Safety and Efficacy of 3 Different Doses of Long Acting Factor VII in Haemophilia A or B Patients With Inhibitors

An Exploratory Multi-Centre, Multi-National, Randomised, Double Blinded, Parallel Arm Trial Evaluating Safety, Pharmacokinetics and Dose-finding of Prophylactic Administration of Long Acting rFVIIa (LA-rFVIIa) in Haemophilia A or B Patients With Inhibitors

This trial is conducted in Asia, Europe, Japan and North America. The aim of this clinical trial is to investigate the safety and the efficacy of a prophylactic treatment option with long acting coagulation factor VII (LA-rFVIIa) for haemophilia patients with inhibitors.

Study Overview

• Status: Completed
• Conditions: Congenital Bleeding Disorder; Haemophilia A With Inhibitors; Haemophilia B With Inhibitors
• Intervention / Treatment: Drug: activated recombinant human factor VII, long acting; Drug: activated recombinant human factor VII, long acting; Drug: activated recombinant human factor VII, long acting

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Rio de Janeiro, Brazil, 20211-030
    • Novo Nordisk Investigational Site
• Former Serbia and Montenegro
  • Belgrade, Former Serbia and Montenegro, 11000
    • Novo Nordisk Investigational Site
• France
  • Le Kremlin Bicetre, France, 94270
    • Novo Nordisk Investigational Site
  • Paris, France, 75015
    • Novo Nordisk Investigational Site
• Japan
  • Kashihara-shi, Nara, Japan, 634 8522
    • Novo Nordisk Investigational Site
  • Kitakyusyu, Fukuoka, Japan, 807 8555
    • Novo Nordisk Investigational Site
  • Nishinomiya-shi, Japan, 663 8051
    • Novo Nordisk Investigational Site
  • Shinjuku-ku, Tokyo, Japan, 160 0023
    • Novo Nordisk Investigational Site
• Malaysia
  • Kuala Lumpur, Malaysia, 50400
    • Novo Nordisk Investigational Site
• Serbia
  • Belgrade, Serbia, 11000
    • Novo Nordisk Investigational Site
• South Africa
  • Gauteng
    • Parktown Johannesburg, Gauteng, South Africa, 2193
      • Novo Nordisk Investigational Site
  • KwaZulu-Natal
    • Durban, KwaZulu-Natal, South Africa, 4013
      • Novo Nordisk Investigational Site
• Sweden
  • Malmö, Sweden, 205 02
    • Novo Nordisk Investigational Site
• Turkey
  • Ankara, Turkey, 06500
    • Novo Nordisk Investigational Site
  • Istanbul, Turkey, 34098
    • Novo Nordisk Investigational Site
• United Kingdom
  • London, United Kingdom, NW3 2QG
    • Novo Nordisk Investigational Site
  • London, United Kingdom, SE1 7EH
    • Novo Nordisk Investigational Site
  • Oxford, United Kingdom, OX3 7LJ
    • Novo Nordisk Investigational Site
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Novo Nordisk Investigational Site
  • California
    • Los Angeles, California, United States, 90027
      • Novo Nordisk Investigational Site
    • Orange, California, United States, 92868
      • Novo Nordisk Investigational Site
  • Florida
    • Tampa, Florida, United States, 33607
      • Novo Nordisk Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Novo Nordisk Investigational Site
  • Oregon
    • Portland, Oregon, United States, 97239
      • Novo Nordisk Investigational Site
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Male haemophilia A or B patients with inhibitors
• Willing to undergo a bleeding preventive regimen of 3 months' duration and a total trial length of approximately 8 months
• Historical or ongoing high titre inhibitor (more than or equal to 5 BU) based on either medical records, laboratory report reviews, patient and/or care provider interviews
• At least 2 bleeding episodes requiring bypassing haemostatic-drug-based treatment within the last month or 12 bleeding episodes within the last 6 months prior to observation period
• Body weight between 30 and 100 kg (both inclusive)

Exclusion Criteria:

• Body Mass Index (BMI) above 30 kg/m2
• Immune tolerance induction therapy within the last month prior to entering observation phase period
• Known active pseudo tumours
• Platelet count less than 50,000 platelets/microL (based on local laboratory value at screening visit)
• Congenital or acquired coagulation disorders other than haemophilia A or B
• Surgery within one month prior to the observation period. Catheter, stents and dental extractions do not count as surgeries, i.e. they will not exclude the patient. Port insertion is classified as surgery
• Scheduled major and/or orthopaedic surgery, during the trial period until Follow up visit. Catheter, stents and dental extractions do not count as surgeries and will not exclude the patient. Port insertion is classified as surgery
• Advanced atherosclerotic disease (i.e. known history of ischemic heart disease, or ischemic stroke)
• Any clinical signs or known history of thromboembolic events incl. known deep vein thrombosis (DVT)
• Known or clinically suspected allergy to activated recombinant human factor VII (NovoSeven®/NovoSeven RT®/Niastase®)
• Prothrombin Time (PT) prolongation (30% above normal limits, or more than 5 seconds compared to control or International Normalised Range (INR) more than 1.7 as defined by local laboratory ranges at screening visit
• Severe liver disease (ALAT more than 4 times of the upper limit of normal reference range) (as defined by local laboratory ranges) within a year of enrolment or at the screening
• Clinical signs of renal dysfunction (dialysis) and/or creatinine levels more than or equal to 20% above upper normal limit (according to local laboratory range at the screening visit)
• Dosing of any investigational drug within the last 30 days prior to the present trial
• Any disease or condition which, according to the investigator's judgement, could imply a potential hazard to the subject, interfere with the trial participation or trial outcome
• HIV positive patients who either have low CD4+ lymphocyte count ( 200/microL or less based on medical records within 6 months or laboratory screening at screening visit), or who are HCV-PCR positive (based on medical records), or who both have low CD4+ lymphocyte count (200/microL or less) and are HCV-PCR positive. If HCV-PCR testing is not locally available, a HIV positive patient who is HCV antibody positive cannot be included
• Need to use other PEGylated pharmaceutical drug during the trial period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A	Drug: activated recombinant human factor VII, long acting; After an observation period of 3 months, every 2nd day intravenous (i.v.) injection with 25 microgrammes/kg activated recombinant human factor VII, long acting, for 3 months; Other Names: NN7128; LA-rFVIIa; Drug: activated recombinant human factor VII, long acting; After an observation period of 3 months, every 2nd day intravenous (i.v.) injection with 100 microgrammes/kg activated recombinant human factor VII, long acting, for 3 months; Other Names: NN7128; LA-rFVIIa; Drug: activated recombinant human factor VII, long acting; After an observation period of 3 months, every 2nd day intravenous (i.v.) injection with 200 microgrammes/kg activated recombinant human factor VII, long acting, for 3 months; Other Names: NN7128; LA-rFVIIa
Experimental: B	Drug: activated recombinant human factor VII, long acting; After an observation period of 3 months, every 2nd day intravenous (i.v.) injection with 25 microgrammes/kg activated recombinant human factor VII, long acting, for 3 months; Other Names: NN7128; LA-rFVIIa; Drug: activated recombinant human factor VII, long acting; After an observation period of 3 months, every 2nd day intravenous (i.v.) injection with 100 microgrammes/kg activated recombinant human factor VII, long acting, for 3 months; Other Names: NN7128; LA-rFVIIa; Drug: activated recombinant human factor VII, long acting; After an observation period of 3 months, every 2nd day intravenous (i.v.) injection with 200 microgrammes/kg activated recombinant human factor VII, long acting, for 3 months; Other Names: NN7128; LA-rFVIIa
Experimental: C	Drug: activated recombinant human factor VII, long acting; After an observation period of 3 months, every 2nd day intravenous (i.v.) injection with 25 microgrammes/kg activated recombinant human factor VII, long acting, for 3 months; Other Names: NN7128; LA-rFVIIa; Drug: activated recombinant human factor VII, long acting; After an observation period of 3 months, every 2nd day intravenous (i.v.) injection with 100 microgrammes/kg activated recombinant human factor VII, long acting, for 3 months; Other Names: NN7128; LA-rFVIIa; Drug: activated recombinant human factor VII, long acting; After an observation period of 3 months, every 2nd day intravenous (i.v.) injection with 200 microgrammes/kg activated recombinant human factor VII, long acting, for 3 months; Other Names: NN7128; LA-rFVIIa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Thrombogenecity	at all scheduled visits (1 - 9)
Immunogenecity: Neutralising Antibody Development	at all scheduled visits (1 - 9)

Secondary Outcome Measures

Outcome Measure	Time Frame
AUC(0-48h) and AUC: Area under the FVIIa activity-time profile in the given time period, which is a measure of total blood exposure	at visit 2 and visit 7 until 48 hours after trial product administration
Annualized bleeding rates	During observation period; from visit 1 until visit 2 and treatment period; from visit 2 until visit 7. In total a period of 6 to 8 months

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

General Publications

• Ljung R, Karim FA, Saxena K, Suzuki T, Arkhammar P, Rosholm A, Giangrande P; Pioneer1 Investigators. 40K glycoPEGylated, recombinant FVIIa: 3-month, double-blind, randomized trial of safety, pharmacokinetics and preliminary efficacy in hemophilia patients with inhibitors. J Thromb Haemost. 2013 Jul;11(7):1260-8. doi: 10.1111/jth.12237.

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2009
• Primary Completion (Actual): March 29, 2011
• Study Completion (Actual): March 29, 2011

Study Registration Dates

• First Submitted: August 3, 2009
• First Submitted That Met QC Criteria: August 3, 2009
• First Posted (Estimate): August 4, 2009

Study Record Updates

• Last Update Posted (Actual): September 5, 2018
• Last Update Submitted That Met QC Criteria: September 3, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Hemostatic Disorders; Hemophilia A; Hemophilia B; Blood Coagulation Disorders
• Other Study ID Numbers: NN7128-1907; 2008-006424-54 (EudraCT Number); JapicCTI-090860 (Registry Identifier: JAPIC); U1111-1111-8584 (Other Identifier: WHO)