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

NCT ID: NCT05181618

Last Updated: 2026-01-26

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 136 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-20
• Study Completion Date: 2027-05-21

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

Severe Hemophilia A; Moderate Hemophilia A

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Cohort 1, Hemophilia A and Without Arthropathy: Emicizumab

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.

Group Type: EXPERIMENTAL

Emicizumab

Intervention Type: 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.

Cohort 2, Hemophilia A and with Synovitis Only: Emicizumab

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).

Group Type: EXPERIMENTAL

Emicizumab

Intervention Type: 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.

Cohort 3, Hemophilia A and with Osteochondral Damage: Emicizumab

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.

Group Type: EXPERIMENTAL

Emicizumab

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Hemlibra; RO5534262; RG6013; ACE910

Eligibility Criteria

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

• Minimum Eligible Age: 13 Years
• Maximum Eligible Age: 69 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Orthopaedic Institute for Children

Los Angeles, California, United States

University of Miami Medical Center

Miami, Florida, United States

Oklahoma Children's Hospital ? Jimmy Everest Center

Oklahoma City, Oklahoma, United States

Hospital das Clinicas - UNICAMP

Campinas, São Paulo, Brazil

Hospital das Clínicas Faculdades Médicas de Ribeirão Preto

Ribeirão Preto, São Paulo, Brazil

Hamilton Health Sciences Corporation

Hamilton, Ontario, Canada

Charité Universitätsklinikum Berlin

Berlin, , Germany

Universitätsklinikum Bonn

Bonn, , Germany

Észak-Pesti Centrumkórház - Honvédkórház

Budapest, , Hungary

AOU Federico II

Napoli, Campania, Italy

Policlinico Univ. A. Gemelli

Rome, Lazio, Italy

IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, Lombardy, Italy

AOU Careggi

Florence, Tuscany, Italy

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

Rabat, , Morocco

University Clinical Centre of Serbia

Belgrade, , Serbia

Complejo Hospitalario Universitario A Coruña (CHUAC)

A Coruña, , Spain

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Hospital Universitario Vall de Hebron

Barcelona, , Spain

Hospital Universitario la Paz

Madrid, , Spain

Hospital Regional Universitario Carlos Haya

Málaga, , Spain

CHU Farhat Hached

Sousse, , Tunisia

Aziza Othmana Hospital

Tunis, , Tunisia

Gazi Universitesi Tip Fakultesi

Ankara, , Turkey (Türkiye)

Akdeniz Uni School of Medicine

Antalya, , Turkey (Türkiye)

Istanbul University Cerrahpasa Medical Faculty

Istanbul, , Turkey (Türkiye)

Ege Uni Medical School

Izmir, , Turkey (Türkiye)

St Thomas Westminster

London, , United Kingdom

Manchester University NHS Foundation Trust (MFT)

Manchester, , United Kingdom

Countries

United States; Brazil; Canada; Germany; Hungary; Italy; Morocco; Serbia; Spain; Tunisia; Turkey (Türkiye); United Kingdom

Other Identifiers

2020-005092-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2023-505747-40-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

ISRCTN10101701

Identifier Type: REGISTRY

Identifier Source: secondary_id

MO42623

Identifier Type: -

Identifier Source: org_study_id