A Research Study Investigating Nonacog Beta Pegol (N9-GP) for Treatment and Prevention of Bleedings in Chinese People With Haemophilia B (Paradigm9)

A Multi-centre, Open-label Trial Evaluating Efficacy, Safety and Pharmacokinetics of Nonacog Beta Pegol When Used for Treatment and Prophylaxis of Bleeding Episodes in Chinese Patients With Haemophilia B

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.

Study Overview

• Status: Completed
• Conditions: Haemophilia B
• Intervention / Treatment: Drug: Nonacog beta pegol

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100045
      • Beijing Children's Hospital, Capital Medical University
    • Beijing, Beijing Municipality, China, 100730
      • Peking Union Medical College Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Fujian Medical University Union Hospital-Hematology
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital, Southern Medical University-Haematology
  • Guizhou
    • Guiyang, Guizhou, China, 550004
      • The Affiliated Hospital of Guizhou Medical University-Hematology
  • Henan
    • Zhengzhou, Henan, China, 450003
      • Henan Cancer Hospital-Hematology
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital, Tongji Medical College of HUST-Hematology
  • Hunan
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital Central-South University
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • The First Affiliated Hospital of Soochow University
  • Shandong
    • Jinan, Shandong, China, 250013
      • Jinan Central Hospital
    • Qingdao, Shandong, China, 266000
      • The Affiliated Hospital of Qingdao University
    • Qingdao, Shandong, China, 266555
      • The Affiliated Hospital of Qingdao University
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300020
      • Institute of hematology and Blood Diseases Hospital, Tianjin-Hematology
  • Yunnan
    • Kunming, Yunnan, China, 650101
      • The Second Affiliated hospital of Kunming Medical University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310052
      • Children's Hospital, Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A - Nonacog beta pegol (On-demand/Prophylaxis); Participants on on-demand treatment for 28 weeks, thereafter prophylactic treatment	Drug: Nonacog beta pegol; Nonacog beta pegol is administered as intravenous injections. Participants will receive nonacog beta pegol as prophylaxis, as on-demand for treatment of bleeding episodes and in relation to surgery.
Experimental: Arm B - Nonacog beta pegol (Prophylaxis); Participants on prophylactic treatment only	Drug: Nonacog beta pegol; Nonacog beta pegol is administered as intravenous injections. Participants will receive nonacog beta pegol as prophylaxis, as on-demand for treatment of bleeding episodes and in relation to surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Haemostatic Effect of Nonacog Beta Pegol When Used for Treatment of Bleeding Episodes During on Demand and Prophylaxis (PPX)	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.	From start of treatment (week 0) until end of treatment (up to week 50)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Treated Bleeding Episodes During Prophylaxis (PPX) Treatment (Arm B Only)	Number of bleeding episodes per year data is reported. Annualised bleeding rate (ABR) is the number of bleeding episodes per year.	From start of treatment (week 0) until end of treatment (week 50)
Consumption of Nonacog Beta Pegol for Treatment of Bleeding Episodes	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).	From start of treatment (week 0) until end of treatment (up to week 50)
Consumption of Nonacog Beta Pegol for Prophylaxis (PPX) Treatment (Arm B Only)	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).	From start of treatment (week 0) until end of treatment (week 50)
FIX Trough Levels During Prophylaxis (PPX) Treatment (Arm B Only)	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.	From start of treatment (week 0) until end of treatment (week 50)
Number of Participants With Inhibitory Antibodies Against FIX Defined as Titre ≥0.6 Bethesda Units (BU)	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.	From start of treatment (week 0) until end of treatment (week 50)
Number of Adverse Events (AEs)	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.	From start of treatment (week 0) until end of treatment (week 50)
Number of Serious Adverse Events (SAEs)	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).	From start of treatment (week 0) until end of treatment (week 50)
Incremental Recovery (IR) (Arm B Only)	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.	Single-dose: 30±10 minutes post injection at week 0, Steady-state: 30±10 minutes post injection at week 12
Terminal Half-life (t½) (Arm B Only)	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.	Single-dose: 30±10 minutes post injection at week 0, Steady-state: 30±10 minutes post injection at week 12
Clearance (CL) (Arm B Only)	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.	Single-dose: 0-168 hours post injection at week 0, Steady-state: 0-168 hours post injection at week 12
Area Under the Curve (AUC) (Arm B Only)	Area under the plasma activity versus time profile from time zero to 168 hours (AUC0-168h) was measured.	Single-dose: 0-168 hours post injection at week 0, Steady-state: 0-168 hours post injection at week 12

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Transparency dept. 2834, Novo Nordisk A/S

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2022
• Primary Completion (Actual): April 11, 2024
• Study Completion (Actual): May 11, 2024

Study Registration Dates

• First Submitted: May 4, 2022
• First Submitted That Met QC Criteria: May 4, 2022
• First Posted (Actual): May 9, 2022

Study Record Updates

• Last Update Posted (Estimated): January 12, 2026
• Last Update Submitted That Met QC Criteria: December 17, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Genetic Diseases, X-Linked; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Hemophilia B; nonacog beta pegol
• Other Study ID Numbers: NN7999-4670; 2021-004947-25 (EudraCT Number); U1111-1260-0438 (Other Identifier: World Health Organization (WHO)); CTR20220763 (Registry Identifier: China Drug Trials (China))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes