Congenital Bleeding DisorderPhase 3paradigm™ 3NCT01386528
Efficacy and Safety of NNC-0156-0000-0009 During Surgical Procedures in Subjects With Haemophilia B
A Phase 3 study testing nonacog beta pegol in people with Congenital Bleeding Disorder and Haemophilia B, run by Novo Nordisk A/S at 41 sites in 17 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 13 to 70 years, men only
- Conditions the study is for
- Congenital Bleeding Disorder, Haemophilia B
- What is being tested?
- nonacog beta pegol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 41 sitesin 17 countries
- Study dates
- 7 Jun 2012to 1 Dec 2013
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 13 to 70 years
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
41 sites in 17 countries.
41 sites in 17 countries
United States7 sites
Novo Nordisk Investigational Site
Augusta, Georgia, 30912
Novo Nordisk Investigational Site
Houston, Texas, 77030
Novo Nordisk Investigational Site
Iowa City, Iowa, 52242
Novo Nordisk Investigational Site
Los Angeles, California, 90027
Novo Nordisk Investigational Site
San Francisco, California, 94143
Novo Nordisk Investigational Site
Syracuse, New York, 13210
Novo Nordisk Investigational Site
Washington D.C., District of Columbia, 20007
Japan6 sites
Novo Nordisk Investigational Site
Kashihara-shi, Nara, 634 8522
Novo Nordisk Investigational Site
Kawasaki-shi, Kanagawa, 216-8511
Novo Nordisk Investigational Site
Nagoya-shi, Aichi, 466 8560
Novo Nordisk Investigational Site
Nishinomiya-shi, 663 8051
Novo Nordisk Investigational Site
Suginami-ku, Tokyo, 167 0035
Novo Nordisk Investigational Site
Tokyo, 108-8639
United Kingdom6 sites
Novo Nordisk Investigational Site
Basingstoke, RG24 9NA
Novo Nordisk Investigational Site
Cardiff, CF14 4XW
Novo Nordisk Investigational Site
London, NW3 2QG
Novo Nordisk Investigational Site
London, SE1 7EH
Novo Nordisk Investigational Site
Manchester, M13 9WL
Novo Nordisk Investigational Site
Oxford, OX3 7LJ
Germany4 sites
Novo Nordisk Investigational Site
Bonn, 53127
Novo Nordisk Investigational Site
Duisburg, 47051
Novo Nordisk Investigational Site
Giessen, 35392
Novo Nordisk Investigational Site
Hanover, 30625
Turkey (Türkiye)3 sites
Novo Nordisk Investigational Site
Ankara, 06500
Novo Nordisk Investigational Site
Kayseri, 38010
Novo Nordisk Investigational Site
Konya, 42090
France2 sites
Novo Nordisk Investigational Site
Le Kremlin-Bicêtre, 94270
Novo Nordisk Investigational Site
Lyon, 69003
Italy2 sites
Novo Nordisk Investigational Site
Florence, 50134
Novo Nordisk Investigational Site
Milan, 20124
Spain2 sites
Novo Nordisk Investigational Site
Madrid, 28046
Novo Nordisk Investigational Site
Valencia, 46026
Romania1 site
Novo Nordisk Investigational Site
Timișoara, Timiș County, 300011
South Africa1 site
Novo Nordisk Investigational Site
Parktown Johannesburg, Gauteng, 2193
About this study
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
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.
- Conditions
- Congenital Bleeding Disorder, Haemophilia B
- Being tested
- nonacog beta pegol
- Medical subject headings
- Hemophilia B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
nonacog beta pegolDrug
Also called NNC-0156-0000-0009
The patients will receive nonacog beta pegol at screening just prior to and during surgical intervention, administered intravenously (into the vein).
| Study group | Role | What they receive |
|---|---|---|
| Patients enrolled in trial | Experimental | New patients will be included as well as transferred patients from Paradigm™ 2 or Paradigm™ 4 trial Receives: Drug: nonacog beta pegol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Haemostatic Effect During Surgery Evaluated by the Four-point Response Scale (Excellent, Good, Moderate, Poor)
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:
- Excellent: Better than expected/predicted in this type of procedure.
- Good: As expected in this type of procedure.
- Moderate: Less than optimal for the type of procedure but haemostatic response maintained without change of treatment regimen.
- Poor: Bleeding due to inadequate therapeutic response with adequate dosing, change of regimen required.
Measured: At the day of surgery
Secondary outcomes (6)
Consumption of NNC-0156-0000-0009 (U/kg Body Weight)
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.
Measured: During surgery (the time from knife to skin until last stitch) and post-operative period (day 1 to day 13)
Transfusion Requirements (Fulfilling Transfusion Criteria)
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.
Measured: during surgery (the time from knife to skin until last stitch) and post-operative period (day 1 to day 13)
Haemoglobin Pre- and Post-surgery Start
The mean pre-surgery and post surgery haemoglobin level.
Measured: 0, 1 hour, 24 hours.
Incidence of Adverse Events (AEs)
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.
Measured: 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)
Incidence of Serious Adverse Events (SAE)
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.
Measured: 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)
Incidence of Inhibitors Against FIX (Coagulation Factor Nine)
Number of patients with inhibitory antibodies
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2011 (estimated)
- Study start7 Jun 2012
- Primary completion1 Dec 2013
- Study completion1 Dec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Congenital Bleeding DisorderStudies of the same condition, open and under way.
- More trials run by Novo Nordisk A/SThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novo Nordisk A/S
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Global Clinical Registry (GCR, 1452), Study director, Novo Nordisk A/S
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01386528
- Sponsor's protocol ID
- NN7999-3773
- Other IDs
- 2010-023070-40, U1111-1121-4554
- Acronym
- paradigm™ 3
- Status last verified
- Jul 2017
- First submitted
- 30 Jun 2011
- Last updated
- 23 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
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]
Study at a glance
From the registry record, last updated by the sponsor on 23 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01386528
- Acronym / sponsor ID
- paradigm™ 3 / NN7999-3773
- Conditions
- Congenital Bleeding Disorder, Haemophilia B
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Novo Nordisk A/SIndustry (pharma, biotech, devices)
- Study start
- 7 Jun 2012 (actual)
- Primary completion
- 1 Dec 2013 (actual)
- Study completion
- 1 Dec 2013 (actual)
- First posted
- 1 Jul 2011 (estimated)
- Results
- Posted 24 Jul 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients enrolled in trial | Experimental | Drug: nonacog beta pegolNew patients will be included as well as transferred patients from Paradigm™ 2 or Paradigm™ 4 trial |
Who may qualify
- Ages
- 13 to 70 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| nonacog beta pegolAlso: NNC-0156-0000-0009The patients will receive nonacog beta pegol at screening just prior to and during surgical intervention, administered intravenously (into the vein). | Drug | Patients enrolled in trial |
Primary outcome
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.
6 secondary outcomes
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)
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)
Haemoglobin Pre- and Post-surgery Start
Time frame: 0, 1 hour, 24 hours.
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)
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)
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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- BackgroundEscobar 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]
- Clinical Trials at Novo NordiskLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Global Clinical Registry (GCR, 1452) study director
Novo Nordisk A/S
41 sites in 17 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing nonacog beta pegol in people with Congenital Bleeding Disorder and Haemophilia B, run by Novo Nordisk A/S at 41 sites in 17 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 41 sites in United States, Japan, United Kingdom, Germany, Turkey (Türkiye) and 12 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Jul 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Haemostatic Effect During Surgery Evaluated by the Four-point Response Scale (Excellent, Good, Moderate, Poor) (time frame: At the day of surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01386528, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Aug 2017.