Observational Registry of NovoSeven® Used as On-demand Treatment of Bleeds in Patients With Haemophilia A and B With Inhibitors (ONE)

A Prospective Observational Registry on the Use of NovoSeven® (Activated Recombinant Human Factor VIIa) for on Demand Treatment of Mild to Moderate Bleeds in Haemophilia A and B Patients With Inhibitors

This study was conducted in Africa, Europe, the Middle-East and South America. The primary objective of this registry was to observe the use of single dose and multi-dose use of activated recombinant human factor VII and to compare short-term outcomes, including effectiveness, safety, quality of life and treatment satisfaction with the approved treatments.

Study Overview

• Status: Completed
• Conditions: Congenital Bleeding Disorder; Haemophilia A With Inhibitors; Haemophilia B With Inhibitors
• Intervention / Treatment: Drug: eptacog alfa (activated)

• Study Type: Observational
• Enrollment (Actual): 102

Contacts and Locations

Study Locations

• Algeria
  • Algiers, Algeria, 16035
    • Novo Nordisk Investigational Site
• Austria
  • Vienna, Austria, A-1010
    • Novo Nordisk Investigational Site
• Belgium
  • Brussels, Belgium, 1070
    • Novo Nordisk Investigational Site
• Czech Republic
  • Prague, Czech Republic, 16000
    • Novo Nordisk Investigational Site
• France
  • Paris La défense cedex, France, 92932
    • Novo Nordisk Investigational Site
• Germany
  • Mainz, Germany, 55127
    • Novo Nordisk Investigational Site
• Italy
  • Rome, Italy, 00144
    • Novo Nordisk Investigational Site
• Netherlands
  • Alphen a/d Rijn, Netherlands
    • Novo Nordisk Investigational Site
• Poland
  • Warszawa, Poland, PL-02-274
    • Novo Nordisk Investigational Site
• Portugal
  • Paco de Arcos, Portugal, 2780-730
    • Novo Nordisk Investigational Site
• Saudi Arabia
  • Riyadh, Saudi Arabia, 3542
    • Novo Nordisk Investigational Site
• South Africa
  • Sandton, South Africa, 2146
    • Novo Nordisk Investigational Site
• Sweden
  • Malmö, Sweden, 202 15
    • Novo Nordisk Investigational Site
• Turkey
  • Istanbul, Turkey, 34335
    • Novo Nordisk Investigational Site
• United Kingdom
  • Crawley, United Kingdom, RH11 9RT
    • Novo Nordisk Investigational Site
• Venezuela
  • Caracas, Venezuela
    • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

Patients with haemophilia A or B with inhibitors, using activated recombinant human factor VII as on-demand treatment

Description

Inclusion Criteria:

• Diagnosed with haemophilia A or B with inhibitors
• Experience mild to moderate spontaneous bleeds which require on-demand treatment and who are currently prescribed activated recombinant human factor VII
• Be able and willing to provide informed consent (or proxy consent by caregiver, if applicable), as required by local research ethics committee, governmental or regulatory authorities
• Be willing to provide information on at least one alternate contact person in the event that the patient be somehow lost-to-follow-up over the course of registry participation (not applicable if patient is withdrawn)

Exclusion Criteria:

• Known hypersensitivity to the active substance or the excipients in the formulation of activated recombinant human factor VII, or to mouse, hamster or bovine protein

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
activated recombinant human factor VII; Male patients above 2 years of age with haemophilia A or B who have developed inhibitors and have been prescribed on-demand treatment of activated recombinant human factor VII at any dose for treatment of mild to moderate spontaneous bleeds	Drug: eptacog alfa (activated); Treatment of patients experiencing bleeds at the discretion of the physician/caregiver; Other Names: activated recombinant human factor VII

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Bleed Treatments Resulting in Effective Bleed Resolution (All Bleed Episodes)	The percentage of bleed treatments successfully resulting in bleed resolution. Analysis only considers the patient's opinion of effectiveness at 9 hours, with a rating of "Effective" considered as successful treatment.	within 9 hours of first injection
Percentage of Bleed Treatments Resulting in Effective Bleed Resolution (Spontaneous Bleed Episodes)	The percentage of bleed treatments successfully resulting in bleed resolution. Analysis only considers the patient's opinion of effectiveness at 9 hours, with a rating of "Effective" considered as successful treatment.	within 9 hours of first injection
Percentage of Bleed Treatments Resulting in Effective Pain Relief (All Bleed Episodes)	The percentage of participants with effective pain relief. Pain relief was a subjective assessment made by the patient during treatment of a bleed episode.	within 9 hours of first injection
Percentage of Bleed Treatments Resulting in Effective Pain Relief (Spontaneous Bleed Episodes)	The percentage of participants with effective pain relief. Pain relief was a subjective assessment made by the patient during treatment of a bleed episode.	within 9 hours of first injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleeds) by Time Point (All Bleed Episodes)	Effective haemostasis at 3 different time points for all bleeds. Patient reported outcomes are reported over 1 hour, 3 hours and 6 hours.	1 hour, 3 hours and 6 hours, respectively, after first injection
Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleeds) by Time Point (Spontaneous Bleed Episodes)	Effective haemostasis at 3 different time points for all bleeds. Patient reported outcomes are reported over 1 hour, 3 hours and 6 hours.	1 hour, 3 hours and 6 hours, respectively, after first injection
Percentage of Bleed Treatments Resulting in Effective Pain Relief by Time Point (All Bleed Episodes)	Effective pain relief at 3 different time points for all bleeds. Patient reported outcomes are reported over 1 hour, 3 hours and 6 hours.	1 hour, 3 hours and 6 hours, respectively, after first injection
Percentage of Bleed Treatments Resulting in Effective Pain Relief by Time Point (Spontaneous Bleed Episodes)	Effective pain relief at 3 different time points for spontaneous bleeds. Patient reported outcomes are reported over 1 hour, 3 hours and 6 hours.	1 hour, 3 hours and 6 hours, respectively, after first injection
Total Number of Injections (All Bleed Episodes)	The median number of injections required to treat individual bleed episodes.	individual bleed episode
Total Number of Injections (Spontaneous Bleed Episodes)	The median number of injections required to treat individual bleed episodes.	individual bleed episode
Total Exposure (Cumulative Dose) to Activated Recombinant Human Factor VII (All Bleed Episodes)	The median total cumulative dose required to treat individual bleed episodes.	individual bleed episode
Total Exposure (Cumulative Dose) to Activated Recombinant Human Factor VII (Spontaneous Bleed Episodes)	The median total cumulative dose required to treat individual bleed episodes.	individual bleed episode
Percentage of Patients Reporting Satisfaction With Symptom Relief (All Bleed Episodes)	Patient rate of satisfaction with symptom relief for the bleed episode overall on a 7-point Likert scale. Completion of questionnaire was voluntary. A Likert scale is an ordered, multiple choice questionnaire from which respondents choose one option that best aligns with their view of the particular outcome being measured. Scale answers ranged from extremely satisfied to extremely dissatisfied. The percentage of bleed episodes for which patients reported "extremely satisfied", "very satisfied" or "satisfied" is presented.	duration of bleed episode
Percentage of Bleed Treatments Resulting in Patient Satisfaction With Symptom Relief (Spontaneous Bleed Episodes)	Patient rate of satisfaction with symptom relief for the bleed episode overall on a 7-point Likert scale. Completion of questionnaire was voluntary. A Likert scale is an ordered, multiple choice questionnaire from which respondents choose one option that best aligns with their view of the particular outcome being measured. Scale answers ranged from extremely satisfied to extremely dissatisfied. The percentage of bleed episodes for which patients reported "extremely satisfied", "very satisfied" or "satisfied" is presented.	duration of bleed episode
Percentage of Bleed Treatments Resulting in Patient Satisfaction With Ease of Use (All Bleed Episodes)	Rate of ease of use related to activated recombinant human factor VII on a 7-point Likert scale. Completion of questionnaire was voluntary. A Likert scale is an ordered, multiple choice questionnaire from which respondents choose one option that best aligns with their view of the particular outcome being measured. Scale answers ranged from extremely difficult to extremely easy. The percentage of bleed episodes for which patients reported "extremely easy", "very easy" or "easy" is presented.	duration of bleed episode
Percentage of Bleed Treatments Resulting in Patient Satisfaction With Ease of Use (Spontaneous Bleed Episodes)	Rate of ease of use related to activated recombinant human factor VII on a 7-point Likert scale. Completion of questionnaire was voluntary. A Likert scale is an ordered, multiple choice questionnaire from which respondents choose one option that best aligns with their view of the particular outcome being measured. Scale answers ranged from extremely difficult to extremely easy. The percentage of bleed episodes for which patients reported "extremely easy", "very easy" or "easy" is presented.	duration of bleed episode
Overall Time to Cessation of Bleed/Achievement of Haemostasis (All Bleed Episodes)	Median time to achievement of haemostasis/bleed cessation calculated using Kaplan Meier life table methods. If approximately 50% or less of bleeds achieved the endpoint in a given initial dose subgroup, the median cannot be calculated and it is reported as not applicable	duration of bleed episode
Overall Time to Cessation of Bleed/Achievement of Haemostasis (Spontaneous Bleed Episodes)	Median time to achievement of haemostasis/bleed cessation calculated using Kaplan Meier life table methods. If approximately 50% or less of bleeds achieved the endpoint in a given initial dose subgroup, the median cannot be calculated and it is reported as not applicable	duration of bleed episode
Overall Time to Cessation/Achievement of Haemostasis (Spontaneous Bleed Episodes)	Median time to achievement of haemostasis/bleed cessation calculated using Kaplan Meier life table methods. If approximately 50% or less of bleeds achieved the endpoint in a given initial dose subgroup, the median cannot be calculated and it is reported as not applicable.	duration of bleed episode
Childrens' Health Related Quality of Life (Haemo-QoL): Overall Score	The Haemo-QoL is a specific multidimensional validated and reliable questionnaire used to assess quality of life in patients with haemophilia. Scores are reported on a 0 to 100 scale-higher scores indicate more impairment.	Baseline (week 0) and and registry discontinuation (up to 28 months)
Adults' Health Related Quality of Life (Haemo-QoL-A): Overall Score	The adult Haemo-QoL-A is a specific multidimensional validated and reliable questionnaire used to assess quality of life in patients with haemophilia. Scores are reported on a 0 to 100 scale-higher scores indicate more impairment.	Baseline (week 0) and and registry discontinuation (up to 28 months)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleed) by Dose Level (All Bleed Episodes)	Percentage of bleeds with effective haemostasis within 9 hours of first injection of activated recombinant human factor VII. Patient reported assessments were sorted into 3 sub-categories: "effective" = bleed resolved or substantially improved; "partially effective" = bleed with some improvement; "ineffective" = bleed with no change or with worsening.	within 9 hours after first injection
Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleed) by Dose Level (Spontaneous Bleed Episodes)	Percentage of bleeds with effective haemostasis within 9 hours of first injection of activated recombinant human factor VII. Patient reported assessments were sorted into 3 sub-categories: "effective" = bleed resolved or substantially improved; "partially effective" = bleed with some improvement; "ineffective" = bleed with no change or with worsening.	within 9 hours after first injection
Percentage of Bleed Treatments Resulting in Effective Pain Relief by Initial Dose (All Bleed Episodes)	Percentage of bleeds with effective pain relief within 9 hours of first injection of activated recombinant human factor VII. Patient reported assessments were sorted into 3 sub-categories: "Better" = pain resolved or decreased substantially; "Same" = no change; "Worsened" = pain worsening.	within 9 hours after first injection
Percentage of Bleed Treatments Resulting in Effective Pain Relief by Initial Dose (Spontaneous Bleed Episodes)	Percentage of bleeds with effective pain relief within 9 hours of first injection of activated recombinant human factor VII. Patient reported assessments were sorted into 3 sub-categories: "Better" = pain resolved or decreased substantially; "Same" = no change; "Worsened" = pain worsening.	within 9 hours after first injection

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): July 1, 2010
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: June 19, 2008
• First Submitted That Met QC Criteria: June 23, 2008
• First Posted (Estimate): June 24, 2008

Study Record Updates

• Last Update Posted (Estimate): January 11, 2017
• Last Update Submitted That Met QC Criteria: November 22, 2016
• Last Verified: November 1, 2016

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: F7HAEM-3507