Congenital Bleeding DisorderPhase 3paradigm™ 4NCT01395810
Safety and Efficacy of NNC-0156-0000-0009 After Long-Term Exposure in Patients With Haemophilia B: An Extension to Trials NN7999-3747 and NN7999-3773
A Phase 3 study testing nonacog beta pegol in people with Congenital Bleeding Disorder and Haemophilia B, run by Novo Nordisk A/S at 49 sites in 18 countries.
Trial summary
This trial is conducted in Asia, Europe, Japan, North America and South Africa. The aim is to evaluate the safety and efficacy of nonacog beta pegol (NNC-0156-0000-0009) after long-term exposure 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
- 71 participants
- Where
- 49 sitesin 18 countries
- Study dates
- 15 Apr 2012to 30 Mar 2014
- 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
- Previous participation in NN7999-3747 (NCT01333111) and/or NN7999-3773
Who cannot join
- Known history of FIX inhibitors based on existing medical records, laboratory report reviews and patient and LAR (legal acceptable representative) interviews
- Current FIX inhibitors above or equal to 0.6 BU (Bethesda Units)
- Congenital or acquired coagulation disorders 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)
- Any disease (liver, kidney, inflammatory and mental disorders included) or condition which, according to the Investigator's (trial physician) judgement, could imply a potential hazard to the patient, interfere with trial participation, or interfere with trial outcome
Trial locations and contacts
49 sites in 18 countries.
49 sites in 18 countries
United States13 sites
Novo Nordisk Investigational Site
Augusta, Georgia, 30912
Novo Nordisk Investigational Site
Baltimore, Maryland, 21287
Novo Nordisk Investigational Site
Houston, Texas, 77030
Novo Nordisk Investigational Site
Iowa City, Iowa, 52242
Novo Nordisk Investigational Site
Jacksonville, Florida, 32207
Novo Nordisk Investigational Site
Los Angeles, California, 90027-6016
Novo Nordisk Investigational Site
Minneapolis, Minnesota, 55404
Novo Nordisk Investigational Site
New York, New York, 10029
Novo Nordisk Investigational Site
Newark, New Jersey, 07102
Novo Nordisk Investigational Site
Omaha, Nebraska, 68198-5456
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
Shinjuku-ku, Tokyo, 160 0023
Novo Nordisk Investigational Site
Suginami-ku, Tokyo, 167 0035
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
Bron, 69677
Novo Nordisk Investigational Site
Le Kremlin-Bicêtre, 94270
Italy2 sites
Novo Nordisk Investigational Site
Florence, 50134
Novo Nordisk Investigational Site
Milan, 20124
Russia2 sites
Novo Nordisk Investigational Site
Moscow, 105077
Novo Nordisk Investigational Site
Saint Petersburg, 191119
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: Safety and Efficacy of NNC-0156-0000-0009 After Long-Term Exposure in Patients With Haemophilia B
This trial is conducted in Asia, Europe, Japan, North America and South Africa. The aim is to evaluate the safety and efficacy of nonacog beta pegol (NNC-0156-0000-0009) after long-term exposure in patients with haemophilia B.
This trial is an extension to trials NN7999-3747 (NCT01333111/paradigm™ 2) and NN7999-3773 (NCT01386528/paradigm™ 3).
- 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
One single dose administered intravenously (into the vein) once weekly. Patients will receive instruction on how to treat any bleeding episode they may experience.
nonacog beta pegolDrug
Also called NNC-0156-0000-0009
One single dose administered intravenously (into the vein). Patients will treat themselves with either a low or a high dose dependent on the severity of the bleeding episode.
nonacog beta pegolDrug
Also called NNC-0156-0000-0009
One single dose administered intravenously (into the vein) every second week. Patients will receive instruction on how to treat any bleeding episode they may experience.
| Study group | Role | What they receive |
|---|---|---|
| Prophylaxis, high dose (once weekly) | Experimental | Not described Receives: Drug: nonacog beta pegol |
| Prophylaxis, low dose (once weekly) | Experimental | Not described Receives: Drug: nonacog beta pegol |
| On-demand | Experimental | Not described Receives: Drug: nonacog beta pegol |
| Prophylaxis, high dose (every second week) | Experimental | Not described Receives: Drug: nonacog beta pegol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Inhibitory Antibodies Against FIX Defined as Titre Above or Equal to 0.6 BU (Bethesda Units)
The primary endpoint was incidence of inhibitors against coagulation factor nine (FIX) defined as titre
≥0.6 Bethesda unit (BU). Number of subjects who developed inhibitors against FIX are reported.
Measured: From Day 1 up to 2 years
Secondary outcomes (5)
Haemostatic Effect of Nonacog Beta Pegol When Used for Treatment of Bleeding Episodes, Assessed as Success/Failure Based on a Four-point Scale for Haemostatic Response (Excellent, Good, Moderate, Poor)
The haemostatic effect was evaluated by a four-point scale where an "excellent" or "good" outcome translated into a successful treatment, and a "moderate" or "poor" outcome was considered a treatment failure. The values mentioned below do not include bleeds with missing response.
Measured: From Day 1 up to 2 years
Number of Bleeding Episodes During Routine Prophylaxis
Annualized bleeding rate is the total number of bleeding episodes/total exposure time. It is analysed by a Poisson regression model with dose as a factor allowing for over-dispersion and using treatment duration as an offset. Median annualized bleeding rate is the median of individual annualized bleeding rates. Numbers are based on the treatment arm at the time of each bleed.
Measured: From Day 1 up to 2 years
FIX Trough Levels
During the trial, the pre-dose FIX levels was measured with the one-stage clotting assay. Measurements taken at least 5 days and no more than 10 days after last dose as well as at least 14 days after last bleeding episode were included in this analysis. The mean FIX trough levels were estimated based on the mixed effects model on the log-transformed plasma concentration with subject as a random effect. The mean FIX trough level was presented back-transformed to the natural scale.
Measured: From Day 1 up to 2 years
Incidence of Adverse Events (AEs)
AEs were summarized by frequency of events and frequency of patients with any event. Incidence of AEs was expressed as number of AEs per subject years of exposure (total number of events /total time in trial).
Measured: From Day 1 up to 2 years
Incidence of Serious Adverse Events (SAEs)
AEs were summarized by frequency of events and frequency of patients with any event. Incidence of serious AEs was expressed as number of serious AEs per subject years of exposure (total number of events /total time in trial).
Measured: From Day 1 up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2011 (estimated)
- Study start15 Apr 2012
- Primary completion30 Mar 2014
- Study completion30 Mar 2014
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 (3)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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 71 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
- NCT01395810
- Sponsor's protocol ID
- NN7999-3775
- Other IDs
- 2010-023072-17, U1111-1121-5408, JapicCTI-121812
- Acronym
- paradigm™ 4
- Status last verified
- Apr 2018
- First submitted
- 30 Jun 2011
- Last updated
- 9 May 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Young G, Collins P, Tehranchi R, Chuansumrit A, Hanabusa H, Lentz SR, Mahlangu J, Mauser-Bunschoten E, Negrier C, Oldenburg J, Patiroglu T, Santagostino E, Zak M, Abdul Karim F. Safety and efficacy of nonacog beta pegol (N9-GP) for prophylaxis and treatment of bleeding episodes in previously-treated patients with hemophilia B: results from an extension trial. American Society of Hematology - 56th Annual Meeting (ASH) in San Francisco, CA, US
Young G, Collins PW, Colberg T, Chuansumrit A, Hanabusa H, Lentz SR, Mahlangu J, Mauser-Bunschoten EP, Negrier C, Oldenburg J, Patiroglu T, Santagostino E, Tehranchi R, Zak M, Karim FA. Nonacog beta pegol (N9-GP) in haemophilia B: A multinational phase III safety and efficacy extension trial (paradigm4). Thromb Res. 2016 May;141:69-76. doi: 10.1016/j.thromres.2016.02.030. Epub 2016 Mar 2.
PubMed 26970716Chowdary P, Kearney S, Regnault A, Hoxer CS, Yee DL. Improvement in health-related quality of life in patients with haemophilia B treated with nonacog beta pegol, a new extended half-life recombinant FIX product. Haemophilia. 2016 Jul;22(4):e267-74. doi: 10.1111/hae.12995. Epub 2016 Jun 28.
PubMed 27352908
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of NNC-0156-0000-0009 After Long-Term Exposure in Patients With Haemophilia B
- ClinicalTrials.gov ID
- NCT01395810
- Acronym / sponsor ID
- paradigm™ 4 / NN7999-3775
- Conditions
- Congenital Bleeding Disorder, Haemophilia B
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 71 participants (actual)
- Lead sponsor
- Novo Nordisk A/SIndustry (pharma, biotech, devices)
- Study start
- 15 Apr 2012 (actual)
- Primary completion
- 30 Mar 2014 (actual)
- Study completion
- 30 Mar 2014 (actual)
- First posted
- 18 Jul 2011 (estimated)
- Results
- Posted 9 May 2018
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 Asia, Europe, Japan, North America and South Africa. The aim is to evaluate the safety and efficacy of nonacog beta pegol (NNC-0156-0000-0009) after long-term exposure in patients with haemophilia B.
This trial is an extension to trials NN7999-3747 (NCT01333111/paradigm™ 2) and NN7999-3773 (NCT01386528/paradigm™ 3).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Prophylaxis, high dose (once weekly) | Experimental | Drug: nonacog beta pegol |
| Prophylaxis, low dose (once weekly) | Experimental | Drug: nonacog beta pegol |
| On-demand | Experimental | Drug: nonacog beta pegol |
| Prophylaxis, high dose (every second week) | Experimental | Drug: nonacog beta pegol |
Who may qualify
- Ages
- 13 to 70 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- Previous participation in NN7999-3747 (NCT01333111) and/or NN7999-3773
Key exclusion criteria (5 listed)
- Known history of FIX inhibitors based on existing medical records, laboratory report reviews and patient and LAR (legal acceptable representative) interviews
- Current FIX inhibitors above or equal to 0.6 BU (Bethesda Units)
- Congenital or acquired coagulation disorders 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)
- Any disease (liver, kidney, inflammatory and mental disorders included) or condition which, according to the Investigator's (trial physician) judgement, could imply a potential hazard to the patient, interfere with trial participation, or interfere with trial outcome
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-0156-0000-0009One single dose administered intravenously (into the vein) once weekly. Patients will receive instruction on how to treat any bleeding episode they may experience. | Drug | Prophylaxis, high dose (once weekly), Prophylaxis, low dose (once weekly) |
| nonacog beta pegolAlso: NNC-0156-0000-0009One single dose administered intravenously (into the vein). Patients will treat themselves with either a low or a high dose dependent on the severity of the bleeding episode. | Drug | On-demand |
| nonacog beta pegolAlso: NNC-0156-0000-0009One single dose administered intravenously (into the vein) every second week. Patients will receive instruction on how to treat any bleeding episode they may experience. | Drug | Prophylaxis, high dose (every second week) |
Primary outcome
Incidence of Inhibitory Antibodies Against FIX Defined as Titre Above or Equal to 0.6 BU (Bethesda Units)
Time frame: From Day 1 up to 2 years
The primary endpoint was incidence of inhibitors against coagulation factor nine (FIX) defined as titre ≥0.6 Bethesda unit (BU). Number of subjects who developed inhibitors against FIX are reported.
5 secondary outcomes
Haemostatic Effect of Nonacog Beta Pegol When Used for Treatment of Bleeding Episodes, Assessed as Success/Failure Based on a Four-point Scale for Haemostatic Response (Excellent, Good, Moderate, Poor)
Time frame: From Day 1 up to 2 years
Number of Bleeding Episodes During Routine Prophylaxis
Time frame: From Day 1 up to 2 years
FIX Trough Levels
Time frame: From Day 1 up to 2 years
Incidence of Adverse Events (AEs)
Time frame: From Day 1 up to 2 years
Incidence of Serious Adverse Events (SAEs)
Time frame: From Day 1 up to 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- BackgroundYoung G, Collins P, Tehranchi R, Chuansumrit A, Hanabusa H, Lentz SR, Mahlangu J, Mauser-Bunschoten E, Negrier C, Oldenburg J, Patiroglu T, Santagostino E, Zak M, Abdul Karim F. Safety and efficacy of nonacog beta pegol (N9-GP) for prophylaxis and treatment of bleeding episodes in previously-treated patients with hemophilia B: results from an extension trial. American Society of Hematology - 56th Annual Meeting (ASH) in San Francisco, CA, US
- Results publication: PubMed 26970716Young G, Collins PW, Colberg T, Chuansumrit A, Hanabusa H, Lentz SR, Mahlangu J, Mauser-Bunschoten EP, Negrier C, Oldenburg J, Patiroglu T, Santagostino E, Tehranchi R, Zak M, Karim FA. Nonacog beta pegol (N9-GP) in haemophilia B: A multinational phase III safety and efficacy extension trial (paradigm4). Thromb Res. 2016 May;141:69-76. doi: 10.1016/j.thromres.2016.02.030. Epub 2016 Mar 2.
- Results publication: PubMed 27352908Chowdary P, Kearney S, Regnault A, Hoxer CS, Yee DL. Improvement in health-related quality of life in patients with haemophilia B treated with nonacog beta pegol, a new extended half-life recombinant FIX product. Haemophilia. 2016 Jul;22(4):e267-74. doi: 10.1111/hae.12995. Epub 2016 Jun 28.
- Clinical Trials at Novo NordiskLink provided by the sponsor.
Related trials for Congenital Bleeding Disorder
RecruitingObservational study
A Study in Children and, Adults With Congenital Thrombotic Thrombocytopenic Purpura (cTTP) Treated With Adzynma
Thrombotic Thrombocytopenic Purpura (TTP)
Not yet recruitingPhase 1
Topical TOR-582 Treatment of Epistaxis in HHT
Hereditary Hemorrhagic Telangiectasia (HHT), Epistaxis
RecruitingPhase 1/2
Harmony-HHT: ATV-1601 in Participants With Hereditary Hemorrhagic Telangiectasia (HHT)
Hereditary Hemorrhagic Telangiectasia (HHT), Osler Weber Rendu Disease
RecruitingObservational study
The CACHE Study: Coronary Artery Care in HaEmophilia
Haemophilia, Cardiovascular Diseases
Recruiting
Optimization of Saturation Targets And Resuscitation Trial (OptiSTART)
Premature Infants, Bronchopulmonary Dysplasia
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
49 sites in 18 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 49 sites in 18 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 1 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 9 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 49 sites in United States, Japan, United Kingdom, Germany, Turkey (Türkiye) and 13 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 9 May 2018). 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?
Incidence of Inhibitory Antibodies Against FIX Defined as Titre Above or Equal to 0.6 BU (Bethesda Units) (time frame: From Day 1 up to 2 years). 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 NCT01395810, which also lists 3 linked publications.
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 9 May 2018.