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

Severe Hemophilia A Clinical Trial

— Beyond ABR  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05181618
• Other study ID #: MO42623
• Secondary ID: 2020-005092-1320
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: June 20, 2022
• Est. completion date: December 28, 2026

Study information

• Verified date: May 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 without FVIII inhibitors who are receiving FVIII prophylaxis and who will start emicizumab treatment as part of this study.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 136
• Est. completion date: December 28, 2026
• Est. primary completion date: December 28, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years to 69 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

• 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

Related Conditions & MeSH terms

• Hemophilia A
• Severe Hemophilia A

Intervention

Drug:
• Emicizumab
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.

Locations

Country	Name	City	State
Brazil	Hospital das Clinicas - UNICAMP; Hemoterapia	Campinas	SP
Brazil	Hospital das Clínicas Faculdades Médicas de Ribeirão Preto	Ribeirao Preto	SP
Canada	Hamilton Health Sciences Corporation	Hamilton	Ontario
Germany	Charité Universitätsklinikum Berlin; Klinik f. Pädiatrie - Onkologie und Hämatologie	Berlin
Germany	Universitätsklinikum Bonn; Institut für Experimentelle Hämatologie und Transfusionsmedizin	Bonn
Hungary	Észak-Pesti Centrumkórház - Honvédkórház; Országos Hemofília Központ	Budapest
Italy	AOU Careggi; SOD Malattie Emorragiche	Firenze	Toscana
Italy	IRCCS Ca' Granda Ospedale Maggiore Policlinico; Centro Emofilia e Trombosi "Angelo Bianchi e Bonomi"	Milano	Lombardia
Italy	AOU Federico II; Medicina Clinica Chirurgia Centro Emocoaugulopatie e Emofilia	Napoli	Campania
Italy	Policlinico Univ. A. Gemelli; Polo di Scienze Oncologiche ed Ematologiche	Roma	Lazio
Morocco	Hôpital d'enfants de Rabat - Service d'hémato-oncologie pédiatrique	Rabat
Serbia	University Clinical Centre of Serbia; Clinic of Hematology	Belgrade
Spain	Hospital de la Santa Creu i Sant Pau; Servicio de Hematologia	Barcelona
Spain	Hospital Universitario Vall de Hebron; Unidad de Hemofília	Barcelona
Spain	Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Hematologia	La Coruna	LA Coruña
Spain	Hospital Universitario la Paz; Servicio de Hematologia	Madrid
Spain	Hospital Regional Universitario Carlos Haya; Servicio de Hematologia	Malaga
Tunisia	CHU Farhat Hached; Service d'hématologie	Sousse
Tunisia	Aziza Othmana Hospital; Haemophilia Center	Tunis
Turkey	Gazi Universitesi Tip Fakultesi; Pediatric Neurology	Ankara
Turkey	Akdeniz Uni School of Medicine; Hematology	Antalya
Turkey	Istanbul University Cerrahpasa Medical Faculty; Hematology Department	Istanbul
Turkey	Ege Uni Medical School; Hematology	Izmir
United Kingdom	St Thomas Westminster	London
United Kingdom	Manchester University NHS Foundation Trust (MFT)	Manchester
United States	University of Miami	Coral Gables	Florida
United States	Orthopaedic Institute for Children	Los Angeles	California
United States	Oklahoma Children's Hospital ? Jimmy Everest Center	Oklahoma City	Oklahoma

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Brazil,  Canada,  Germany,  Hungary,  Italy,  Morocco,  Serbia,  Spain,  Tunisia,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		6 Months
Primary	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		12 Months
Primary	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		24 Months
Primary	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		36 Months
Primary	Clinical Joint Status at 6 Months, Based on the Hemophilia Joint Health Score (HJHS v2.1) Excluding Gait Assessment		6 Months
Primary	Clinical Joint Status at 12 Months, Based on the Hemophilia Joint Health Score (HJHS v2.1) Excluding Gait Assessment		12 Months
Primary	Clinical Joint Status at 24 Months, Based on the Hemophilia Joint Health Score (HJHS v2.1) Excluding Gait Assessment		24 Months
Primary	Clinical Joint Status at 36 Months, Based on the Hemophilia Joint Health Score (HJHS v2.1) Excluding Gait Assessment		36 Months
Primary	Joint Status at 36 Months, Based on Centrally Reviewed International Prophylaxis Study Group (IPSG) Score (with MRI)		36 Months
Primary	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.	6 Months
Primary	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.	12 Months
Primary	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.	24 Months
Primary	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.	36 Months
Primary	Percentage of Joints That are Problem Joints at 6 Months		6 Months
Primary	Percentage of Joints That are Problem Joints at 12 Months		12 Months
Primary	Percentage of Joints That are Problem Joints at 24 Months		24 Months
Primary	Percentage of Joints That are Problem Joints at 36 Months		36 Months
Primary	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		At Baseline (Day 1), Months 3, 6, 9, 12, 18, 24, 30, and 36
Primary	Change from Baseline in the CATCH Domain Scores Over Time, as Assessed with the CATCH Questionnaire for Pediatric Participants		At Baseline (Day 1), Months 3, 6, 9, 12, 18, 24, 30, and 36
Primary	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)		At Baseline (Day 1), Months 3, 6, 9, 12, 18, 24, 30, and 36
Primary	Daily Step Count Over Time, as Measured with a Wearable Activity Tracker		From Baseline until end of treatment period (up to 36 months)
Primary	Daily Metabolic Equivalents of Tasks (METs) Over Time, as Measured with a Wearable Activity Tracker		From Baseline until end of treatment period (up to 36 months)
Primary	Daily Time Spent in Moderate to Vigorous Physical Activity (MVPA) Over Time, as per the Activity Tracker Default Categorization		From Baseline until end of treatment period (up to 36 months)
Primary	Daily Active Minutes of Physical Activity Over Time, as Measured with a Wearable Activity Tracker		From Baseline until end of treatment period (up to 36 months)
Primary	Model-Based Annualized Bleed Rates for All Bleeds, Treated Bleeds, Spontaneous Bleeds, Joint Bleeds, Treated Joint Bleeds, and Target Joint Bleeds		From Baseline until end of treatment period (up to 36 months)
Primary	Mean Calculated Annualized Bleed Rates for All Bleeds, Treated Bleeds, Spontaneous Bleeds, Joint Bleeds, Treated Joint Bleeds, and Target Joint Bleeds		From Baseline until end of treatment period (up to 36 months)
Primary	Median Calculated Annualized Bleed Rates for All Bleeds, Treated Bleeds, Spontaneous Bleeds, Joint Bleeds, Treated Joint Bleeds, and Target Joint Bleeds		From Baseline until end of treatment period (up to 36 months)
Primary	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		At Month 6
Secondary	Number of Participants with at Least One Adverse Event, with Severity Determined According to the World Health Organization (WHO) Toxicity Scale		From Baseline until 24 weeks after the final dose of emicizumab (up to 3.5 years)
Secondary	Number of Participants with at Least One Thromboembolic Event		From Baseline until 24 weeks after the final dose of emicizumab (up to 3.5 years)
Secondary	Number of Participants with at Least One Event of Thrombotic Microangiopathy (TMA)		From Baseline until 24 weeks after the final dose of emicizumab (up to 3.5 years)
Secondary	Number of Participants with at Least One Severe Hypersensitivity, Anaphylaxis, and Anaphylactoid Event		From Baseline until 24 weeks after the final dose of emicizumab (up to 3.5 years)
Secondary	Number of Participants with at Least One Injection-Site Reaction		From Baseline until 24 weeks after the final dose of emicizumab (up to 3.5 years)
Secondary	Number of Participants with Anti-Drug Antibodies (ADAs) Against Emicizumab at Baseline and During the Study		At Baseline, Months 6, 12, 24, and 36
Secondary	Number of Participants who Develop Anti-FVIII Inhibitors During the Study		At Months 6, 12, 24, and 36