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)
- Conditions
- Haemophilia A
- Interventions
- Drug: turoctocog alfa pegol (N8-GP)
- Registration Number
- NCT05082116
- Lead Sponsor
- Novo Nordisk A/S
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 36
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description N8-GP prophylaxis turoctocog alfa pegol (N8-GP) All patients will receive prophylaxis with 50 IU/kg N8-GP every 4 days for a treatment period of at least 28 weeks (with the possibility of switching to twice-weekly dosing during the treatment period at the discretion of the investigator).
- Primary Outcome Measures
Name Time Method Number of Bleeding Episodes Per Year (Annualised Bleeding Rate) From start of treatment (Week 0) until Week 28 Number of bleeding episodes per year (Annualised Bleeding Rate) data is reported. Annualised bleeding rate (ABR) is the number of bleeding episodes per year.
- Secondary Outcome Measures
Name Time Method FVIII Trough Activity 96 h Post-injection (C96h) Single-dose: 96 h ± 8 h post-injection at Week 0, Steady-state: 96 h ± 8 h post-injection at Week 28 FVIII plasma activity was measured after 96 h of injection. This was measured at two time points Week 0 and Week 28 during the study. Chromogenic assay was performed.
Area Under the Curve (AUC0-inf) 0-96 hours post-injection at Week 0 and Week 28 Area under the plasma activity versus time profile from time zero to infinity (AUC0-inf) was measured.
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) From start of treatment (Week 0) until Week 28 Haemostatic effect of N8-GP for treatment of bleeding episodes was assessed by 4-point response scale: none, moderate, good or excellent. Evaluation during trial was done by participant and/or parent(s)/caregiver within approximately 8 hours after a single injection as follows: Excellent: Abrupt pain relief and/or clear improvement in objective signs of bleeding within approximately 8 hrs after a single injection; Good: Definite pain relief and/or improvement in signs of bleeding within approximately 8 hrs 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 Injections Needed to Treat Bleeding Episodes From start of treatment (Week 0) until Week 28 The mean number of injections of N8-GP used for treatment of a bleed from start to stop of a bleed was reported.
FVIII Trough Activity During Prophylaxis From start of treatment (Week 0) (excluding the first exposure) until Week 28 Trough levels of FVIII was reported for all participnats who received prophylaxis treatment. Chromogenic assay was performed with N8-GP product specific standard (PSS) as a calibrator. The analysis is based on a mixed model on the log transformed plasma FVIII activity with age group as fixed effect and participant as a random effect. The mean trough is presented back-transformed to the natural scale.
Number of Adverse Events (AEs) From start of treatment (Week 0) until end of trial (Week 32) An adverse event (AE) was defined as any unfavorable 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 presented AEs are treatment-emergent. A treatment-emergent adverse event was defined as an event with onset after first N8-GP administration.
Number of Serious Adverse Events (SAEs) From start of treatment (Week 0) until end of trial (Week 32) A serious adverse event (SAE) is defined as any untoward medical occurrence that at any dose results in death, or is life-threatening, or requires inpatient hospitalization or causes prolongation of existing hospitalization results in persistent or significant disability/incapacity, or may have caused a congenital anomaly/birth defect, or requires intervention to prevent permanent impairment or damage. All presented SAEs are treatment-emergent (any serious adverse events which occurred after trial product administration).
Incremental Recovery (IR) 30 min post-injection at Week 0, Week 28 The incremental recovery was calculated by subtracting the FVIII activity (IU/mL) measured in plasma at time 0 from that measured at time 30 min after dosing and dividing this difference by the dose injected at time 0 expressed as IU/kg body weight. FVIII activity was measured with a chromogenic assay.
Percentage of Participants With Incidence Rate of Confirmed FVIII Inhibitors ≥0.6 BU From start of treatment (Week 0) until Week 28 Percentage of participants who developed inhibitory antibodies against FVIII was presented. A participant was said to have FVIII-inhibitors if two consecutive tests, preferably within 2 weeks, were positive (greater than or equal to (≥) 0.6 bethesda unit (BU)). For the calculation of the inhibitor rate the numerator was included for all participants with neutralising antibodies while the denominator was included for all participants with a minimum of 50 exposures plus any participants with less than 50 exposures but with neutralising inhibitor.
FVIII Activity 30 Min Post-injection (C30min) 30 min post-injection at Week 0, Week 28 FVIII plasma activity was measured after 30 mins of injection. FVIII activity was measured with a chromogenic assay.
Area Under the Curve (0-t) 0-96 hours post-injection at Week 0 and Week 28 Area under the plasma activity versus time profile from time zero to last measurable activity (AUC0-t) was measured.
Area Under the Curve (0-96h) 0-96 hours post-injection at Week 0 and Week 28 Area under the plasma activity versus time profile from time zero to 96 hours (AUC0-96h) was measured.
Clearance (CL) Single-dose: 0-96 h post-injection at Week 0, Steady-state: 0-96 h post-injection at Week 28 Clearance (CL) of drug after intravenous administration was reported. Clearance was calculated using the formula CL= Dose / AUC(0-inf) for single dose and CL= Dose / AUC(0-96) h for steady state.
Apparent Volume of Distribution (Vz) Based on the Terminal Phase 0-96 hours post-injection on Week 0 and Week 28 Apparent volume of distribution (Vz) based on the terminal phase was measured. Apparent volume of distribution was calculated using formula: total plasma clearance divided by terminal elimination rate constant (Vz= CL/λz).
Consumption of N8-GP for Prophylaxis From start of treatment (Week 0) until Week 28 The mean consumption of N8-GP for prophylaxis per year per participant was reported and it was measured in international units per kilogram per year (IU/kg/year).
Accumulation Ratio 0-96 hours post-injection on Week 28 Accumulation ratio was calculated as AUC(0-96h) at steady state/AUC(0-96h) at single dose. AUC(0-96) is the area under the plasma activity versus time profile from time zero to 96 hours.
Terminal Half-life (t½) 0-96 hours post-injection on Week 0 and Week 28 Terminal half life was calculated as ln(2)/λz; where λz is the terminal elimination rate constant. The terminal elimination rate constant was estimated using linear regression on the terminal part of the log (activity) versus time profile.
Mean Residence Time 0-96 hours post-injection on Week 0 and Week 28 Mean residence time (MRT) calculated as area under the first moment plasma concentration-time curve (AUMC \[0-inf\]) divided by AUC (0-inf). (AUMC \[0-inf\]) is the area under the first moment plasma concentration-time curve from time 0 to infinity.
Terminal Elimination Rate Constant (λz) 0-96 hours post-injection on Week 0 and Week 28 The terminal elimination rate constant was estimated using linear regression on the terminal part of the log(activity) versus time profile.
Apparent Volume of Distribution (Vss) Based on Steady-state 0-96 h post-injection at Week 28 Apparent volume of distribution (Vss) at steady-state was measured. Apparent volume of distribution (Vss) was calculated using formula: total plasma clearance multiplied by mean residence time (Vss=CL\*MRT).
Extrapolated Area Under the Curve (AUC Percent [%] Extrap 0-96 hours post-injection on Week 0 and Week 28 Percentage of AUC(0-inf) determined by extrapolation. It was calulating using formula: Area under the plasma activity versus time profile from given measurable time to infinity (AUCt-inf)/Area under the plasma activity versus time profile from time zero to infinity (AUC0-inf).
Trial Locations
- Locations (8)
Beijing Children's Hospital，Capital Medical University
🇨🇳Beijing, Beijing, China
Fujian Medical University Union Hospital-Hematology
🇨🇳Fuzhou, Fujian, China
Haemotology, Nanfang Hospital, Southern Medical University
🇨🇳Guangzhou, Guangdong, China
The Affiliated hospital of Guizhou Medical University-Hemato
🇨🇳Guiyang, Guizhou, China
Qinghai Provincial People's Hospital
🇨🇳Xining, Qinghai, China
Jinan Central Hospital
🇨🇳Ji'nan, Shandong, China
Institute of hematology and Blood Diseases Hospital, Tianjin
🇨🇳Tianjin, Tianjin, China
The Second Affiliated Hospital of Kunming Medical University
🇨🇳Kunming, Yunnan, China