Trial Outcomes & Findings for Study of Recombinant Coagulation Factor IX Fc Fusion Protein, BIIB029, in Previously Treated Pediatric Participants With Hemophilia B (NCT NCT01440946)

Last Updated: 2020-12-19

Results Overview

An inhibitor test result ≥ 0.6 Bethesda units (BU)/mL, confirmed on 2 separate samples drawn 2 to 4 weeks apart, was considered positive. Both tests were to be performed by the central laboratory using the Nijmegen-modified Bethesda Assay. Incidences were summarized for any positive inhibitor for participants with ≥ 50 exposure days (EDs) to rFIXFc. In addition, the incidence for all participants, regardless of their EDs to rFIXFc, was also summarized. An exact 95% CI for the proportion of participants with a confirmed inhibitor was calculated using the Clopper-Pearson exact method for a binomial proportion.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

30 participants

Primary outcome timeframe

Up to 50 weeks +/- 7 days, or up to 50 EDs if reached prior to Week 50

Results posted on

2020-12-19

Participant Flow

Participant milestones

Participant milestones
Measure	Participants < 6 Years Old At Baseline and at Day 1, participants received a single intravenous (IV) injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last pharmacokinetic (PK) sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.	Participants 6 to < 12 Years Old At Baseline and at Day 1, participants received a single IV injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.
Overall Study STARTED	15	15
Overall Study COMPLETED	13	14
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Participants < 6 Years Old At Baseline and at Day 1, participants received a single intravenous (IV) injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last pharmacokinetic (PK) sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.	Participants 6 to < 12 Years Old At Baseline and at Day 1, participants received a single IV injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.
Overall Study Lost to Follow-up	1	1
Overall Study Physician Decision	1	0

Baseline Characteristics

Study of Recombinant Coagulation Factor IX Fc Fusion Protein, BIIB029, in Previously Treated Pediatric Participants With Hemophilia B

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Participants < 6 Years Old n=15 Participants At Baseline and at Day 1, participants received a single IV injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.	Participants 6 to < 12 Years Old n=15 Participants At Baseline and at Day 1, participants received a single IV injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.	Total n=30 Participants Total of all reporting groups
Age, Continuous	2.6 years STANDARD_DEVIATION 0.99 • n=5 Participants	8.3 years STANDARD_DEVIATION 1.45 • n=7 Participants	5.5 years STANDARD_DEVIATION 3.16 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	15 Participants n=7 Participants	30 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 50 weeks +/- 7 days, or up to 50 EDs if reached prior to Week 50

Population: Safety Analysis Set: participants who received at least 1 dose of prestudy FIX, or at least 1 dose of rFIXFc; n=number of participants with given number of EDs who had a valid inhibitor test.

Outcome measures

Outcome measures
Measure	Participants < 6 Years Old n=15 Participants At Baseline and at Day 1, participants received a single IV injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.	Participants 6 to < 12 Years Old n=15 Participants At Baseline and at Day 1, participants received a single IV injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.	Total n=30 Participants All Participants
Occurence of Factor IX (FIX) Inhibitor Development Participants with ≥ 50 EDs; n=10, 13, 23	0 percentage of participants Interval 0.0 to 30.85	0 percentage of participants Interval 0.0 to 23.16	0 percentage of participants Interval 0.0 to 14.25
Occurence of Factor IX (FIX) Inhibitor Development All participants regardless of # of EDs;n=15,15,30	0 percentage of participants Interval 0.0 to 21.8	0 percentage of participants Interval 0.0 to 21.8	0 percentage of participants Interval 0.0 to 11.57

SECONDARY outcome

Timeframe: Up to 50 weeks +/- 7 days (efficacy period as defined in description)

Population: Full Analysis Set: participants who received at least 1 dose of rFIXFc; based on the number of participants whose efficacy period was of at least 1 day in duration.

Annualized bleeding rate = (number of bleeding episodes during the efficacy period / total number of days during the efficacy period)\*365.25. The efficacy period begins with the first prophylactic dose of rFIXFc and ends with the last dose (for prophylaxis or a bleeding episode). Surgery/rehabilitation periods and PK evaluation periods are not included in the efficacy period. A bleeding episode started from the first sign of bleeding and ended no more than 72 hours after the last treatment for the bleeding episode, within which any symptoms of bleeding at the same location or injections less than or equal to 72 hours apart were considered the same bleeding episode. Any injection to treat the bleeding episode taken more than 72 hours after the preceding one was considered the first injection to treat a new bleeding episode at the same location. Any bleeding at a different location was considered a separate bleeding episode, regardless of time from last injection.

Outcome measures

Outcome measures
Measure	Participants < 6 Years Old n=15 Participants At Baseline and at Day 1, participants received a single IV injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.	Participants 6 to < 12 Years Old n=15 Participants At Baseline and at Day 1, participants received a single IV injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.	Total All Participants
Annualized Bleeding Rate	1.09 bleeding episodes per participant per yr Interval 0.0 to 2.9	2.13 bleeding episodes per participant per yr Interval 0.0 to 4.17	—

SECONDARY outcome

Timeframe: Up to 50 weeks +/- 7 days (efficacy period as defined in description)

Population: Full Analysis Set: participants who received at least 1 dose of rFIXFc; based on the number of participants whose efficacy period is of at least 1 day in duration.

Annualized bleeding rate for spontaneous joint bleeding episode=(number of bleeding episodes meeting those criteria during the efficacy period/total number of days during the efficacy period)\*365.25. Efficacy period begins with the first prophylactic dose of rFIXFc and ends with the last dose (for prophylaxis or a bleeding episode). Surgery/rehabilitation periods and PK evaluation periods are not included in the efficacy period. A bleeding episode started from the first sign of bleeding and ended ≤ 72 hours after the last treatment for the bleeding episode, within which any symptoms of bleeding at the same location or injections ≤ 72 hours apart were considered the same bleeding episode. Any injection to treat the bleeding episode taken \> 72 hours after the preceding 1 was considered the first injection to treat a new bleeding episode at the same location. Any bleeding at a different location was considered a separate bleeding episode, regardless of time from last injection.

Outcome measures

Outcome measures
Measure	Participants < 6 Years Old n=15 Participants At Baseline and at Day 1, participants received a single IV injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.	Participants 6 to < 12 Years Old n=15 Participants At Baseline and at Day 1, participants received a single IV injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.	Total All Participants
Annualized Joint Bleeding Rate (Spontaneous)	0.00 bleeding episodes per participant per yr Interval 0.0 to 1.2	0.00 bleeding episodes per participant per yr Interval 0.0 to 2.2	—

SECONDARY outcome

Timeframe: Up to 50 weeks +/- 7 days

Population: Full Analysis Set: participants who received at least 1 dose of rFIXFc and had ≥ 1 bleeding episode; based on the number of injections with an evaluation.

Participant's assessment of the response (provided by the caregiver) to the first rFIXFc injection for each bleeding episode. Percentages were based on the number of bleeding episodes for which a response was provided for the first injection, using the following 4-point scale: excellent=abrupt pain relief and/or improvement in signs of bleeding within approximately 8 hours after the initial injection; good=definite pain relief and/or improvement in signs of bleeding within approximately 8 hours after an injection, but possibly requiring more than one injection after 24 to 48 hours for complete resolution; moderate=probable or slight beneficial effect within 8 hours after the initial injection and requiring more than one injection; no response=no improvement, or condition worsened, within approximately 8 hours after the initial injection.

Outcome measures

Outcome measures
Measure	Participants < 6 Years Old n=19 Injections At Baseline and at Day 1, participants received a single IV injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.	Participants 6 to < 12 Years Old n=34 Injections At Baseline and at Day 1, participants received a single IV injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.	Total All Participants
Participant Assessment of Response to Injections to Treat a Bleeding Episode Excellent or Good	89.5 percent of 1st injections w/ a response	88.2 percent of 1st injections w/ a response	—
Participant Assessment of Response to Injections to Treat a Bleeding Episode Excellent	52.6 percent of 1st injections w/ a response	41.2 percent of 1st injections w/ a response	—
Participant Assessment of Response to Injections to Treat a Bleeding Episode Good	36.8 percent of 1st injections w/ a response	47.1 percent of 1st injections w/ a response	—
Participant Assessment of Response to Injections to Treat a Bleeding Episode Moderate	5.3 percent of 1st injections w/ a response	11.8 percent of 1st injections w/ a response	—
Participant Assessment of Response to Injections to Treat a Bleeding Episode No Response	5.3 percent of 1st injections w/ a response	0 percent of 1st injections w/ a response	—

SECONDARY outcome

Timeframe: Up to 50 weeks +/- 7 days

Population: Full Analysis Set: participants who received ≥ 1 dose of rFIXFc; based on the number of responses.

Investigators assessed each participant's response to his rFIXFc regimen using a 4-point scale: excellent=bleeding episodes responded to ≤ the usual number of injections or ≤ the usual dose of rFIXFc or the rate of breakthrough bleeding during prophylaxis was ≤ that usually observed; effective=most bleeding episodes responded to the same number of injections and dose, but some required more injections or higher doses, or there was a minor increase in the rate of breakthrough bleeding; partially effective=bleeding episodes most often required more injections and/or higher doses than expected, or adequate breakthrough bleeding prevention during prophylaxis required more frequent injections and/or higher doses; ineffective=routine failure to control hemostasis, or hemostatic control required additional agents. Percentages are based on the total number of responses; multiple responses per participant are counted.

Outcome measures

Outcome measures
Measure	Participants < 6 Years Old n=48 responses At Baseline and at Day 1, participants received a single IV injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.	Participants 6 to < 12 Years Old n=59 responses At Baseline and at Day 1, participants received a single IV injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.	Total All Participants
Physician's Global Assessment of the Participant's Response to His rFIXFc Regimen Excellent	85.4 percentage of responses	89.8 percentage of responses	—
Physician's Global Assessment of the Participant's Response to His rFIXFc Regimen Effective	14.6 percentage of responses	10.2 percentage of responses	—
Physician's Global Assessment of the Participant's Response to His rFIXFc Regimen Partially Effective	0 percentage of responses	0 percentage of responses	—
Physician's Global Assessment of the Participant's Response to His rFIXFc Regimen Ineffective	0 percentage of responses	0 percentage of responses	—

SECONDARY outcome

Timeframe: Up to 50 weeks +/- 7 days (efficacy period as defined in description)

Population: Full Analysis Set: participants who received at least 1 dose of rFIXFc.

Annualized consumption of rFIXFc for prevention of bleeding (prophylactic), treatment of bleeding, and other rFIXFc injections. Consumption is calculated for the efficacy period. The efficacy period began with the first prophylactic dose of rFIXFc and ended with the last dose (regardless of the reason for dosing). Surgery/rehabilitation and PK evaluation periods were not included in the efficacy period. Annualized consumption = (total IU/kg of study treatment received during the efficacy period / total number of days during the efficacy period)\*365.25. Participants who did not have a particular injection type are counted as having zero injections for that type.

Outcome measures

Outcome measures
Measure	Participants < 6 Years Old n=15 Participants At Baseline and at Day 1, participants received a single IV injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.	Participants 6 to < 12 Years Old n=15 Participants At Baseline and at Day 1, participants received a single IV injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.	Total All Participants
Annualized rFIXFc Consumption by Type of Injection Prophylactic injections	3041.5 IU/kg rFIXFc per year Standard Deviation 577.55	3185.6 IU/kg rFIXFc per year Standard Deviation 683.71	—
Annualized rFIXFc Consumption by Type of Injection Injections for bleeding	147.9 IU/kg rFIXFc per year Standard Deviation 209.89	293.8 IU/kg rFIXFc per year Standard Deviation 515.59	—
Annualized rFIXFc Consumption by Type of Injection Other injections	29.2 IU/kg rFIXFc per year Standard Deviation 48.93	16.9 IU/kg rFIXFc per year Standard Deviation 44.90	—

SECONDARY outcome

Timeframe: Up to 50 weeks +/- 7 days (efficacy period as defined in description)

Population: Full Analysis Set: participants who received at least 1 dose of rFIXFc; number of participants and number of episodes were determined for participants with at least 1 evaluable spontaneous bleeding episode.

The number of days from the last prophylaxis injection to the onset of a new spontaneous bleeding episode, analyzed across all evaluable bleeding episodes per participant and per episode, based on the efficacy period. Evaluable bleeding episodes are those for which both a date and time are available for both the onset of the bleeding episode and the previous prophylactic injection. The efficacy period begins with the first prophylactic dose of rFIXFc and ends with the last dose (for prophylaxis or a bleeding episode). Surgery/rehabilitation periods and PK evaluation periods are not included in the efficacy period. For 'Per participant' values, the number of days from the last prophylactic injection to a spontaneous bleeding episode is averaged across all evaluable spontaneous bleeding episodes per participant.

Outcome measures

Outcome measures
Measure	Participants < 6 Years Old n=5 Evaluable Spontaneous Bleeding Episodes At Baseline and at Day 1, participants received a single IV injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.	Participants 6 to < 12 Years Old n=11 Evaluable Spontaneous Bleeding Episodes At Baseline and at Day 1, participants received a single IV injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.	Total All Participants
Number of Days From the Last Prophylaxis Injection to a Spontaneous Bleeding Episode Per spontaneous bleeding episode	3.97 days Interval 0.71 to 4.27	5.55 days Interval 3.3 to 6.04	—
Number of Days From the Last Prophylaxis Injection to a Spontaneous Bleeding Episode Per participant	4.12 days Interval 2.33 to 5.3	5.52 days Interval 4.41 to 6.04	—

SECONDARY outcome

Timeframe: Up to 50 weeks +/- 7 days (efficacy period as defined in description)

The number of injections required to resolve a bleeding episode per participant and per episode, based on the efficacy period. The efficacy period begins with the first prophylactic dose of rFIXFc and ends with the last dose (for prophylaxis or a bleeding episode). Surgery/rehabilitation periods and PK evaluation periods are not included in the efficacy period. All injections given from the initial sign of a bleeding episode, until the last date/time within the bleeding episode window are counted. The resolution of a bleeding episode is defined as no sign of bleeding following injection for the bleeding episode. For 'Per participant' values, the number of injections required to resolve each bleeding episode is averaged across all bleeding episodes per participant.

Outcome measures

Outcome measures
Measure	Participants < 6 Years Old n=22 Bleeding Episodes At Baseline and at Day 1, participants received a single IV injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.	Participants 6 to < 12 Years Old n=38 Bleeding Episodes At Baseline and at Day 1, participants received a single IV injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.	Total All Participants
Number of Injections Required for Resolution of a Bleeding Episode Per bleeding episode	1.0 injections Interval 1.0 to 1.0	1.0 injections Interval 1.0 to 2.0	—
Number of Injections Required for Resolution of a Bleeding Episode Per participant	1.0 injections Interval 1.0 to 1.2	1.0 injections Interval 1.0 to 1.7	—

SECONDARY outcome

Timeframe: Up to 50 weeks +/- 7 days (efficacy period as defined in description)

Population: Full Analysis Set: participants who received at least 1 dose of rFIXFc; number of participants and number of episodes were determined for participants who had complete information on the dose administered to treat a bleeding episode.

The total dose required to resolve a bleeding episode per participant and per episode, based on the efficacy period. The efficacy period begins with the first prophylactic dose of rFIXFc and ends with the last dose (for prophylaxis or a bleeding episode). Surgery/rehabilitation periods and PK evaluation periods are not included in the efficacy period. For 'Per bleeding episode' values, for each bleeding episode, the total dose is the sum of the doses (IU/kg) administered across all injections given to treat that bleeding episode. For 'Per participant' values, the total dose (IU/kg) used to resolve each bleeding episode is averaged across all bleeding episodes per participant.

Outcome measures

Outcome measures
Measure	Participants < 6 Years Old n=22 Bleeding Episodes At Baseline and at Day 1, participants received a single IV injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.	Participants 6 to < 12 Years Old n=38 Bleeding Episodes At Baseline and at Day 1, participants received a single IV injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.	Total All Participants
Total Dose Required for Resolution of a Bleeding Episode Per bleeding episode	65.37 IU/kg Interval 50.68 to 125.0	89.77 IU/kg Interval 50.92 to 140.86	—
Total Dose Required for Resolution of a Bleeding Episode Per participant	70.22 IU/kg Interval 55.4 to 97.22	52.22 IU/kg Interval 27.03 to 161.06	—

SECONDARY outcome

Timeframe: Baseline (28±7 days before Day 1) Prestudy FIX Dosing: predose; 30±5 min, 3 hrs±30 min, 10±2 hrs, 24±3 hrs, 48±4 hrs postdose. Day 1 rFIXFc Dosing: predose; 30±5 min, 3 hrs ±30 min, 10±2 hrs, 24±3 hrs, 72±7 hrs, 120±12 hrs, 168±16 hrs postdose.

Population: PK Analysis Set: all participants with adequate PK data, defined as complete and evaluable PK samples through 168 hours after rFIXFc dosing. Complete means the availability of the 168-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.

Cmax: maximum plasma FIX activity during a dosing interval. The values for Cmax were adjusted to the nominal dose of 50 IU/kg. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.

Outcome measures

Outcome measures
Measure	Participants < 6 Years Old n=11 Participants At Baseline and at Day 1, participants received a single IV injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.	Participants 6 to < 12 Years Old n=13 Participants At Baseline and at Day 1, participants received a single IV injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.	Total All Participants
Maximum Plasma Activity (Cmax; One-stage Activated Partial Thromboplastin Time [aPTT] Clotting Assay)	29.78 IU/dL Interval 26.18 to 33.87	35.84 IU/dL Interval 30.56 to 42.03	—

SECONDARY outcome

t1/2: time required for the concentration of the drug to reach half of its original value in the body. Non-compartmental methods. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.

Outcome measures

Outcome measures
Measure	Participants < 6 Years Old n=11 Participants At Baseline and at Day 1, participants received a single IV injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.	Participants 6 to < 12 Years Old n=13 Participants At Baseline and at Day 1, participants received a single IV injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.	Total All Participants
Terminal Half Life (t1/2; One-stage aPTT Clotting Assay)	66.49 hours Interval 55.86 to 79.14	70.34 hours Interval 60.95 to 81.17	—

SECONDARY outcome

CL: the measure of the efficiency of the body to remove the drug and the unit is the volume of the plasma or blood cleared of drug per unit time. Non-compartmental methods. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.

Outcome measures

Outcome measures
Measure	Participants < 6 Years Old n=11 Participants At Baseline and at Day 1, participants received a single IV injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.	Participants 6 to < 12 Years Old n=13 Participants At Baseline and at Day 1, participants received a single IV injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.	Total All Participants
Clearance (CL; One-stage aPTT Clotting Assay)	4.365 mL/h/kg Interval 3.901 to 4.885	3.505 mL/h/kg Interval 3.006 to 4.087	—

SECONDARY outcome

Vss: volume of distribution at steady state. Non-compartmental methods. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.

Outcome measures

Outcome measures
Measure	Participants < 6 Years Old n=11 Participants At Baseline and at Day 1, participants received a single IV injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.	Participants 6 to < 12 Years Old n=13 Participants At Baseline and at Day 1, participants received a single IV injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.	Total All Participants
Volume of Distribution at Steady State (Vss; One-stage aPTT Clotting Assay)	365.1 mL/kg Interval 316.2 to 421.6	289.0 mL/kg Interval 236.7 to 352.9	—

SECONDARY outcome

DNAUC: dose normalized area under the drug concentration-time curve (extent of unmetabolized drug in circulation). Non-compartmental methods. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.

Outcome measures

Outcome measures
Measure	Participants < 6 Years Old n=11 Participants At Baseline and at Day 1, participants received a single IV injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.	Participants 6 to < 12 Years Old n=13 Participants At Baseline and at Day 1, participants received a single IV injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.	Total All Participants
Dose Normalized Area Under the Curve (DNAUC; One-stage aPTT Clotting Assay)	22.71 IU*h/dL per IU/kg Interval 20.32 to 25.38	28.53 IU*h/dL per IU/kg Interval 24.47 to 33.27	—

SECONDARY outcome

MRT: the average time for all the drug molecules to reside in the body. Non-compartmental methods. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.

Outcome measures

Outcome measures
Measure	Participants < 6 Years Old n=11 Participants At Baseline and at Day 1, participants received a single IV injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.	Participants 6 to < 12 Years Old n=13 Participants At Baseline and at Day 1, participants received a single IV injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.	Total All Participants
Mean Residence Time (MRT; One-stage aPTT Clotting Assay)	83.65 hours Interval 71.76 to 97.51	82.46 hours Interval 72.65 to 93.6	—

SECONDARY outcome

IR for FIX activity following rFIXFc dosing: IU/dL rise in plasma FIX per IU/kg drug administered. Non-compartmental methods. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.

Outcome measures

Outcome measures
Measure	Participants < 6 Years Old n=11 Participants At Baseline and at Day 1, participants received a single IV injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.	Participants 6 to < 12 Years Old n=13 Participants At Baseline and at Day 1, participants received a single IV injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.	Total All Participants
Incremental Recovery (IR; One-stage aPTT Clotting Assay)	0.5898 IU/dL per IU/kg Interval 0.5152 to 0.6752	0.7170 IU/dL per IU/kg Interval 0.6115 to 0.8407	—

Adverse Events

Participants < 6 Years Old

Serious events: 3 serious events

Other events: 12 other events

Deaths: 0 deaths

Participants 6 to < 12 Years Old

Serious events: 1 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Participants < 6 Years Old n=15 participants at risk At Baseline and at Day 1, participants received a single IV injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.	Participants 6 to < 12 Years Old n=15 participants at risk At Baseline and at Day 1, participants received a single IV injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg was administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.
Gastrointestinal disorders Duodenal Ulcer Haemorrhage	0.00% 0/15 • Serious adverse events (AEs): from informed consent up to 21 days after last dose; AEs: from Baseline (28 ± 7 days prior to Day 1) up to 14 (+7) days after last dose. Length of rFIXFc dosing was up to 50 weeks ± 7 days. Serious and non-serious AEs that were treatment-emergent with respect to rFIXFc are presented for those subjects in the Safety Analysis Set who were treated with rFIXFc.	6.7% 1/15 • Serious adverse events (AEs): from informed consent up to 21 days after last dose; AEs: from Baseline (28 ± 7 days prior to Day 1) up to 14 (+7) days after last dose. Length of rFIXFc dosing was up to 50 weeks ± 7 days. Serious and non-serious AEs that were treatment-emergent with respect to rFIXFc are presented for those subjects in the Safety Analysis Set who were treated with rFIXFc.
General disorders Device Occlusion	6.7% 1/15 • Serious adverse events (AEs): from informed consent up to 21 days after last dose; AEs: from Baseline (28 ± 7 days prior to Day 1) up to 14 (+7) days after last dose. Length of rFIXFc dosing was up to 50 weeks ± 7 days. Serious and non-serious AEs that were treatment-emergent with respect to rFIXFc are presented for those subjects in the Safety Analysis Set who were treated with rFIXFc.	0.00% 0/15 • Serious adverse events (AEs): from informed consent up to 21 days after last dose; AEs: from Baseline (28 ± 7 days prior to Day 1) up to 14 (+7) days after last dose. Length of rFIXFc dosing was up to 50 weeks ± 7 days. Serious and non-serious AEs that were treatment-emergent with respect to rFIXFc are presented for those subjects in the Safety Analysis Set who were treated with rFIXFc.
Infections and infestations Gastroenteritis	6.7% 1/15 • Serious adverse events (AEs): from informed consent up to 21 days after last dose; AEs: from Baseline (28 ± 7 days prior to Day 1) up to 14 (+7) days after last dose. Length of rFIXFc dosing was up to 50 weeks ± 7 days. Serious and non-serious AEs that were treatment-emergent with respect to rFIXFc are presented for those subjects in the Safety Analysis Set who were treated with rFIXFc.	0.00% 0/15 • Serious adverse events (AEs): from informed consent up to 21 days after last dose; AEs: from Baseline (28 ± 7 days prior to Day 1) up to 14 (+7) days after last dose. Length of rFIXFc dosing was up to 50 weeks ± 7 days. Serious and non-serious AEs that were treatment-emergent with respect to rFIXFc are presented for those subjects in the Safety Analysis Set who were treated with rFIXFc.
Injury, poisoning and procedural complications Fall	13.3% 2/15 • Serious adverse events (AEs): from informed consent up to 21 days after last dose; AEs: from Baseline (28 ± 7 days prior to Day 1) up to 14 (+7) days after last dose. Length of rFIXFc dosing was up to 50 weeks ± 7 days. Serious and non-serious AEs that were treatment-emergent with respect to rFIXFc are presented for those subjects in the Safety Analysis Set who were treated with rFIXFc.	0.00% 0/15 • Serious adverse events (AEs): from informed consent up to 21 days after last dose; AEs: from Baseline (28 ± 7 days prior to Day 1) up to 14 (+7) days after last dose. Length of rFIXFc dosing was up to 50 weeks ± 7 days. Serious and non-serious AEs that were treatment-emergent with respect to rFIXFc are presented for those subjects in the Safety Analysis Set who were treated with rFIXFc.
Injury, poisoning and procedural complications Head Injury	13.3% 2/15 • Serious adverse events (AEs): from informed consent up to 21 days after last dose; AEs: from Baseline (28 ± 7 days prior to Day 1) up to 14 (+7) days after last dose. Length of rFIXFc dosing was up to 50 weeks ± 7 days. Serious and non-serious AEs that were treatment-emergent with respect to rFIXFc are presented for those subjects in the Safety Analysis Set who were treated with rFIXFc.	0.00% 0/15 • Serious adverse events (AEs): from informed consent up to 21 days after last dose; AEs: from Baseline (28 ± 7 days prior to Day 1) up to 14 (+7) days after last dose. Length of rFIXFc dosing was up to 50 weeks ± 7 days. Serious and non-serious AEs that were treatment-emergent with respect to rFIXFc are presented for those subjects in the Safety Analysis Set who were treated with rFIXFc.

Other adverse events

Additional Information

Bioverativ Study Medical Director

Bioverativ

Email: [email protected]

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