Trial Outcomes & Findings for Safety and Efficacy of Benefix in Patients With Hemophilia B in Usual Care Settings in China (NCT NCT02336178)

NCT ID: NCT02336178

Last Updated: 2017-05-04

Results Overview

Factor IX (FIX) inhibitor development was defined as any Bethesda inhibitor titer greater than the laboratory's normal range or Bethesda inhibitor titer \>=0.6 Bethesda Unit (BU)/mL.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 70 participants
• Primary outcome timeframe: Up to 6 months
• Results posted on: 2017-05-04

Participant Flow

This study enrolled 70 participants.

Participant milestones

Measure	BeneFIX Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.
Overall Study STARTED	70
Overall Study COMPLETED	66
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Measure	BeneFIX Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.
Overall Study Lost to Follow-up	1
Overall Study Protocol Violation	1
Overall Study Withdrawal by Subject	1
Overall Study Other	1

Baseline Characteristics

Safety and Efficacy of Benefix in Patients With Hemophilia B in Usual Care Settings in China

Baseline characteristics by cohort

Measure	BeneFIX n=70 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.
Age, Continuous	7.8 years STANDARD_DEVIATION 7.2 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	70 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 6 months

Population: All participants who received at least 1 dose of BeneFIX during the study. Participants in each arm were not mutually exclusive.

Factor IX (FIX) inhibitor development was defined as any Bethesda inhibitor titer greater than the laboratory's normal range or Bethesda inhibitor titer >=0.6 Bethesda Unit (BU)/mL.

Outcome measures

Measure	Pediatric Participants <6 Years of Age n=30 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Pediatric Participants ≥6 to ≤12 Years of Age n=31 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Previously Untreated Participants (PUPs) n=11 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Participants Receiving Prophylaxis Treatment n=57 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first. This reporting arm included all participants who received prophylaxis treatment after enrollment in the study.	Severe Participants (Factor IX Activity <1%) n=36 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Overall Participants n=70 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first. This reporting arm included all participants who received at least 1 dose of BeneFIX during the study.
Percentage of Participants Who Developed Factor IX Inhibitor	3.3 percentage of participants Interval 0.1 to 17.2	0.0 percentage of participants Interval 0.0 to 11.2	0.0 percentage of participants Interval 0.0 to 28.5	1.8 percentage of participants Interval 0.0 to 9.4	0.0 percentage of participants Interval 0.0 to 9.7	1.4 percentage of participants Interval 0.0 to 7.7

PRIMARY outcome

Timeframe: Up to 6 months

Population: All participants who received at least 1 dose of BeneFIX during the study. Participants in each arm were not mutually exclusive.

FIX product allergy was defined as a hypersensitivity reaction to a FIX product with symptoms such as hives, urticaria, tightness of chest, wheezing, hypotension, and anaphylaxis based on investigator's judgments.

Outcome measures

Measure	Pediatric Participants <6 Years of Age n=30 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Pediatric Participants ≥6 to ≤12 Years of Age n=31 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Previously Untreated Participants (PUPs) n=11 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Participants Receiving Prophylaxis Treatment n=57 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first. This reporting arm included all participants who received prophylaxis treatment after enrollment in the study.	Severe Participants (Factor IX Activity <1%) n=36 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Overall Participants n=70 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first. This reporting arm included all participants who received at least 1 dose of BeneFIX during the study.
Number of Participants With Allergic Reactions	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants

PRIMARY outcome

Timeframe: Up to 6 months

Population: All participants who received at least 1 dose of BeneFIX during the study. Participants in each arm were not mutually exclusive.

Thrombotic event was defined as any event associated with formation of a blood clot including catheter-associated thrombi and thrombotic complications.

Outcome measures

Measure	Pediatric Participants <6 Years of Age n=30 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Pediatric Participants ≥6 to ≤12 Years of Age n=31 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Previously Untreated Participants (PUPs) n=11 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Participants Receiving Prophylaxis Treatment n=57 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first. This reporting arm included all participants who received prophylaxis treatment after enrollment in the study.	Severe Participants (Factor IX Activity <1%) n=36 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Overall Participants n=70 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first. This reporting arm included all participants who received at least 1 dose of BeneFIX during the study.
Number of Participants With Thrombotic Events	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Up to 7 months (28 calendar days after end of 6-month or 50-exposure day study treatment)

Population: All participants who received at least 1 dose of BeneFIX during the study. Participants in each arm were not mutually exclusive.

An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device, regardless of the causality with the treatment or usage. A serious adverse event (SAE) was any untoward occurrence at any dose that resulted in death; was life threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both serious and non-serious AEs. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study drug.

Outcome measures

Measure	Pediatric Participants <6 Years of Age n=30 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Pediatric Participants ≥6 to ≤12 Years of Age n=31 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Previously Untreated Participants (PUPs) n=11 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Participants Receiving Prophylaxis Treatment n=57 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first. This reporting arm included all participants who received prophylaxis treatment after enrollment in the study.	Severe Participants (Factor IX Activity <1%) n=36 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Overall Participants n=70 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first. This reporting arm included all participants who received at least 1 dose of BeneFIX during the study.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) AEs	28 participants	26 participants	10 participants	46 participants	30 participants	62 participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) SAEs	2 participants	0 participants	0 participants	2 participants	0 participants	2 participants

SECONDARY outcome

Timeframe: Up to 6 months or 50 exposure days whichever occurred first

Population: All participants who participated in at least 1 day of a prophylaxis period (ie, had at least 1 prophylaxis dose). Participants in each arm were not mutually exclusive.

For prophylaxis period, annualized bleeding rate (ABR) was derived for each participant by the following formula: ABR = number of bleeds in prophylaxis period / (number of days in prophylaxis period/365.25). A prophylaxis period was defined as time from first prophylaxis infusion through 6 calendar days after the day of last prophylaxis infusion, or the day of study conclusion visit, whichever was earlier. A break in the prophylaxis period was any period of 28 days or longer in which no prophylaxis infusions were given. For a prophylaxis regimen to have been qualified to have ABR calculated, the sum of its periods needed to be >=14 days.

Outcome measures

Measure	Pediatric Participants <6 Years of Age n=27 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Pediatric Participants ≥6 to ≤12 Years of Age n=28 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Previously Untreated Participants (PUPs) n=7 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Participants Receiving Prophylaxis Treatment n=57 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first. This reporting arm included all participants who received prophylaxis treatment after enrollment in the study.	Severe Participants (Factor IX Activity <1%) n=29 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Overall Participants n=57 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first. This reporting arm included all participants who received at least 1 dose of BeneFIX during the study.
Annualized Bleeding Rates (ABRs) in Participants Receiving Prophylaxis Treatment With BeneFIX During Their Prophylaxis Period	5.9 episodes/year Standard Deviation 9.46	7.5 episodes/year Standard Deviation 8.97	0.3 episodes/year Standard Deviation 0.72	6.5 episodes/year Standard Deviation 9.06	5.5 episodes/year Standard Deviation 7.94	6.5 episodes/year Standard Deviation 9.06

SECONDARY outcome

Timeframe: Up to 6 months or 50 exposure days whichever occurred first

Population: All participants with any spontaneous/non-traumatic breakthrough bleeds within 48 hours of a prophylaxis dose. Participants in each arm were not mutually exclusive.

The prophylaxis infusion time, bleed start time and bleed type (etiology) were used to determine the number of spontaneous, non-traumatic breakthrough bleeds that occurred <=48 hours after a prophylaxis infusion. If there was more than 1 bleed location (eg, ankle and joint) with identical bleed start date and time, it was treated as 1 bleed occurrence.

Outcome measures

Measure	Pediatric Participants <6 Years of Age n=5 Prophylaxis Infusions with Bleeds Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Pediatric Participants ≥6 to ≤12 Years of Age n=18 Prophylaxis Infusions with Bleeds Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Previously Untreated Participants (PUPs) Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Participants Receiving Prophylaxis Treatment n=23 Prophylaxis Infusions with Bleeds Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first. This reporting arm included all participants who received prophylaxis treatment after enrollment in the study.	Severe Participants (Factor IX Activity <1%) n=18 Prophylaxis Infusions with Bleeds Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Overall Participants n=23 Prophylaxis Infusions with Bleeds Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first. This reporting arm included all participants who received at least 1 dose of BeneFIX during the study.
Number of Spontaneous/Non-traumatic Breakthrough Bleeds Within 48 Hours of a Prophylaxis Dose of BeneFIX	1.3 breakthrough bleeds Standard Deviation 0.50	2.6 breakthrough bleeds Standard Deviation 2.30	—	2.1 breakthrough bleeds Standard Deviation 1.92	2.6 breakthrough bleeds Standard Deviation 2.30	2.1 breakthrough bleeds Standard Deviation 1.92

SECONDARY outcome

Timeframe: Up to 6 months or 50 exposure days whichever occurred first

Population: All participants who received on-demand treatment during on-demand period. Participants in each arm were not mutually exclusive.

For on-demand period, the annualized bleeding rate (ABR) was derived for each participant by the following formula: ABR = number of bleeds in on-demand period / (number of days in on-demand period/365.25). The on-demand period was defined as the entire time of enrollment in the study (ie, from the date of the enrollment visit through the day before the Final/Early Termination visit) except time in any prophylaxis period. The breaks in the prophylaxis period were considered on-demand periods. For an on-demand regimen to have been qualified to have ABR calculated, the sum of its periods needed to be >= 14 days.

Outcome measures

Measure	Pediatric Participants <6 Years of Age n=5 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Pediatric Participants ≥6 to ≤12 Years of Age n=6 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Previously Untreated Participants (PUPs) n=4 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Participants Receiving Prophylaxis Treatment n=10 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first. This reporting arm included all participants who received prophylaxis treatment after enrollment in the study.	Severe Participants (Factor IX Activity <1%) n=18 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Overall Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first. This reporting arm included all participants who received at least 1 dose of BeneFIX during the study.
Annualized Bleeding Rates (ABRs) in Participants Receiving On-demand Treatment With BeneFIX During Their On-demand Period	14.8 episodes/year Standard Deviation 15.59	28.2 episodes/year Standard Deviation 26.16	6.2 episodes/year Standard Deviation 2.40	29.3 episodes/year Standard Deviation 25.95	26.3 episodes/year Standard Deviation 23.08	—

SECONDARY outcome

Timeframe: Up to 6 months or 50 exposure days whichever occurred first

Population: All participants who had a bleed during the study for which on-demand treatment with BeneFIX was administered. Participants in each arm were not mutually exclusive.

Response was assessed using 4-point On-Demand Hemostasis Efficacy Rating Scale. Excellent means definite pain relief and/or improvement in signs of bleeding starting within 8 hours after an infusion, with no additional infusion administered; good means definite pain relief and/or improvement in signs of bleeding starting within 8 hours after an infusion, with at least one additional infusion administered for complete resolution of the bleeding episode, or definite pain relief and/or improvement in signs of bleeding starting after 8 hours following the infusion, with no additional infusion administered; moderate means probable or slight improvement starting after 8 hours following the infusion, with at least one additional infusion administered for complete resolution of the bleeding episode; no response means no improvement between infusions or during the 24 hour interval following an infusion, or condition worsens. Both first infusions and follow-up infusions were included.

Outcome measures

Measure	Pediatric Participants <6 Years of Age n=164 Infusions Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Pediatric Participants ≥6 to ≤12 Years of Age n=211 Infusions Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Previously Untreated Participants (PUPs) n=18 Infusions Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Participants Receiving Prophylaxis Treatment n=249 Infusions Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first. This reporting arm included all participants who received prophylaxis treatment after enrollment in the study.	Severe Participants (Factor IX Activity <1%) n=302 Infusions Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Overall Participants n=520 Infusions Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first. This reporting arm included all participants who received at least 1 dose of BeneFIX during the study.
Number of Infusions Resulted in the Following Response to On-demand Treatment of Bleeds: Excellent, Good, Moderate, no Response Excellent	77 infusions	94 infusions	9 infusions	133 infusions	122 infusions	254 infusions
Number of Infusions Resulted in the Following Response to On-demand Treatment of Bleeds: Excellent, Good, Moderate, no Response Good	60 infusions	91 infusions	9 infusions	96 infusions	145 infusions	204 infusions
Number of Infusions Resulted in the Following Response to On-demand Treatment of Bleeds: Excellent, Good, Moderate, no Response Moderate	22 infusions	23 infusions	0 infusions	19 infusions	33 infusions	54 infusions
Number of Infusions Resulted in the Following Response to On-demand Treatment of Bleeds: Excellent, Good, Moderate, no Response No response	5 infusions	3 infusions	0 infusions	1 infusions	2 infusions	8 infusions

SECONDARY outcome

Timeframe: Up to 6 months or 50 exposure days whichever occurred first

Population: All participants who had a bleed during the study for which on-demand treatment with BeneFIX was administered. Participants in each arm were not mutually exclusive.

The number of BeneFIX infusions administered to treat each new bleed was calculated by adding the on-demand initial treatment and any on-demand follow-up treatments for the same bleed. If there was more than one bleed location (eg, ankle and joint) with identical bleed start date and time, it was treated as one bleed occurrence.

Outcome measures

Measure	Pediatric Participants <6 Years of Age n=96 Bleeds Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Pediatric Participants ≥6 to ≤12 Years of Age n=137 Bleeds Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Previously Untreated Participants (PUPs) n=16 Bleeds Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Participants Receiving Prophylaxis Treatment n=162 Bleeds Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first. This reporting arm included all participants who received prophylaxis treatment after enrollment in the study.	Severe Participants (Factor IX Activity <1%) n=198 Bleeds Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Overall Participants n=353 Bleeds Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first. This reporting arm included all participants who received at least 1 dose of BeneFIX during the study.
Number of BeneFIX Infusions to Treat Each New Bleed	1.7 infusions Standard Deviation 1.72	1.5 infusions Standard Deviation 2.03	1.1 infusions Standard Deviation 0.34	1.5 infusions Standard Deviation 1.23	1.5 infusions Standard Deviation 2.01	1.5 infusions Standard Deviation 1.71

SECONDARY outcome

Timeframe: Up to 6 months or 50 exposure days whichever occurred first

Population: All participants who had a bleed during the study for which on-demand treatment with BeneFIX was administered. Participants in each arm were not mutually exclusive.

The total amount (international units [IU]) infused for each BeneFIX infusion was summed to calculate the total factor IX consumption for each participant. The average infusion dose for each participant was calculated as his total factor IX consumption (in IU) divided by the number of infusions administered.

Outcome measures

Measure	Pediatric Participants <6 Years of Age n=18 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Pediatric Participants ≥6 to ≤12 Years of Age n=20 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Previously Untreated Participants (PUPs) n=5 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Participants Receiving Prophylaxis Treatment n=32 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first. This reporting arm included all participants who received prophylaxis treatment after enrollment in the study.	Severe Participants (Factor IX Activity <1%) n=24 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Overall Participants n=46 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first. This reporting arm included all participants who received at least 1 dose of BeneFIX during the study.
Average Infusion Dose and Total Factor IX Consumption in On-demand Setting Total FIX consumption	4277.8 IU Standard Deviation 4659.47	6550.0 IU Standard Deviation 6540.66	1770.0 IU Standard Deviation 1173.46	4418.8 IU Standard Deviation 3449.75	11672.9 IU Standard Deviation 16304.85	9826.1 IU Standard Deviation 14816.34
Average Infusion Dose and Total Factor IX Consumption in On-demand Setting Average infusion dose	451.1 IU Standard Deviation 161.44	658.5 IU Standard Deviation 370.35	518.6 IU Standard Deviation 295.70	607.7 IU Standard Deviation 309.34	803.8 IU Standard Deviation 549.75	731.6 IU Standard Deviation 498.58

SECONDARY outcome

Timeframe: Up to 6 months or 50 exposure days whichever occurred first

Population: All participants who received at least 1 dose of prophylaxis BeneFIX treatment during the study. Participants in each arm were not mutually exclusive.

The total amount (international units [IU]) infused for each BeneFIX infusion was summed to calculate the total factor IX consumption for each participant. The average infusion dose for each participant was calculated as his total factor IX consumption (in IU) divided by the number of infusions administered.

Outcome measures

Measure	Pediatric Participants <6 Years of Age n=27 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Pediatric Participants ≥6 to ≤12 Years of Age n=28 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Previously Untreated Participants (PUPs) n=7 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Participants Receiving Prophylaxis Treatment n=57 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first. This reporting arm included all participants who received prophylaxis treatment after enrollment in the study.	Severe Participants (Factor IX Activity <1%) n=29 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Overall Participants n=57 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first. This reporting arm included all participants who received at least 1 dose of BeneFIX during the study.
Average Infusion Dose and Total Factor IX Consumption in Prophylaxis Setting Total FIX consumption	14709.3 IU Standard Deviation 8910.57	22102.7 IU Standard Deviation 18860.51	13846.4 IU Standard Deviation 5868.21	19224.1 IU Standard Deviation 15424.70	20628.4 IU Standard Deviation 19894.00	19224.1 IU Standard Deviation 15424.70
Average Infusion Dose and Total Factor IX Consumption in Prophylaxis Setting Average infusion dose	429.3 IU Standard Deviation 193.52	623.1 IU Standard Deviation 377.99	351.9 IU Standard Deviation 194.48	540.1 IU Standard Deviation 316.56	557.0 IU Standard Deviation 407.05	540.1 IU Standard Deviation 316.56

SECONDARY outcome

Timeframe: Up to 6 months or 50 exposure days whichever occurred first

Population: All participants who received at least 1 recovery infusion with BeneFIX during the study. Participants in each arm were not mutually exclusive.

The total amount (international units [IU]) infused for each BeneFIX infusion was summed to calculate the total factor IX consumption for each participant. The average infusion dose for each participant was calculated as his total factor IX consumption (in IU) divided by the number of infusions administered.

Outcome measures

Measure	Pediatric Participants <6 Years of Age n=12 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Pediatric Participants ≥6 to ≤12 Years of Age n=9 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Previously Untreated Participants (PUPs) n=1 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Participants Receiving Prophylaxis Treatment n=20 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first. This reporting arm included all participants who received prophylaxis treatment after enrollment in the study.	Severe Participants (Factor IX Activity <1%) n=13 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Overall Participants n=24 Participants Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first. This reporting arm included all participants who received at least 1 dose of BeneFIX during the study.
Average Infusion Dose and Total Factor IX Consumption in Recovery Setting Total FIX consumption	1156.3 IU Standard Deviation 1341.14	1688.9 IU Standard Deviation 1123.27	250.0 IU Standard Deviation NA Analysis population only included 1 participant, therefore, the standard deviation was not calculated.	1378.8 IU Standard Deviation 1291.66	1467.3 IU Standard Deviation 1318.28	1419.8 IU Standard Deviation 1192.62
Average Infusion Dose and Total Factor IX Consumption in Recovery Setting Average infusion dose	773.4 IU Standard Deviation 371.46	890.7 IU Standard Deviation 270.46	250.0 IU Standard Deviation NA Analysis population only included 1 participant, therefore, the standard deviation was not calculated.	889.9 IU Standard Deviation 502.77	962.0 IU Standard Deviation 556.45	929.1 IU Standard Deviation 475.75

SECONDARY outcome

Timeframe: Up to 6 months or 50 exposure days whichever occurred first

Population: All participants who had a bleed during the study for which on-demand treatment with BeneFIX was administered. Participants in each arm were not mutually exclusive.

Less than expected therapeutic effect (LETE) in the on-demand setting was defined as 2 successive "no response" ratings recorded after 2 successive BeneFIX drug infusions, respectively.

Outcome measures

Measure	Pediatric Participants <6 Years of Age n=96 Bleeding Episodes Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Pediatric Participants ≥6 to ≤12 Years of Age n=137 Bleeding Episodes Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Previously Untreated Participants (PUPs) n=16 Bleeding Episodes Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Participants Receiving Prophylaxis Treatment n=162 Bleeding Episodes Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first. This reporting arm included all participants who received prophylaxis treatment after enrollment in the study.	Severe Participants (Factor IX Activity <1%) n=198 Bleeding Episodes Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Overall Participants n=353 Bleeding Episodes Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first. This reporting arm included all participants who received at least 1 dose of BeneFIX during the study.
Percentage of Infusions With Less Than Expected Therapeutic Effects (LETEs) in On-demand Setting	0 percentage of infusions Interval 0.0 to 3.8	0 percentage of infusions Interval 0.0 to 2.7	0 percentage of infusions Interval 0.0 to 20.6	0 percentage of infusions Interval 0.0 to 2.3	0 percentage of infusions Interval 0.0 to 1.8	0 percentage of infusions Interval 0.0 to 1.0

SECONDARY outcome

Timeframe: Up to 6 months or 50 exposure days whichever occurred first

Population: All participants who received at least 1 dose of prophylaxis BeneFIX treatment during the study. Participants in each arm were not mutually exclusive.

Less than expected therapeutic effect (LETE) in the prophylaxis setting was defined as occurrence of any spontaneous bleed within 48 hours after a regularly scheduled prophylactic dose of BeneFIX (which was not used to treat a bleed).

Outcome measures

Measure	Pediatric Participants <6 Years of Age n=934 Prophylaxis Infusions Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Pediatric Participants ≥6 to ≤12 Years of Age n=1006 Prophylaxis Infusions Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Previously Untreated Participants (PUPs) n=287 Prophylaxis Infusions Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Participants Receiving Prophylaxis Treatment n=2032 Prophylaxis Infusions Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first. This reporting arm included all participants who received prophylaxis treatment after enrollment in the study.	Severe Participants (Factor IX Activity <1%) n=1069 Prophylaxis Infusions Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.	Overall Participants n=2032 Prophylaxis Infusions Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first. This reporting arm included all participants who received at least 1 dose of BeneFIX during the study.
Percentage of Infusions With Less Than Expected Therapeutic Effects (LETEs) in Prophylaxis Setting	0.1 percentage of infusions Interval 0.0 to 0.6	0.1 percentage of infusions Interval 0.0 to 0.6	0 percentage of infusions Interval 0.0 to 1.3	0.1 percentage of infusions Interval 0.0 to 0.4	0.2 percentage of infusions Interval 0.0 to 0.7	0.1 percentage of infusions Interval 0.0 to 0.4

Adverse Events

BeneFIX

Serious events: 2 serious events

Other events: 55 other events

Deaths: 0 deaths

Serious adverse events

Measure	BeneFIX n=70 participants at risk Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.
Blood and lymphatic system disorders Factor IX inhibition	1.4% 1/70 • Number of events 1 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Oral mucosa haematoma	1.4% 1/70 • Number of events 1 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.

Other adverse events

Measure	BeneFIX n=70 participants at risk Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first.
Gastrointestinal disorders Diarrhoea	7.1% 5/70 • Number of events 6 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
General disorders Peripheral swelling	8.6% 6/70 • Number of events 9 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
General disorders Pyrexia	15.7% 11/70 • Number of events 18 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Nasopharyngitis	27.1% 19/70 • Number of events 27 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Upper respiratory tract infection	7.1% 5/70 • Number of events 8 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Injury, poisoning and procedural complications Contusion	7.1% 5/70 • Number of events 7 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Injury, poisoning and procedural complications Fall	11.4% 8/70 • Number of events 10 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Musculoskeletal and connective tissue disorders Arthralgia	24.3% 17/70 • Number of events 76 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Musculoskeletal and connective tissue disorders Joint range of motion decreased	8.6% 6/70 • Number of events 20 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Musculoskeletal and connective tissue disorders Joint swelling	21.4% 15/70 • Number of events 32 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Musculoskeletal and connective tissue disorders Pain in extremity	10.0% 7/70 • Number of events 8 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Respiratory, thoracic and mediastinal disorders Cough	17.1% 12/70 • Number of events 14 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.

Additional Information

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Results disclosure agreements

• Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
• Publication restrictions are in place

Restriction type: OTHER