Safety and Efficacy of Turoctocog Alfa Pegol (N8-GP) in Previously Untreated Patients With Haemophilia A

An Open-label Single-arm Multicentre Non-controlled Phase 3a Trial Investigating Safety and Efficacy of N8-GP in Prophylaxis and Treatment of Bleeding Episodes in Previously Untreated Paediatric Patients With Severe Haemophilia A

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02137850

Acronym

pathfinder™6

Enrollment

124

Registered

2014-05-14

Start date

2014-06-26

Completion date

2023-06-07

Last updated

2025-12-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Congenital Bleeding Disorder, Haemophilia A

Brief summary

This trial is conducted globally. The aim of the trial is to investigate the safety and efficacy of turoctocog alfa pegol (N8-GP) in previously untreated patients (PUPs) with haemophilia A.

Interventions

DRUGturoctocog alfa pegol

For intravenous (i.v.) injection. Frequency and dosage (20-75 U/kg) dependent on whether given as treatment for bleeding episode or as prophylaxis

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

MALE

Age

0 Years to 6 Years

Healthy volunteers

Inclusion criteria

* Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial * Male, age below 6 years of age at the time of signing informed consent * Diagnosis of severe haemophilia A (FVIII activity level 1%) based on medical records or central laboratory results * No prior use of purified clotting factor products (5 previous exposures to blood components is acceptable)

Exclusion criteria

* Any history of FVIII inhibitor (defined by medical records) - Known or suspected hypersensitivity to trial product or related products * Previous participation in this trial. Participation is defined as first dose administered of trial product * Receipt of any investigational medicinal product within 30 days before screening * Congenital or acquired coagulation disorder other than haemophilia A * Any chronic disorder or severe disease which, in the opinion of the Investigator, might jeopardise the patient's safety or compliance with the protocol * Patient's parent(s')/legally acceptable representative (LAR(s')) mental incapacity, unwillingness to cooperate, or a language barrier precluding adequate understanding and cooperation

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Inhibitory Antibodies Against Coagulation Factor VIII (FVIII)	From start of the treatment up to 7 years	Number of participants with inhibitory antibodies against coagulation factor VIII (FVIII) was reported during the main and extension phase of the trial.

Secondary

Measure	Time frame	Description
Number of Participants With Confirmed High Titre Inhibitors (Defined as Inhibitor Titre Above 5 Bethesda Units (BU)	From start of the treatment up to 8.9 years	Number of participants with confirmed high titre inhibitors (defined as inhibitor titre above 5 Bethesda Units (BU) was reported during the main and extension phase of the trial.
Number of Breakthrough Bleeding Episodes During Prophylaxis With N8-GP (Annualised Bleeding Rate)	From start of the treatment up to 8.9 years	The number of bleeding episodes per year reported during the prophylactic treatment with N8-GP was reported.
Haemostatic Effect of N8-GP in Treatment of Bleeding Episodes, Assessed by a Predefined 4-point Haemostatic Response Scale (Excellent, Good, Moderate and None)	From start of the treatment up to 8.9 years	Haemostatic effect of turoctocog alfa pegol for treatment of bleeding episodes was assessed by 4-point response scale: none, moderate, good or excellent. Excellent: Abrupt pain relief and/or clear improvement in objective signs of bleeding within approximately 8 hours after a single injection; Good: Definite pain relief and/or improvement in signs of bleeding within approximately 8 hours after a single injection, but possibly requiring more than one injection for complete resolution; Moderate: Probable or slight beneficial effect within approximately 8 hours after the first injection, but usually requiring more than one injection; None: No improvement, or worsening of symptoms. Number of bleeding episodes in each category is reported.
Consumption of N8-GP for Prophylaxis (International Unit Per Kilogram (IU/Kg))	From start of the treatment up to 8.9 years	Consumption of N8-GP for prophylaxis is reported. Consumption used for treatment includes all doses given. Yearly consumption is only calculated for patients with a exposure time of at least 30 days. Average dose consumption in IU/kg during main and extension phase is reported.
Number of Adverse Events Including Serious Adverse Events and Medical Events of Special Interest	From start of the treatment up to 8.9 years	Number of adverse events including serious adverse events and medical events of special interest reported during the main and extension phase of the trial. An adverse event (AE) is any untoward medical occurrence in a patient administered a product, and which does not necessarily have a causal relationship with this treatment. Serious adverse event (SAE) is an experience that at any dose results in any of the following: Death, a life-threatening experience, in-patient hospitalisation or prolongation of existing hospitalisation, persistent or significant disability or incapacity, congenital anomaly or birth defect and important medical events that may not result in death, be life threatening or require hospitalisation. Medical event of special interest (MESI) is an event which, in the evaluation of safety, has a special focus.
Consumption of N8-GP for Treatment of Bleeding Episodes (International Unit Per Kilogram Per Bleed (IU/kg/Bleed))	From start of the treatment up to 8.9 years	Consumption of N8-GP for treatment of bleeding episodes (IU/kg/bleed) is reported. Average dose consumption in IU/kg/bleed during main and extension phase is reported.
Consumption of N8-GP for Treatment of Bleeding Episodes (Number of Injections)	From start of the treatment up to 8.9 years	Consumption of N8-GP for treatment of bleeding episodes (number of injections) is reported. Number of average injections required for treatment of per bleed is reported.
Total Consumption of N8-GP Per Patient (Prevention and Treatment of Bleeding Episodes) Annualised Value	From start of the treatment up to 8.9 years	Total consumption of N8-GP per patient (prevention and treatment of bleeding episodes) annualised value is presented. Consumption used for treatment includes all doses given. Yearly consumption is only calculated for patients with a exposure time of at least 30 days. Consumption used for treatment per year per patient (IU/kg/year/patient) is reported.
Outcome of ITI, Assessed by a Predefined 4-point ITI Outcome Scale (Success, Partial Success, Failure, Other)	From start of the treatment up to 8.9 years	The outcome of ITI was evaluated by predefined 4-point outcome of ITI scale ('success', 'partial success', 'failure', 'other'). Success: An inhibitor titre less than (\<) 0.6 BU. A normalised FVIII recovery, defined as greater than or equal to (≥) 66 percentage (%) of expected incremental recovery. An N8-GP half-life (t½) ≥9 hours after a 72-hour treatment-free washout period. Partial success: Reduction in inhibitor titre to less than or equal to (≤) 5 BU. Clinical effect of N8-GP therapy as judged by the investigator. Failure: Failure to attain defined success or partial success within 24 months of uninterrupted ITI with N8-GP. Inhibitor decrease less than (\<) 20% after one year of ITI treatment. Other: Not fulfilling the above criteria. Number of participants in each category is reported.
Consumption of N8-GP for Prophylaxis (Number of Injections)	From start of the treatment up to 8.9 years	Consumption of N8-GP for prophylaxis is reported. Consumption used for treatment includes all doses given. Yearly consumption is only calculated for patients with a exposure time of at least 30 days. Number of injections consumption per patient during main and extension phase is reported.

Countries

Algeria, Argentina, Australia, Austria, Bulgaria, Canada, France, Germany, Greece, Israel, Italy, Japan, Malaysia, Mexico, Portugal, Puerto Rico, Romania, Serbia, Spain, Taiwan, Thailand, Ukraine, United States

Participant flow

Recruitment details

The trial was conducted in 14 countries as follows: Australia (2), Austria (2), Bulgaria (1), Canada (1), Germany (1), Greece (2), Israel (1), Italy (1), Japan (3), Malaysia (3), Spain (2), Taiwan (1), Thailand (3), United States (8).

Pre-assignment details

A total of 81 participants were exposed to Turoctocog alfa pegol (N8-GP). Trial consists of main phase: pre-prophylaxis, prophylaxis & immune tolerance induction (ITI) and extension phase: prophylaxis period until end of treatment. Pre-prophylaxis was optional and allowed participants to receive treatment until 24 months of age/upon reaching 20EDs, whichever came first. Other participants directly started on prophylaxis treatment at visit 1.

Participants by arm

Arm	Count
All Participants Participants received pre-prophylaxis treatment of N8-GP 60 IU/kg intravenous injection as slow start prophylaxis and on-demand treatment of bleeding episodes until they were 24 months of age or until 20 exposure days (ED) on pre-prophylaxis, whichever came first in the main phase. After which they switched to prophylaxis treatment. In prophylaxis, participants received N8-GP 60 IU/kg intravenous injection twice weekly with doses separated by at least 3, and no more than 4, calendar days. Furthermore, it was permissible to start prophylaxis in the main phase with an every 3rd day or once-weekly dosing regimen. In the extension phase, subjects were to continue the prophylaxis dosing regimen as prescribed at the end of the main phase.	81
Total	81

Arm

Count

All Participants

Participants received pre-prophylaxis treatment of N8-GP 60 IU/kg intravenous injection as slow start prophylaxis and on-demand treatment of bleeding episodes until they were 24 months of age or until 20 exposure days (ED) on pre-prophylaxis, whichever came first in the main phase. After which they switched to prophylaxis treatment. In prophylaxis, participants received N8-GP 60 IU/kg intravenous injection twice weekly with doses separated by at least 3, and no more than 4, calendar days. Furthermore, it was permissible to start prophylaxis in the main phase with an every 3rd day or once-weekly dosing regimen. In the extension phase, subjects were to continue the prophylaxis dosing regimen as prescribed at the end of the main phase.

Total

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Extension Phase: Prophylaxis	Adverse Event	0	1	0
Extension Phase: Prophylaxis	Early site closure	0	2	0
Extension Phase: Prophylaxis	Other	0	1	0
Extension Phase: Prophylaxis	Protocol Violation	0	1	0
Extension Phase: Prophylaxis	Withdrawal by parent/guardian	0	1	0
Immune Tolerance Induction	Lack of Efficacy	0	0	1
Immune Tolerance Induction	Undergone minor surgery	0	0	2
Immune Tolerance Induction	Withdrawal by parent/guardian	0	0	1
Main Phase: Pre-Prophylaxis	Adverse Event	3	0	0
Main Phase: Pre-Prophylaxis	Lack of Efficacy	1	0	0
Main Phase: Pre-Prophylaxis	Other	3	0	0
Main Phase: Pre-Prophylaxis	Protocol Violation	1	0	0
Main Phase: Pre-Prophylaxis	Withdrawal by parent/guardian	1	0	0
Main Phase: Pre-Prophylaxis	Withdrawal by Subject	2	0	0
Main Phase: Prophylaxis	Adverse Event	0	4	0
Main Phase: Prophylaxis	Early site closure	0	2	0
Main Phase: Prophylaxis	Lack of Efficacy	0	1	0
Main Phase: Prophylaxis	Lost to Follow-up	0	1	0
Main Phase: Prophylaxis	Other	0	1	0
Main Phase: Prophylaxis	Protocol Violation	0	1	0
Main Phase: Prophylaxis	Switched to ITI without completing main phase	0	2	0
Main Phase: Prophylaxis	Withdrawal by parent/guardian	0	2	0

Baseline characteristics

Characteristic	All Participants
Age, Continuous	10.2 Years STANDARD_DEVIATION 11
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	74 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	24 Participants
Race (NIH/OMB) Black or African American	2 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	6 Participants
Race (NIH/OMB) White	49 Participants
Sex: Female, Male Female	0 Participants
Sex: Female, Male Male	81 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 55	0 / 69	0 / 8
other Total, other adverse events	28 / 55	51 / 69	7 / 8
serious Total, serious adverse events	18 / 55	34 / 69	1 / 8

Outcome results

Primary

Number of Participants With Inhibitory Antibodies Against Coagulation Factor VIII (FVIII)

Number of participants with inhibitory antibodies against coagulation factor VIII (FVIII) was reported during the main and extension phase of the trial.

Time frame: From start of the treatment up to 7 years

Population: Results were based on safety analysis set (SAS). The SAS consist of all participants exposed to N8-GP. Number of participants analyzed=participants with available data for this endpoint. This outcome is applicable only for the reported arms.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Pre-prophylaxis	Number of Participants With Inhibitory Antibodies Against Coagulation Factor VIII (FVIII)	11 Participants
Prophylaxis	Number of Participants With Inhibitory Antibodies Against Coagulation Factor VIII (FVIII)	10 Participants

Secondary

Consumption of N8-GP for Prophylaxis (International Unit Per Kilogram (IU/Kg))

Consumption of N8-GP for prophylaxis is reported. Consumption used for treatment includes all doses given. Yearly consumption is only calculated for patients with a exposure time of at least 30 days. Average dose consumption in IU/kg during main and extension phase is reported.