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 (Beyond ABR)
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| ClinicalTrials.gov Identifier: NCT05181618 |
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Recruitment Status :
Active, not recruiting
First Posted : January 6, 2022
Last Update Posted : April 16, 2024
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Sponsor:
Hoffmann-La Roche
Information provided by (Responsible Party):
Hoffmann-La Roche
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Severe Hemophilia A Moderate Hemophilia A | Drug: Emicizumab | Phase 4 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 136 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Single Group Assignment |
| Intervention 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) |
| Primary Purpose: | Basic Science |
| 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 |
| Actual Study Start Date : | June 20, 2022 |
| Estimated Primary Completion Date : | December 28, 2026 |
| Estimated Study Completion Date : | December 28, 2026 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Hemophilia
MedlinePlus related topics:
Hemophilia
Drug Information
available for:
Emicizumab
| Arm | Intervention/treatment |
|---|---|
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Experimental: 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.
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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.
Other Names:
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Experimental: 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).
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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.
Other Names:
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Experimental: 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.
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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.
Other Names:
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Primary Outcome Measures :
- 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 36 Months ]
- Clinical Joint Status at 6 Months, Based on the Hemophilia Joint Health Score (HJHS v2.1) Excluding Gait Assessment [ Time Frame: 6 Months ]
- Clinical Joint Status at 12 Months, Based on the Hemophilia Joint Health Score (HJHS v2.1) Excluding Gait Assessment [ Time Frame: 12 Months ]
- Clinical Joint Status at 24 Months, Based on the Hemophilia Joint Health Score (HJHS v2.1) Excluding Gait Assessment [ Time Frame: 24 Months ]
- Clinical Joint Status at 36 Months, Based on the Hemophilia Joint Health Score (HJHS v2.1) Excluding Gait Assessment [ Time Frame: 36 Months ]
- Joint Status at 36 Months, Based on Centrally Reviewed International Prophylaxis Study Group (IPSG) Score (with MRI) [ Time Frame: 36 Months ]
- Number of Problem Joints at 6 Months [ Time Frame: 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.
- Number of Problem Joints at 12 Months [ Time Frame: 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.
- Number of Problem Joints at 24 Months [ Time Frame: 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.
- Number of Problem Joints at 36 Months [ Time Frame: 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.
- Percentage of Joints That are Problem Joints at 6 Months [ Time Frame: 6 Months ]
- Percentage of Joints That are Problem Joints at 12 Months [ Time Frame: 12 Months ]
- Percentage of Joints That are Problem Joints at 24 Months [ Time Frame: 24 Months ]
- Percentage of Joints That are Problem Joints at 36 Months [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: At Month 6 ]
Secondary Outcome Measures :
- Number of Participants with at Least One Adverse Event, with Severity Determined According to the World Health Organization (WHO) Toxicity Scale [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: At Baseline, Months 6, 12, 24, and 36 ]
- Number of Participants who Develop Anti-FVIII Inhibitors During the Study [ Time Frame: At Months 6, 12, 24, and 36 ]
Information from the National Library of Medicine
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| Ages Eligible for Study: | 13 Years to 69 Years (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05181618
Locations
Show 28 study locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
| Study Director: | Clinical Trials | Hoffmann-La Roche |
| Responsible Party: | Hoffmann-La Roche |
| ClinicalTrials.gov Identifier: | NCT05181618 |
| Other Study ID Numbers: |
MO42623 2020-005092-13 ( EudraCT Number ) 2023-505747-40-00 ( Registry Identifier: EU CT Number ) ISRCTN10101701 ( Registry Identifier: ISRCTN ) |
| First Posted: | January 6, 2022 Key Record Dates |
| Last Update Posted: | April 16, 2024 |
| Last Verified: | April 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Plan Description: | For eligible studies, qualified researchers may request access to individual patient level data through the request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/innovation/process/clinical-trials/data-sharing/). |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Hemophilia A Blood Coagulation Disorders, Inherited Blood Coagulation Disorders Hematologic Diseases |
Coagulation Protein Disorders Hemorrhagic Disorders Genetic Diseases, Inborn |