Clinical trial NCT05082116: Efficacy and Safety of Turoctocog Alfa Pegol (N8-GP) for Prophylaxis and Treatment of Bleeding Episodes in Previously Treated Chinese Patients With Haemophilia A (pathfinder10)
Official title: A Multi-centre, Open-label Trial Evaluating Efficacy, Safety and Pharmacokinetics of Turoctocog Alfa Pegol (N8-GP) When Used for Treatment and Prophylaxis of Bleeding Episodes in Previously Treated Chinese Patients With Haemophilia A
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Haemophilia A
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2021-10-18
Enrollment: 36
Sex: MALE
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The study investigates how well the medicine called turoctocog alfa pegol (N8-GP) works in previously treated Chinese patients with severe haemophilia A.

Participants will be treated with N8-GP. This is a medicine that doctors can already prescribe in other countries.

The medicine will be injected into a vein (intravenous injections) and blood samples will be collected.

The study will last for about 7-8 months. Participants will have between 8 and 15 visits to the clinic and possibly a number of phone calls with the study doctor.


Eligibility criteria: 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 Chinese patient with severe congenital haemophilia A with a FVIII activity below 1% according to medical records.
* Aged greater than or equal to 12 years at the time of signing informed consent.
* History of at least 150 exposure days (EDs) to other FVIII products.
* The patient and/or caregiver is capable of assessing a bleeding episode, keeping a diary, performing home treatment of bleeding episodes and otherwise following the trial procedures at the discretion of the investigator.

Exclusion Criteria:

* Known or suspected hypersensitivity to trial product or related products.
* Previous participation in this trial. Participation is defined as signed informed consent.
* Participation in any clinical trial of an approved or non-approved investigational medicinal product within 5 half-lives or 30 days from screening, whichever is longer.
* Known history of FVIII inhibitors based on existing medical records, laboratory report reviews and patient and/or caregiver interviews.
* Current FVIII inhibitors greater than or equal to 0.6 BU.
* Congenital or acquired coagulation disorder other than haemophilia According to medical records.
* HIV positive, defined by medical records, with CD4+ count less than or equal 200/L and a viral load greater than 200 particles/μl or greater than 400000 copies/mL within 6 months of the trial entry. If the data are not available in medical records within last 6 months, then the test must be performed at screening visit.
* Previous significant thromboembolic events (e.g. myocardial infarction, cerebrovascular disease or deep venous thrombosis) as defined by available medical records.
* Hepatic dysfunction defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) greater than 3 times limit of normal combined with total bilirubin greater than 1.5 times the upper limit of normal at screening, as defined by central laboratory
* Renal impairment defined as estimated glomerular filtration rate (eGFR) below or equal to 30 mL/min/1.73 m\^2 for serum creatinine measured at screening, as defined by central laboratory.
* Platelet count below 50×109/L at screening based on central laboratory values at screening.
* Ongoing immune modulating or chemotherapeutic medication.
* Any disorder, except for conditions associated with haemophilia A, which in the investigator's opinion might jeopardise the patient's safety or compliance with the protocol.
* Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation.

Primary outcomes:
measure: Number of Bleeding Episodes Per Year (Annualised Bleeding Rate)
timeFrame: From start of treatment (Week 0) until Week 28
Secondary outcomes:
measure: Haemostatic Effect of N8-GP When Used for Treatment of Bleeding Episodes, Assessed on a Four-point Scale for Haemostatic Response (Excellent, Good, Moderate and None)
timeFrame: From start of treatment (Week 0) until Week 28
measure: Number of Injections Needed to Treat Bleeding Episodes
timeFrame: From start of treatment (Week 0) until Week 28
measure: Consumption of N8-GP for Prophylaxis
timeFrame: From start of treatment (Week 0) until Week 28
measure: FVIII Trough Activity During Prophylaxis
timeFrame: From start of treatment (Week 0) (excluding the first exposure) until Week 28
measure: Percentage of Participants With Incidence Rate of Confirmed FVIII Inhibitors ≥0.6 BU
timeFrame: From start of treatment (Week 0) until Week 28
measure: Number of Adverse Events (AEs)
timeFrame: From start of treatment (Week 0) until end of trial (Week 32)
measure: Number of Serious Adverse Events (SAEs)
timeFrame: From start of treatment (Week 0) until end of trial (Week 32)
measure: Incremental Recovery (IR)
timeFrame: 30 min post-injection at Week 0, Week 28
measure: FVIII Activity 30 Min Post-injection (C30min)
timeFrame: 30 min post-injection at Week 0, Week 28
measure: FVIII Trough Activity 96 h Post-injection (C96h)
timeFrame: Single-dose: 96 h ± 8 h post-injection at Week 0, Steady-state: 96 h ± 8 h post-injection at Week 28
measure: Area Under the Curve (AUC0-inf)
timeFrame: 0-96 hours post-injection at Week 0 and Week 28
measure: Area Under the Curve (0-t)
timeFrame: 0-96 hours post-injection at Week 0 and Week 28
measure: Area Under the Curve (0-96h)
timeFrame: 0-96 hours post-injection at Week 0 and Week 28
measure: Accumulation Ratio
timeFrame: 0-96 hours post-injection on Week 28
measure: Terminal Half-life (t½)
timeFrame: 0-96 hours post-injection on Week 0 and Week 28
measure: Clearance (CL)
timeFrame: Single-dose: 0-96 h post-injection at Week 0, Steady-state: 0-96 h post-injection at Week 28
measure: Apparent Volume of Distribution (Vz) Based on the Terminal Phase
timeFrame: 0-96 hours post-injection on Week 0 and Week 28
measure: Apparent Volume of Distribution (Vss) Based on Steady-state
timeFrame: 0-96 h post-injection at Week 28
measure: Extrapolated Area Under the Curve (AUC Percent [%] Extrap
timeFrame: 0-96 hours post-injection on Week 0 and Week 28
measure: Mean Residence Time
timeFrame: 0-96 hours post-injection on Week 0 and Week 28
measure: Terminal Elimination Rate Constant (λz)
timeFrame: 0-96 hours post-injection on Week 0 and Week 28
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Children's Hospital，Capital Medical University
state: Beijing
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital-Hematology
state: Fujian
city: Guangzhou
country: China
facility: Haemotology, Nanfang Hospital, Southern Medical University
state: Guangdong
city: Guiyang
country: China
facility: The Affiliated hospital of Guizhou Medical University-Hemato
state: Guizhou
city: Xining
country: China
facility: Qinghai Provincial People's Hospital
state: Qinghai
city: Ji'nan
country: China
facility: Jinan Central Hospital
state: Shandong
city: Tianjin
country: China
facility: Institute of hematology and Blood Diseases Hospital, Tianjin
state: Tianjin
city: Kunming
country: China
facility: The Second Affiliated Hospital of Kunming Medical University
state: Yunnan
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Transparency (dept. 1452)
role: STUDY_DIRECTOR
References: