A Research Study Investigating Nonacog Beta Pegol (N9-GP) for Treatment and Prevention of Bleedings in Chinese People With Haemophilia B

Phase 3

Completed

Conditions: Haemophilia B

Interventions: Drug: Nonacog beta pegol

Registration Number: NCT05365217

Lead Sponsor: Novo Nordisk A/S

Brief Summary: The study investigates how well the medicine called nonacog beta pegol (N9-GP) works in Chinese people with haemophilia B. Participants will be treated with N9-GP. This is a medicine that doctors can already prescribe in other countries. The medicine will be injected into a vein (intravenous injection). At the visits to the clinic, the medicine will be injected by the study doctor. When treating themselves at home, participants inject the medicine using a needle and vial set. The study will last for about 12-16 months. The participants will have between 9 and 19 visits to the clinic and possibly also some phone calls with the study doctor. At all visits to the clinic, the participants will have blood samples taken.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 30

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 moderate to severe congenital haemophilia B with a factor IX (FIX) activity less than or equal to 2 percent according to medical records.
Aged 12-70 years (both inclusive) at the time of signing informed consent.
History of at least 100 exposure days (EDs) to products containing FIX.1.
Patients currently on prophylaxis or patients currently treated on-demand with at least 6 bleeding episodes during the last 12 months or at least 3 bleeding episodes during the last 6 months.
The patient, legally authorised representative (LAR) and/or caregiver are capable of assessing a bleeding episode, keeping a diary, performing home treatment of bleeding episodes and otherwise following the trial procedures.

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 FIX inhibitors based on existing medical records, laboratory report reviews and patient and LAR interviews.
Current FIX inhibitors greater than or equal to 0.6 Bethesda unit (BU).
HIV positive, defined by medical records, with CD4+ count less than or equal 200 per microlitre (μL) and a viral load greater than 200 particles per microlitre or greater than 400000 copies per millilitre (mL) within 6 months of the trial entry. If the data are not available in the medical records within the last 6 months, then the test must be performed at the screening visit.
Congenital or acquired coagulation disorder other than haemophilia B.
Previous arterial thrombotic events (e.g. myocardial infarction and intracranial thrombosis) or previous deep venous thrombosis or pulmonary embolism (as defined by available medical records).
Hepatic dysfunction defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) greater than 3 times the upper limit of normal combined with total bilirubin greater than 1.5 times the upper limit of normal at screening.
Renal impairment defined as estimated glomerular filtration rate (eGFR) less than or equal to 30 mL/min/1.73 m^2 for serum creatinine measured at screening.
Any disorder, except for conditions associated with haemophilia B, which in the investigator's opinion might jeopardise the patient's safety or compliance with the protocol.
Platelet count less than 50×10^9/L at screening.
Immune modulating or chemotherapeutic medication.
Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A - Nonacog beta pegol (On-demand/Prophylaxis)	Nonacog beta pegol	Participants on on-demand treatment for 28 weeks, thereafter prophylactic treatment
Arm B - Nonacog beta pegol (Prophylaxis)	Nonacog beta pegol	Participants on prophylactic treatment only

Primary Outcome Measures

Name	Time	Method
Haemostatic Effect of Nonacog Beta Pegol When Used for Treatment of Bleeding Episodes During on Demand and Prophylaxis (PPX)	From start of treatment (week 0) until end of treatment (up to week 50)	Haemostatic effect of N9-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.

Secondary Outcome Measures

Name	Time	Method
Number of Treated Bleeding Episodes During Prophylaxis (PPX) Treatment (Arm B Only)	From start of treatment (week 0) until end of treatment (week 50)	Number of bleeding episodes per year data is reported. Annualised bleeding rate (ABR) is the number of bleeding episodes per year.
Consumption of Nonacog Beta Pegol for Treatment of Bleeding Episodes	From start of treatment (week 0) until end of treatment (up to week 50)	The mean number of injections of N9-GP used for treatment of a bleed from start to stop of a bleed was reported and it was measured in international units per kilogram per bleed (IU/kg/bleed).
Consumption of Nonacog Beta Pegol for Prophylaxis (PPX) Treatment (Arm B Only)	From start of treatment (week 0) until end of treatment (week 50)	The mean consumption of N9-GP for prophylaxis per year per participant was reported and it was measured in international units per kilogram per year (IU/kg/year).
FIX Trough Levels During Prophylaxis (PPX) Treatment (Arm B Only)	From start of treatment (week 0) until end of treatment (week 50)	Trough levels of FVIII was reported for all participants who received prophylaxis treatment. Chromogenic assay was performed with N9-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 participants as a random effect. The mean trough is presented back-transformed to the natural scale. The estimated mean/average steady state trough level of FVIII over time (all visits from start of treatment (week 0) until end of treatment) was presented. Data is reported for specific treatment in which participants were a part of at any time from week 0 to end of the treatment (EOT) Week 50, not at specific time points assessed from week 0 to EOT.
Number of Participants With Inhibitory Antibodies Against FIX Defined as Titre ≥0.6 Bethesda Units (BU)	From start of treatment (week 0) until end of treatment (week 50)	Number of participants who developed inhibitory antibodies (IA) 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.
Number of Adverse Events (AEs)	From start of treatment (week 0) until end of treatment (week 50)	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 N9-GP administration.
Number of Serious Adverse Events (SAEs)	From start of treatment (week 0) until end of treatment (week 50)	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) (Arm B Only)	Single-dose: 30±10 minutes post injection at week 0, Steady-state: 30±10 minutes post injection at week 12	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 international units per kilogram (IU/kg) body weight. FVIII activity was measured with a chromogenic assay.
Terminal Half-life (t½) (Arm B Only)	Single-dose: 30±10 minutes post injection at week 0, Steady-state: 30±10 minutes post injection at week 12	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.
Clearance (CL) (Arm B Only)	Single-dose: 0-168 hours post injection at week 0, Steady-state: 0-168 hours post injection at week 12	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.
Area Under the Curve (AUC) (Arm B Only)	Single-dose: 0-168 hours post injection at week 0, Steady-state: 0-168 hours post injection at week 12	Area under the plasma activity versus time profile from time zero to 168 hours (AUC0-168h) was measured.

Trial Locations

Locations (14): Henan Cancer Hospital-Hematology
🇨🇳
Zhengzhou, Henan, China
Tongji Hospital, Tongji Medical College of HUST-Hematology
🇨🇳
Wuhan, Hubei, China
Institute of hematology and Blood Diseases Hospital, Tianjin-Hematology
🇨🇳
Tianjin, Tianjin, China
Children's Hospital, Zhejiang University school of medicine
🇨🇳
Hangzhou, Zhejiang, China
Beijing Children's Hospital，Capital Medical University
🇨🇳
Beijing, Beijing, China
Peking Union Medical College Hospital
🇨🇳
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
Xiangya Hospital Central-South University
🇨🇳
Changsha, Hunan, China
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Henan Cancer Hospital-Hematology
🇨🇳Zhengzhou, Henan, China