Trial Outcomes & Findings for BAX 326 (rFIX) Continuation Study (NCT NCT01286779)

NCT ID: NCT01286779

Last Updated: 2021-05-20

Results Overview

Possibly or probably related adverse events that occurred during or after first BAX326 infusion.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 117 participants
• Primary outcome timeframe: Assessed (based on patient diary) every 3 months until study completion (when BAX326 is licensed in the respective country or the participant has accumulated approximately 100 exposure days to BAX 326, whichever is last).
• Results posted on: 2021-05-20

Participant Flow

Enrollment was conducted at 40 clinical sites in 18 countries. A total of 117 participants were enrolled. Of these, 65 participants transitioned from BAX326 pivotal study, 20 participants transitioned from BAX326 pediatric study and 32 participants were newly recruited.

Of 117 enrolled participants, 115 received treatment with IP. All 85 participants who transitioned from the pivotal/pediatric studies continued to receive IP in this study. Of the 32 newly recruited participants, 30 received treatment with IP. 1 participant did not meet the entry criteria and 1 participant discontinued the study prior treatment.

Participant milestones

Measure	BAX 326 Participants treated with BAX 326
Overall Study STARTED	115
Overall Study COMPLETED	96
Overall Study NOT COMPLETED	19

Reasons for withdrawal

Measure	BAX 326 Participants treated with BAX 326
Overall Study Withdrawal by Subject	9
Overall Study Protocol Violation	5
Overall Study Physician Decision	2
Overall Study Participant had scheduled surgery	1
Overall Study Participant moved to another country	1
Overall Study Discontinued by sponsor	1

Baseline Characteristics

BAX 326 (rFIX) Continuation Study

Baseline characteristics by cohort

Measure	BAX 326 n=115 Participants Participants treated with BAX 326
Age, Continuous	29.6 years STANDARD_DEVIATION 16.39 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	115 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	99 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	1 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	10 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: Assessed (based on patient diary) every 3 months until study completion (when BAX326 is licensed in the respective country or the participant has accumulated approximately 100 exposure days to BAX 326, whichever is last).

Possibly or probably related adverse events that occurred during or after first BAX326 infusion.

Outcome measures

Measure	BAX 326 n=115 Participants Participants treated with BAX 326	Standard Prophylaxis Participants treated with BAX 326 with twice weekly prophylactic infusions of 50 IU/kg	Modified Prophylaxis Participants treated with BAX 326 with prophylactic treatment determined by the investigator. The dose could be increased up to 100 IU/kg if indicated.	PK Tailored Prophylaxis Participants treated with BAX 326 with PK tailored prophylaxis base on participant's individual PK with maximum dose of 120 IU/kg.	Overall Prophylaxis All participants who received BAX 326 as prophylactic regimen (standard prophylaxis, modified prophylaxis and PK-tailored prophylaxis)	On-Demand All participants who received BAX 326 as on-demand regimen.
Adverse Events Possibly or Probably Related to the Investigational Product	2 Adverse Events	—	—	—	—	—

SECONDARY outcome

Timeframe: Throughout the study from screening to study completion (when BAX326 is licensed in the respective country or the participant has accumulated approximately 100 exposure days to BAX 326, whichever is last).

Population: Only bleeding episodes that were exclusively treated with BAX 326 are considered.

Number of Infusions of BAX326 that were required until bleed resolution.

Outcome measures

Measure	BAX 326 n=1112 Bleeding episodes Participants treated with BAX 326	Standard Prophylaxis n=542 Bleeding episodes Participants treated with BAX 326 with twice weekly prophylactic infusions of 50 IU/kg	Modified Prophylaxis n=108 Bleeding episodes Participants treated with BAX 326 with prophylactic treatment determined by the investigator. The dose could be increased up to 100 IU/kg if indicated.	PK Tailored Prophylaxis n=8 Bleeding episodes Participants treated with BAX 326 with PK tailored prophylaxis base on participant's individual PK with maximum dose of 120 IU/kg.	Overall Prophylaxis n=658 Bleeding episodes All participants who received BAX 326 as prophylactic regimen (standard prophylaxis, modified prophylaxis and PK-tailored prophylaxis)	On-Demand n=454 Bleeding episodes All participants who received BAX 326 as on-demand regimen.
Treatment of Bleeding Episodes: Number of Infusions Per Bleeding Episode Required Until Bleed Resolution	1.8 Number of infusions Standard Deviation 1.65	2.1 Number of infusions Standard Deviation 2.12	1.9 Number of infusions Standard Deviation 1.41	1.3 Number of infusions Standard Deviation 0.46	2.0 Number of infusions Standard Deviation 2.01	1.5 Number of infusions Standard Deviation 0.79

SECONDARY outcome

Timeframe: Throughout the study from screening to study completion (when BAX326 is licensed in the respective country or the participant has accumulated approximately 100 exposure days to BAX 326, whichever is last).

Population: Only bleeding episodes that were exclusively treated with BAX 326 are considered.

Overall clinical efficacy rating of bleeding episodes was done at resolution of bleed according these rating scale: Excellent=Full relief of pain and cessation of objective signs of bleeding after a single infusion. No additional infusion is required for the control of bleeding. Administration of further infusion would not affect the scoring. Good=Definite pain relief and/or improvement in signs of bleeding after a single infusion. Possibly requires more than 1 infusion for complete resolution. Fair=Probable and/or slight relief of pain and slight improvement in signs of bleeding after a single infusion. Required more than 1 infusion for complete resolution. None=No improvement or condition worsens.

Outcome measures

Measure	BAX 326 n=1112 Bleeding Episodes Participants treated with BAX 326	Standard Prophylaxis n=542 Bleeding Episodes Participants treated with BAX 326 with twice weekly prophylactic infusions of 50 IU/kg	Modified Prophylaxis n=108 Bleeding Episodes Participants treated with BAX 326 with prophylactic treatment determined by the investigator. The dose could be increased up to 100 IU/kg if indicated.	PK Tailored Prophylaxis n=8 Bleeding Episodes Participants treated with BAX 326 with PK tailored prophylaxis base on participant's individual PK with maximum dose of 120 IU/kg.	Overall Prophylaxis n=658 Bleeding Episodes All participants who received BAX 326 as prophylactic regimen (standard prophylaxis, modified prophylaxis and PK-tailored prophylaxis)	On-Demand n=454 Bleeding Episodes All participants who received BAX 326 as on-demand regimen.
Treatment of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Resolution of Bleed Excellent	341 Number of infusions	168 Number of infusions	51 Number of infusions	0 Number of infusions	219 Number of infusions	122 Number of infusions
Treatment of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Resolution of Bleed Good	650 Number of infusions	281 Number of infusions	40 Number of infusions	0 Number of infusions	321 Number of infusions	329 Number of infusions
Treatment of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Resolution of Bleed Fair	115 Number of infusions	90 Number of infusions	17 Number of infusions	6 Number of infusions	113 Number of infusions	2 Number of infusions
Treatment of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Resolution of Bleed None	6 Number of infusions	3 Number of infusions	0 Number of infusions	2 Number of infusions	5 Number of infusions	1 Number of infusions

SECONDARY outcome

Timeframe: For prophylactic treatment the period from first to last prophylactic infusion is considered.

Population: Only participants with an observation period of at least 3 months with BAX326 on prophylactic treatment were included in the analysis.

Annualized bleed rate (ABR) was calculated as (number of bleeding episodes/observed treatment period in days)*365.25

Outcome measures

Measure	BAX 326 n=106 Participants Participants treated with BAX 326	Standard Prophylaxis n=22 Participants Participants treated with BAX 326 with twice weekly prophylactic infusions of 50 IU/kg	Modified Prophylaxis n=2 Participants Participants treated with BAX 326 with prophylactic treatment determined by the investigator. The dose could be increased up to 100 IU/kg if indicated.	PK Tailored Prophylaxis n=108 Participants Participants treated with BAX 326 with PK tailored prophylaxis base on participant's individual PK with maximum dose of 120 IU/kg.	Overall Prophylaxis All participants who received BAX 326 as prophylactic regimen (standard prophylaxis, modified prophylaxis and PK-tailored prophylaxis)	On-Demand All participants who received BAX 326 as on-demand regimen.
Annualized Bleed Rate During Prophylaxis Treatment	1.3 Bleeds per year Interval 0.0 to 78.7	1.4 Bleeds per year Interval 0.0 to 34.6	1.9 Bleeds per year Interval 0.5 to 3.3	1.3 Bleeds per year Interval 0.0 to 52.2	—	—

SECONDARY outcome

Timeframe: Throughout the study from screening to study completion (when BAX326 is licensed in the respective country or the participant has accumulated approximately 100 exposure days to BAX 326, whichever is last).

The number of infusions consumed per month and per year for the prophylactic and on-demand treatment regimens.

Outcome measures

Measure	BAX 326 n=108 Participants Participants treated with BAX 326	Standard Prophylaxis n=26 Participants Participants treated with BAX 326 with twice weekly prophylactic infusions of 50 IU/kg	Modified Prophylaxis n=3 Participants Participants treated with BAX 326 with prophylactic treatment determined by the investigator. The dose could be increased up to 100 IU/kg if indicated.	PK Tailored Prophylaxis n=110 Participants Participants treated with BAX 326 with PK tailored prophylaxis base on participant's individual PK with maximum dose of 120 IU/kg.	Overall Prophylaxis n=13 Participants All participants who received BAX 326 as prophylactic regimen (standard prophylaxis, modified prophylaxis and PK-tailored prophylaxis)	On-Demand All participants who received BAX 326 as on-demand regimen.
Consumption of BAX 326: Number of Infusions Per Month and Per Year Number of infusions per month	8.5 Number of infusions Standard Deviation 1.25	10.8 Number of infusions Standard Deviation 4.34	4.0 Number of infusions Standard Deviation 0.60	8.4 Number of infusions Standard Deviation 1.38	3.6 Number of infusions Standard Deviation 2.44	—
Consumption of BAX 326: Number of Infusions Per Month and Per Year Number of infusions per year	101.8 Number of infusions Standard Deviation 15.03	130.2 Number of infusions Standard Deviation 52.13	48.3 Number of infusions Standard Deviation 7.23	101.1 Number of infusions Standard Deviation 16.50	43.1 Number of infusions Standard Deviation 29.28	—

SECONDARY outcome

Timeframe: Throughout the study from screening to study completion (when BAX326 is licensed in the respective country or the participant has accumulated approximately 100 exposure days to BAX 326, whichever is last).

The weight adjusted consumption of BAX 326 per month and per year for the prophylactic and on-demand treatment regimens.

Outcome measures

Measure	BAX 326 n=108 Participants Participants treated with BAX 326	Standard Prophylaxis n=26 Participants Participants treated with BAX 326 with twice weekly prophylactic infusions of 50 IU/kg	Modified Prophylaxis n=3 Participants Participants treated with BAX 326 with prophylactic treatment determined by the investigator. The dose could be increased up to 100 IU/kg if indicated.	PK Tailored Prophylaxis n=110 Participants Participants treated with BAX 326 with PK tailored prophylaxis base on participant's individual PK with maximum dose of 120 IU/kg.	Overall Prophylaxis n=13 Participants All participants who received BAX 326 as prophylactic regimen (standard prophylaxis, modified prophylaxis and PK-tailored prophylaxis)	On-Demand All participants who received BAX 326 as on-demand regimen.
Consumption of BAX 326: Weight Adjusted Consumption Per Month and Per Year Weight adjusted BAX 326 consumption per month	462.3 IU/kg Standard Deviation 102.05	684.4 IU/kg Standard Deviation 337.70	250.9 IU/kg Standard Deviation 41.37	464.2 IU/kg Standard Deviation 111.46	199.8 IU/kg Standard Deviation 124.18	—
Consumption of BAX 326: Weight Adjusted Consumption Per Month and Per Year Weight adjusted BAX 326 consumption per year	5547.8 IU/kg Standard Deviation 1224.65	8212.4 IU/kg Standard Deviation 4052.36	3010.3 IU/kg Standard Deviation 496.44	5570.7 IU/kg Standard Deviation 1337.53	2397.4 IU/kg Standard Deviation 1490.22	—

SECONDARY outcome

Timeframe: Throughout the study from screening to study completion (when BAX326 is licensed in the respective country or the participant has accumulated approximately 100 exposure days to BAX 326, whichever is last).

The weight adjusted consumption of BAX 326 per bleeding episode for the prophylactic and on-demand treatment regimens. Only infusions required until the resolution of bleed are considered.

Outcome measures

Measure	BAX 326 n=542 Bleeding episodes Participants treated with BAX 326	Standard Prophylaxis n=109 Bleeding episodes Participants treated with BAX 326 with twice weekly prophylactic infusions of 50 IU/kg	Modified Prophylaxis n=8 Bleeding episodes Participants treated with BAX 326 with prophylactic treatment determined by the investigator. The dose could be increased up to 100 IU/kg if indicated.	PK Tailored Prophylaxis n=659 Bleeding episodes Participants treated with BAX 326 with PK tailored prophylaxis base on participant's individual PK with maximum dose of 120 IU/kg.	Overall Prophylaxis n=453 Bleeding episodes All participants who received BAX 326 as prophylactic regimen (standard prophylaxis, modified prophylaxis and PK-tailored prophylaxis)	On-Demand All participants who received BAX 326 as on-demand regimen.
Consumption of BAX326: Weight Adjusted Consumption Per Bleeding Episode	124.2 IU/kg Standard Deviation 140.70	114.8 IU/kg Standard Deviation 99.41	67.4 IU/kg Standard Deviation 34.39	122.0 IU/kg Standard Deviation 134.02	82.6 IU/kg Standard Deviation 48.21	—

SECONDARY outcome

Timeframe: Laboratory assessment for immunology were done at screening, at exposure day 1, at week 4 (± 1 week), at month 3 (±1 week), thereafter, every 3 months (± 1 week) and at study completion/termination.

Testing for inhibitory and total binding antibodies to Factor IX (FIX). Development during study means negative at screening and positive at any subsequent visit. Treatment emergent means more than 2-dilution increase as compared to the pre-study titer at screening.

Outcome measures

Measure	BAX 326 n=115 Participants Participants treated with BAX 326	Standard Prophylaxis Participants treated with BAX 326 with twice weekly prophylactic infusions of 50 IU/kg	Modified Prophylaxis Participants treated with BAX 326 with prophylactic treatment determined by the investigator. The dose could be increased up to 100 IU/kg if indicated.	PK Tailored Prophylaxis Participants treated with BAX 326 with PK tailored prophylaxis base on participant's individual PK with maximum dose of 120 IU/kg.	Overall Prophylaxis All participants who received BAX 326 as prophylactic regimen (standard prophylaxis, modified prophylaxis and PK-tailored prophylaxis)	On-Demand All participants who received BAX 326 as on-demand regimen.
Development of Inhibitory and Total Binding Antibodies to Factor IX Inhibitory antibodies to FIX-develop. during study	0 Participants	—	—	—	—	—
Development of Inhibitory and Total Binding Antibodies to Factor IX Inhibitory antibodies to FIX-treatment emergent	0 Participants	—	—	—	—	—
Development of Inhibitory and Total Binding Antibodies to Factor IX Total bind. antibodies to FIX-develop.during study	0 Participants	—	—	—	—	—
Development of Inhibitory and Total Binding Antibodies to Factor IX Total binding antibodies to FIX-treatment emergent	0 Participants	—	—	—	—	—

SECONDARY outcome

Timeframe: Laboratory assessment for immunology were done at screening, at exposure day 1, at week 4 (± 1 week), at month 3 (±1 week), thereafter, every 3 months (± 1 week) and at study completion/termination.

Testing for antibodies to CHO proteins and rFurin. Development during study means negative at screening and positive at any subsequent visit. Treatment emergent means more than 2-dilution increase as compared to the pre-study titer at screening.

Outcome measures

Measure	BAX 326 n=115 Participants Participants treated with BAX 326	Standard Prophylaxis Participants treated with BAX 326 with twice weekly prophylactic infusions of 50 IU/kg	Modified Prophylaxis Participants treated with BAX 326 with prophylactic treatment determined by the investigator. The dose could be increased up to 100 IU/kg if indicated.	PK Tailored Prophylaxis Participants treated with BAX 326 with PK tailored prophylaxis base on participant's individual PK with maximum dose of 120 IU/kg.	Overall Prophylaxis All participants who received BAX 326 as prophylactic regimen (standard prophylaxis, modified prophylaxis and PK-tailored prophylaxis)	On-Demand All participants who received BAX 326 as on-demand regimen.
Development of Antibodies to Chinese Hamster Ovary Proteins (CHO Proteins) and rFurin Antibodies to CHO - developed during study	0 Participants	—	—	—	—	—
Development of Antibodies to Chinese Hamster Ovary Proteins (CHO Proteins) and rFurin Antibodies to CHO - treatment emergent	0 Participants	—	—	—	—	—
Development of Antibodies to Chinese Hamster Ovary Proteins (CHO Proteins) and rFurin Antibodies to rFurin - developed during study	4 Participants	—	—	—	—	—
Development of Antibodies to Chinese Hamster Ovary Proteins (CHO Proteins) and rFurin Antibodies to rFurin - treatment emergent	4 Participants	—	—	—	—	—

SECONDARY outcome

Timeframe: Throughout the study from screening to study completion (when BAX326 is licensed in the respective country or the participant has accumulated approximately 100 exposure days to BAX 326, whichever is last).

The occurrence of severe allergic reactions and thrombotic events was assessed.

Outcome measures

Measure	BAX 326 n=115 Participants Participants treated with BAX 326	Standard Prophylaxis Participants treated with BAX 326 with twice weekly prophylactic infusions of 50 IU/kg	Modified Prophylaxis Participants treated with BAX 326 with prophylactic treatment determined by the investigator. The dose could be increased up to 100 IU/kg if indicated.	PK Tailored Prophylaxis Participants treated with BAX 326 with PK tailored prophylaxis base on participant's individual PK with maximum dose of 120 IU/kg.	Overall Prophylaxis All participants who received BAX 326 as prophylactic regimen (standard prophylaxis, modified prophylaxis and PK-tailored prophylaxis)	On-Demand All participants who received BAX 326 as on-demand regimen.
Occurrence of Severe Allergic Reactions and Thrombotic Events Severe allergic reactions	0 Participants	—	—	—	—	—
Occurrence of Severe Allergic Reactions and Thrombotic Events Thrombotic events	0 Participants	—	—	—	—	—

SECONDARY outcome

Timeframe: Measurements at screening and at study completion/termination are included in the analysis.

Hematology panel consists of complete blood count (hemoglobin, hematocrit, erythrocytes, leukocytes) with differential (ie, basophils, eosinophils, lymphocytes, monocytes, neutrophils), mean corpuscular volume, mean corpuscular hemoglobin concentration and platelet count. Clinical chemistry panel consists of sodium, potassium, chloride, bicarbonate, total protein, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, alkaline phosphatase, blood urea nitrogen, creatinine and glucose. Vital signs include body temperature, respiratory rate, pulse rate, supine systolic and diastolic blood pressure. CS=clinically significant, NCS=not clinically significant. Change from Screening to End of Study is reported.

Outcome measures

Measure	BAX 326 n=115 Participants Participants treated with BAX 326	Standard Prophylaxis Participants treated with BAX 326 with twice weekly prophylactic infusions of 50 IU/kg	Modified Prophylaxis Participants treated with BAX 326 with prophylactic treatment determined by the investigator. The dose could be increased up to 100 IU/kg if indicated.	PK Tailored Prophylaxis Participants treated with BAX 326 with PK tailored prophylaxis base on participant's individual PK with maximum dose of 120 IU/kg.	Overall Prophylaxis All participants who received BAX 326 as prophylactic regimen (standard prophylaxis, modified prophylaxis and PK-tailored prophylaxis)	On-Demand All participants who received BAX 326 as on-demand regimen.
Clinical Significant Changes in Routine Laboratory Parameters and Vital Signs Hematology: Change from normal to abnormal CS	2 Participants	—	—	—	—	—
Clinical Significant Changes in Routine Laboratory Parameters and Vital Signs Hematology:Change from abnormal NCS to abnormal CS	1 Participants	—	—	—	—	—
Clinical Significant Changes in Routine Laboratory Parameters and Vital Signs Chemistry: Change from normal to abnormal, CS	1 Participants	—	—	—	—	—
Clinical Significant Changes in Routine Laboratory Parameters and Vital Signs Chemistry: Change from abnormal NCS to abnormal CS	3 Participants	—	—	—	—	—
Clinical Significant Changes in Routine Laboratory Parameters and Vital Signs Change in vital signs	0 Participants	—	—	—	—	—

SECONDARY outcome

Timeframe: IR over time was measured as Baseline and at Completion/Termination visit within 30 minutes pre-infusion and at 30 (± 5) minutes post-infusion.

Population: Analysis was done on all participants who received investigational product. All cases with a dosage higher than 120 IU/kg were excluded from the analysis.

PK infusion with investigational product was administered after a wash out period of at least 5 days. Incremental recovery is calculated as IR30min = (C30min [IU/dL] - Cpre-infusion [IU/dL]) / dose per kg body weight [IU/kg] where C30min and Cpre-infusion relate to the unadjusted concentration values.

Outcome measures

Measure	BAX 326 n=115 Participants Participants treated with BAX 326	Standard Prophylaxis Participants treated with BAX 326 with twice weekly prophylactic infusions of 50 IU/kg	Modified Prophylaxis Participants treated with BAX 326 with prophylactic treatment determined by the investigator. The dose could be increased up to 100 IU/kg if indicated.	PK Tailored Prophylaxis Participants treated with BAX 326 with PK tailored prophylaxis base on participant's individual PK with maximum dose of 120 IU/kg.	Overall Prophylaxis All participants who received BAX 326 as prophylactic regimen (standard prophylaxis, modified prophylaxis and PK-tailored prophylaxis)	On-Demand All participants who received BAX 326 as on-demand regimen.
Pharmacokinetics: Incremental Recovery (IR) Over Time Baseline	0.85 (IU/dL):(IU/kg) Standard Deviation 0.207	—	—	—	—	—
Pharmacokinetics: Incremental Recovery (IR) Over Time End of Study	0.85 (IU/dL):(IU/kg) Standard Deviation 0.286	—	—	—	—	—
Pharmacokinetics: Incremental Recovery (IR) Over Time Change from baseline to end of study	-0.005 (IU/dL):(IU/kg) Standard Deviation 0.259	—	—	—	—	—

SECONDARY outcome

Timeframe: PK assessments were done within 30 minutes pre-infusion and post-infusion at 30 (± 5) minutes, 9 hours (± 30 minutes), 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours

Population: The pharmacokinetic analysis set comprises all participants who underwent an abbreviated PK study.

After a wash out period of at least 5 days PK infusion with investigational product was administered. AUC 0-∞ is defined as AUC 0-t + Ct/lambda z, where t is the time of last quantifiable concentration, Ct is the last quantifiable concentration.

Outcome measures

Measure	BAX 326 n=6 Participants Participants treated with BAX 326	Standard Prophylaxis Participants treated with BAX 326 with twice weekly prophylactic infusions of 50 IU/kg	Modified Prophylaxis Participants treated with BAX 326 with prophylactic treatment determined by the investigator. The dose could be increased up to 100 IU/kg if indicated.	PK Tailored Prophylaxis Participants treated with BAX 326 with PK tailored prophylaxis base on participant's individual PK with maximum dose of 120 IU/kg.	Overall Prophylaxis All participants who received BAX 326 as prophylactic regimen (standard prophylaxis, modified prophylaxis and PK-tailored prophylaxis)	On-Demand All participants who received BAX 326 as on-demand regimen.
Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity (AUC 0-∞)	1335.56 IU*hr/dL Standard Deviation 299.83	—	—	—	—	—

SECONDARY outcome

Timeframe: PK assessments were done within 30 minutes pre-infusion and post-infusion at 30 (± 5) minutes, 9 hours (± 30 minutes), 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours

Population: The pharmacokinetic analysis set comprises all participants who underwent an abbreviated PK study.

PK infusion with investigational product was administered after a wash out period of at least 5 days. Elimination phase half-life is calculated as T1/2=log e (2) / lambda z where the elimination rate constant (lambda z) will be obtained by log e - linear fitting using least squares deviation to at least the last 3 quantifiable concentrations above pre-infusion level.

Outcome measures

Measure	BAX 326 n=6 Participants Participants treated with BAX 326	Standard Prophylaxis Participants treated with BAX 326 with twice weekly prophylactic infusions of 50 IU/kg	Modified Prophylaxis Participants treated with BAX 326 with prophylactic treatment determined by the investigator. The dose could be increased up to 100 IU/kg if indicated.	PK Tailored Prophylaxis Participants treated with BAX 326 with PK tailored prophylaxis base on participant's individual PK with maximum dose of 120 IU/kg.	Overall Prophylaxis All participants who received BAX 326 as prophylactic regimen (standard prophylaxis, modified prophylaxis and PK-tailored prophylaxis)	On-Demand All participants who received BAX 326 as on-demand regimen.
Pharmacokinetics: Elimination Phase Half-life (T1/2)	28.52 hours Standard Deviation 4.12	—	—	—	—	—

SECONDARY outcome

Timeframe: PK assessments were done within 30 minutes pre-infusion and post-infusion at 30 (± 5) minutes, 9 hours (± 30 minutes), 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours

Population: The pharmacokinetic analysis set comprises all participants who underwent an abbreviated PK study.

PK infusion with investigational product was administered after a wash out period of at least 5 days. Mean residence time is calculated as total area under the moment curve divided by the total area under the curve. MRT=(AUMC0-∞[h2*IU/dL])/(AUC0-∞[h*IU/dL]) - TI/2 where AUMC0-∞ is determined in a similar manner as AUC0-∞ and TI represents infusion duration in hours.

Outcome measures

Measure	BAX 326 n=6 Participants Participants treated with BAX 326	Standard Prophylaxis Participants treated with BAX 326 with twice weekly prophylactic infusions of 50 IU/kg	Modified Prophylaxis Participants treated with BAX 326 with prophylactic treatment determined by the investigator. The dose could be increased up to 100 IU/kg if indicated.	PK Tailored Prophylaxis Participants treated with BAX 326 with PK tailored prophylaxis base on participant's individual PK with maximum dose of 120 IU/kg.	Overall Prophylaxis All participants who received BAX 326 as prophylactic regimen (standard prophylaxis, modified prophylaxis and PK-tailored prophylaxis)	On-Demand All participants who received BAX 326 as on-demand regimen.
Pharmacokinetics: Mean Residence Time (MRT)	29.97 hours Standard Deviation 2.72	—	—	—	—	—

SECONDARY outcome

Timeframe: PK assessments were done within 30 minutes pre-infusion and post-infusion at 30 (± 5) minutes, 9 hours (± 30 minutes), 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours

Population: The pharmacokinetic analysis set comprises all participants who underwent an abbreviated PK study.

PK infusion with investigational product was administered after a wash out period of at least 5 days. Systemic clearance is balculated as the dose in IU/kg divided by the total AUC. CL= Dose[IU/kg] / AUC0-∞[h*IU/dL]

Outcome measures

Measure	BAX 326 n=6 Participants Participants treated with BAX 326	Standard Prophylaxis Participants treated with BAX 326 with twice weekly prophylactic infusions of 50 IU/kg	Modified Prophylaxis Participants treated with BAX 326 with prophylactic treatment determined by the investigator. The dose could be increased up to 100 IU/kg if indicated.	PK Tailored Prophylaxis Participants treated with BAX 326 with PK tailored prophylaxis base on participant's individual PK with maximum dose of 120 IU/kg.	Overall Prophylaxis All participants who received BAX 326 as prophylactic regimen (standard prophylaxis, modified prophylaxis and PK-tailored prophylaxis)	On-Demand All participants who received BAX 326 as on-demand regimen.
Pharmacokinetics: Systemic Clearance (CL)	0.06 dL/kg/hours Standard Deviation 0.014	—	—	—	—	—

SECONDARY outcome

Timeframe: PK assessments were done within 30 minutes pre-infusion and post-infusion at 30 (± 5) minutes, 9 hours (± 30 minutes), 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours

Population: The pharmacokinetic analysis set comprises all participants who underwent an abbreviated PK study.

PK infusion with investigational product was administered after a wash out period of at least 5 days. Apparent steady state volume of distribution is calculated as Vss = CL * MRT CL=Systemic Clearance and MRT=Mean residence time

Outcome measures

Measure	BAX 326 n=6 Participants Participants treated with BAX 326	Standard Prophylaxis Participants treated with BAX 326 with twice weekly prophylactic infusions of 50 IU/kg	Modified Prophylaxis Participants treated with BAX 326 with prophylactic treatment determined by the investigator. The dose could be increased up to 100 IU/kg if indicated.	PK Tailored Prophylaxis Participants treated with BAX 326 with PK tailored prophylaxis base on participant's individual PK with maximum dose of 120 IU/kg.	Overall Prophylaxis All participants who received BAX 326 as prophylactic regimen (standard prophylaxis, modified prophylaxis and PK-tailored prophylaxis)	On-Demand All participants who received BAX 326 as on-demand regimen.
Pharmacokinetics: Volume of Distribution at Steady State (Vss)	1.78 dL/kg Standard Deviation 0.42	—	—	—	—	—

SECONDARY outcome

Timeframe: PK assessments were done within 30 minutes pre-infusion and post-infusion at 30 (± 5) minutes, 9 hours (± 30 minutes), 24 (± 2) hours, 48 (± 2) hours and 72 (± 2) hours.

Population: The pharmacokinetic analysis set comprises all participants who underwent an abbreviated PK study.

PK infusion with investigational product was administered after a wash out period of at least 5 days. Incremental recovery is calculated as IR30min = (C30min [IU/dL] - Cpre-infusion [IU/dL]) / dose per kg body weight [IU/kg] where C30min and Cpre-infusion relate to the unadjusted concentration values.

Outcome measures

Measure	BAX 326 n=6 Participants Participants treated with BAX 326	Standard Prophylaxis Participants treated with BAX 326 with twice weekly prophylactic infusions of 50 IU/kg	Modified Prophylaxis Participants treated with BAX 326 with prophylactic treatment determined by the investigator. The dose could be increased up to 100 IU/kg if indicated.	PK Tailored Prophylaxis Participants treated with BAX 326 with PK tailored prophylaxis base on participant's individual PK with maximum dose of 120 IU/kg.	Overall Prophylaxis All participants who received BAX 326 as prophylactic regimen (standard prophylaxis, modified prophylaxis and PK-tailored prophylaxis)	On-Demand All participants who received BAX 326 as on-demand regimen.
Pharmacokinetics: Incremental Recovery (IR)	0.85 (IU/dL):(IU/kg) Standard Deviation 0.196	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline at exposure day 1 and at study completion/termination.

Population: Only newly recruited participants are included as baseline values were not reported for transitioning participants. Only subjects how received prophylaxis treatment are included.

The Short Form (36) Health Survey (SF-36) is a 36-item validated, generic HR QoL instrument suitable for participants of 17 years of age or older. The SF-36 consists of eight scaled scores (vitality, physical functioning, bodily pain, general health, mental health, physical role functioning, emotional role functioning, social role functioning) which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability. The mental health component summary score ranged from 19.5 to 64.2 with higher scores indicating less disability. The physical health component summary scores ranged from 18.6 to 59.6 with higher scores indicating less disability.

Outcome measures

Measure	BAX 326 n=24 Participants Participants treated with BAX 326	Standard Prophylaxis Participants treated with BAX 326 with twice weekly prophylactic infusions of 50 IU/kg	Modified Prophylaxis Participants treated with BAX 326 with prophylactic treatment determined by the investigator. The dose could be increased up to 100 IU/kg if indicated.	PK Tailored Prophylaxis Participants treated with BAX 326 with PK tailored prophylaxis base on participant's individual PK with maximum dose of 120 IU/kg.	Overall Prophylaxis All participants who received BAX 326 as prophylactic regimen (standard prophylaxis, modified prophylaxis and PK-tailored prophylaxis)	On-Demand All participants who received BAX 326 as on-demand regimen.
Changes in Health Related Quality of Life (HR QoL) Based on Questionnaire SF-36 SF-36 Bodily Pain	6.7 Score on a scale Standard Deviation 12.66	—	—	—	—	—
Changes in Health Related Quality of Life (HR QoL) Based on Questionnaire SF-36 SF-36 General Health	3.2 Score on a scale Standard Deviation 9.32	—	—	—	—	—
Changes in Health Related Quality of Life (HR QoL) Based on Questionnaire SF-36 SF-36 Mental Health	0.7 Score on a scale Standard Deviation 14.72	—	—	—	—	—
Changes in Health Related Quality of Life (HR QoL) Based on Questionnaire SF-36 SF-36 Mental Health Component Score	0.8 Score on a scale Standard Deviation 12.08	—	—	—	—	—
Changes in Health Related Quality of Life (HR QoL) Based on Questionnaire SF-36 SF-36 Physical Functioning	4.2 Score on a scale Standard Deviation 10.46	—	—	—	—	—
Changes in Health Related Quality of Life (HR QoL) Based on Questionnaire SF-36 SF-36 Physical Health Component Score	5.7 Score on a scale Standard Deviation 8.43	—	—	—	—	—
Changes in Health Related Quality of Life (HR QoL) Based on Questionnaire SF-36 SF-36 Role-Emotional	2.3 Score on a scale Standard Deviation 11.57	—	—	—	—	—
Changes in Health Related Quality of Life (HR QoL) Based on Questionnaire SF-36 SF-36 Role-Physical	4.5 Score on a scale Standard Deviation 10.28	—	—	—	—	—
Changes in Health Related Quality of Life (HR QoL) Based on Questionnaire SF-36 SF-36 Social Functioning	4.5 Score on a scale Standard Deviation 11.67	—	—	—	—	—
Changes in Health Related Quality of Life (HR QoL) Based on Questionnaire SF-36 SF-36 Vitality	2.0 Score on a scale Standard Deviation 8.87	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline at exposure day 1 and at study completion/termination.

Population: Only newly recruited participants are included as baseline values were not reported for transitioning participants. Only subjects how received prophylaxis treatment are included.

The Pediatric Quality of Life Inventory (Peds QL) is a generic health related quality of life instrument designed specifically for a pediatric population and captures following domains: physical functioning, emotional functioning, social functioning and school functioning. The Peds-QL total score consist of all 23 items of all domains. Score range from 0-100 and higher scores indicate better quality of life (collected scores ranged from 44.6 to 98.9). The Peds-QL Physical Health Summary score consists of 8 items from the physical functioning domain. Score range from 0-100 and higher scores indicate better quality of life (collected scores ranged from 40.6 to 100.0) The Psychosocial Health Summary score consists of 15 items from the emotional, social and school functioning domains. Score range from 0 to 100 and higher scores indicate better quality of life (collected scores ranged from 46.7 to 100.0).

Outcome measures

Measure	BAX 326 n=4 Participants Participants treated with BAX 326	Standard Prophylaxis Participants treated with BAX 326 with twice weekly prophylactic infusions of 50 IU/kg	Modified Prophylaxis Participants treated with BAX 326 with prophylactic treatment determined by the investigator. The dose could be increased up to 100 IU/kg if indicated.	PK Tailored Prophylaxis Participants treated with BAX 326 with PK tailored prophylaxis base on participant's individual PK with maximum dose of 120 IU/kg.	Overall Prophylaxis All participants who received BAX 326 as prophylactic regimen (standard prophylaxis, modified prophylaxis and PK-tailored prophylaxis)	On-Demand All participants who received BAX 326 as on-demand regimen.
Changes in Health Related Quality of Life Using the Peds QL Peds-QL Physical Health Summary Score	-2.3 Score on a scale Standard Deviation 18.47	—	—	—	—	—
Changes in Health Related Quality of Life Using the Peds QL Peds-QL Psychosocial Health Summary Score	3.8 Score on a scale Standard Deviation 5.99	—	—	—	—	—
Changes in Health Related Quality of Life Using the Peds QL Peds-QL Total Score	1.6 Score on a scale Standard Deviation 10.14	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline at exposure day 1 and at study completion/termination.

Population: Only newly recruited participants are included as baseline values were not reported for transitioning participants. Only subjects how received prophylaxis treatment are included.

The Hemophilia Quality of Life Questionnaire (Haemo-QoL) and the Hemophilia Quality of Life Questionnaire for Adults (Haem-A-Qol) instruments have been developed and used in hemophilia A patients. As a hemophilia-specific instrument, this measure assesses very specific aspects of dealing with hemophilia. The areas covered by this instrument are: physical health, sports/leisure, school/work, dealing with hemophilia, and outlook for the future. Haemo-QoL is used for participants aged 8 to 16 years and total scores range from 0 to 100 with higher scores indicating low quality of life (collected scores ranged from 0.0 to 44.3) Haem-A-QoL is used for participants aged 17 years and older and total scores range from 0 to 100 with higher scores indicating low quality of life (collected scores ranged from 4.9 to 76.8).

Outcome measures

Measure	BAX 326 n=16 Participants Participants treated with BAX 326	Standard Prophylaxis Participants treated with BAX 326 with twice weekly prophylactic infusions of 50 IU/kg	Modified Prophylaxis Participants treated with BAX 326 with prophylactic treatment determined by the investigator. The dose could be increased up to 100 IU/kg if indicated.	PK Tailored Prophylaxis Participants treated with BAX 326 with PK tailored prophylaxis base on participant's individual PK with maximum dose of 120 IU/kg.	Overall Prophylaxis All participants who received BAX 326 as prophylactic regimen (standard prophylaxis, modified prophylaxis and PK-tailored prophylaxis)	On-Demand All participants who received BAX 326 as on-demand regimen.
Changes in Health Related Quality of Life (HR QoL) Based on Questionnaire Haemo-QoL and Haem-A-QoL Haem-A-QoL Total Score	-3.0 Score on a scale Standard Deviation 9.45	—	—	—	—	—
Changes in Health Related Quality of Life (HR QoL) Based on Questionnaire Haemo-QoL and Haem-A-QoL Haemo-QoL Total Score	-0.7 Score on a scale Standard Deviation NA only 1 participant analyzed	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline at exposure day 1 and at study completion/termination.

Population: Only newly recruited participants are included as baseline values were not reported for transitioning participants. Only subjects how received prophylaxis treatment are included.

The EQ-5D captures overall HR QoL (phyiscal, mental and social functioning). A health utility score can be calculated from this measure, adult and proxy versions available. EQ-5D Visual Analog Scale (EQ-5D VAS):Respondents specify their level of agreement to a statement by indicating a position along a continuous line between two endpoints (scale range from 0 to 100). Score 0 corresponds to the worst health you can imagine and score 100 corresponds to the best health you can imagine (collected scores ranged from 10-100). EQ-5D Total Index is based on general population valuation surveys. Responses to 5 questions are converted to an Index value and score range from 0 to 1, with higher scores indicating better quality of life. Total Index was derived on US population (collected scores ranged from 0.4-1). General pain assessment (Pain score) is done through a visual analog scale (VAS), scores ranging from 0 to 100 with higher scores indicating more pain (collected scores ranged 0-87).

Outcome measures

Measure	BAX 326 n=26 Participants Participants treated with BAX 326	Standard Prophylaxis Participants treated with BAX 326 with twice weekly prophylactic infusions of 50 IU/kg	Modified Prophylaxis Participants treated with BAX 326 with prophylactic treatment determined by the investigator. The dose could be increased up to 100 IU/kg if indicated.	PK Tailored Prophylaxis Participants treated with BAX 326 with PK tailored prophylaxis base on participant's individual PK with maximum dose of 120 IU/kg.	Overall Prophylaxis All participants who received BAX 326 as prophylactic regimen (standard prophylaxis, modified prophylaxis and PK-tailored prophylaxis)	On-Demand All participants who received BAX 326 as on-demand regimen.
Changes in Health Related Quality of Life (HR QoL) Based on Questionnaire EQ-5D and Pain Score. EQ-5D Total Index	0.0 Score on a scale Standard Deviation 0.13	—	—	—	—	—
Changes in Health Related Quality of Life (HR QoL) Based on Questionnaire EQ-5D and Pain Score. EQ-5D VAS	5.1 Score on a scale Standard Deviation 21.75	—	—	—	—	—
Changes in Health Related Quality of Life (HR QoL) Based on Questionnaire EQ-5D and Pain Score. Pain Score	-8.0 Score on a scale Standard Deviation 36.62	—	—	—	—	—

Adverse Events

BAX 326

Serious events: 9 serious events

Other events: 63 other events

Deaths: 0 deaths

Serious adverse events

Measure	BAX 326 n=115 participants at risk Participants treated with BAX 326
Gastrointestinal disorders Abdominal pain	0.87% 1/115 • Number of events 1 • Throughout the entire study period from screening to completion/termination. Overall 6 years and 2 months. For each participant the duration of study depended on when the participant has accumulated a total of 100 exposure days during the course of the pivotal/pediatric studies and this study.
Gastrointestinal disorders Duodenal ulcer hemorrhage	0.87% 1/115 • Number of events 1 • Throughout the entire study period from screening to completion/termination. Overall 6 years and 2 months. For each participant the duration of study depended on when the participant has accumulated a total of 100 exposure days during the course of the pivotal/pediatric studies and this study.
Infections and infestations Corneal abscess	0.87% 1/115 • Number of events 1 • Throughout the entire study period from screening to completion/termination. Overall 6 years and 2 months. For each participant the duration of study depended on when the participant has accumulated a total of 100 exposure days during the course of the pivotal/pediatric studies and this study.
Injury, poisoning and procedural complications Brain contusion	0.87% 1/115 • Number of events 1 • Throughout the entire study period from screening to completion/termination. Overall 6 years and 2 months. For each participant the duration of study depended on when the participant has accumulated a total of 100 exposure days during the course of the pivotal/pediatric studies and this study.
Injury, poisoning and procedural complications Extradural hematoma	0.87% 1/115 • Number of events 1 • Throughout the entire study period from screening to completion/termination. Overall 6 years and 2 months. For each participant the duration of study depended on when the participant has accumulated a total of 100 exposure days during the course of the pivotal/pediatric studies and this study.
Injury, poisoning and procedural complications Head injury	0.87% 1/115 • Number of events 1 • Throughout the entire study period from screening to completion/termination. Overall 6 years and 2 months. For each participant the duration of study depended on when the participant has accumulated a total of 100 exposure days during the course of the pivotal/pediatric studies and this study.
Injury, poisoning and procedural complications Scroctal haematoma	0.87% 1/115 • Number of events 1 • Throughout the entire study period from screening to completion/termination. Overall 6 years and 2 months. For each participant the duration of study depended on when the participant has accumulated a total of 100 exposure days during the course of the pivotal/pediatric studies and this study.
Nervous system disorders Seizure	0.87% 1/115 • Number of events 1 • Throughout the entire study period from screening to completion/termination. Overall 6 years and 2 months. For each participant the duration of study depended on when the participant has accumulated a total of 100 exposure days during the course of the pivotal/pediatric studies and this study.
Nervous system disorders Transient ischaemic attack	0.87% 1/115 • Number of events 1 • Throughout the entire study period from screening to completion/termination. Overall 6 years and 2 months. For each participant the duration of study depended on when the participant has accumulated a total of 100 exposure days during the course of the pivotal/pediatric studies and this study.
Renal and urinary disorders Haematuria	0.87% 1/115 • Number of events 3 • Throughout the entire study period from screening to completion/termination. Overall 6 years and 2 months. For each participant the duration of study depended on when the participant has accumulated a total of 100 exposure days during the course of the pivotal/pediatric studies and this study.
Renal and urinary disorders Renal colic	1.7% 2/115 • Number of events 3 • Throughout the entire study period from screening to completion/termination. Overall 6 years and 2 months. For each participant the duration of study depended on when the participant has accumulated a total of 100 exposure days during the course of the pivotal/pediatric studies and this study.
Reproductive system and breast disorders Testicular appendage torsion	0.87% 1/115 • Number of events 1 • Throughout the entire study period from screening to completion/termination. Overall 6 years and 2 months. For each participant the duration of study depended on when the participant has accumulated a total of 100 exposure days during the course of the pivotal/pediatric studies and this study.

Other adverse events

Measure	BAX 326 n=115 participants at risk Participants treated with BAX 326
General disorders Pyrexia	12.2% 14/115 • Number of events 23 • Throughout the entire study period from screening to completion/termination. Overall 6 years and 2 months. For each participant the duration of study depended on when the participant has accumulated a total of 100 exposure days during the course of the pivotal/pediatric studies and this study.
Infections and infestations Bronchitis	5.2% 6/115 • Number of events 8 • Throughout the entire study period from screening to completion/termination. Overall 6 years and 2 months. For each participant the duration of study depended on when the participant has accumulated a total of 100 exposure days during the course of the pivotal/pediatric studies and this study.
Infections and infestations Influenza	7.0% 8/115 • Number of events 8 • Throughout the entire study period from screening to completion/termination. Overall 6 years and 2 months. For each participant the duration of study depended on when the participant has accumulated a total of 100 exposure days during the course of the pivotal/pediatric studies and this study.
Infections and infestations Nasopharyngitis	21.7% 25/115 • Number of events 55 • Throughout the entire study period from screening to completion/termination. Overall 6 years and 2 months. For each participant the duration of study depended on when the participant has accumulated a total of 100 exposure days during the course of the pivotal/pediatric studies and this study.
Infections and infestations Pharyngitis	5.2% 6/115 • Number of events 8 • Throughout the entire study period from screening to completion/termination. Overall 6 years and 2 months. For each participant the duration of study depended on when the participant has accumulated a total of 100 exposure days during the course of the pivotal/pediatric studies and this study.
Infections and infestations Rhinitis	7.0% 8/115 • Number of events 15 • Throughout the entire study period from screening to completion/termination. Overall 6 years and 2 months. For each participant the duration of study depended on when the participant has accumulated a total of 100 exposure days during the course of the pivotal/pediatric studies and this study.
Infections and infestations Upper respiratory tract infection	9.6% 11/115 • Number of events 17 • Throughout the entire study period from screening to completion/termination. Overall 6 years and 2 months. For each participant the duration of study depended on when the participant has accumulated a total of 100 exposure days during the course of the pivotal/pediatric studies and this study.
Musculoskeletal and connective tissue disorders Arthralgia	13.0% 15/115 • Number of events 48 • Throughout the entire study period from screening to completion/termination. Overall 6 years and 2 months. For each participant the duration of study depended on when the participant has accumulated a total of 100 exposure days during the course of the pivotal/pediatric studies and this study.
Nervous system disorders Headache	7.0% 8/115 • Number of events 20 • Throughout the entire study period from screening to completion/termination. Overall 6 years and 2 months. For each participant the duration of study depended on when the participant has accumulated a total of 100 exposure days during the course of the pivotal/pediatric studies and this study.
Respiratory, thoracic and mediastinal disorders Cough	9.6% 11/115 • Number of events 15 • Throughout the entire study period from screening to completion/termination. Overall 6 years and 2 months. For each participant the duration of study depended on when the participant has accumulated a total of 100 exposure days during the course of the pivotal/pediatric studies and this study.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.2% 6/115 • Number of events 6 • Throughout the entire study period from screening to completion/termination. Overall 6 years and 2 months. For each participant the duration of study depended on when the participant has accumulated a total of 100 exposure days during the course of the pivotal/pediatric studies and this study.
Vascular disorders Hypertension	5.2% 6/115 • Number of events 6 • Throughout the entire study period from screening to completion/termination. Overall 6 years and 2 months. For each participant the duration of study depended on when the participant has accumulated a total of 100 exposure days during the course of the pivotal/pediatric studies and this study.

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: ClinicalTransparency@shire.com

Results disclosure agreements

• Principal investigator is a sponsor employee Agreements may vary with individual PIs, but contain common elements. For this study, PIs are restricted from independently publishing results until the earlier of the primary multicenter publication or up to 2 years after study completion. The sponsor requires a review of results communication (e .g. for confidential information) ≥ 60 days prior to submission and may request an additional delay up to 6 months (e .g. for intellectual property protection). Prior authorization may be required.
• Publication restrictions are in place

Restriction type: OTHER