pathfinder8: A Research Study Looking at How a Factor VIII Medicine Called Turoctocog Alfa Pegol (N8-GP) Works in People With Haemophilia A

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03528551
• Collaborator: (none)
• Enrollment: 160
• Locations: 67
• Arms: 3
• Actual Duration (Months): 31.1
• Patients Per Site: 2.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study will look at how a known study medicine N8-GP works in previously N8-GP treated people with haemophilia A. The aim is to look at how N8-GP works during regular use. Participants will get N8-GP. N8-GP has been tested in more than 200 people with haemophilia A for several years. Participants will get an injection of N8-GP into a blood vessel, one, two or three times weekly. Participants will get more doses if they bleed or if they will need a surgery. The study will last for about 2 years. Participants will have at least 9 visits with the study doctor. If participants agree to be in this study, they will get their first injection (in this study) at the first visit. Participants will also get an injection at visit 3, 5 and 7. Participants will be trained to give all other injections themselves. Participants must not use any clotting factors other than N8-GP or any anticoagulants (blood thinners) during the study.

Condition or Disease	Intervention/Treatment	Phase
Congenital Bleeding Disorder; Haemophilia A	Drug: Turoctocog alfa pegol; Drug: Turoctocog alfa pegol; Drug: Turoctocog alfa pegol	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 160 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Safety and Efficacy of Turoctocog Alfa Pegol (N8-GP) in Prophylaxis and Treatment of Bleeds in Previously N8-GP Treated Patients With Severe Haemophilia A
• Actual Study Start Date: Apr 30, 2018
• Actual Primary Completion Date: Dec 3, 2020
• Actual Study Completion Date: Dec 3, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: N8-GP, once weekly All participants will receive turoctocog alfa pegol (N8-GP) once weekly.	Drug: Turoctocog alfa pegol; Turoctocog alfa pegol 75 IU/kg body weight will be administered once weekly as intravenous injections for a duration of 2 years.
Experimental: N8-GP, twice weekly All participants will receive N8-GP twice weekly.	Drug: Turoctocog alfa pegol; Turoctocog alfa pegol 60 IU/kg body weight (for patients younger than 12 years) and 50 IU/kg body weight (for patients, 12 years or older) will be administered twice weekly as intravenous injections for a duration of 2 years.
Experimental: N8-GP, three times weekly All participants will receive N8-GP three times weekly.	Drug: Turoctocog alfa pegol; Turoctocog alfa pegol 50 IU/kg body weight will be administered three times weekly as intravenous injections for a duration of 2 years.

Outcome Measures

Primary Outcome Measures

1. Number of Adverse Events Reported [Week 0 to week 108]

   An adverse event (AE) was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. All AEs mentioned here are treatment emergent adverse events (TEAEs). The TEAE is defined as an event reported from date of first trial product administration until end of the treatment visit (week 104) or follow-up visit if relevant (1 month after end of the treatment).

Secondary Outcome Measures

1. Number of Participants With Inhibitory Antibodies Against Coagulation Factor VIII (FVIII) ≥0.6 Bethesda Units (BU) [Week 0 to week 104]

   The Incidence of inhibitors against coagulation factor eight (FVIII) is defined as titre greater than or equal to (≥) 0.6 Bethesda unit. The inhibitor antibodies were measured using a heat modified Nijmegen FVIII Bethesda assay. The number of participants who developed inhibitors against FVIII are reported.

2. Number of Bleeding Episodes on Prophylaxis [Week 0 to week 104]

   Number of bleeding episodes per participant in the prophylaxis regimen was evaluated during 104 weeks.

3. Number of Spontaneous Bleeding Episodes on Prophylaxis [Week 0 to week 104]

   Spontaneous bleeding referred as bleeding episodes that occurred without apparent cause. The number of spontaneous bleeding episodes were evaluated during 104 weeks.

4. Haemostatic Effect of N8-GP When Used for Treatment of Bleeding Episodes Assessed as: Excellent, Good, Moderate, or None [Week 0 to week 104]

   The haemostatic effect after treatment of a bleed with N8-GP was assessed using a 4-point scale: 'excellent', 'good', 'moderate' or 'none'. The evaluation was done as follows: 1. Excellent: Abrupt pain relief and/or unequivocal improvement in objective signs of bleeding within approximately 8 hours after a single injection. 2. Good: Definite pain relief and/or improvement in signs of bleeding within approximately 8 hours after an injection, but possibly requiring more than one injection for complete resolution. 3. Moderate: Probable or slight beneficial effect within approximately 8 hours after the first injection; usually requiring more than one injection 4. None: No improvement or worsening of symptoms.

5. Mean Number of N8-GP Injections Required Per Bleeding Episode [Week 0 to week 104]

   The mean number of N8-GP injections required per bleeding episode from start to stop of a bleed for participants was presented from week 0 to week 104.

6. Pre-dose FVIII Activity Levels on N8-GP Prophylaxis [Week 0 to week 104]

   The pre-dose FVIII activity levels were assessed in International units per millilitre (IU/mL) units from week 0 to week 104 to get an estimate of the pre-dose level for N8-GP at steady-state using mixed model.

7. Change in Joint Health Status From Start to End of Trial (Based on Haemophilia Joint Health Score) [Week 0, Week 104]

   Haemophilia Joint Health Score is a validated outcome tool developed for the assessment of joint health in patients with hemophilia. It comprises an evaluation of the elbow, knee and ankle joints with regards to swelling, muscular atrophy, crepitation and range of motion, joint pain, strength, motion and axial alignment. The score range is from 0 to 24 points (a score of 0 indicates no joint damage. Higher the score higher the joint damage). Change from week 0 to end of trial (week 104) in the domain scores was presented.

8. Haemostatic Response During Major Surgical Interventions Assessed as: Excellent, Good, Moderate, or None [Week 0 to week 104]

   The Haemostatic response to N8-GP during major surgical interventions was assessed using a 4-point scale: 'excellent', 'good', 'moderate' or 'none'. The evaluation was done as follows: 1. Excellent: Better than expected/predicted in this type of procedure. 2. Good: As expected in this type of procedure 3. Moderate: Less than optimal for the type of procedure but haemostatic response maintained without change of treatment regimen 4. None: Bleeding due to inadequate therapeutic response with adequate dosing, change of regimen required. This endpoint was measured from week 0 to week 104.

9. Consumption of N8-GP Per Bleed [Week 0 to week 104]

   The average dose of N8-GP consumed for treatment of bleed was assessed in International units per kilogram per bleed(IU/kg/bleed). This endpoint was evaluated from week 0 to week 104.

10. Consumption of N8-GP During Prophylaxis Treatment [Week 0 to week 104]

    The average dose of N8-GP consumed for prevention of bleed was assessed. This endpoint was evaluated from week 0 to week 104.

11. Change From Start Till End of Trial in Treatment Satisfaction (Based on Hemo-SAT Score) [Week 0, Week 104]

    The treatment satisfaction of a bleed with N8-GP was assessed using HEMO-SAT assessment tool which contains a questionnaire with 6 domains (Ease and convenience, efficacy, burden, specialist/nurses, centre/hospital, general satisfaction), with a scale of 0-100. The lower scores reflecting greater treatment satisfaction. In other words, decrease in the score would mean improvement. The summary of change presented was based on individual changes since week 0. Data is presented for total score.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male patients of all ages with the diagnosis of severe congenital haemophilia A (coagulation Factor VIII [FVIII] activity less than 1%) based on medical records

• On-going participation in NN7088-3859 (pathfinder2), or NN7088-3885 (pathfinder5) at the time of transfer

Exclusion Criteria:

• Known or suspected hypersensitivity to trial product including allergy to hamster protein or related products

• Any disorder, except for conditions associated with haemophilia, which in the investigator's opinion might jeopardise patient's safety or compliance with the protocol - Current participation in any clinical trial (except NN7088-3859 (pathfinder2) or NN7088-3885 (pathfinder5)) of an approved or non-approved investigational medicinal product

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Phoenix	Arizona	United States	85016-7710
2	Novo Nordisk Investigational Site	Long Beach	California	United States	90806
3	Novo Nordisk Investigational Site	Iowa City	Iowa	United States	52242
4	Novo Nordisk Investigational Site	New Orleans	Louisiana	United States	70118-5720
5	Novo Nordisk Investigational Site	Baltimore	Maryland	United States	21205
6	Novo Nordisk Investigational Site	Detroit	Michigan	United States	48201
7	Novo Nordisk Investigational Site	East Lansing	Michigan	United States	48824
8	Novo Nordisk Investigational Site	Minneapolis	Minnesota	United States	55404
9	Novo Nordisk Investigational Site	New Hyde Park	New York	United States	11040
10	Novo Nordisk Investigational Site	Charlotte	North Carolina	United States	28204
11	Novo Nordisk Investigational Site	Cincinnati	Ohio	United States	45229
12	Novo Nordisk Investigational Site	Dayton	Ohio	United States	45404
13	Novo Nordisk Investigational Site	Portland	Oregon	United States	97239
14	Novo Nordisk Investigational Site	Philadelphia	Pennsylvania	United States	19104
15	Novo Nordisk Investigational Site	Charleston	South Carolina	United States	29425
16	Novo Nordisk Investigational Site	Nashville	Tennessee	United States	37232-9830
17	Novo Nordisk Investigational Site	Houston	Texas	United States	77030
18	Novo Nordisk Investigational Site	Norfolk	Virginia	United States	23507
19	Novo Nordisk Investigational Site	Camperdown	New South Wales	Australia	2050
20	Novo Nordisk Investigational Site	Parkville	Victoria	Australia	3052
21	Novo Nordisk Investigational Site	Campinas	Sao Paulo	Brazil	13081-970
22	Novo Nordisk Investigational Site	Toronto	Ontario	Canada	M5G1X8
23	Novo Nordisk Investigational Site	Zagreb		Croatia	10 000
24	Novo Nordisk Investigational Site	Århus N		Denmark	8200
25	Novo Nordisk Investigational Site	Bron Cedex		France	69677
26	Novo Nordisk Investigational Site	Kremlin-Bicêtre		France	94270
27	Novo Nordisk Investigational Site	Nantes Cedex 1		France	44093
28	Novo Nordisk Investigational Site	Berlin		Germany	10249
29	Novo Nordisk Investigational Site	Frankfurt/M.		Germany	60590
30	Novo Nordisk Investigational Site	Homburg		Germany	66421
31	Novo Nordisk Investigational Site	Athens		Greece	GR-11527
32	Novo Nordisk Investigational Site	Budapest		Hungary	H-1134
33	Novo Nordisk Investigational Site	Debrecen		Hungary	4012
34	Novo Nordisk Investigational Site	Tel-Hashomer		Israel	52621
35	Novo Nordisk Investigational Site	Milano		Italy	20124
36	Novo Nordisk Investigational Site	Vicenza		Italy	36100
37	Novo Nordisk Investigational Site	Kitakyusyu-shi, Fukuoka		Japan	807 8555
38	Novo Nordisk Investigational Site	Nara		Japan	634-8522
39	Novo Nordisk Investigational Site	Tokyo		Japan	167-0035
40	Novo Nordisk Investigational Site	Daejeon		Korea, Republic of	35233
41	Novo Nordisk Investigational Site	Vilnius		Lithuania	08406
42	Novo Nordisk Investigational Site	Selangor Darul Ehsan		Malaysia	68000
43	Novo Nordisk Investigational Site	Groningen		Netherlands	9713 GZ
44	Novo Nordisk Investigational Site	Rotterdam		Netherlands	3015 CE
45	Novo Nordisk Investigational Site	Oslo		Norway	0027
46	Novo Nordisk Investigational Site	Porto		Portugal	4200-319
47	Novo Nordisk Investigational Site	San Juan		Puerto Rico	00936
48	Novo Nordisk Investigational Site	Madrid		Spain	28046
49	Novo Nordisk Investigational Site	Málaga		Spain	29010
50	Novo Nordisk Investigational Site	Bellinzona		Switzerland	6500
51	Novo Nordisk Investigational Site	Lausanne		Switzerland	1011
52	Novo Nordisk Investigational Site	Zürich		Switzerland	8032
53	Novo Nordisk Investigational Site	Zürich		Switzerland	8091
54	Novo Nordisk Investigational Site	Taipei		Taiwan	100
55	Novo Nordisk Investigational Site	Adana		Turkey	01130
56	Novo Nordisk Investigational Site	Antalya		Turkey	01010
57	Novo Nordisk Investigational Site	Bornova-IZMIR		Turkey	35100
58	Novo Nordisk Investigational Site	Izmit		Turkey	41380
59	Novo Nordisk Investigational Site	Samsun		Turkey	55030
60	Novo Nordisk Investigational Site	Lviv		Ukraine	79044
61	Novo Nordisk Investigational Site	Basingstoke		United Kingdom	RG24 9NA
62	Novo Nordisk Investigational Site	Cardiff		United Kingdom	CF14 4XW
63	Novo Nordisk Investigational Site	London		United Kingdom	NW3 2QG
64	Novo Nordisk Investigational Site	London		United Kingdom	SE1 7EH
65	Novo Nordisk Investigational Site	Oxford		United Kingdom	OX3 7LJ
66	Novo Nordisk Investigational Site	Oxford		United Kingdom	OX3 9DU
67	Novo Nordisk Investigational Site	Sheffield		United Kingdom	S10 2JF

Sponsors and Collaborators

• Novo Nordisk A/S

Investigators

• Study Director: Clinical Reporting Anchor and Disclosure 1452, Novo Nordisk A/S

Study Documents (Full-Text)

• Study Protocol - Jun 18, 2019
• Statistical Analysis Plan - Sep 10, 2020

More Information

Publications

None provided.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT03528551
• Other Study ID Numbers: NN7088-4410; U1111-1202-2780; 2017-003788-36; JapicCTI-183952
• First Posted: May 18, 2018
• Last Update Posted: Nov 30, 2021
• Last Verified: Nov 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Hemostatic Disorders; Hemophilia A; Blood Coagulation Disorders; Factor VIII

Study Results

Participant Flow

Recruitment Details

The trial was conducted at 66 sites in 25 countries: Australia(2), Brazil(1), Canada(1), Croatia(1), Denmark(1), France(2), Germany(2), Greece(1), Hungary(2), Israel(1), Italy(2), Japan(3), Korea(1), Lithuania(1), Malaysia(1), Netherlands(2), Norway(1), Portugal(1), Spain(2), Switzerland(4), Taiwan(1), Turkey(5), Ukraine(1), United Kingdom (8), United States (USA) (19).

Pre-assignment Detail

Out of 160 participants enrolled in this study, 102 came from trial NN7088-3859 and 58 came from trial NN7088-3885. The participants received turoctocog alfa pegol (N8-GP) injections either as once-weekly, twice weekly or three times weekly during the 104 weeks treatment period. Despite 160 participants started the trial, the total number of participants considered are 167 as 2 participants switched to twice weekly and 5 participants switched to three times weekly regimen.

Arm/Group Title	N8-GP, Once Weekly	N8-GP, Twice Weekly	N8-GP, Three Times Weekly
Arm/Group Description	Participants received once weekly (dosing every 7 day) prophylaxis doses of N8-GP, 75 IU/kg (International Units per kilogram) intravenous injections for 104 weeks. Participants treated with N8-GP once weekly or were on the on demand regimen in the previous trial NN7088-3859 (pathfinder2) were included in this arm. At the investigator's discretion an intensification of the dosing regimen to twice weekly was allowed if the participant experienced more than 2 bleeds within an 8 week period or experienced a severe bleed requiring hospitalization.	Participants received twice weekly (dosing every 3 and 4 days) prophylaxis doses of N8-GP intravenous injections for 104 weeks: N8-GP, 50 IU/kg for participants aged ≥ 12 years and N8-GP, 60 IU/kg for participants aged < 12 years. Participants treated with N8-GP in the previous trials NN7088-3859 (pathfinder2) and NN7088-3885 (pathfinder5) were included in this arm. At the investigator's discretion, an intensification of the dosing regimen to thrice weekly was allowed if the participant experienced spontaneous bleeding episodes. Participants in this arm were permitted to switch to three times weekly at any time if clinically justified. Otherwise any treatment regimen was preferably be kept for a minimum of 6 months.	Participants received three times weekly (dosing every 2, 2 and 3 days) prophylaxis doses of N8-GP, 50 IU/kg as intravenous injections for a duration of 104 weeks. Participants treated with N8-GP in the previous trials NN7088-3859 (pathfinder2) and NN7088-3885 (pathfinder5) were included in this arm. Participants in this arm were permitted to switch to twice weekly at any time if clinically justified. Otherwise any treatment regimen was preferably be kept for a minimum of 6 months.
Period Title: Overall Study
STARTED	25	133	2
COMPLETED	23	114	2
NOT COMPLETED	2	19	0

Baseline Characteristics

Arm/Group Title	N8-GP, Once Weekly	N8-GP, Twice Weekly	N8-GP, Three Times Weekly	Total
Arm/Group Description	Participants received once weekly (dosing every 7 day) prophylaxis doses of N8-GP, 75 IU/kg (International Units per kilogram) intravenous injections for 104 weeks. Participants treated with N8-GP once weekly or were on the on demand regimen in the previous trial NN7088-3859 (pathfinder2) were included in this arm. At the investigator's discretion an intensification of the dosing regimen to twice weekly was allowed if the participant experienced more than 2 bleeds within an 8 week period or experienced a severe bleed requiring hospitalization.	Participants received twice weekly (dosing every 3 and 4 days) prophylaxis doses of N8-GP intravenous injections for 104 weeks: N8-GP, 50 IU/kg for participants aged ≥ 12 years and N8-GP, 60 IU/kg for participants aged < 12 years. Participants treated with N8-GP in the previous trials NN7088-3859 (pathfinder2) and NN7088-3885 (pathfinder5) were included in this arm. At the investigator's discretion, an intensification of the dosing regimen to thrice weekly was allowed if the participant experienced spontaneous bleeding episodes. Participants in this arm were permitted to switch to three times weekly at any time if clinically justified. Otherwise any treatment regimen was preferably be kept for a minimum of 6 months.	Participants received three times weekly (dosing every 2, 2 and 3 days) prophylaxis doses of N8-GP, 50 IU/kg as intravenous injections for a duration of 104 weeks. Participants treated with N8-GP in the previous trials NN7088-3859 (pathfinder2) and NN7088-3885 (pathfinder5) were included in this arm. Participants in this arm were permitted to switch to twice weekly at any time if clinically justified. Otherwise any treatment regimen was preferably be kept for a minimum of 6 months.	Total of all reporting groups
Overall Participants	25	133	2	160
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	35.1 (12.7)	27.3 (16.8)	25.3 (17.8)	28.4 (16.4)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%
Male	25 100%	133 100%	2 100%	160 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	8 6%	0 0%	8 5%
Not Hispanic or Latino	25 100%	124 93.2%	2 100%	151 94.4%
Unknown or Not Reported	0 0%	1 0.8%	0 0%	1 0.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	3 12%	17 12.8%	1 50%	21 13.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	1 4%	4 3%	0 0%	5 3.1%
White	21 84%	108 81.2%	1 50%	130 81.3%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	4 3%	0 0%	4 2.5%

Outcome Measures

1. Primary Outcome

Title	Number of Adverse Events Reported
Description	An adverse event (AE) was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. All AEs mentioned here are treatment emergent adverse events (TEAEs). The TEAE is defined as an event reported from date of first trial product administration until end of the treatment visit (week 104) or follow-up visit if relevant (1 month after end of the treatment).
Time Frame	Week 0 to week 108

Outcome Measure Data

Analysis Population Description

Safety analysis set (SAS) included all enrolled participants who were exposed to the trial product.

Arm/Group Title	N8-GP, Once Weekly	N8-GP, Twice Weekly	N8-GP, Three Times Weekly
Arm/Group Description	Participants received once weekly (dosing every 7 day) prophylaxis doses of N8-GP, 75 IU/kg (International Units per kilogram) intravenous injections for 104 weeks. Participants treated with N8-GP once weekly or were on the on demand regimen in the previous trial NN7088-3859 (pathfinder2) were included in this arm. At the investigator's discretion an intensification of the dosing regimen to twice weekly was allowed if the participant experienced more than 2 bleeds within an 8 week period or experienced a severe bleed requiring hospitalization.	Participants received twice weekly (dosing every 3 and 4 days) prophylaxis doses of N8-GP intravenous injections for 104 weeks: N8-GP, 50 IU/kg for participants aged ≥ 12 years and N8-GP, 60 IU/kg for participants aged < 12 years. Participants treated with N8-GP in the previous trials NN7088-3859 (pathfinder2) and NN7088-3885 (pathfinder5) were included in this arm. At the investigator's discretion, an intensification of the dosing regimen to thrice weekly was allowed if the participant experienced spontaneous bleeding episodes. Participants in this arm were permitted to switch to three times weekly at any time if clinically justified. Otherwise any treatment regimen was preferably be kept for a minimum of 6 months. During the trial, 2 participants switched from once weekly to twice weekly regimen for treatment intensification. Thus, though 133 participants have started the trial with twice weekly regimen, the data is presented for 135 participants in this arm (i.e. 133+2 = 135).	Participants received three times weekly (dosing every 2, 2 and 3 days) prophylaxis doses of N8-GP, 50 IU/kg as intravenous injections for a duration of 104 weeks. Participants treated with N8-GP in the previous trials NN7088-3859 (pathfinder2) and NN7088-3885 (pathfinder5) were included in this arm. Participants in this arm were permitted to switch to twice weekly at any time if clinically justified. Otherwise any treatment regimen was preferably be kept for a minimum of 6 months. During the trial, 5 participants switched from twice weekly to three times weekly regimen for treatment intensification. Thus, though 2 participants have started the trial with three times regimen, the data is presented for 7 participants in this arm (i.e. 2+5 = 7).
Measure Participants	25	135	7
Number [Events]	58	444	8

2. Secondary Outcome

Title	Number of Participants With Inhibitory Antibodies Against Coagulation Factor VIII (FVIII) ≥0.6 Bethesda Units (BU)
Description	The Incidence of inhibitors against coagulation factor eight (FVIII) is defined as titre greater than or equal to (≥) 0.6 Bethesda unit. The inhibitor antibodies were measured using a heat modified Nijmegen FVIII Bethesda assay. The number of participants who developed inhibitors against FVIII are reported.
Time Frame	Week 0 to week 104

Outcome Measure Data

Analysis Population Description

FAS included all participants exposed to at least one dose of trial product in the current trial.

Arm/Group Title	N8-GP, Once Weekly	N8-GP, Twice Weekly	N8-GP, Three Times Weekly
Arm/Group Description	Participants received once weekly (dosing every 7 day) prophylaxis doses of N8-GP, 75 IU/kg (International Units per kilogram) intravenous injections for 104 weeks. Participants treated with N8-GP once weekly or were on the on demand regimen in the previous trial NN7088-3859 (pathfinder2) were included in this arm. At the investigator's discretion an intensification of the dosing regimen to twice weekly was allowed if the participant experienced more than 2 bleeds within an 8 week period or experienced a severe bleed requiring hospitalization.	Participants received twice weekly (dosing every 3 and 4 days) prophylaxis doses of N8-GP intravenous injections for 104 weeks: N8-GP, 50 IU/kg for participants aged ≥ 12 years and N8-GP, 60 IU/kg for participants aged < 12 years. Participants treated with N8-GP in the previous trials NN7088-3859 (pathfinder2) and NN7088-3885 (pathfinder5) were included in this arm. At the investigator's discretion, an intensification of the dosing regimen to thrice weekly was allowed if the participant experienced spontaneous bleeding episodes. Participants in this arm were permitted to switch to three times weekly at any time if clinically justified. Otherwise any treatment regimen was preferably be kept for a minimum of 6 months. During the trial, 2 participants switched from once weekly to twice weekly regimen for treatment intensification. Thus, though 133 participants have started the trial with twice weekly regimen, the data is presented for 135 participants in this arm (i.e. 133+2 = 135).	Participants received three times weekly (dosing every 2, 2 and 3 days) prophylaxis doses of N8-GP, 50 IU/kg as intravenous injections for a duration of 104 weeks. Participants treated with N8-GP in the previous trials NN7088-3859 (pathfinder2) and NN7088-3885 (pathfinder5) were included in this arm. Participants in this arm were permitted to switch to twice weekly at any time if clinically justified. Otherwise any treatment regimen was preferably be kept for a minimum of 6 months. During the trial, 5 participants switched from twice weekly to three times weekly regimen for treatment intensification. Thus, though 2 participants have started the trial with three times regimen, the data is presented for 7 participants in this arm (i.e. 2+5 = 7).
Measure Participants	25	135	7
Number [Participants]	0 0%	0 0%	0 0%

3. Secondary Outcome

Title	Number of Bleeding Episodes on Prophylaxis
Description	Number of bleeding episodes per participant in the prophylaxis regimen was evaluated during 104 weeks.
Time Frame	Week 0 to week 104

Outcome Measure Data

Analysis Population Description

FAS included all participants exposed to at least one dose of trial product in the current trial.

Arm/Group Title	N8-GP, Once Weekly	N8-GP, Twice Weekly	N8-GP, Three Times Weekly
Arm/Group Description	Participants received once weekly (dosing every 7 day) prophylaxis doses of N8-GP, 75 IU/kg (International Units per kilogram) intravenous injections for 104 weeks. Participants treated with N8-GP once weekly or were on the on demand regimen in the previous trial NN7088-3859 (pathfinder2) were included in this arm. At the investigator's discretion an intensification of the dosing regimen to twice weekly was allowed if the participant experienced more than 2 bleeds within an 8 week period or experienced a severe bleed requiring hospitalization.	Participants received twice weekly (dosing every 3 and 4 days) prophylaxis doses of N8-GP intravenous injections for 104 weeks: N8-GP, 50 IU/kg for participants aged ≥ 12 years and N8-GP, 60 IU/kg for participants aged < 12 years. Participants treated with N8-GP in the previous trials NN7088-3859 (pathfinder2) and NN7088-3885 (pathfinder5) were included in this arm. At the investigator's discretion, an intensification of the dosing regimen to thrice weekly was allowed if the participant experienced spontaneous bleeding episodes. Participants in this arm were permitted to switch to three times weekly at any time if clinically justified. Otherwise any treatment regimen was preferably be kept for a minimum of 6 months. During the trial, 2 participants switched from once weekly to twice weekly regimen for treatment intensification. Thus, though 133 participants have started the trial with twice weekly regimen, the data is presented for 135 participants in this arm (i.e. 133+2 = 135).	Participants received three times weekly (dosing every 2, 2 and 3 days) prophylaxis doses of N8-GP, 50 IU/kg as intravenous injections for a duration of 104 weeks. Participants treated with N8-GP in the previous trials NN7088-3859 (pathfinder2) and NN7088-3885 (pathfinder5) were included in this arm. Participants in this arm were permitted to switch to twice weekly at any time if clinically justified. Otherwise any treatment regimen was preferably be kept for a minimum of 6 months. During the trial, 5 participants switched from twice weekly to three times weekly regimen for treatment intensification. Thus, though 2 participants have started the trial with three times regimen, the data is presented for 7 participants in this arm (i.e. 2+5 = 7).
Measure Participants	25	135	7
Number [Episodes]	123	190	14

4. Secondary Outcome

Title	Number of Spontaneous Bleeding Episodes on Prophylaxis
Description	Spontaneous bleeding referred as bleeding episodes that occurred without apparent cause. The number of spontaneous bleeding episodes were evaluated during 104 weeks.
Time Frame	Week 0 to week 104

Outcome Measure Data

Analysis Population Description

FAS included all participants exposed to at least one dose of trial product in the current trial.

Arm/Group Title	N8-GP, Once Weekly	N8-GP, Twice Weekly	N8-GP, Three Times Weekly
Arm/Group Description	Participants received once weekly (dosing every 7 day) prophylaxis doses of N8-GP, 75 IU/kg (International Units per kilogram) intravenous injections for 104 weeks. Participants treated with N8-GP once weekly or were on the on demand regimen in the previous trial NN7088-3859 (pathfinder2) were included in this arm. At the investigator's discretion an intensification of the dosing regimen to twice weekly was allowed if the participant experienced more than 2 bleeds within an 8 week period or experienced a severe bleed requiring hospitalization.	Participants received twice weekly (dosing every 3 and 4 days) prophylaxis doses of N8-GP intravenous injections for 104 weeks: N8-GP, 50 IU/kg for participants aged ≥ 12 years and N8-GP, 60 IU/kg for participants aged < 12 years. Participants treated with N8-GP in the previous trials NN7088-3859 (pathfinder2) and NN7088-3885 (pathfinder5) were included in this arm. At the investigator's discretion, an intensification of the dosing regimen to thrice weekly was allowed if the participant experienced spontaneous bleeding episodes. Participants in this arm were permitted to switch to three times weekly at any time if clinically justified. Otherwise any treatment regimen was preferably be kept for a minimum of 6 months. During the trial, 2 participants switched from once weekly to twice weekly regimen for treatment intensification. Thus, though 133 participants have started the trial with twice weekly regimen, the data is presented for 135 participants in this arm (i.e. 133+2 = 135).	Participants received three times weekly (dosing every 2, 2 and 3 days) prophylaxis doses of N8-GP, 50 IU/kg as intravenous injections for a duration of 104 weeks. Participants treated with N8-GP in the previous trials NN7088-3859 (pathfinder2) and NN7088-3885 (pathfinder5) were included in this arm. Participants in this arm were permitted to switch to twice weekly at any time if clinically justified. Otherwise any treatment regimen was preferably be kept for a minimum of 6 months. During the trial, 5 participants switched from twice weekly to three times weekly regimen for treatment intensification. Thus, though 2 participants have started the trial with three times regimen, the data is presented for 7 participants in this arm (i.e. 2+5 = 7).
Measure Participants	25	135	7
Number [Episodes]	98	73	8

5. Secondary Outcome

Title	Haemostatic Effect of N8-GP When Used for Treatment of Bleeding Episodes Assessed as: Excellent, Good, Moderate, or None
Description	The haemostatic effect after treatment of a bleed with N8-GP was assessed using a 4-point scale: 'excellent', 'good', 'moderate' or 'none'. The evaluation was done as follows: 1. Excellent: Abrupt pain relief and/or unequivocal improvement in objective signs of bleeding within approximately 8 hours after a single injection. 2. Good: Definite pain relief and/or improvement in signs of bleeding within approximately 8 hours after an injection, but possibly requiring more than one injection for complete resolution. 3. Moderate: Probable or slight beneficial effect within approximately 8 hours after the first injection; usually requiring more than one injection 4. None: No improvement or worsening of symptoms.
Time Frame	Week 0 to week 104

Outcome Measure Data

Analysis Population Description

FAS included all participants exposed to at least one dose of trial product in the current trial.

Arm/Group Title	N8-GP, Once Weekly	N8-GP, Twice Weekly	N8-GP, Three Times Weekly
Arm/Group Description	Participants received once weekly (dosing every 7 day) prophylaxis doses of N8-GP, 75 IU/kg (International Units per kilogram) intravenous injections for 104 weeks. Participants treated with N8-GP once weekly or were on the on demand regimen in the previous trial NN7088-3859 (pathfinder2) were included in this arm. At the investigator's discretion an intensification of the dosing regimen to twice weekly was allowed if the participant experienced more than 2 bleeds within an 8 week period or experienced a severe bleed requiring hospitalization.	Participants received twice weekly (dosing every 3 and 4 days) prophylaxis doses of N8-GP intravenous injections for 104 weeks: N8-GP, 50 IU/kg for participants aged ≥ 12 years and N8-GP, 60 IU/kg for participants aged < 12 years. Participants treated with N8-GP in the previous trials NN7088-3859 (pathfinder2) and NN7088-3885 (pathfinder5) were included in this arm. At the investigator's discretion, an intensification of the dosing regimen to thrice weekly was allowed if the participant experienced spontaneous bleeding episodes. Participants in this arm were permitted to switch to three times weekly at any time if clinically justified. Otherwise any treatment regimen was preferably be kept for a minimum of 6 months. During the trial, 2 participants switched from once weekly to twice weekly regimen for treatment intensification. Thus, though 133 participants have started the trial with twice weekly regimen, the data is presented for 135 participants in this arm (i.e. 133+2 = 135).	Participants received three times weekly (dosing every 2, 2 and 3 days) prophylaxis doses of N8-GP, 50 IU/kg as intravenous injections for a duration of 104 weeks. Participants treated with N8-GP in the previous trials NN7088-3859 (pathfinder2) and NN7088-3885 (pathfinder5) were included in this arm. Participants in this arm were permitted to switch to twice weekly at any time if clinically justified. Otherwise any treatment regimen was preferably be kept for a minimum of 6 months. During the trial, 5 participants switched from twice weekly to three times weekly regimen for treatment intensification. Thus, though 2 participants have started the trial with three times regimen, the data is presented for 7 participants in this arm (i.e. 2+5 = 7).
Measure Participants	25	135	7
Excellent	114	94	8
Good	8	80	6
Moderate	0	4	0
None	0	0	0
Missing	0	8	0

6. Secondary Outcome

Title	Mean Number of N8-GP Injections Required Per Bleeding Episode
Description	The mean number of N8-GP injections required per bleeding episode from start to stop of a bleed for participants was presented from week 0 to week 104.
Time Frame	Week 0 to week 104

Outcome Measure Data

Analysis Population Description

FAS included all participants exposed to at least one dose of trial product in the current trial.

Arm/Group Title	N8-GP, Once Weekly	N8-GP, Twice Weekly	N8-GP, Three Times Weekly
Arm/Group Description	Participants received once weekly (dosing every 7 day) prophylaxis doses of N8-GP, 75 IU/kg (International Units per kilogram) intravenous injections for 104 weeks. Participants treated with N8-GP once weekly or were on the on demand regimen in the previous trial NN7088-3859 (pathfinder2) were included in this arm. At the investigator's discretion an intensification of the dosing regimen to twice weekly was allowed if the participant experienced more than 2 bleeds within an 8 week period or experienced a severe bleed requiring hospitalization.	Participants received twice weekly (dosing every 3 and 4 days) prophylaxis doses of N8-GP intravenous injections for 104 weeks: N8-GP, 50 IU/kg for participants aged ≥ 12 years and N8-GP, 60 IU/kg for participants aged < 12 years. Participants treated with N8-GP in the previous trials NN7088-3859 (pathfinder2) and NN7088-3885 (pathfinder5) were included in this arm. At the investigator's discretion, an intensification of the dosing regimen to thrice weekly was allowed if the participant experienced spontaneous bleeding episodes. Participants in this arm were permitted to switch to three times weekly at any time if clinically justified. Otherwise any treatment regimen was preferably be kept for a minimum of 6 months. During the trial, 2 participants switched from once weekly to twice weekly regimen for treatment intensification. Thus, though 133 participants have started the trial with twice weekly regimen, the data is presented for 135 participants in this arm (i.e. 133+2 = 135).	Participants received three times weekly (dosing every 2, 2 and 3 days) prophylaxis doses of N8-GP, 50 IU/kg as intravenous injections for a duration of 104 weeks. Participants treated with N8-GP in the previous trials NN7088-3859 (pathfinder2) and NN7088-3885 (pathfinder5) were included in this arm. Participants in this arm were permitted to switch to twice weekly at any time if clinically justified. Otherwise any treatment regimen was preferably be kept for a minimum of 6 months. During the trial, 5 participants switched from twice weekly to three times weekly regimen for treatment intensification. Thus, though 2 participants have started the trial with three times regimen, the data is presented for 7 participants in this arm (i.e. 2+5 = 7).
Measure Participants	25	135	7
Mean (Standard Deviation) [Injections per bleed]	1.2 (0.6)	1.5 (1.3)	1.1 (0.4)

7. Secondary Outcome

Title	Pre-dose FVIII Activity Levels on N8-GP Prophylaxis
Description	The pre-dose FVIII activity levels were assessed in International units per millilitre (IU/mL) units from week 0 to week 104 to get an estimate of the pre-dose level for N8-GP at steady-state using mixed model.
Time Frame	Week 0 to week 104

Outcome Measure Data

Analysis Population Description

FAS included all participants exposed to at least one dose of trial product in the current trial.

Arm/Group Title	N8-GP, Once Weekly	N8-GP, Twice Weekly	N8-GP, Three Times Weekly
Arm/Group Description	Participants received once weekly (dosing every 7 day) prophylaxis doses of N8-GP, 75 IU/kg (International Units per kilogram) intravenous injections for 104 weeks. Participants treated with N8-GP once weekly or were on the on demand regimen in the previous trial NN7088-3859 (pathfinder2) were included in this arm. At the investigator's discretion an intensification of the dosing regimen to twice weekly was allowed if the participant experienced more than 2 bleeds within an 8 week period or experienced a severe bleed requiring hospitalization.	Participants received twice weekly (dosing every 3 and 4 days) prophylaxis doses of N8-GP intravenous injections for 104 weeks: N8-GP, 50 IU/kg for participants aged ≥ 12 years and N8-GP, 60 IU/kg for participants aged < 12 years. Participants treated with N8-GP in the previous trials NN7088-3859 (pathfinder2) and NN7088-3885 (pathfinder5) were included in this arm. At the investigator's discretion, an intensification of the dosing regimen to thrice weekly was allowed if the participant experienced spontaneous bleeding episodes. Participants in this arm were permitted to switch to three times weekly at any time if clinically justified. Otherwise any treatment regimen was preferably be kept for a minimum of 6 months. During the trial, 2 participants switched from once weekly to twice weekly regimen for treatment intensification. Thus, though 133 participants have started the trial with twice weekly regimen, the data is presented for 135 participants in this arm (i.e. 133+2 = 135).	Participants received three times weekly (dosing every 2, 2 and 3 days) prophylaxis doses of N8-GP, 50 IU/kg as intravenous injections for a duration of 104 weeks. Participants treated with N8-GP in the previous trials NN7088-3859 (pathfinder2) and NN7088-3885 (pathfinder5) were included in this arm. Participants in this arm were permitted to switch to twice weekly at any time if clinically justified. Otherwise any treatment regimen was preferably be kept for a minimum of 6 months. During the trial, 5 participants switched from twice weekly to three times weekly regimen for treatment intensification. Thus, though 2 participants have started the trial with three times regimen, the data is presented for 7 participants in this arm (i.e. 2+5 = 7).
Measure Participants	25	135	7
Mean (95% Confidence Interval) [IU/mL]	0.016	0.042	0.049

8. Secondary Outcome

Title	Change in Joint Health Status From Start to End of Trial (Based on Haemophilia Joint Health Score)
Description	Haemophilia Joint Health Score is a validated outcome tool developed for the assessment of joint health in patients with hemophilia. It comprises an evaluation of the elbow, knee and ankle joints with regards to swelling, muscular atrophy, crepitation and range of motion, joint pain, strength, motion and axial alignment. The score range is from 0 to 24 points (a score of 0 indicates no joint damage. Higher the score higher the joint damage). Change from week 0 to end of trial (week 104) in the domain scores was presented.
Time Frame	Week 0, Week 104

Outcome Measure Data

Analysis Population Description

FAS included all participants exposed to at least one dose of trial product in the current trial. 'Overall Number of Participants Analyzed' = participants with available data.

Arm/Group Title	N8-GP, Once Weekly	N8-GP, Twice Weekly	N8-GP, Three Times Weekly
Arm/Group Description	Participants received once weekly (dosing every 7 day) prophylaxis doses of N8-GP, 75 IU/kg (International Units per kilogram) intravenous injections for 104 weeks. Participants treated with N8-GP once weekly or were on the on demand regimen in the previous trial NN7088-3859 (pathfinder2) were included in this arm. At the investigator's discretion an intensification of the dosing regimen to twice weekly was allowed if the participant experienced more than 2 bleeds within an 8 week period or experienced a severe bleed requiring hospitalization.	Participants received twice weekly (dosing every 3 and 4 days) prophylaxis doses of N8-GP intravenous injections for 104 weeks: N8-GP, 50 IU/kg for participants aged ≥ 12 years and N8-GP, 60 IU/kg for participants aged < 12 years. Participants treated with N8-GP in the previous trials NN7088-3859 (pathfinder2) and NN7088-3885 (pathfinder5) were included in this arm. At the investigator's discretion, an intensification of the dosing regimen to thrice weekly was allowed if the participant experienced spontaneous bleeding episodes. Participants in this arm were permitted to switch to three times weekly at any time if clinically justified. Otherwise any treatment regimen was preferably be kept for a minimum of 6 months. During the trial, 2 participants switched from once weekly to twice weekly regimen for treatment intensification. Thus, though 133 participants have started the trial with twice weekly regimen, the data is presented for 135 participants in this arm (i.e. 133+2 = 135).	Participants received three times weekly (dosing every 2, 2 and 3 days) prophylaxis doses of N8-GP, 50 IU/kg as intravenous injections for a duration of 104 weeks. Participants treated with N8-GP in the previous trials NN7088-3859 (pathfinder2) and NN7088-3885 (pathfinder5) were included in this arm. Participants in this arm were permitted to switch to twice weekly at any time if clinically justified. Otherwise any treatment regimen was preferably be kept for a minimum of 6 months. During the trial, 5 participants switched from twice weekly to three times weekly regimen for treatment intensification. Thus, though 2 participants have started the trial with three times regimen, the data is presented for 7 participants in this arm (i.e. 2+5 = 7).
Measure Participants	21	112	2
Mean (Standard Deviation) [Score on a scale]	0.238 (7.75)	-0.116 (7.40)	-10.0 (14.1)

9. Secondary Outcome

Title	Haemostatic Response During Major Surgical Interventions Assessed as: Excellent, Good, Moderate, or None
Description	The Haemostatic response to N8-GP during major surgical interventions was assessed using a 4-point scale: 'excellent', 'good', 'moderate' or 'none'. The evaluation was done as follows: 1. Excellent: Better than expected/predicted in this type of procedure. 2. Good: As expected in this type of procedure 3. Moderate: Less than optimal for the type of procedure but haemostatic response maintained without change of treatment regimen 4. None: Bleeding due to inadequate therapeutic response with adequate dosing, change of regimen required. This endpoint was measured from week 0 to week 104.
Time Frame	Week 0 to week 104

Outcome Measure Data

Analysis Population Description

FAS included all participants exposed to at least one dose of trial product in the current trial.

Arm/Group Title	N8-GP, Once Weekly	N8-GP, Twice Weekly	N8-GP, Three Times Weekly
Arm/Group Description	Participants received once weekly (dosing every 7 day) prophylaxis doses of N8-GP, 75 IU/kg (International Units per kilogram) intravenous injections for 104 weeks. Participants treated with N8-GP once weekly or were on the on demand regimen in the previous trial NN7088-3859 (pathfinder2) were included in this arm. At the investigator's discretion an intensification of the dosing regimen to twice weekly was allowed if the participant experienced more than 2 bleeds within an 8 week period or experienced a severe bleed requiring hospitalization.	Participants received twice weekly (dosing every 3 and 4 days) prophylaxis doses of N8-GP intravenous injections for 104 weeks: N8-GP, 50 IU/kg for participants aged ≥ 12 years and N8-GP, 60 IU/kg for participants aged < 12 years. Participants treated with N8-GP in the previous trials NN7088-3859 (pathfinder2) and NN7088-3885 (pathfinder5) were included in this arm. At the investigator's discretion, an intensification of the dosing regimen to thrice weekly was allowed if the participant experienced spontaneous bleeding episodes. Participants in this arm were permitted to switch to three times weekly at any time if clinically justified. Otherwise any treatment regimen was preferably be kept for a minimum of 6 months. During the trial, 2 participants switched from once weekly to twice weekly regimen for treatment intensification. Thus, though 133 participants have started the trial with twice weekly regimen, the data is presented for 135 participants in this arm (i.e. 133+2 = 135).	Participants received three times weekly (dosing every 2, 2 and 3 days) prophylaxis doses of N8-GP, 50 IU/kg as intravenous injections for a duration of 104 weeks. Participants treated with N8-GP in the previous trials NN7088-3859 (pathfinder2) and NN7088-3885 (pathfinder5) were included in this arm. Participants in this arm were permitted to switch to twice weekly at any time if clinically justified. Otherwise any treatment regimen was preferably be kept for a minimum of 6 months. During the trial, 5 participants switched from twice weekly to three times weekly regimen for treatment intensification. Thus, though 2 participants have started the trial with three times regimen, the data is presented for 7 participants in this arm (i.e. 2+5 = 7).
Measure Participants	25	135	7
Excellent	3	8	0
Good	1	4	0
Moderate	0	0	0
None	0	0	0
Missing	0	1	0

10. Secondary Outcome

Title	Consumption of N8-GP Per Bleed
Description	The average dose of N8-GP consumed for treatment of bleed was assessed in International units per kilogram per bleed(IU/kg/bleed). This endpoint was evaluated from week 0 to week 104.
Time Frame	Week 0 to week 104

Outcome Measure Data

Analysis Population Description

FAS included all participants exposed to at least one dose of trial product in the current trial. 'Overall Number of Participants Analyzed' = participants with available data.

Arm/Group Title	N8-GP, Once Weekly	N8-GP, Twice Weekly	N8-GP, Three Times Weekly
Arm/Group Description	Participants received once weekly (dosing every 7 day) prophylaxis doses of N8-GP, 75 IU/kg (International Units per kilogram) intravenous injections for 104 weeks. Participants treated with N8-GP once weekly or were on the on demand regimen in the previous trial NN7088-3859 (pathfinder2) were included in this arm. At the investigator's discretion an intensification of the dosing regimen to twice weekly was allowed if the participant experienced more than 2 bleeds within an 8 week period or experienced a severe bleed requiring hospitalization.	Participants received twice weekly (dosing every 3 and 4 days) prophylaxis doses of N8-GP intravenous injections for 104 weeks: N8-GP, 50 IU/kg for participants aged ≥ 12 years and N8-GP, 60 IU/kg for participants aged < 12 years. Participants treated with N8-GP in the previous trials NN7088-3859 (pathfinder2) and NN7088-3885 (pathfinder5) were included in this arm. At the investigator's discretion, an intensification of the dosing regimen to thrice weekly was allowed if the participant experienced spontaneous bleeding episodes. Participants in this arm were permitted to switch to three times weekly at any time if clinically justified. Otherwise any treatment regimen was preferably be kept for a minimum of 6 months. During the trial, 2 participants switched from once weekly to twice weekly regimen for treatment intensification. Thus, though 133 participants have started the trial with twice weekly regimen, the data is presented for 135 participants in this arm (i.e. 133+2 = 135).	Participants received three times weekly (dosing every 2, 2 and 3 days) prophylaxis doses of N8-GP, 50 IU/kg as intravenous injections for a duration of 104 weeks. Participants treated with N8-GP in the previous trials NN7088-3859 (pathfinder2) and NN7088-3885 (pathfinder5) were included in this arm. Participants in this arm were permitted to switch to twice weekly at any time if clinically justified. Otherwise any treatment regimen was preferably be kept for a minimum of 6 months. During the trial, 5 participants switched from twice weekly to three times weekly regimen for treatment intensification. Thus, though 2 participants have started the trial with three times regimen, the data is presented for 7 participants in this arm (i.e. 2+5 = 7).
Measure Participants	10	61	3
Mean (Standard Deviation) [IU/kg/bleed]	91.3 (85.0)	81.9 (55.9)	61.1 (12.0)

11. Secondary Outcome

Title	Consumption of N8-GP During Prophylaxis Treatment
Description	The average dose of N8-GP consumed for prevention of bleed was assessed. This endpoint was evaluated from week 0 to week 104.
Time Frame	Week 0 to week 104

Outcome Measure Data

Analysis Population Description

FAS included all participants exposed to at least one dose of trial product in the current trial.

Arm/Group Title	N8-GP, Once Weekly	N8-GP, Twice Weekly	N8-GP, Three Times Weekly
Arm/Group Description	Participants received once weekly (dosing every 7 day) prophylaxis doses of N8-GP, 75 IU/kg (International Units per kilogram) intravenous injections for 104 weeks. Participants treated with N8-GP once weekly or were on the on demand regimen in the previous trial NN7088-3859 (pathfinder2) were included in this arm. At the investigator's discretion an intensification of the dosing regimen to twice weekly was allowed if the participant experienced more than 2 bleeds within an 8 week period or experienced a severe bleed requiring hospitalization.	Participants received twice weekly (dosing every 3 and 4 days) prophylaxis doses of N8-GP intravenous injections for 104 weeks: N8-GP, 50 IU/kg for participants aged ≥ 12 years and N8-GP, 60 IU/kg for participants aged < 12 years. Participants treated with N8-GP in the previous trials NN7088-3859 (pathfinder2) and NN7088-3885 (pathfinder5) were included in this arm. At the investigator's discretion, an intensification of the dosing regimen to thrice weekly was allowed if the participant experienced spontaneous bleeding episodes. Participants in this arm were permitted to switch to three times weekly at any time if clinically justified. Otherwise any treatment regimen was preferably be kept for a minimum of 6 months. During the trial, 2 participants switched from once weekly to twice weekly regimen for treatment intensification. Thus, though 133 participants have started the trial with twice weekly regimen, the data is presented for 135 participants in this arm (i.e. 133+2 = 135).	Participants received three times weekly (dosing every 2, 2 and 3 days) prophylaxis doses of N8-GP, 50 IU/kg as intravenous injections for a duration of 104 weeks. Participants treated with N8-GP in the previous trials NN7088-3859 (pathfinder2) and NN7088-3885 (pathfinder5) were included in this arm. Participants in this arm were permitted to switch to twice weekly at any time if clinically justified. Otherwise any treatment regimen was preferably be kept for a minimum of 6 months. During the trial, 5 participants switched from twice weekly to three times weekly regimen for treatment intensification. Thus, though 2 participants have started the trial with three times regimen, the data is presented for 7 participants in this arm (i.e. 2+5 = 7).
Measure Participants	25	135	7
Mean (Standard Deviation) [IU/kg]	3878 (296.4)	5320 (565.0)	7646 (877.2)

12. Secondary Outcome

Title	Change From Start Till End of Trial in Treatment Satisfaction (Based on Hemo-SAT Score)
Description	The treatment satisfaction of a bleed with N8-GP was assessed using HEMO-SAT assessment tool which contains a questionnaire with 6 domains (Ease and convenience, efficacy, burden, specialist/nurses, centre/hospital, general satisfaction), with a scale of 0-100. The lower scores reflecting greater treatment satisfaction. In other words, decrease in the score would mean improvement. The summary of change presented was based on individual changes since week 0. Data is presented for total score.
Time Frame	Week 0, Week 104

Outcome Measure Data

Analysis Population Description

FAS included all participants exposed to at least one dose of trial product in the current trial. 'Overall Number of Participants Analyzed' = participants with available data. Number analysed = Number of participants who contributed to the analysis. In the N8-GP, once weekly arm; none of the subjects were aged <=16 years. Hence the number analyzed is mentioned as zero.

Arm/Group Title	N8-GP, Once Weekly	N8-GP, Twice Weekly	N8-GP, Three Times Weekly
Arm/Group Description	Participants received once weekly (dosing every 7 day) prophylaxis doses of N8-GP, 75 IU/kg (International Units per kilogram) intravenous injections for 104 weeks. Participants treated with N8-GP once weekly or were on the on demand regimen in the previous trial NN7088-3859 (pathfinder2) were included in this arm. At the investigator's discretion an intensification of the dosing regimen to twice weekly was allowed if the participant experienced more than 2 bleeds within an 8 week period or experienced a severe bleed requiring hospitalization.	Participants received twice weekly (dosing every 3 and 4 days) prophylaxis doses of N8-GP intravenous injections for 104 weeks: N8-GP, 50 IU/kg for participants aged ≥ 12 years and N8-GP, 60 IU/kg for participants aged < 12 years. Participants treated with N8-GP in the previous trials NN7088-3859 (pathfinder2) and NN7088-3885 (pathfinder5) were included in this arm. At the investigator's discretion, an intensification of the dosing regimen to thrice weekly was allowed if the participant experienced spontaneous bleeding episodes. Participants in this arm were permitted to switch to three times weekly at any time if clinically justified. Otherwise any treatment regimen was preferably be kept for a minimum of 6 months. During the trial, 2 participants switched from once weekly to twice weekly regimen for treatment intensification. Thus, though 133 participants have started the trial with twice weekly regimen, the data is presented for 135 participants in this arm (i.e. 133+2 = 135).	Participants received three times weekly (dosing every 2, 2 and 3 days) prophylaxis doses of N8-GP, 50 IU/kg as intravenous injections for a duration of 104 weeks. Participants treated with N8-GP in the previous trials NN7088-3859 (pathfinder2) and NN7088-3885 (pathfinder5) were included in this arm. Participants in this arm were permitted to switch to twice weekly at any time if clinically justified. Otherwise any treatment regimen was preferably be kept for a minimum of 6 months. During the trial, 5 participants switched from twice weekly to three times weekly regimen for treatment intensification. Thus, though 2 participants have started the trial with three times regimen, the data is presented for 7 participants in this arm (i.e. 2+5 = 7).
Measure Participants	23	118	7
Total Score (participants aged >= 17 years)	-4.65 (8.16)	-2.11 (7.48)	-12.3 (23.78)
Total Score (participants aged <=16 years)	-1.78 (8.54)	1.43 (7.31)

Adverse Events

Time Frame	Week 0 to week 108
Adverse Event Reporting Description	All adverse events are treatment emergent (TEAEs). The TEAEs were defined as the events reported from date of first trial product administration until end of the treatment visit (week 104) or follow-up visit if relevant (1 month after end of the treatment). SAS included all enrolled participants as they were previously been exposed to trial product.
Arm/Group Title	N8-GP, Once Weekly		N8-GP, Twice Weekly		N8-GP, Three Times Weekly		Total
Arm/Group Description	Participants received once weekly (dosing every 7 day) prophylaxis doses of N8-GP, 75 IU/kg (International Units per kilogram) intravenous injections for 104 weeks. Participants treated with N8-GP once weekly or were on the on demand regimen in the previous trial NN7088-3859 (pathfinder2) were included in this arm. At the investigator's discretion an intensification of the dosing regimen to twice weekly was allowed if the participant experienced more than 2 bleeds within an 8 week period or experienced a severe bleed requiring hospitalization.		Participants received twice weekly (dosing every 3 and 4 days) prophylaxis doses of N8-GP intravenous injections for 104 weeks: N8-GP, 50 IU/kg for participants aged ≥ 12 years and N8-GP, 60 IU/kg for participants aged < 12 years. Participants treated with N8-GP in the previous trials NN7088-3859 (pathfinder2) and NN7088-3885 (pathfinder5) were included in this arm. At the investigator's discretion, an intensification of the dosing regimen to thrice weekly was allowed if the participant experienced spontaneous bleeding episodes. Participants in this arm were permitted to switch to three times weekly at any time if clinically justified. Otherwise any treatment regimen was preferably be kept for a minimum of 6 months. During the trial, 2 participants switched from once weekly to twice weekly regimen for treatment intensification. Thus, though 133 participants have started the trial with twice weekly regimen, AE data is presented for 135 participants in this arm (i.e. 133+2 = 135).		Participants received three times weekly (dosing every 2, 2 and 3 days) prophylaxis doses of N8-GP, 50 IU/kg as intravenous injections for a duration of 104 weeks. Participants treated with N8-GP in the previous trials NN7088-3859 (pathfinder2) and NN7088-3885 (pathfinder5) were included in this arm. Participants in this arm were permitted to switch to twice weekly at any time if clinically justified. Otherwise any treatment regimen was preferably be kept for a minimum of 6 months. During the trial, 5 participants switched from twice weekly to three times weekly regimen for treatment intensification. Thus, though 2 participants have started the trial with three times regimen, AE data is presented for 7 participants in this arm (i.e. 2+5 = 7).		Total number of participants
All Cause Mortality
	N8-GP, Once Weekly		N8-GP, Twice Weekly		N8-GP, Three Times Weekly		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		1/135 (0.7%)		0/7 (0%)		1/160 (0.6%)
Serious Adverse Events
	N8-GP, Once Weekly		N8-GP, Twice Weekly		N8-GP, Three Times Weekly		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/25 (16%)		15/135 (11.1%)		0/7 (0%)		19/160 (11.9%)
Hepatobiliary disorders
Cholecystitis	1/25 (4%)	1	0/135 (0%)	0	0/7 (0%)	0	1/160 (0.6%)	1
Infections and infestations
Arthritis bacterial	0/25 (0%)	0	1/135 (0.7%)	1	0/7 (0%)	0	1/160 (0.6%)	1
Subcutaneous abscess	1/25 (4%)	1	0/135 (0%)	0	0/7 (0%)	0	1/160 (0.6%)	1
Injury, poisoning and procedural complications
Humerus fracture	0/25 (0%)	0	1/135 (0.7%)	1	0/7 (0%)	0	1/160 (0.6%)	1
Procedural haemorrhage	1/25 (4%)	1	0/135 (0%)	0	0/7 (0%)	0	1/160 (0.6%)	1
Road traffic accident	1/25 (4%)	1	0/135 (0%)	0	0/7 (0%)	0	1/160 (0.6%)	1
Skin laceration	0/25 (0%)	0	1/135 (0.7%)	1	0/7 (0%)	0	1/160 (0.6%)	1
Traumatic haemorrhage	0/25 (0%)	0	1/135 (0.7%)	1	0/7 (0%)	0	1/160 (0.6%)	1
Wound secretion	0/25 (0%)	0	1/135 (0.7%)	1	0/7 (0%)	0	1/160 (0.6%)	1
Musculoskeletal and connective tissue disorders
Arthropathy	1/25 (4%)	1	0/135 (0%)	0	0/7 (0%)	0	1/160 (0.6%)	1
Intervertebral disc protrusion	1/25 (4%)	1	0/135 (0%)	0	0/7 (0%)	0	1/160 (0.6%)	1
Osteoarthritis	0/25 (0%)	0	1/135 (0.7%)	1	0/7 (0%)	0	1/160 (0.6%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma	0/25 (0%)	0	1/135 (0.7%)	1	0/7 (0%)	0	1/160 (0.6%)	1
Melanocytic naevus	0/25 (0%)	0	1/135 (0.7%)	1	0/7 (0%)	0	1/160 (0.6%)	1
Squamous cell carcinoma of the tongue	0/25 (0%)	0	1/135 (0.7%)	1	0/7 (0%)	0	1/160 (0.6%)	1
Nervous system disorders
Cervical radiculopathy	1/25 (4%)	1	0/135 (0%)	0	0/7 (0%)	0	1/160 (0.6%)	1
Presyncope	0/25 (0%)	0	1/135 (0.7%)	1	0/7 (0%)	0	1/160 (0.6%)	1
Seizure	0/25 (0%)	0	3/135 (2.2%)	3	0/7 (0%)	0	3/160 (1.9%)	3
Psychiatric disorders
Depression suicidal	0/25 (0%)	0	1/135 (0.7%)	1	0/7 (0%)	0	1/160 (0.6%)	1
Surgical and medical procedures
Mole excision	0/25 (0%)	0	1/135 (0.7%)	1	0/7 (0%)	0	1/160 (0.6%)	1
Other (Not Including Serious) Adverse Events
	N8-GP, Once Weekly		N8-GP, Twice Weekly		N8-GP, Three Times Weekly		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/25 (36%)		46/135 (34.1%)		4/7 (57.1%)		56/160 (35%)
Gastrointestinal disorders
Dental caries	3/25 (12%)	3	0/135 (0%)	0	0/7 (0%)	0	3/160 (1.9%)	3
Infections and infestations
Influenza	0/25 (0%)	0	9/135 (6.7%)	9	0/7 (0%)	0	9/160 (5.6%)	9
Nasopharyngitis	3/25 (12%)	3	21/135 (15.6%)	23	0/7 (0%)	0	24/160 (15%)	26
Upper respiratory tract infection	4/25 (16%)	13	11/135 (8.1%)	18	1/7 (14.3%)	2	16/160 (10%)	33
Injury, poisoning and procedural complications
Fall	0/25 (0%)	0	3/135 (2.2%)	3	1/7 (14.3%)	1	3/160 (1.9%)	4
Metabolism and nutrition disorders
Vitamin B12 deficiency	2/25 (8%)	2	0/135 (0%)	0	0/7 (0%)	0	2/160 (1.3%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	2/25 (8%)	2	11/135 (8.1%)	12	1/7 (14.3%)	1	14/160 (8.8%)	15
Limb discomfort	0/25 (0%)	0	0/135 (0%)	0	1/7 (14.3%)	1	1/160 (0.6%)	1
Nervous system disorders
Headache	0/25 (0%)	0	10/135 (7.4%)	11	0/7 (0%)	0	10/160 (6.3%)	11
Psychiatric disorders
Attention deficit hyperactivity disorder	0/25 (0%)	0	0/135 (0%)	0	1/7 (14.3%)	1	1/160 (0.6%)	1
Depression	0/25 (0%)	0	1/135 (0.7%)	1	2/7 (28.6%)	2	3/160 (1.9%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

At the end of the trial, one or more scientific publications may be prepared collaboratively by the investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for up to 60 days to protect intellectual property.