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

NCT05181618 | Active Not Recruiting Phase 4 FDA Drug

• 4 other identifiers: MO426232020-005092-132023-505747-40-00ISRCTN10101701
• Study Type: interventional
• Target: 136
• Locations: 11 countries
• Sites: 24

Brief 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.

Conditions

Moderate Hemophilia A; Severe Hemophilia A

Outcome Measures

Primary Outcomes (28)

• 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

• 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

• 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

• 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

• Clinical Joint Status at 6 Months, Based on the Hemophilia Joint Health Score (HJHS v2.1) Excluding Gait Assessment

  6 Months

• Clinical Joint Status at 12 Months, Based on the Hemophilia Joint Health Score (HJHS v2.1) Excluding Gait Assessment

  12 Months

• Clinical Joint Status at 24 Months, Based on the Hemophilia Joint Health Score (HJHS v2.1) Excluding Gait Assessment

  24 Months

• Clinical Joint Status at 36 Months, Based on the Hemophilia Joint Health Score (HJHS v2.1) Excluding Gait Assessment

  36 Months

• Joint Status at 36 Months, Based on Centrally Reviewed International Prophylaxis Study Group (IPSG) Score (with MRI)

  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.

  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.

  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.

  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.

  36 Months

• Percentage of Joints That are Problem Joints at 6 Months

  6 Months

• Percentage of Joints That are Problem Joints at 12 Months

  12 Months

• Percentage of Joints That are Problem Joints at 24 Months

  24 Months

• Percentage of Joints That are Problem Joints at 36 Months

  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

  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

  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)

  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

  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

  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

  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

  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

  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

  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

  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

  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

  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

  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)

  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

  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

  From Baseline until 24 weeks after the final dose of emicizumab (up to 3.5 years)

Study Arms (3)

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.

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).

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.

Drug: Emicizumab

Interventions

Emicizumab DRUG

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.

Also known as: Hemlibra, RO5534262, RG6013, ACE910

Cohort 1, Hemophilia A and Without Arthropathy: Emicizumab; Cohort 2, Hemophilia A and with Synovitis Only: Emicizumab; Cohort 3, Hemophilia A and with Osteochondral Damage: Emicizumab

Eligibility Criteria

• Age: 13 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (28)

Orthopaedic Institute for Children

Los Angeles, California, 90007, United States

Location

University of Miami Medical Center

Miami, Florida, 33136, United States

Location

Oklahoma Children's Hospital ? Jimmy Everest Center

Oklahoma City, Oklahoma, 73104, United States

Location

Hospital das Clinicas - UNICAMP

Campinas, São Paulo, 13083-878, Brazil

Location

Hospital das Clínicas Faculdades Médicas de Ribeirão Preto

Ribeirão Preto, São Paulo, 14051-140, Brazil

Location

Hamilton Health Sciences Corporation

Hamilton, Ontario, L9H 2B7, Canada

Location

Charité Universitätsklinikum Berlin

Berlin, 13353, Germany

Location

Universitätsklinikum Bonn

Bonn, 53127, Germany

Location

Észak-Pesti Centrumkórház - Honvédkórház

Budapest, 1134, Hungary

Location

AOU Federico II

Naples, Campania, 80131, Italy

Location

Policlinico Univ. A. Gemelli

Rome, Lazio, 00168, Italy

Location

IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, Lombardy, 20122, Italy

Location

AOU Careggi

Florence, Tuscany, 50134, Italy

Location

Hôpital d'enfants de Rabat - Service d'hémato-oncologie pédiatrique

Rabat, 10090, Morocco

Location

University Clinical Centre of Serbia

Belgrade, 11000, Serbia

Location

Complejo Hospitalario Universitario A Coruña (CHUAC)

A Coruña, 15006, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08025, Spain

Location

Hospital Universitario Vall de Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario la Paz

Madrid, 28046, Spain

Location

Hospital Regional Universitario Carlos Haya

Málaga, 29010, Spain

Location

CHU Farhat Hached

Sousse, 4000, Tunisia

Location

Aziza Othmana Hospital

Tunis, Tunisia

Location

Gazi Universitesi Tip Fakultesi

Ankara, 06500, Turkey (Türkiye)

Location

Akdeniz Uni School of Medicine

Antalya, 07059, Turkey (Türkiye)

Location

Istanbul University Cerrahpasa Medical Faculty

Istanbul, 34098, Turkey (Türkiye)

Location

Ege Uni Medical School

Izmir, 35100, Turkey (Türkiye)

Location

St Thomas Westminster

London, SE1 7EH, United Kingdom

Location

Manchester University NHS Foundation Trust (MFT)

Manchester, M13 9WL, United Kingdom

Location

MeSH Terms

Conditions

Hemophilia A

Interventions

emicizumab

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The intervention study model is "single group" because all three cohorts of participants with hemophilia A will be receiving the same intervention: emicizumab.

Study Record Dates

• First Submitted: December 6, 2021
• First Posted: January 6, 2022
• Study Start: June 20, 2022
• Primary Completion (Estimated): December 4, 2026
• Study Completion (Estimated): May 21, 2027
• Last Updated: April 27, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); DE (2); HU (1); GB (2); IT (4); MO (1); BR (2); TU (2); US (3); ES (5); SE (1)