Efficacy and Safety of NNC-0156-0000-0009 During Surgical Procedures in Subjects With Haemophilia B (paradigm™ 3)

• ClinicalTrials.gov Identifier: NCT01386528
• Recruitment Status: Completed
• First Posted: July 1, 2011
• Results First Posted: July 24, 2017
• Last Update Posted: August 23, 2017
• Sponsor: Novo Nordisk A/S
• Information provided by (Responsible Party): Novo Nordisk A/S

Study Description

Brief Summary:

This trial is conducted in Africa, Asia, Europe and the United States of America (USA).

The aim of the trial is to evaluate the safety and efficacy of NNC-0156-0000-0009 (nonacog beta pegol) during surgical procedures in patients with haemophilia B.

Condition or disease	Intervention/treatment	Phase
Congenital Bleeding Disorder; Haemophilia B	Drug: nonacog beta pegol	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 13 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Multi-centre, Un-controlled Trial to Assess Efficacy and Safety of NNC-0156-0000-0009 During Surgical Procedures in Patients With Haemophilia B
• Actual Study Start Date: June 7, 2012
• Actual Primary Completion Date: December 1, 2013
• Actual Study Completion Date: December 1, 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: Patients enrolled in trial; New patients will be included as well as transferred patients from Paradigm™ 2 or Paradigm™ 4 trial	Drug: nonacog beta pegol; The patients will receive nonacog beta pegol at screening just prior to and during surgical intervention, administered intravenously (into the vein).; Other Name: NNC-0156-0000-0009

Outcome Measures

Primary Outcome Measures :

1. Haemostatic Effect During Surgery Evaluated by the Four-point Response Scale (Excellent, Good, Moderate, Poor) [ Time Frame: At the day of surgery ]

   Haemostatic effect during surgery was evaluated immediately after surgery (last stitch) using a fourpoint response scale:

   - Four-point response scale: Excellent, good, moderate, poor. The evaluation was done by the surgeon, anaesthesiologist and/or investigator based on experience as follows:

   1. Excellent: Better than expected/predicted in this type of procedure.
   2. Good: As expected in this type of procedure.
   3. Moderate: Less than optimal for the type of procedure but haemostatic response maintained without change of treatment regimen.
   4. Poor: Bleeding due to inadequate therapeutic response with adequate dosing, change of regimen required.

Secondary Outcome Measures :

1. Consumption of NNC-0156-0000-0009 (U/kg Body Weight) [ Time Frame: During surgery (the time from knife to skin until last stitch) and post-operative period (day 1 to day 13) ]
   Mean consumption of nonacog beta pegol (U/kg) used for treatment per patient before surgery, during surgery (the time from knife to skin until last stitch) and post-operative period.
2. Transfusion Requirements (Fulfilling Transfusion Criteria) [ Time Frame: during surgery (the time from knife to skin until last stitch) and post-operative period (day 1 to day 13) ]
   Mean quantity of transfusion during surgery (the time from knife to skin until last stitch) and the postoperative period (Day 1-13).None of the patients required transfusions beyond Day 6 hence no values presented for days 7-13.
3. Haemoglobin Pre- and Post-surgery Start [ Time Frame: 0, 1 hour, 24 hours. ]
   The mean pre-surgery and post surgery haemoglobin level.
4. Incidence of Adverse Events (AEs) [ Time Frame: during the trial period (2-8 weeks prior to day of surgery (transferred subjects) or 2-4 weeks prior to day of surgery (new subjects) until 4 weeks after post-operative period (day 1 to day 13) ]
   The number of adverse events per patient years of exposure, reported during the trial period. Number is the only available option here, the data presented are rate of AEs.
5. Incidence of Serious Adverse Events (SAE) [ Time Frame: During the trial period (2-8 weeks prior to day of surgery (transferred subjects) or 2-4 weeks prior to day of surgery (new subjects) until 4 weeks after post-operative period (day 1 to day 13) ]
   The number of serious adverse events per patient years of exposure, reported during the trial period. Number is the only available option here, the data presented are rate of AEs.
6. Incidence of Inhibitors Against FIX (Coagulation Factor Nine) [ Time Frame: During the trial period (2-8 weeks prior to day of surgery (transferred subjects) or 2-4 weeks prior to day of surgery (new subjects) and every 4 weeks after post-operative period (day 1 to day 13) ]
   Number of patients with inhibitory antibodies

Eligibility Criteria

• Ages Eligible for Study: 13 Years to 70 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patients with haemophilia B with a FIX activity below or equal to 2%
• Male patients with moderately severe or severe congenital haemophilia B with a FIX activity below or equal to 2% according to medical records
• History of at least 150 exposure days to other FIX products
• Scheduled major surgery

Exclusion Criteria:

• Known history of FIX (coagulation factor nine) inhibitors based on existing medical records, laboratory report reviews and patient and LAR (legal acceptable representative) interviews
• Current FIX (coagulation factor nine) inhibitors above or equal to 0.6 Bethesda Units (central laboratory)
• 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)
• ALT (alanine aminotransferase) 3 times the upper limit of normal reference ranges at screening (central laboratory)
• Immune modulating or chemotherapeutic medication

Contacts and Locations

Locations

United States, California

Novo Nordisk Investigational Site

Los Angeles, California, United States, 90027

Novo Nordisk Investigational Site

San Francisco, California, United States, 94143

United States, District of Columbia

Novo Nordisk Investigational Site

Washington, D.C., District of Columbia, United States, 20007

United States, Georgia

Novo Nordisk Investigational Site

Augusta, Georgia, United States, 30912

United States, Iowa

Novo Nordisk Investigational Site

Iowa City, Iowa, United States, 52242

United States, New York

Novo Nordisk Investigational Site

Syracuse, New York, United States, 13210

United States, Texas

Novo Nordisk Investigational Site

Houston, Texas, United States, 77030

Austria

Novo Nordisk Investigational Site

Wien, Austria, 1090

France

Novo Nordisk Investigational Site

Kremlin-Bicêtre, France, 94270

Novo Nordisk Investigational Site

Lyon, France, 69003

Germany

Novo Nordisk Investigational Site

Bonn, Germany, 53127

Novo Nordisk Investigational Site

Duisburg, Germany, 47051

Novo Nordisk Investigational Site

Giessen, Germany, 35392

Novo Nordisk Investigational Site

Hannover, Germany, 30625

Greece

Novo Nordisk Investigational Site

Athens, Greece, GR-11527

Italy

Novo Nordisk Investigational Site

Firenze, Italy, 50134

Novo Nordisk Investigational Site

Milano, Italy, 20124

Japan

Novo Nordisk Investigational Site

Kashihara-shi, Nara, Japan, 634 8522

Novo Nordisk Investigational Site

Kawasaki-shi, Kanagawa, Japan, 216-8511

Novo Nordisk Investigational Site

Nagoya-shi, Aichi, Japan, 466 8560

Novo Nordisk Investigational Site

Nishinomiya-shi, Japan, 663 8051

Novo Nordisk Investigational Site

Suginami-ku, Tokyo, Japan, 167 0035

Novo Nordisk Investigational Site

Tokyo, Japan, 108-8639

Macedonia, The Former Yugoslav Republic of

Novo Nordisk Investigational Site

Skopje, Macedonia, The Former Yugoslav Republic of, 1000

Malaysia

Novo Nordisk Investigational Site

Kuala Lumpur, Malaysia, 50400

Netherlands

Novo Nordisk Investigational Site

Utrecht, Netherlands, 3584 CX

Romania

Novo Nordisk Investigational Site

Timisoara, Timis, Romania, 300011

South Africa

Novo Nordisk Investigational Site

Parktown Johannesburg, Gauteng, South Africa, 2193

Spain

Novo Nordisk Investigational Site

Madrid, Spain, 28046

Novo Nordisk Investigational Site

Valencia, Spain, 46026

Taiwan

Novo Nordisk Investigational Site

Taipei, Taiwan, 100

Thailand

Novo Nordisk Investigational Site

Bangkok, Thailand, 10400

Turkey

Novo Nordisk Investigational Site

Ankara, Turkey, 06500

Novo Nordisk Investigational Site

Kayseri, Turkey, 38010

Novo Nordisk Investigational Site

Konya, Turkey, 42090

United Kingdom

Novo Nordisk Investigational Site

Basingstoke, United Kingdom, RG24 9NA

Novo Nordisk Investigational Site

Cardiff, United Kingdom, CF14 4XW

Novo Nordisk Investigational Site

London, United Kingdom, NW3 2QG

Novo Nordisk Investigational Site

London, United Kingdom, SE1 7EH

Novo Nordisk Investigational Site

Manchester, United Kingdom, M13 9WL

Novo Nordisk Investigational Site

Oxford, United Kingdom, OX3 7LJ

Sponsors and Collaborators

Novo Nordisk A/S

Investigators

• Study Director: Global Clinical Registry (GCR, 1452); Novo Nordisk A/S

More Information

Additional Information:

Clinical Trials at Novo Nordisk 

Publications:

Escobar M, Colberg T, Karim F, Caliskan U, Chowdary P, Giangrande P, Giermasz A, Mancuso ME, Serban M, Tsay W, Zak M and Mahlangu J. Perioperative hemostatic management of major surgery in hemophilia B with long-acting recombinant glycopegylated factor IX: results from the paradigm™3 clinical trial. Journal of Thrombosis and Haemostasis (Abstracts) 2015; 13 (Supplement S2): 1-997 [OR348]

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT01386528
• Other Study ID Numbers: NN7999-3773; 2010-023070-40 ( EudraCT Number ); U1111-1121-4554 ( Other Identifier: WHO )
• First Posted: July 1, 2011
• Results First Posted: July 24, 2017
• Last Update Posted: August 23, 2017
• Last Verified: July 2017

Additional relevant MeSH terms:

Hemostatic Disorders; Hemophilia A; Hemophilia B; Blood Coagulation Disorders; Blood Coagulation Disorders, Inherited; Hematologic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Vascular Diseases; Cardiovascular Diseases