Clinical Trial Results:
An Interventional Open-Label Multicenter Phase IV Study to Evaluate the Impact of Emicizumab on Health-Related Quality of Life, Physical Activity, and Joint Health in Patients With Severe Hemophilia A Without FVIII Inhibitors in the Nordic Countries
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Summary
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EudraCT number |
2020-003256-32 |
Trial protocol |
SE NO FI DK |
Global end of trial date |
08 Jul 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
01 Jan 2025
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First version publication date |
01 Jan 2025
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
MO42245
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
F. Hoffmann-La Roche AG
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Sponsor organisation address |
Grenzacherstrasse 124, Basel, Switzerland, 4058
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Public contact |
F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
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Scientific contact |
F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
08 Jul 2024
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
14 Mar 2024
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Global end of trial reached? |
Yes
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Global end of trial date |
08 Jul 2024
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The study aims to evaluate the impact of emicizumab on aspects of health-related quality of life (HRQoL) in subjects with severe hemophilia A without factor VIII (FVIII) inhibitors.
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Protection of trial subjects |
All study subjects were required to read and sign an Informed Consent Form.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
04 Apr 2022
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
6 Months | ||
Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Denmark: 6
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Country: Number of subjects enrolled |
Finland: 5
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Country: Number of subjects enrolled |
Norway: 6
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Country: Number of subjects enrolled |
Sweden: 11
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Worldwide total number of subjects |
28
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EEA total number of subjects |
28
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
12
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Adults (18-64 years) |
16
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Subjects who completed at least 24 weeks of observation period in the non-interventional study (NIS) MO42590 took part in this study in Denmark, Finland, Norway, and Sweden from 04 April 2022 to 08 July 2024. | ||||||||||
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Pre-assignment
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Screening details |
A total of 28 male adolescent and adult subjects with severe hemophilia A enrolled in this study to receive emicizumab. | ||||||||||
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Period 1
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Period 1 title |
Overall Period
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||
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Arms
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Arm title
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Emicizumab | ||||||||||
Arm description |
Subjects received emicizumab, as subcutaneous (SC) injection, at a loading dose of 3 milligrams/kilograms (mg/kg), every week (QW) for 4 weeks followed by a maintenance dose of 1.5 mg/kg, QW or 3 mg/kg , every 2 weeks (Q2W) or 6 mg/kg, every 4 weeks (Q4W) for 44 weeks or until discontinuation from the study for any reason. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Emicizumab
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Investigational medicinal product code |
RO5534262
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Other name |
Hemlibra, RG6013, ACE910
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Emicizumab, 3mg/kg, QW, as SC injection for 4 weeks followed by a maintenance dose of 1.5 mg/kg, QW or 3 mg/kg, Q2W, or 6 mg/kg (Q4W) for 44 weeks or until discontinuation from the study for any reason.
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Baseline characteristics reporting groups
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Reporting group title |
Emicizumab
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Reporting group description |
Subjects received emicizumab, as subcutaneous (SC) injection, at a loading dose of 3 milligrams/kilograms (mg/kg), every week (QW) for 4 weeks followed by a maintenance dose of 1.5 mg/kg, QW or 3 mg/kg , every 2 weeks (Q2W) or 6 mg/kg, every 4 weeks (Q4W) for 44 weeks or until discontinuation from the study for any reason. | |||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Emicizumab
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Reporting group description |
Subjects received emicizumab, as subcutaneous (SC) injection, at a loading dose of 3 milligrams/kilograms (mg/kg), every week (QW) for 4 weeks followed by a maintenance dose of 1.5 mg/kg, QW or 3 mg/kg , every 2 weeks (Q2W) or 6 mg/kg, every 4 weeks (Q4W) for 44 weeks or until discontinuation from the study for any reason. | ||
Subject analysis set title |
Emicizumab: Adults
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subjects aged ≥ 18 years received emicizumab, SC injection, at a loading dose of 3 mg/kg, QW for 4 weeks followed by a maintenance dose of 1.5 mg/kg, QW or 3 mg/kg, Q2W or 6 mg/kg, Q4W for 44 weeks or until discontinuation from the study for any reason.
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Subject analysis set title |
Emicizumab: Adolescents
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subjects aged 12-<18 years received emicizumab, SC injection, at a loading dose of 3 mg/kg, QW for 4 weeks followed by a maintenance dose of 1.5 mg/kg, QW or 3 mg/kg, Q2W or 6 mg/kg, Q4W for 44 weeks or until discontinuation from the study for any reason.
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Subject analysis set title |
FVIII Prophylaxis
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subjects received FVIII prophylaxis and participated in the NIS MO42590 for up to 24 weeks.
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End point title |
Change from Baseline in Risk Perception &Restrictions Experienced in Recreational Activities,Preoccupation With Disease,Impact of Treatment Burden on HRQoL & Pain Severity Assessed by Comprehensive Assessment Tool of Challenges in Hemophilia(CATCH) Scores [1] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
CATCH assesses impact of hemophilia & its treatment on pediatric (8−17 years) & adult (≥18 years) subjects. Each version has 7 domains: daily activity risk perception (RP) & impact, social activity RP & impact, recreational activity (RA) RP & impact, work impact/school impact, preoccupation, treatment burden, & pain. Each domain has multiple items based on version used & is scored on ordinal scales with 11-point numeric rating scale for pain. Raw scores are linearly transformed on a scale of 0-100. Higher scores=higher perceived risk, higher impact & greater perceived burden of hemophilia. For adolescents higher score in treatment burden domain=lower perceived burden of hemophilia. Baseline (BL) = Week 24 assessment from NIS MO42590. Safety population. Number analysed=subjects with data available for analyses. n=subjects with data available for analyses at specified timepoints. 9999=No subjects were analysed at this timepoint.
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End point type |
Primary
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End point timeframe |
Baseline, Week 25 and Week 49
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All analysis was descriptive only and no formal hypothesis testing was done. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Level of Physical Activity (PA) Assessed by Daily Step Count (DSC) | ||||||||||||||
End point description |
Level of PA was measured using a Fitbit model Charge 4 and their standard algorithms for subjects aged 13 years and older (at Week 9 of this study). Subjects wore the activity tracker while they were awake every day on the same wrist. Baseline was defined as Week 9-16 assessment period of this study. Safety population included all subjects who received at least one dose of emicizumab. Number analysed included subjects who wore the device for at least 7 hours per day and with at least 100 steps recorded, on at least 21 days. n=subjects with data available for analysis at the specified timepoint.
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End point type |
Secondary
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End point timeframe |
Weeks 9-16, Weeks 25-32 and Weeks 41-48
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Level of PA Assessed by Daily Active Minutes, Moderate to Vigorous Physical Activity (MVPA), and Sedentary Time | ||||||||||||||||||||||||||||||||||||||||||||
End point description |
Level of PA was measured using a Fitbit model Charge 4 and their standard algorithms for subjects aged 13 years and older (at Week 9 of this study). Subjects wore the activity tracker while they were awake every day on the same wrist. Active minutes identify the possibility of increased activity intensity. The subject must be active for at least ten minutes to earn active minutes. Intensity refers to the rate at which the activity was being performed/ the magnitude of the effort required to perform an activity/ exercise. MVPA was defined as per Fitbit default categorization. Sedentary time was calculated as time when there was no movement. Baseline was defined as Week 9-16 assessment period of this study. Safety population included all subjects who received at least one dose of emicizumab. Number analysed included subjects who wore the device for at least 7 hours per day and with at least 100 steps recorded, on at least 21 days.
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End point type |
Secondary
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End point timeframe |
Week 9-16, Week 25-32 and Week 41-48
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Level of PA Assessed Using Metabolic Equivalent Tasks (METs) | ||||||||||||||
End point description |
Level of PA was measured using a Fitbit model Charge 4 and their standard algorithms for subjects aged 13 years and older (at Week 9 of this study). Subjects wore the activity tracker while they were awake every day on the same wrist. The METs measures energy expenditure during PA and were used to express the intensity of PAs. Light=<3 METs; Moderate=3 to 6 METs; Vigorours=>6 METs. Baseline was defined as Week 9-16 assessment period of this study. Safety population included all subjects who received at least one dose of emicizumab. Number analysed included subjects who wore the device for at least 7 hours per day and with at least 100 steps recorded, on at least 21 days. n=subjects with data available for analysis at the specified timepoint.
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End point type |
Secondary
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End point timeframe |
Week 9-16, Week 25-32 and Week 41-48
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Time and Intensity Level of PA Assessed Using International Physical Activity Questionnaire-Short Form (IPAQ-SF) Score Every Three Months | ||||||||||||||||||||||||||||||||||||||
End point description |
The IPAQ-SF measured overall PA in last 7 days of adolescent subjects aged ≥ 15 years. It was completed via electronic patient-reported outcome (ePRO) in a smartphone application (app). The IPAQ comprises a set of 4 questionnaires to assess 3 specific types of activity undertaken in 4 domains (leisure time physical activity, domestic and gardening (yard) activities, work-related physical activity, transport-related physical activity). Specific types of activity assessed were walking, moderate-intensity & vigorous-intensity activities. The items in IPAQ-SF questionnaire were structured to provide separate scores on walking, moderate-intensity & vigorous-intensity activity, expressed in MET-minutes/week. Higher scores=better PA. Week1=Baseline assessment in MO42245. Safety population=subjects who received at least 1 dose of emicizumab.Number analysed=subjects aged 15 years & older with data available for analysis. n=subjects available with data for analysis at that specified timepoint.
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End point type |
Secondary
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End point timeframe |
Weeks 1, 13, 25, 37, and 49
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||
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End point title |
Intra-Patient Analysis of Change from Baseline in Level of PA, Assessed From DSC Using Activity Tracker as Compared with Study MO42590 | ||||||||
End point description |
Level of PA was measured using a Fitbit model Charge 4 and their standard algorithms for subjects aged 13 years and older. Subjects wore the activity tracker while they were awake every day on the same wrist. Safety population included all subjects who received at least one dose of emicizumab. Number analysed included subjects who wore the device for at least 7 hours per day and with at least 100 steps recorded, on at least 21 days. Baseline was defined as the Weeks 17-24 assessment in NIS MO42590.
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End point type |
Secondary
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End point timeframe |
Baseline and Weeks 41-48
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| No statistical analyses for this end point | |||||||||
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End point title |
Intra-Patient Analysis of Change from Baseline in Level of PA Assessed From METs Using Activity Tracker as Compared with Study MO42590 | ||||||||
End point description |
Level of PA was measured using a Fitbit model Charge 4 and their standard algorithms for subjects aged 13 years and older. Subjects wore the activity tracker while they were awake every day on the same wrist. The METs measures energy expenditure during PA and were used to express the intensity of PAs. Light=<3 METs; Moderate=3 to 6 METs; Vigorours=>6 METs. Safety population included all subjects who received at least one dose of emicizumab. Number analysed included subjects who wore the device for at least 7 hours per day and with at least 100 steps recorded, on at least 21 days. Baseline was defined as the Week 17-24 assessment in NIS MO42590.
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End point type |
Secondary
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End point timeframe |
Baseline and Weeks 41-48
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| No statistical analyses for this end point | |||||||||
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End point title |
Intra-Patient Analysis of Change from Baseline in Level of PA Assessed From Daily Active Minutes, MVPA and Sedentary Time Using Activity Tracker as Compared with Study MO42590 | ||||||||||||||||||||
End point description |
Level of PA was measured using a Fitbit model Charge 4 and their standard algorithms for subjects aged 13 years and older. Subjects wore the activity tracker while they were awake every day on the same wrist. Active minutes identify the possibility of increased activity intensity. The subject must be active for at least ten minutes to earn active minutes. Intensity refers to the rate at which the activity was being performed/ the magnitude of the effort required to perform an activity/ exercise. MVPA was defined as per Fitbit default categorization. Sedentary time was calculated as time when there was no movement. Safety population included all subjects who received at least one dose of emicizumab. Number analysed included subjects who wore the device for at least 7 hours per day and with at least 100 steps recorded, on at least 21 days. Baseline was defined as the Week 17-24 assessment in NIS MO42590.
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End point type |
Secondary
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End point timeframe |
Baseline and Weeks 41-48
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Intra-Patient Analysis of Change from Baseline in Level of PA Assessed Using IPAQ-SF as Compared with Study MO42590 | ||||||||||||||||||||||||||||||||||||||||||||
End point description |
The IPAQ-SF measured overall PA in last 7 days of adolescent subjects aged ≥15 years. IPAQ-SF questionnaire was completed via ePRO in a smartphone application (app). The IPAQ comprises a set of 4 questionnaires to assess 3 specific types of activity undertaken in 4 domains (leisure time physical activity, domestic and gardening (yard) activities, work-related physical activity, transport-related physical activity). Specific types of activity assessed were walking, moderate-intensity & vigorous-intensity activities. The items in IPAQ-SF questionnaire were structured to provide separate scores on walking, moderate-intensity & vigorous-intensity activity, expressed in MET-minutes/week. Higher scores=better PA. Safety population=subjects who received at least 1 dose of emicizumab. Baseline was defined as the Week 1 assessment in NIS MO42590. Number analysed=subjects with assessments performed at all planned visits. n=subjects with data available for analysis at the specified timepoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Weeks 1, 13, 25, 37, and 49
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Joint Health Assessed Using Hemophilia Early Arthropathy Detection With Ultrasound (HEAD-US) Score | ||||||||||||
End point description |
The HEAD-US was a method for early detection of hemophilic arthropathy with ultrasound. HEAD-US assesses the following 3 domains for 6 joints (knees, elbows, and ankles): hypertrophic synovium, disease damage on cartilage & disease damaged on bone, with a maximum score of 8 points/joints. Scores were categorized based on severity. Joint abnormalities can be quantified using an additive scoring scale. A total HEAD-US score per subject was calculated as sum of total scores per joints, for subjects with all joints assessed. Higher scores=worse joint health. Week 1=MO42245 baseline assessment. Safety population=subjects who received at least one dose of emicizumab. Number analysed=subjects with data available for analysis.
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End point type |
Secondary
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End point timeframe |
Week 1, Week 49
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Joint Health Assessed Using Hemophilia Joint Health Score (HJHS) 2.1 | ||||||||||||
End point description |
HJHS measures joint health, in domains of body structure & function (impairment) of joints most affected by bleeding in hemophilia: knees, ankles & elbows. It consists of assessment of swelling (0=None‐3=Severe); duration of swelling (0=no swelling/<6 months‐1=≥6 months); muscle atrophy (0=None‐2=Severe); crepitus on motion (0=None‐2=Severe); flexion loss & extension loss (0=<5°‐3=>20°); joint pain (0=No pain through active range of motion‐2=Pain); strength (0=Holds test position against gravity within maximum resistance‐4=Trace/no contraction); & Global Gait Score (GGS; 0=All skills in normal limits(NL)‐4=No skills in NL). HJHS Total Score=sum of all joint domain scores (6*20 points+4 points for GGS). Higher score=worse joint health. Clinically relevant improvements=≥4-point reduction in Total HJHS/≥2-point reduction in HJHS joints domain. Week 1=MO42245 baseline. Safety population; subjects with all joints assessed by HJHS & GGS. n=number of subjects analysed at that timepoint.
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End point type |
Secondary
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End point timeframe |
Week 1, Week 49
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Annualized Bleeding Rate (ABR) for Treated Bleeds Over Time | ||||||||||||
End point description |
An event was considered a treated bleed if coagulation factors were administered to treat signs or symptoms of bleeding (e.g., pain, swelling, etc.). Bleeds and treatment of bleeds were captured through the Bleed Medication Questionnaire (BMQ). The number of treated bleeds was estimated as an ABR using a negative binomial regression model, which accounts for different follow-up times. Bleed rate was calculated over the 48 weeks of MO42245 compared to 24 weeks of MO42590. ABR was derived as follows: number of bleeds/number of days during observational period (the time that each subject stays in the study) * 365.25. Safety population included all subjects who received at least one dose of emicizumab.
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End point type |
Secondary
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End point timeframe |
Up to Week 49
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| No statistical analyses for this end point | |||||||||||||
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End point title |
ABR for Treated Spontaneous or Traumatic Bleeds Over Time | ||||||||||||||||||
End point description |
An event was considered a treated bleed if coagulation factors were administered to treat signs or symptoms of bleeding (e.g., pain, swelling, etc.). Bleeds were classified as spontaneous if a subject recorded a bleed when there was no known contributing factor such as definite trauma, antecedent “strenuous” activity or “overuse” or “procedure/surgery.” Bleeds were classified as traumatic if a subject recorded a bleed when there was a known or believed reason for the bleed. Bleeds & treatment of bleeds were captured through the BMQ. Number of treated bleeds was estimated as an ABR using a negative binomial regression model, which accounts for different follow-up times. Bleed rate was calculated over the 48 weeks of MO42245 compared to 24 weeks of MO42590. ABR was derived as follows: number of bleeds/number of days during observational period (the time that each subject stays in the study) * 365.25. Safety population=all subjects who received at least 1 dose of emicizumab.
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End point type |
Secondary
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End point timeframe |
Up to Week 49
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
ABR for All Bleeds Over Time | ||||||||||||
End point description |
All bleeds included both treated and non-treated bleeds. An event was considered a treated bleed if coagulation factors were administered to treat signs or symptoms of bleeding (e.g., pain, swelling, etc.). Bleeds and treatment of bleeds were captured through the BMQ. The number of treated bleeds was estimated as ABR using a negative binomial regression model, which accounts for different follow-up times. Bleed rate was calculated over the 48 weeks of MO42245 compared to 24 weeks of MO42590. ABR was derived as follows: number of bleeds/number of days during observational period (the time that each subject stays in the study) * 365.25. Safety population included all subjects who received at least one dose of emicizumab.
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End point type |
Secondary
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End point timeframe |
Up to Week 49
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of Subjects With Zero Treated Bleeds Over Time | |||||||||
End point description |
An event was considered a treated bleed if coagulation factors were administered to treat signs or symptoms of bleeding (e.g., pain, swelling, etc.). Bleeds and treatment of bleeds were captured through the BMQ. Bleed rate was calculated over the 48 weeks of MO42245 compared to 24 weeks of MO42590. Safety population included all subjects who received at least one dose of emicizumab.
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End point type |
Secondary
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End point timeframe |
Up to Week 49
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| No statistical analyses for this end point | ||||||||||
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End point title |
ABR for Treated Joint Bleeds Over Time | ||||||||||||
End point description |
An event was considered a treated bleed if coagulation factors were administered to treat signs or symptoms of bleeding (e.g., pain, swelling, etc.). Treated joint bleeds were treated bleeds where joint bleed was accompanied by increased swelling or warmth of the skin over the joint, increasing pain or decreased range of motion or difficulty using the joint compared with Baseline. Bleeds and treatment of bleeds were captured through the BMQ. The number of treated bleeds was estimated as an ABR using a negative binomial regression model, which accounts for different follow-up times. Bleed rate was calculated over the 48 weeks of MO42245 compared to 24 weeks of MO42590. ABR was derived as follows: number of bleeds/number of days during observational period (the time that each subject stays in the study) * 365.25. Safety population included all subjects who received at least one dose of emicizumab.
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End point type |
Secondary
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End point timeframe |
Up to Week 49
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| No statistical analyses for this end point | |||||||||||||
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End point title |
ABR for Treated Target Joint Bleeds Over Time | ||||||||||||
End point description |
A treated bleed occurred if coagulation factors were administered to treat signs or symptoms of bleeding (e.g., pain, swelling, etc.). Treated target joint bleeds: treated joint bleeds that occurred in a target joint, defined as a joint in which 3 or more treated joint bleeds occurred during the 24 weeks prior to study entry. Bleeds and treatment of bleeds were captured through the BMQ. The number of treated bleeds was estimated as an ABR using a negative binomial regression model, which accounts for different follow-up times. Bleed rate was calculated over the 48 weeks of MO42245 compared to 24 weeks of MO42590. ABR was derived as follows: number of bleeds/number of days during observational period (the time that each subject stays in the study) * 365.25. Safety population. 99999=number and 95% confidence interval (CI) were not estimable as no subjects had an event.
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End point type |
Secondary
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End point timeframe |
Up to Week 49
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of FVIII Infusions Required to Treat a Breakthrough Bleed | ||||||||||||||||||
End point description |
The non-emicizumab Factor VIII (FVIII) infusions used to treat a bleed were categorized as standard half-life [SHL] and extended half-life [EHL]. The number of FVIII infusions was counted per bleed (all treatments that are linked to the same bleed per the 72h rule were considered to belong to the same bleed). If the same treatment(s) were associated with multiple bleeds, these were counted multiple times, i.e. linked to both bleeds. Participants experienced a total of 82 and 39 bleeds that required treatment with coagulation factors, while on FVIII and emicizumab prophylaxis respectively. Safety population included all subjects who received at least one dose of emicizumab.
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End point type |
Secondary
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End point timeframe |
Up to Week 49
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Amount of Doses Required to Treat a Breakthrough Bleed | ||||||||||||||||||
End point description |
The number and percentages of subjects with non-emicizumab hemophilia medications was summarized by category of hemophilia medication [(SHL) and EHL)]. The number of FVIII doses and the cumulative doses were summarized by category of hemophilia medication. Safety population included all subjects who received at least one dose of emicizumab.
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End point type |
Secondary
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End point timeframe |
Up to Week 49
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Number of Subjects who Preferred for Emicizumab SC Treatment Assessed Using Emicizumab Preference (EmiPref) Questionnaire | ||||||||||
End point description |
EmiPref questionnaire was used to assess subjects’ preference of SC emicizumab over their former IV hemophilia treatment. The questionnaire builds on the results from previous studies, which noted that subjects expressed preference for treatments that did not have negative effects (e.g., pain that results from infusions), were not time consuming, were not associated with high treatment burden, and had a goal of achieving a “normal life”. Safety population included all subjects who received at least one dose of emicizumab.
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End point type |
Secondary
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End point timeframe |
Week 25 and Week 49
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| No statistical analyses for this end point | |||||||||||
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End point title |
Health Status Assessed Using European Quality of Life Five-Dimension-Five Level Questionnaire (EQ-5D-5L) | ||||||||||||||
End point description |
The EQ-5D-5L was a validated, self-report, health status questionnaire that was used to calculate a health status utility score. The EQ-5D-5L consists of two parts, the first : health state classification, contains five dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/ depression). Overall scores typically range from 0 to 1. Low scores represent a higher level of dysfunction. The second part: VAS assesses current health status. using a score range of 0 to 100-points. Higher scores indicate better health. VAS was to be analysed from the EQ-5D-5L Week 1= MO42245 baseline assessment. Safety population included all subjects who received at least one dose of emicizumab. Number analysed included subjects with data available for analysis. n=subjects with data available for analysis at that specified timepoint.
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End point type |
Secondary
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End point timeframe |
Week 1, Week 25 and Week 49
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Caregiver Burden Assessed Using Hemophilia Associated Caregiver Burden Scale (HEMOCAB) Total Score | ||||||||||||
End point description |
HEMOCAB is a caregiver questionnaire comprising 54 questions pertaining to 13 domains (emotional stress, financial burden, personal sacrifice and limitations, job-related burden, interactions with others, interaction of child with others, school, perception of child, dealing with child's hemophilia, medical management, work situation related to hemophilia, interaction with the child's father, and impact of child's hemophilia). Responses to each domain were answered on a five-point Likert scale, with the scale assessing the nine frequency of burden domains ranging from “never” to “always,” and assessing the intensity of the four perceived burden domains ranging from “not at all” to “very much.” High values imply high burden. Week 1= MO42245 baseline assessment. HEMOCAB was completed by the parent/caregiver of adolescents 12-17 years old. Safety population included all subjects who received at least one dose of emicizumab. Number analysed includes subjects with available data.
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End point type |
Secondary
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End point timeframe |
Week 1 and Week 49
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of Subjects with at Least One Adverse Event | ||||||
End point description |
An adverse event (AE) is untoward medical occurrence in participant administered a pharmaceutical product & regardless of causal relationship with this treatment. An AE can therefore be any unfavorable & unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to investigational product. Safety population included all subjects who received at least one dose of emicizumab.
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End point type |
Secondary
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End point timeframe |
From study start until 24 weeks after the last dose of the study drug (up to 72 weeks)
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| No statistical analyses for this end point | |||||||
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Adverse events information
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Timeframe for reporting adverse events |
From study start until 24 weeks after the last dose of the study drug (up to 72 weeks)
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Adverse event reporting additional description |
Safety Population included all subjects who received at least one dose of emicizumab.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
27.0
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Reporting groups
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Reporting group title |
Emicizumab
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Reporting group description |
Subjects received emicizumab, as SC injection, at a loading dose of 3 mg/kg, QW for 4 weeks followed by a maintenance dose of 1.5 mg/kg, QW or 3 mg/kg, Q2W or 6 mg/kg, Q4W for 44 weeks until discontinuation from the study for any reason, whichever occurred first. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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29 Apr 2021 |
Protocol Version 2: 1. Fitbit activity tracker data collection was limited to subjects aged 13 and older and the specific data collected by the Fitbit Charge 4 device were explicitly defined to refine the objective for the activity tracker.
2. Intensity of physical activity was included when evaluating bleeds related to exercise.
3. Clarifications were made to differentiate between non-electronic case report form (eCRF) and eCRF data.
4. The socio-demographic section was removed from HEMOCAB.
5. New guidance was included to manage potential cases of neutralizing anti-drug antibodies, especially in scenarios where a loss of efficacy is noted. |
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17 Mar 2022 |
Protocol Version 3: 1. The total number of subjects was reduced from approximately 50 subjects to approximately 30 subjects. The adjustment has been done based on the recruitment at the time and realistic estimation of potential subjects from each site.
2. The inclusion criteria age was changed from ≥ 12-51 years old to ≥12-61 years, to provide adequate numbers for age group analysis considering the reduced total number of subjects.
3. HEMOCAB has been updated to the latest shortened version.
4. Use of FVIII, given before an activity, has been changed to “allowed under certain circumstances,” where FVIII can be given before intense physical activity and the Medical Monitor should be informed in advance.
5. The anticipated recruitment period has been prolonged from 44 to 55 weeks. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
