Clinical trial NCT05181618: 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
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 type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Severe Hemophilia A
Moderate Hemophilia A
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2022-01-06
Enrollment: 136
Sex: ALL
Minimum age (years): 13
Maximum age (years): 69
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
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.
Primary purpose: BASIC_SCIENCE

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.


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

Primary outcomes:
measure: 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
timeFrame: 6 Months
measure: 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
timeFrame: 12 Months
measure: 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
timeFrame: 24 Months
measure: 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
timeFrame: 36 Months
measure: Clinical Joint Status at 6 Months, Based on the Hemophilia Joint Health Score (HJHS v2.1) Excluding Gait Assessment
timeFrame: 6 Months
measure: Clinical Joint Status at 12 Months, Based on the Hemophilia Joint Health Score (HJHS v2.1) Excluding Gait Assessment
timeFrame: 12 Months
measure: Clinical Joint Status at 24 Months, Based on the Hemophilia Joint Health Score (HJHS v2.1) Excluding Gait Assessment
timeFrame: 24 Months
measure: Clinical Joint Status at 36 Months, Based on the Hemophilia Joint Health Score (HJHS v2.1) Excluding Gait Assessment
timeFrame: 36 Months
measure: Joint Status at 36 Months, Based on Centrally Reviewed International Prophylaxis Study Group (IPSG) Score (with MRI)
timeFrame: 36 Months
measure: Number of Problem Joints at 6 Months
timeFrame: 6 Months
measure: Number of Problem Joints at 12 Months
timeFrame: 12 Months
measure: Number of Problem Joints at 24 Months
timeFrame: 24 Months
measure: Number of Problem Joints at 36 Months
timeFrame: 36 Months
measure: Percentage of Joints That are Problem Joints at 6 Months
timeFrame: 6 Months
measure: Percentage of Joints That are Problem Joints at 12 Months
timeFrame: 12 Months
measure: Percentage of Joints That are Problem Joints at 24 Months
timeFrame: 24 Months
measure: Percentage of Joints That are Problem Joints at 36 Months
timeFrame: 36 Months
measure: 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
timeFrame: At Baseline (Day 1), Months 3, 6, 9, 12, 18, 24, 30, and 36
measure: Change from Baseline in the CATCH Domain Scores Over Time, as Assessed with the CATCH Questionnaire for Pediatric Participants
timeFrame: At Baseline (Day 1), Months 3, 6, 9, 12, 18, 24, 30, and 36
measure: 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)
timeFrame: At Baseline (Day 1), Months 3, 6, 9, 12, 18, 24, 30, and 36
measure: Daily Step Count Over Time, as Measured with a Wearable Activity Tracker
timeFrame: From Baseline until end of treatment period (up to 36 months)
measure: Daily Metabolic Equivalents of Tasks (METs) Over Time, as Measured with a Wearable Activity Tracker
timeFrame: From Baseline until end of treatment period (up to 36 months)
measure: Daily Time Spent in Moderate to Vigorous Physical Activity (MVPA) Over Time, as per the Activity Tracker Default Categorization
timeFrame: From Baseline until end of treatment period (up to 36 months)
measure: Daily Active Minutes of Physical Activity Over Time, as Measured with a Wearable Activity Tracker
timeFrame: From Baseline until end of treatment period (up to 36 months)
measure: Model-Based Annualized Bleed Rates for All Bleeds, Treated Bleeds, Spontaneous Bleeds, Joint Bleeds, Treated Joint Bleeds, and Target Joint Bleeds
timeFrame: From Baseline until end of treatment period (up to 36 months)
measure: Mean Calculated Annualized Bleed Rates for All Bleeds, Treated Bleeds, Spontaneous Bleeds, Joint Bleeds, Treated Joint Bleeds, and Target Joint Bleeds
timeFrame: From Baseline until end of treatment period (up to 36 months)
measure: Median Calculated Annualized Bleed Rates for All Bleeds, Treated Bleeds, Spontaneous Bleeds, Joint Bleeds, Treated Joint Bleeds, and Target Joint Bleeds
timeFrame: From Baseline until end of treatment period (up to 36 months)
measure: 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
timeFrame: At Month 6
Secondary outcomes:
measure: Number of Participants with at Least One Adverse Event, with Severity Determined According to the World Health Organization (WHO) Toxicity Scale
timeFrame: From Baseline until 24 weeks after the final dose of emicizumab (up to 3.5 years)
measure: Number of Participants with at Least One Thromboembolic Event
timeFrame: From Baseline until 24 weeks after the final dose of emicizumab (up to 3.5 years)
measure: Number of Participants with at Least One Event of Thrombotic Microangiopathy (TMA)
timeFrame: From Baseline until 24 weeks after the final dose of emicizumab (up to 3.5 years)
measure: Number of Participants with at Least One Severe Hypersensitivity, Anaphylaxis, and Anaphylactoid Event
timeFrame: From Baseline until 24 weeks after the final dose of emicizumab (up to 3.5 years)
measure: Number of Participants with at Least One Injection-Site Reaction
timeFrame: From Baseline until 24 weeks after the final dose of emicizumab (up to 3.5 years)
measure: Number of Participants with Anti-Drug Antibodies (ADAs) Against Emicizumab at Baseline and During the Study
timeFrame: At Baseline, Months 6, 12, 24, and 36
measure: Number of Participants who Develop Anti-FVIII Inhibitors During the Study
timeFrame: At Months 6, 12, 24, and 36
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Orthopaedic Institute for Children
state: California
city: Miami
country: United States
facility: Mailman Center for Child Development
state: Florida
city: Oklahoma City
country: United States
facility: Oklahoma Children's Hospital ? Jimmy Everest Center
state: Oklahoma
city: Campinas
country: Brazil
facility: Hospital das Clinicas - UNICAMP
state: São Paulo
city: Ribeirao Preto
country: Brazil
facility: Hospital das Clínicas Faculdades Médicas de Ribeirão Preto
state: São Paulo
city: Hamilton
country: Canada
facility: Hamilton Health Sciences Corporation
state: Ontario
city: Berlin
country: Germany
facility: Charité Universitätsklinikum Berlin
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
city: Budapest
country: Hungary
facility: Észak-Pesti Centrumkórház - Honvédkórház
city: Napoli
country: Italy
facility: AOU Federico II
state: Campania
city: Roma
country: Italy
facility: Policlinico Univ. A. Gemelli
state: Lazio
city: Firenze
country: Italy
facility: AOU Careggi
state: Toscana
city: Rabat
country: Morocco
facility: Hôpital d'enfants de Rabat - Service d'hémato-oncologie pédiatrique
city: Belgrade
country: Serbia
facility: University Clinical Centre of Serbia
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitario Vall de Hebron
city: La Coruna
country: Spain
facility: Complejo Hospitalario Universitario A Coruña (CHUAC)
city: Madrid
country: Spain
facility: Hospital Universitario la Paz
city: Malaga
country: Spain
facility: Hospital Regional Universitario Carlos Haya
city: Sousse
country: Tunisia
facility: CHU Farhat Hached
city: Tunis
country: Tunisia
facility: Aziza Othmana Hospital
city: Ankara
country: Turkey
facility: Gazi Universitesi Tip Fakultesi
city: Antalya
country: Turkey
facility: Akdeniz Uni School of Medicine
city: Istanbul
country: Turkey
facility: Istanbul University Cerrahpasa Medical Faculty
city: Izmir
country: Turkey
facility: Ege Uni Medical School
city: London
country: United Kingdom
facility: St Thomas Westminster
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust (MFT)
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: