxis thereafter up to 3 years or the time it takes to achieve 50 EDs. The dose of rIX-FP administered will be based on the pharmacokinetic data.
Overall Study STARTED	83	14
Overall Study COMPLETED	77	10
Overall Study NOT COMPLETED	6	4

Reasons for withdrawal

Reasons for withdrawal
Measure	CSL654 (PTPs) Previously treated patients (PTPs) will administer CSL654 (rIX-FP) by intravenous infusion as routine prophylaxis, prevention, and on-demand treatment during a treatment period of approximately 5 years or the time it takes to reach 100 exposure days (EDs). The dose of rIX-FP administered will be based on the subject's previous rIX-FP use and/or pharmacokinetic data.	CSL654 (PUPs) Previously untreated patients (PUPs) will administer CSL654 (rIX-FP) by intravenous infusion as weekly prophylaxis and/or on-demand treatment during the first 12 months, and as weekly routine prophylaxis thereafter up to 3 years or the time it takes to achieve 50 EDs. The dose of rIX-FP administered will be based on the pharmacokinetic data.
Overall Study Physician Decision	0	1
Overall Study Development of High titer FIX inhibitor	0	1
Overall Study Lack of Efficacy	1	0
Overall Study Adverse Event	1	0
Overall Study Withdrawal by Subject	2	2
Overall Study The patient was not compliant to the study procedure	1	0
Overall Study Patient reached minimum number of exposure days and was allowed to stop	1	0

Baseline Characteristics

Safety Population (SP) was used. It was pre-specified in the Statistical Analysis Plan to collect age data separately for PTPs and PUPs and to not calculate the age for the total overall population.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CSL654 (PTPs) n=83 Participants Previously treated patients (PTPs) will administer CSL654 (rIX-FP) by intravenous infusion as routine prophylaxis, prevention, and on-demand treatment during a treatment period of approximately 5 years or the time it took to reach 100 exposure days (EDs). The dose of rIX-FP administered will be based on the subject's previous rIX-FP use and/or pharmacokinetic data.	CSL654 (PUPs) n=14 Participants Previously untreated patients (PUPs) administered CSL654 (rIX-FP) intravenously as weekly prophylaxis and/or on-demand treatment during the first 12 months, and as weekly routine prophylaxis thereafter up to 3 years or the time it takes to achieve 50 EDs. The dose of rIX-FP administered will be based on the subject's previous rIX-FP use and/or pharmacokinetic data.	Total n=97 Participants Total of all reporting groups
Age, Categorical <=18 years	30 Participants n=83 Participants	14 Participants n=14 Participants	44 Participants n=97 Participants
Age, Categorical Between 18 and 65 years	53 Participants n=83 Participants	0 Participants n=14 Participants	53 Participants n=97 Participants
Age, Categorical >=65 years	0 Participants n=83 Participants	0 Participants n=14 Participants	0 Participants n=97 Participants
Age, Continuous CSL654 (PTPs)	27.7 years STANDARD_DEVIATION 17.81 • n=83 Participants • Safety Population (SP) was used. It was pre-specified in the Statistical Analysis Plan to collect age data separately for PTPs and PUPs and to not calculate the age for the total overall population.	—	27.7 years STANDARD_DEVIATION 17.81 • n=83 Participants • Safety Population (SP) was used. It was pre-specified in the Statistical Analysis Plan to collect age data separately for PTPs and PUPs and to not calculate the age for the total overall population.
Age, Continuous CSL654 (PUPs)	—	1.3 years STANDARD_DEVIATION 3.11 • n=12 Participants • Safety Population (SP) was used. It was pre-specified in the Statistical Analysis Plan to collect age data separately for PTPs and PUPs and to not calculate the age for the total overall population.	1.3 years STANDARD_DEVIATION 3.11 • n=12 Participants • Safety Population (SP) was used. It was pre-specified in the Statistical Analysis Plan to collect age data separately for PTPs and PUPs and to not calculate the age for the total overall population.
Sex: Female, Male Female	0 Participants n=83 Participants	0 Participants n=14 Participants	0 Participants n=97 Participants
Sex: Female, Male Male	83 Participants n=83 Participants	14 Participants n=14 Participants	97 Participants n=97 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=83 Participants • SP was used	0 Participants n=12 Participants • SP was used	2 Participants n=95 Participants • SP was used
Ethnicity (NIH/OMB) Not Hispanic or Latino	81 Participants n=83 Participants • SP was used	12 Participants n=12 Participants • SP was used	93 Participants n=95 Participants • SP was used
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=83 Participants • SP was used	0 Participants n=12 Participants • SP was used	0 Participants n=95 Participants • SP was used
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=83 Participants • SP was used	0 Participants n=12 Participants • SP was used	0 Participants n=95 Participants • SP was used
Race (NIH/OMB) Asian	12 Participants n=83 Participants • SP was used	1 Participants n=12 Participants • SP was used	13 Participants n=95 Participants • SP was used
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=83 Participants • SP was used	0 Participants n=12 Participants • SP was used	0 Participants n=95 Participants • SP was used
Race (NIH/OMB) Black or African American	3 Participants n=83 Participants • SP was used	0 Participants n=12 Participants • SP was used	3 Participants n=95 Participants • SP was used
Race (NIH/OMB) White	68 Participants n=83 Participants • SP was used	10 Participants n=12 Participants • SP was used	78 Participants n=95 Participants • SP was used
Race (NIH/OMB) More than one race	0 Participants n=83 Participants • SP was used	0 Participants n=12 Participants • SP was used	0 Participants n=95 Participants • SP was used
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=83 Participants • SP was used	1 Participants n=12 Participants • SP was used	1 Participants n=95 Participants • SP was used
Region of Enrollment Czechia	3 participants n=83 Participants	0 participants n=14 Participants	3 participants n=97 Participants
Region of Enrollment United States	2 participants n=83 Participants	4 participants n=14 Participants	6 participants n=97 Participants
Region of Enrollment Japan	9 participants n=83 Participants	0 participants n=14 Participants	9 participants n=97 Participants
Region of Enrollment Philippines	1 participants n=83 Participants	1 participants n=14 Participants	2 participants n=97 Participants
Region of Enrollment Malaysia	2 participants n=83 Participants	0 participants n=14 Participants	2 participants n=97 Participants
Region of Enrollment Spain	6 participants n=83 Participants	0 participants n=14 Participants	6 participants n=97 Participants
Region of Enrollment Canada	1 participants n=83 Participants	0 participants n=14 Participants	1 participants n=97 Participants
Region of Enrollment Austria	4 participants n=83 Participants	1 participants n=14 Participants	5 participants n=97 Participants
Region of Enrollment Italy	10 participants n=83 Participants	2 participants n=14 Participants	12 participants n=97 Participants
Region of Enrollment South Africa	2 participants n=83 Participants	0 participants n=14 Participants	2 participants n=97 Participants
Region of Enrollment Israel	15 participants n=83 Participants	0 participants n=14 Participants	15 participants n=97 Participants
Region of Enrollment Bulgaria	4 participants n=83 Participants	0 participants n=14 Participants	4 participants n=97 Participants
Region of Enrollment Australia	2 participants n=83 Participants	3 participants n=14 Participants	5 participants n=97 Participants
Region of Enrollment France	14 participants n=83 Participants	0 participants n=14 Participants	14 participants n=97 Participants
Region of Enrollment Germany	8 participants n=83 Participants	3 participants n=14 Participants	11 participants n=97 Participants

PRIMARY outcome

Timeframe: For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it takes to achieve 50 EDs.

Population: Safety Population (SP) consisted of all participants who received ≥ 1 dose of rIX-FP during this study

Outcome measures

Outcome measures
Measure	CSL654 (PTPs) n=83 Participants Previously treated patients (PTPs) will administer CSL654 (rIX-FP) by intravenous infusion as routine prophylaxis, prevention, and on-demand treatment during a treatment period of approximately 5 years or the time it took to reach 100 exposure days (EDs). The dose of rIX-FP administered will be based on the subject's previous rIX-FP use and/or pharmacokinetic data.	CSL654 (PUPs) n=12 Participants Previously untreated patients (PUPs) administered CSL654 (rIX-FP) intravenously as weekly prophylaxis and/or on-demand treatment during the first 12 months, and as weekly routine prophylaxis thereafter up to 3 years or the time it takes to achieve 50 EDs. The dose of rIX-FP administered will be based on the subject's previous rIX-FP use and/or pharmacokinetic data.
Total Number of Participants Who Developed Inhibitors Against Factor IX (FIX)	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Approximately 30 minutes after infusion of CSL654

Population: Pharmacokinetic (PK) Population consisted of participants who received ≥ 1 dose of rIX-FP and had a sufficient number of analyzable PK blood samples (ie, ≥ 1 PK parameter calculated) for the PK assessment of rIX-FP. Participants were excluded from the analyses if an insufficient number of analyzable PK samples was obtained to permit the evaluation of ≥ 1 PK parameter. Only PUPs were analyzed for this endpoint.

Incremental Recovery: The increase in plasma concentration per IU/kg of factor administered.

Outcome measures

Outcome measures
Measure	CSL654 (PTPs) Previously treated patients (PTPs) will administer CSL654 (rIX-FP) by intravenous infusion as routine prophylaxis, prevention, and on-demand treatment during a treatment period of approximately 5 years or the time it took to reach 100 exposure days (EDs). The dose of rIX-FP administered will be based on the subject's previous rIX-FP use and/or pharmacokinetic data.	CSL654 (PUPs) n=8 Participants Previously untreated patients (PUPs) administered CSL654 (rIX-FP) intravenously as weekly prophylaxis and/or on-demand treatment during the first 12 months, and as weekly routine prophylaxis thereafter up to 3 years or the time it takes to achieve 50 EDs. The dose of rIX-FP administered will be based on the subject's previous rIX-FP use and/or pharmacokinetic data.
Mean Incremental Recovery of a 50 IU/kg Dose of CSL654 in Previously Untreated Patients (PUPs) Uncorrected FIX Activity	—	1.295 (IU/dL)/(IU/kg) Standard Deviation 0.3578
Mean Incremental Recovery of a 50 IU/kg Dose of CSL654 in Previously Untreated Patients (PUPs) Baseline-corrected FIX Activity	—	1.231 (IU/dL)/(IU/kg) Standard Deviation 0.3729

SECONDARY outcome

Timeframe: For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).

Population: Efficacy Population (EP) consisted of all participants in the Safety Population (SP). Only PTPs were analyzed for this endpoint. Participants were assigned under multiple regimens during the study, but were counted only once in any given regimen group. Annualized Bleeding Rate was derived only for subjects who were on the given regimen for at least 12 weeks.

Outcome measures

Outcome measures
Measure	CSL654 (PTPs) n=83 Participants Previously treated patients (PTPs) will administer CSL654 (rIX-FP) by intravenous infusion as routine prophylaxis, prevention, and on-demand treatment during a treatment period of approximately 5 years or the time it took to reach 100 exposure days (EDs). The dose of rIX-FP administered will be based on the subject's previous rIX-FP use and/or pharmacokinetic data.	CSL654 (PUPs) Previously untreated patients (PUPs) administered CSL654 (rIX-FP) intravenously as weekly prophylaxis and/or on-demand treatment during the first 12 months, and as weekly routine prophylaxis thereafter up to 3 years or the time it takes to achieve 50 EDs. The dose of rIX-FP administered will be based on the subject's previous rIX-FP use and/or pharmacokinetic data.
Total Annualized Bleeding Rate (ABR) by Prophylaxis Regimen in Previously Treated Patients (PTPs) 7-Day Regimen	2.89 Bleeds/Year/Participant Standard Deviation 3.115	—
Total Annualized Bleeding Rate (ABR) by Prophylaxis Regimen in Previously Treated Patients (PTPs) 10-Day Regimen	2.72 Bleeds/Year/Participant Standard Deviation 2.827	—
Total Annualized Bleeding Rate (ABR) by Prophylaxis Regimen in Previously Treated Patients (PTPs) 14-Day Regimen	2.72 Bleeds/Year/Participant Standard Deviation 3.395	—
Total Annualized Bleeding Rate (ABR) by Prophylaxis Regimen in Previously Treated Patients (PTPs) 21-Day Regimen	1.19 Bleeds/Year/Participant Standard Deviation 1.572	—

SECONDARY outcome

Timeframe: For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).

Population: EP. Only PTPs were analyzed for this endpoint. Participants may be assigned under multiple regimens during the study, but will be counted only once in any given regimen group. Annualized Bleeding Rate is derived only for subjects who are on the given regimen for at least 12 weeks.

Outcome measures

Outcome measures
Measure	CSL654 (PTPs) n=83 Participants Previously treated patients (PTPs) will administer CSL654 (rIX-FP) by intravenous infusion as routine prophylaxis, prevention, and on-demand treatment during a treatment period of approximately 5 years or the time it took to reach 100 exposure days (EDs). The dose of rIX-FP administered will be based on the subject's previous rIX-FP use and/or pharmacokinetic data.	CSL654 (PUPs) Previously untreated patients (PUPs) administered CSL654 (rIX-FP) intravenously as weekly prophylaxis and/or on-demand treatment during the first 12 months, and as weekly routine prophylaxis thereafter up to 3 years or the time it takes to achieve 50 EDs. The dose of rIX-FP administered will be based on the subject's previous rIX-FP use and/or pharmacokinetic data.
Spontaneous ABR by Prophylaxis Regimen in PTPs 7-Day Regimen	0.95 Bleeds/Year/Participant Standard Deviation 1.672	—
Spontaneous ABR by Prophylaxis Regimen in PTPs 10-Day Regimen	0.98 Bleeds/Year/Participant Standard Deviation 1.689	—
Spontaneous ABR by Prophylaxis Regimen in PTPs 14-Day Regimen	1.32 Bleeds/Year/Participant Standard Deviation 2.205	—
Spontaneous ABR by Prophylaxis Regimen in PTPs 21-Day Regimen	0.60 Bleeds/Year/Participant Standard Deviation 1.408	—

SECONDARY outcome

Timeframe: For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it takes to achieve 50 EDs.

Population: EP

Outcome measures

Outcome measures
Measure	CSL654 (PTPs) n=83 Participants Previously treated patients (PTPs) will administer CSL654 (rIX-FP) by intravenous infusion as routine prophylaxis, prevention, and on-demand treatment during a treatment period of approximately 5 years or the time it took to reach 100 exposure days (EDs). The dose of rIX-FP administered will be based on the subject's previous rIX-FP use and/or pharmacokinetic data.	CSL654 (PUPs) n=12 Participants Previously untreated patients (PUPs) administered CSL654 (rIX-FP) intravenously as weekly prophylaxis and/or on-demand treatment during the first 12 months, and as weekly routine prophylaxis thereafter up to 3 years or the time it takes to achieve 50 EDs. The dose of rIX-FP administered will be based on the subject's previous rIX-FP use and/or pharmacokinetic data.
Average Amount of CSL654 (rIX-FP) Consumed Per Month Per Subject During Routine Prophylaxis Treatment.	181.8 IU/kg per month Standard Deviation 35.16	188.53 IU/kg per month Standard Deviation 24.096

SECONDARY outcome

Timeframe: For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it takes to achieve 50 EDs.

Population: SP

Outcome measures

Outcome measures
Measure	CSL654 (PTPs) n=83 Participants Previously treated patients (PTPs) will administer CSL654 (rIX-FP) by intravenous infusion as routine prophylaxis, prevention, and on-demand treatment during a treatment period of approximately 5 years or the time it took to reach 100 exposure days (EDs). The dose of rIX-FP administered will be based on the subject's previous rIX-FP use and/or pharmacokinetic data.	CSL654 (PUPs) n=12 Participants Previously untreated patients (PUPs) administered CSL654 (rIX-FP) intravenously as weekly prophylaxis and/or on-demand treatment during the first 12 months, and as weekly routine prophylaxis thereafter up to 3 years or the time it takes to achieve 50 EDs. The dose of rIX-FP administered will be based on the subject's previous rIX-FP use and/or pharmacokinetic data.
Percentage of Participants With at Least One Treatment Emergent Adverse Event (TEAE) and the Percentage of Participants With at Least One CSL654-related TEAE AEs	89.2 percentage of participants	91.7 percentage of participants
Percentage of Participants With at Least One Treatment Emergent Adverse Event (TEAE) and the Percentage of Participants With at Least One CSL654-related TEAE Related AEs	2.4 percentage of participants	16.7 percentage of participants

SECONDARY outcome

Timeframe: Up to 3 years or the time it takes to achieve 50 EDs

Population: EP. This endpoint was for PUPs only. No major bleeding events were reported. Therefore, no data for this endpoint.

The investigator will rate the efficacy of the rIX-FP treatment based on a hemostatic efficacy four point rating scale of excellent, good, moderate, or poor/no response.

Outcome measures

Outcome measures
Measure	CSL654 (PTPs) Previously treated patients (PTPs) will administer CSL654 (rIX-FP) by intravenous infusion as routine prophylaxis, prevention, and on-demand treatment during a treatment period of approximately 5 years or the time it took to reach 100 exposure days (EDs). The dose of rIX-FP administered will be based on the subject's previous rIX-FP use and/or pharmacokinetic data.	CSL654 (PUPs) n=12 Participants Previously untreated patients (PUPs) administered CSL654 (rIX-FP) intravenously as weekly prophylaxis and/or on-demand treatment during the first 12 months, and as weekly routine prophylaxis thereafter up to 3 years or the time it takes to achieve 50 EDs. The dose of rIX-FP administered will be based on the subject's previous rIX-FP use and/or pharmacokinetic data.
Number of Participants With Investigator's Overall Clinical Assessment of Hemostatic Efficacy for the Treatment of Major Bleeding Events With CSL654 in PUPs	—	0 Participants

SECONDARY outcome

Timeframe: For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).

Population: EP. Only PTPs were analyzed for this endpoint. Participants may be assigned under multiple regimens during the study, but will be counted only once in any given regimen group. Number of participants analyzed are those who received at least 12 weeks of treatment in the respective regimen.

Outcome measures

Outcome measures
Measure	CSL654 (PTPs) n=14 Participants Previously treated patients (PTPs) will administer CSL654 (rIX-FP) by intravenous infusion as routine prophylaxis, prevention, and on-demand treatment during a treatment period of approximately 5 years or the time it took to reach 100 exposure days (EDs). The dose of rIX-FP administered will be based on the subject's previous rIX-FP use and/or pharmacokinetic data.	CSL654 (PUPs) Previously untreated patients (PUPs) administered CSL654 (rIX-FP) intravenously as weekly prophylaxis and/or on-demand treatment during the first 12 months, and as weekly routine prophylaxis thereafter up to 3 years or the time it takes to achieve 50 EDs. The dose of rIX-FP administered will be based on the subject's previous rIX-FP use and/or pharmacokinetic data.
Total ABR for On-demand Regimen vs. 14-Day Regimen in PTPs On-demand Regimen	17.51 Bleeds/Year/Subject Standard Deviation 7.130	—
Total ABR for On-demand Regimen vs. 14-Day Regimen in PTPs 14-Day Regimen	3.01 Bleeds/Year/Subject Standard Deviation 4.204	—

SECONDARY outcome

Timeframe: For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).

Population: EP. Only PTPs were analyzed for this endpoint. Participants may be assigned under multiple regimens during the study, but will be counted only once in any given regimen group. Number of participants analyzed are those who received at least 12 weeks of treatment in the respective regimen.

Outcome measures

Outcome measures
Measure	CSL654 (PTPs) n=14 Participants Previously treated patients (PTPs) will administer CSL654 (rIX-FP) by intravenous infusion as routine prophylaxis, prevention, and on-demand treatment during a treatment period of approximately 5 years or the time it took to reach 100 exposure days (EDs). The dose of rIX-FP administered will be based on the subject's previous rIX-FP use and/or pharmacokinetic data.	CSL654 (PUPs) Previously untreated patients (PUPs) administered CSL654 (rIX-FP) intravenously as weekly prophylaxis and/or on-demand treatment during the first 12 months, and as weekly routine prophylaxis thereafter up to 3 years or the time it takes to achieve 50 EDs. The dose of rIX-FP administered will be based on the subject's previous rIX-FP use and/or pharmacokinetic data.
Spontaneous ABR for On-demand Regimen vs. 14-Day Regimen in PTPs On-demand Regimen	13.17 Bleeds/Year/Subject Standard Deviation 5.873	—
Spontaneous ABR for On-demand Regimen vs. 14-Day Regimen in PTPs 14-Day Regimen	1.93 Bleeds/Year/Subject Standard Deviation 3.363	—

SECONDARY outcome

Timeframe: For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).

Population: EP. Only PTPs were analyzed for this endpoint. Participants may be assigned under multiple regimens during the study, but will be counted only once in any given regimen group. Number of participants analyzed are those who received at least 12 weeks of treatment in the respective regimen.

Outcome measures

Outcome measures
Measure	CSL654 (PTPs) n=41 Participants Previously treated patients (PTPs) will administer CSL654 (rIX-FP) by intravenous infusion as routine prophylaxis, prevention, and on-demand treatment during a treatment period of approximately 5 years or the time it took to reach 100 exposure days (EDs). The dose of rIX-FP administered will be based on the subject's previous rIX-FP use and/or pharmacokinetic data.	CSL654 (PUPs) Previously untreated patients (PUPs) administered CSL654 (rIX-FP) intravenously as weekly prophylaxis and/or on-demand treatment during the first 12 months, and as weekly routine prophylaxis thereafter up to 3 years or the time it takes to achieve 50 EDs. The dose of rIX-FP administered will be based on the subject's previous rIX-FP use and/or pharmacokinetic data.
Total ABR for Subjects >=12 Years: 7-Day Regimen vs. 14-Day Regimen in PTPs 7-Day Regimen	1.12 Bleeds/Year/Subject Standard Deviation 1.697	—
Total ABR for Subjects >=12 Years: 7-Day Regimen vs. 14-Day Regimen in PTPs 14-Day Regimen	2.19 Bleeds/Year/Subject Standard Deviation 3.000	—

SECONDARY outcome

Timeframe: For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).

Population: EP. Only PTPs were analyzed for this endpoint. Participants may be assigned under multiple regimens during the study, but will be counted only once in any given regimen group. Number of participants analyzed are those who received at least 12 weeks of treatment in the respective regimen.

Outcome measures

Outcome measures
Measure	CSL654 (PTPs) n=41 Participants Previously treated patients (PTPs) will administer CSL654 (rIX-FP) by intravenous infusion as routine prophylaxis, prevention, and on-demand treatment during a treatment period of approximately 5 years or the time it took to reach 100 exposure days (EDs). The dose of rIX-FP administered will be based on the subject's previous rIX-FP use and/or pharmacokinetic data.	CSL654 (PUPs) Previously untreated patients (PUPs) administered CSL654 (rIX-FP) intravenously as weekly prophylaxis and/or on-demand treatment during the first 12 months, and as weekly routine prophylaxis thereafter up to 3 years or the time it takes to achieve 50 EDs. The dose of rIX-FP administered will be based on the subject's previous rIX-FP use and/or pharmacokinetic data.
Spontaneous ABR for Subjects >=12 Years: 7-Day Regimen vs. 14-Day Regimen in PTPs 14-Day Regimen	1.33 Bleeds/Year/Subject Standard Deviation 2.349	—
Spontaneous ABR for Subjects >=12 Years: 7-Day Regimen vs. 14-Day Regimen in PTPs 7-Day Regimen	0.49 Bleeds/Year/Subject Standard Deviation 1.135	—

SECONDARY outcome

Timeframe: For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).

Population: EP. Only PTPs were analyzed for this endpoint. Participants may be assigned under multiple regimens during the study, but will be counted only once in any given regimen group. Number of participants analyzed are those who received at least 12 weeks of treatment in the respective regimen.

Outcome measures

Outcome measures
Measure	CSL654 (PTPs) n=49 Participants Previously treated patients (PTPs) will administer CSL654 (rIX-FP) by intravenous infusion as routine prophylaxis, prevention, and on-demand treatment during a treatment period of approximately 5 years or the time it took to reach 100 exposure days (EDs). The dose of rIX-FP administered will be based on the subject's previous rIX-FP use and/or pharmacokinetic data.	CSL654 (PUPs) Previously untreated patients (PUPs) administered CSL654 (rIX-FP) intravenously as weekly prophylaxis and/or on-demand treatment during the first 12 months, and as weekly routine prophylaxis thereafter up to 3 years or the time it takes to achieve 50 EDs. The dose of rIX-FP administered will be based on the subject's previous rIX-FP use and/or pharmacokinetic data.
Total ABR for Subjects >=12 Years: 7-Day Regimen vs. (10 or 14)-Day Regimen in PTPs 7-Day Regimen	1.31 Bleeds/Year/Subject Standard Deviation 1.868	—
Total ABR for Subjects >=12 Years: 7-Day Regimen vs. (10 or 14)-Day Regimen in PTPs (10 or 14)-Day Regimen	2.01 Bleeds/Year/Subject Standard Deviation 2.700	—

SECONDARY outcome

Timeframe: For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).

Population: EP. Only PTPs were analyzed for this endpoint. Participants may be assigned under multiple regimens during the study, but will be counted only once in any given regimen group. Number of participants analyzed are those who received at least 12 weeks of treatment in the respective regimen.

Outcome measures

Outcome measures
Measure	CSL654 (PTPs) n=49 Participants Previously treated patients (PTPs) will administer CSL654 (rIX-FP) by intravenous infusion as routine prophylaxis, prevention, and on-demand treatment during a treatment period of approximately 5 years or the time it took to reach 100 exposure days (EDs). The dose of rIX-FP administered will be based on the subject's previous rIX-FP use and/or pharmacokinetic data.	CSL654 (PUPs) Previously untreated patients (PUPs) administered CSL654 (rIX-FP) intravenously as weekly prophylaxis and/or on-demand treatment during the first 12 months, and as weekly routine prophylaxis thereafter up to 3 years or the time it takes to achieve 50 EDs. The dose of rIX-FP administered will be based on the subject's previous rIX-FP use and/or pharmacokinetic data.
Spontaneous ABR for Subjects >=12 Years: 7-Day Regimen vs. (10 or 14)-Day Regimen in PTPs 7-Day Regimen	0.57 Bleeds/Year/Subject Standard Deviation 1.192	—
Spontaneous ABR for Subjects >=12 Years: 7-Day Regimen vs. (10 or 14)-Day Regimen in PTPs (10 or 14)-Day Regimen	1.05 Bleeds/Year/Subject Standard Deviation 2.022	—

Adverse Events

CSL654 (PTPs)

Serious events: 17 serious events

Other events: 69 other events

Deaths: 1 deaths

CSL654 (PUPs)

Serious events: 5 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

CSL Behring

Phone: 610-878-4000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	CSL654 (PTPs) n=83 participants at risk Previously treated patients (PTPs) will administer CSL654 (rIX-FP) by intravenous infusion as routine prophylaxis, prevention, and on-demand treatment during a treatment period of approximately 5 years or the time it took to reach 100 exposure days (EDs). The dose of rIX-FP administered will be based on the subject's previous rIX-FP use and/or pharmacokinetic data.	CSL654 (PUPs) n=12 participants at risk Previously untreated patients (PUPs) administered CSL654 (rIX-FP) intravenously as weekly prophylaxis and/or on-demand treatment during the first 12 months, and as weekly routine prophylaxis thereafter up to 3 years or the time it takes to achieve 50 EDs. The dose of rIX-FP administered will be based on the subject's previous rIX-FP use and/or pharmacokinetic data.
Vascular disorders Haematoma	1.2% 1/83 • Number of events 1 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.	0.00% 0/12 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.
Vascular disorders Peripheral Ischaemia	1.2% 1/83 • Number of events 1 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.	0.00% 0/12 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.
Injury, poisoning and procedural complications Head injury	3.6% 3/83 • Number of events 4 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.	8.3% 1/12 • Number of events 1 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.
Injury, poisoning and procedural complications Contusion	1.2% 1/83 • Number of events 1 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.	0.00% 0/12 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.
Injury, poisoning and procedural complications Extradural Haematoma	1.2% 1/83 • Number of events 1 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.	0.00% 0/12 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.
Injury, poisoning and procedural complications Muscle injury	1.2% 1/83 • Number of events 1 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.	0.00% 0/12 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.
Injury, poisoning and procedural complications Road traffic accident	1.2% 1/83 • Number of events 1 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.	0.00% 0/12 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.
Injury, poisoning and procedural complications Femur fracture	1.2% 1/83 • Number of events 1 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.	0.00% 0/12 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.
Injury, poisoning and procedural complications Post procedural haemorrhage	1.2% 1/83 • Number of events 1 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.	0.00% 0/12 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.
Investigations Serum ferritin decreased	1.2% 1/83 • Number of events 1 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.	0.00% 0/12 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.
Investigations Anti factor IX antibody increased	0.00% 0/83 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.	8.3% 1/12 • Number of events 1 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.
Respiratory, thoracic and mediastinal disorders Epistaxis	1.2% 1/83 • Number of events 1 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.	0.00% 0/12 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.
Blood and lymphatic system disorders Iron deficiency anaemia	2.4% 2/83 • Number of events 4 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.	0.00% 0/12 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.
Blood and lymphatic system disorders Anaemia	1.2% 1/83 • Number of events 1 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.	0.00% 0/12 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.
Nervous system disorders Haemorrhage intracranial	1.2% 1/83 • Number of events 1 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.	0.00% 0/12 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.
Gastrointestinal disorders Haemorrhoids	1.2% 1/83 • Number of events 1 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.	0.00% 0/12 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.
Gastrointestinal disorders Large intestine polyp	1.2% 1/83 • Number of events 1 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.	0.00% 0/12 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.
Gastrointestinal disorders Oesophagitis	1.2% 1/83 • Number of events 1 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.	0.00% 0/12 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.
Renal and urinary disorders Haematuria	1.2% 1/83 • Number of events 1 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.	0.00% 0/12 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.
Musculoskeletal and connective tissue disorders Haemarthrosis	2.4% 2/83 • Number of events 2 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.	0.00% 0/12 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.
Musculoskeletal and connective tissue disorders Arthralgia	1.2% 1/83 • Number of events 1 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.	0.00% 0/12 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.
Musculoskeletal and connective tissue disorders Arthritis	1.2% 1/83 • Number of events 1 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.	0.00% 0/12 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.
Musculoskeletal and connective tissue disorders Haemophilic arthropathy	1.2% 1/83 • Number of events 1 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.	0.00% 0/12 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.
Musculoskeletal and connective tissue disorders Joint Swelling	1.2% 1/83 • Number of events 1 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.	0.00% 0/12 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.
Infections and infestations Abscess Jaw	1.2% 1/83 • Number of events 1 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.	0.00% 0/12 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.
Infections and infestations Appendicitis	1.2% 1/83 • Number of events 1 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.	0.00% 0/12 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.
Infections and infestations Peritonsillar abscess	1.2% 1/83 • Number of events 1 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.	0.00% 0/12 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.
Infections and infestations Pneumonia	0.00% 0/83 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.	8.3% 1/12 • Number of events 1 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.
Infections and infestations Device related infection	0.00% 0/83 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.	8.3% 1/12 • Number of events 1 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.
Infections and infestations Influenza	0.00% 0/83 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.	8.3% 1/12 • Number of events 1 • For PTPs: up to 5 years or the time it took to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it took to achieve 50 EDs. Safety Population was used.