Severe Hemophilia APhase 4Beyond ABRNCT05181618
A Study to Evaluate Overall Health, Physical Activity, and Joint Outcomes in Participants With Severe or Moderate Hemophilia A Without Factor VIII Inhibitors on Emicizumab Prophylaxis
A Phase 4 study testing Emicizumab in people with Severe Hemophilia A and Moderate Hemophilia A, run by Hoffmann-La Roche at 26 sites in 12 countries.
Trial summary
Study MO42623 is a Phase IV, multicenter, open-label, three cohort study designed to evaluate the impact of emicizumab prophylaxis on overall health, physical activity, and joint outcomes in participants aged ≥13 and <70 years with severe hemophilia A without factor VIII (FVIII) inhibitors or moderate hemophilia A… Read more about this study
- Who is it for?
- Ages 13 to 69 years
- Conditions the study is for
- Severe Hemophilia A, Moderate Hemophilia A
- What is being tested?
- Emicizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 136 participants
- Where
- 26 sitesin 12 countries
- Study dates
- 20 Jun 2022to 21 Dec 2026
- Phase
- Phase 4
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 69 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Diagnosis of severe congenital hemophilia A (intrinsic factor VIII [FVIII] level <1%) or moderate congenital hemophilia A (intrinsic FVIII level ≤5%) if previously prescribed prophylaxis
- A negative test for FVIII inhibitor (i.e., <0.6 Bethesda Units) during screening period
- No history of FVIII inhibitory antibodies (<0.6 BU/mL using the Bethesda assay) in the last 5 years. Participants who completed successful immune tolerance induction (ITI) at least 5 years before screening are eligible, provided they have had no evidence of inhibitor recurrence (permanent or temporary) as may be indicated by detection of an inhibitor, FVIII half-life <6 hours, or FVIII recovery <66% since completing ITI
- Participants who were on standard FVIII prophylaxis, defined as the regular administration of FVIII to prevent bleeding, for at least the last 24 weeks, can be enrolled regardless of the number of bleeds during this period
- Adequate hematologic, hepatic and renal function
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception during the treatment period and for at least 24 weeks after the final dose of emicizumab
Who cannot join
- Inherited or acquired bleeding disorder other than severe congenital hemophilia A (intrinsic FVIII level <1%) or moderate congenital hemophilia A (intrinsic FVIII level ≤5%) without FVIII inhibitors who were previously prescribed prophylaxis for at least 24 weeks
- Participants who have previously received emicizumab prophylaxis
- Participants that plan to have joint replacement, joint procedure, synovectomy or synoviorthesis at screening
- Participants who had joint replacement, joint procedure, synovectomy or synoviorthesis: Less than 2 years ago; OR, More than 3 years ago and are still experiencing pain in the joint. For participants who had joint replacement, joint procedure, synovectomy or synoviorthesis more than 2 years ago who are not experiencing pain in the joint(s), the participant may be enrolled but the specific joint(s) in which the procedure was conducted will be excluded from the study
- Participants who have conditions other than hemophilia A that can affect joint health and structure (e.g., osteoarthritis) or with severely impaired mobility due to conditions other than hemophilia A
- Participants with known reduced bone mineral density defined as clinically relevant vitamin D deficiency
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- Participants with pre-existing uncontrolled or unstable cardiovascular disease not receiving targeted medication or in a stable condition
- Participants not eligible for MRI
- History of illicit drug or alcohol abuse within 48 weeks prior to screening in the investigator's judgement
- Participants who are at high risk for thrombotic microangiopathy (TMA)
- Previous (within the last 12 months) or current treatment for thromboembolic disease (with the exception of previous catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing) or signs of thromboembolic disease
- Other conditions (e.g., certain autoimmune diseases) that may currently increase the risk of bleeding or thrombosis
- History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the emicizumab injection
- Planned surgery during the emicizumab loading dose phase
- Known HIV infection not controlled by medication
- Concomitant disease, condition, significant abnormality on screening evaluation or laboratory tests, or treatment that could interfere with the conduct of the study, or that would in the opinion of the investigator, pose an additional unacceptable risk in administering study drug to the participant
- Receipt of any of the following: An investigational drug to treat or reduce the risk of hemophilic bleeds within 5 half-lives of last drug administration at screening; A non-hemophilia-related investigational drug within last 30 days or 5 half-lives at screening, whichever is shorter; or, Any other investigational drug currently being administered or planned to be administered
- Inability to comply with the study protocol
- Pregnant or breastfeeding, or intending to become pregnant during the study
Trial locations and contacts
26 sites in 12 countries.
26 sites in 12 countries
Spain5 sites
Complejo Hospitalario Universitario A Coruña (CHUAC)
A Coruña, 15006
Hospital de la Santa Creu i Sant Pau
Barcelona, 08025
Hospital Universitario Vall de Hebron
Barcelona, 08035
Hospital Universitario la Paz
Madrid, 28046
Hospital Regional Universitario Carlos Haya
Málaga, 29010
Turkey (Türkiye)4 sites
Gazi Universitesi Tip Fakultesi
Ankara, 06500
Akdeniz Uni School of Medicine
Antalya, 07059
Istanbul University Cerrahpasa Medical Faculty
Istanbul, 34098
Ege Uni Medical School
Izmir, 35100
Italy3 sites
AOU Careggi
Florence, Tuscany, 50134
IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milan, Lombardy, 20122
Policlinico Univ. A. Gemelli
Rome, Lazio, 00168
United States2 sites
University of Miami Medical Center
Miami, Florida, 33136
Oklahoma Children's Hospital ? Jimmy Everest Center
Oklahoma City, Oklahoma, 73104
Brazil2 sites
Hospital das Clinicas - UNICAMP
Campinas, São Paulo, 13083-878
Hospital das Clínicas Faculdades Médicas de Ribeirão Preto
Ribeirão Preto, São Paulo, 14051-140
Germany2 sites
Charité Universitätsklinikum Berlin
Berlin, 13353
Universitätsklinikum Bonn
Bonn, 53127
United Kingdom2 sites
St Thomas Westminster
London, SE1 7EH
Manchester University NHS Foundation Trust (MFT)
Manchester, M13 9WL
Morocco1 site
Hôpital d'enfants de Rabat - Service d'hémato-oncologie pédiatrique
Rabat, 10090
About this study
Official title: A Multicenter, Open-Label Phase IV Study to Evaluate Overall Health, Physical Activity, and Joint Outcomes, in Participants Aged ≥13 and <70 Years With Severe or Moderate Hemophilia A Without FVIII Inhibitors on Emicizumab Prophylaxis
Study MO42623 is a Phase IV, multicenter, open-label, three cohort study designed to evaluate the impact of emicizumab prophylaxis on overall health, physical activity, and joint outcomes in participants aged ≥13 and <70 years with severe hemophilia A without factor VIII (FVIII) inhibitors or moderate hemophilia A without FVIII inhibitors who are receiving FVIII prophylaxis and who will start emicizumab treatment as part of this study.
- Conditions
- Severe Hemophilia A, Moderate Hemophilia A
- Being tested
- Emicizumab
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EmicizumabDrug
Also called Hemlibra, RO5534262, RG6013, ACE910
The emicizumab dosing regimen will be 3 milligrams per kilogram of body weight (mg/kg) subcutaneously (SC) once a week (QW) for 4 weeks followed by participant preference of one of the following maintenance regimens: 1.5 mg/kg QW, 3 mg/kg once every 2 weeks (Q2W), or 6 mg/kg once every 4 weeks (Q4W) in agreement with the investigator.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1, Hemophilia A and Without Arthropathy: Emicizumab | Experimental | Cohort 1 comprises participants with severe or moderate hemophilia A and with no synovitis and no osteochondral damage (Haemophilia Early Arthropathy Detection with Ultrasound [HEAD-US] score of 0) in all index joints. Receives: Drug: Emicizumab |
| Cohort 2, Hemophilia A and with Synovitis Only: Emicizumab | Experimental | Cohort 2 comprises participants with severe or moderate hemophilia A and with synovitis (HEAD-US synovitis score of ≥1) in at least one index joint and no osteochondral damage (HEAD-US bone and cartilage score of 0). Receives: Drug: Emicizumab |
| Cohort 3, Hemophilia A and with Osteochondral Damage: Emicizumab | Experimental | Cohort 3 comprises participants with severe or moderate hemophilia A and with osteochondral damage (HEAD-US bone and cartilage score of ≥1) in at least one index joint and with any synovitis score. Receives: Drug: Emicizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Joint Status at 6 Months, Based on Centrally Reviewed Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) Scores with a Specific Focus on the Synovitis Score in Participants with Synovitis
Measured: 6 Months
Joint Status at 12 Months, Based on Centrally Reviewed Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) Scores with a Specific Focus on the Synovitis Score in Participants with Synovitis
Measured: 12 Months
Joint Status at 24 Months, Based on Centrally Reviewed Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) Scores with a Specific Focus on the Synovitis Score in Participants with Synovitis
Measured: 24 Months
Joint Status at 36 Months, Based on Centrally Reviewed Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) Scores with a Specific Focus on the Synovitis Score in Participants with Synovitis
Measured: 36 Months
Clinical Joint Status at 6 Months, Based on the Hemophilia Joint Health Score (HJHS v2.1) Excluding Gait Assessment
Measured: 6 Months
Clinical Joint Status at 12 Months, Based on the Hemophilia Joint Health Score (HJHS v2.1) Excluding Gait Assessment
Measured: 12 Months
Clinical Joint Status at 24 Months, Based on the Hemophilia Joint Health Score (HJHS v2.1) Excluding Gait Assessment
Measured: 24 Months
Clinical Joint Status at 36 Months, Based on the Hemophilia Joint Health Score (HJHS v2.1) Excluding Gait Assessment
Measured: 36 Months
Joint Status at 36 Months, Based on Centrally Reviewed International Prophylaxis Study Group (IPSG) Score (with MRI)
Measured: 36 Months
Number of Problem Joints at 6 Months
Problem joints are defined as joints having chronic joint pain and/or limited range of movement due to compromised joint integrity (i.e., chronic synovitis and/or hemophilic arthropathy) with or without persistent bleeding.
Measured: 6 Months
Number of Problem Joints at 12 Months
Problem joints are defined as joints having chronic joint pain and/or limited range of movement due to compromised joint integrity (i.e., chronic synovitis and/or hemophilic arthropathy) with or without persistent bleeding.
Measured: 12 Months
Number of Problem Joints at 24 Months
Problem joints are defined as joints having chronic joint pain and/or limited range of movement due to compromised joint integrity (i.e., chronic synovitis and/or hemophilic arthropathy) with or without persistent bleeding.
Measured: 24 Months
Number of Problem Joints at 36 Months
Problem joints are defined as joints having chronic joint pain and/or limited range of movement due to compromised joint integrity (i.e., chronic synovitis and/or hemophilic arthropathy) with or without persistent bleeding.
Measured: 36 Months
Percentage of Joints That are Problem Joints at 6 Months
Measured: 6 Months
Percentage of Joints That are Problem Joints at 12 Months
Measured: 12 Months
Percentage of Joints That are Problem Joints at 24 Months
Measured: 24 Months
Percentage of Joints That are Problem Joints at 36 Months
Measured: 36 Months
Change from Baseline in the CATCH Domain Scores Over Time, as Assessed with the Comprehensive Assessment Tool of Challenges in Hemophilia (CATCH) Questionnaire for Adult Participants
Measured: At Baseline (Day 1), Months 3, 6, 9, 12, 18, 24, 30, and 36
Change from Baseline in the CATCH Domain Scores Over Time, as Assessed with the CATCH Questionnaire for Pediatric Participants
Measured: At Baseline (Day 1), Months 3, 6, 9, 12, 18, 24, 30, and 36
Change from Baseline in the Average Daily Time Spent Doing Physical Activities by Intensity Level Over Time, as Assessed by Participant Responses to the International Physical Activity Questionnaire Short Format (IPAQ-SF)
Measured: At Baseline (Day 1), Months 3, 6, 9, 12, 18, 24, 30, and 36
Daily Step Count Over Time, as Measured with a Wearable Activity Tracker
Measured: From Baseline until end of treatment period (up to 36 months)
Daily Metabolic Equivalents of Tasks (METs) Over Time, as Measured with a Wearable Activity Tracker
Measured: From Baseline until end of treatment period (up to 36 months)
Daily Time Spent in Moderate to Vigorous Physical Activity (MVPA) Over Time, as per the Activity Tracker Default Categorization
Measured: From Baseline until end of treatment period (up to 36 months)
Daily Active Minutes of Physical Activity Over Time, as Measured with a Wearable Activity Tracker
Measured: From Baseline until end of treatment period (up to 36 months)
Model-Based Annualized Bleed Rates for All Bleeds, Treated Bleeds, Spontaneous Bleeds, Joint Bleeds, Treated Joint Bleeds, and Target Joint Bleeds
Measured: From Baseline until end of treatment period (up to 36 months)
Mean Calculated Annualized Bleed Rates for All Bleeds, Treated Bleeds, Spontaneous Bleeds, Joint Bleeds, Treated Joint Bleeds, and Target Joint Bleeds
Measured: From Baseline until end of treatment period (up to 36 months)
Median Calculated Annualized Bleed Rates for All Bleeds, Treated Bleeds, Spontaneous Bleeds, Joint Bleeds, Treated Joint Bleeds, and Target Joint Bleeds
Measured: From Baseline until end of treatment period (up to 36 months)
Number of Participants who Prefer Emicizumab SC Treatment, Their Previous Hemophilia IV Treatment, or Have No Preference, as Assessed Through Use of the Emicizumab Preference Survey at Month 6
Measured: At Month 6
Secondary outcomes (7)
Number of Participants with at Least One Adverse Event, with Severity Determined According to the World Health Organization (WHO) Toxicity Scale
Measured: From Baseline until 24 weeks after the final dose of emicizumab (up to 3.5 years)
Number of Participants with at Least One Thromboembolic Event
Measured: From Baseline until 24 weeks after the final dose of emicizumab (up to 3.5 years)
Number of Participants with at Least One Event of Thrombotic Microangiopathy (TMA)
Measured: From Baseline until 24 weeks after the final dose of emicizumab (up to 3.5 years)
Number of Participants with at Least One Severe Hypersensitivity, Anaphylaxis, and Anaphylactoid Event
Measured: From Baseline until 24 weeks after the final dose of emicizumab (up to 3.5 years)
Number of Participants with at Least One Injection-Site Reaction
Measured: From Baseline until 24 weeks after the final dose of emicizumab (up to 3.5 years)
Number of Participants with Anti-Drug Antibodies (ADAs) Against Emicizumab at Baseline and During the Study
Measured: At Baseline, Months 6, 12, 24, and 36
Number of Participants who Develop Anti-FVIII Inhibitors During the Study
Measured: At Months 6, 12, 24, and 36
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2022
- Study start20 Jun 2022
- Primary completion19 Nov 2026 (estimated)
- Study completion21 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Severe Hemophilia AStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe 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 4
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- The intervention study model is "single group" because all three cohorts of participants with hemophilia A will be receiving the same intervention: emicizumab.
- Masking
- None (open label)
- Enrolment
- 136 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05181618
- Sponsor's protocol ID
- MO42623
- Other IDs
- 2020-005092-13, 2023-505747-40-00, ISRCTN10101701, 2023
- Acronym
- Beyond ABR
- Status last verified
- Oct 2026
- First submitted
- 6 Dec 2021
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No