Clinical trial NCT04131036: Effects of Emicizumab vs. Factor VIII Prophylaxis on Joint and Bone Health in Severe Hemophilia A
Official title: Effects of Emicizumab vs. Factor VIII Prophylaxis on Joint and Bone Health in Severe Hemophilia A
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Hemophilia A
Keywords: Hemophilia A
Joint Health
Bone Density
Emicizumab
factor VIII prophylaxis
Lead sponsor: Washington Institute for Coagulation
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2019-10-18
Enrollment: 40
Sex: MALE
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Male severe Hemophilia A patients at one of the several Hemophilia Treatment Center sites participating in this study and who meet the eligibility criteria and are interested in participating in the study.

Brief summary: The investigators propose to study longitudinal joint and bone density changes in patients with severe Hemophilia A. Per current standard of care, most patients are on prophylactic FVIII replacement therapy intravenously several times weekly with a goal of keeping the trough \>1% FVIII. Recent phase 3 data suggest superior bleed protection with emicizumab prophylaxis every 1-2 weeks. It is the purpose of this study to longitudinally assess joint health and bone density over 3 years and to compare the effect of routine factor VIII prophylaxis with emicizumab prophylaxis.

Detailed description: Summary: This retrospective/prospective, non-randomized controlled study, whereby patients will be included in 1 of 2 groups depending on their current treatments as outlined below. Patients will be assigned to a specific group by the clinician/PI based on their current regimen with the intent to stay on this regimen for the next 3 years.

Duration of Study and Subject Participation: Study subject enrollment is anticipated to occur over about 12 months and study duration per subject will be 3 years. Thus a total study duration of 4 years is anticipated.

Intervention: By using musculoskeletal ultrasound, the investigators will measure joint health among participants and assess joint health changes over 3 years compared between group A (factor prophylaxis) vs. group B (emicizumab prophylaxis) as assessed by MSKUS at baseline and after 3 years. Other outcomes such as bone density, comparative assessment of joint and overall health status, and exploration of potential biomarkers for joint and bone health will also be assessed.

Eligibility criteria: Inclusion Criteria:

* Male gender
* Severe hemophilia A (factor VIII \< 1%)
* Age ≥ 16 year
* Either on prophylaxis with factor VIII or emicizumab with the intention to stay on the current regimen for the next 3 years
* Willing and able to give written informed consent/assent
* Willing to undergo MSKUS, DEXA scan +/- collection of blood sampling for repository biomarkers
* Willing to come in for baseline and 3 yearly visits
* Willing to answer phone survey for bleeding and safety every 3 months

Exclusion Criteria:

* Current FVIII inhibitor of \> 0.6 BU
* Unable to take FVIII replacement
* Other known bleeding disorder
* Other rheumatologic disorder affecting joints
* Other known neuromotor defect (making physical exam difficult)

Primary outcomes:
measure: joint health comparison
timeFrame: 3 years
Secondary outcomes:
measure: bone density comparison
timeFrame: 3 years
measure: comparative assessment of joint and overall health
timeFrame: 3 years
measure: mid-point assessment of joint health and bone density
timeFrame: 2 years
measure: biomarkers for joint and bone health
timeFrame: through completion of study, average 3 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Orthopedic Hemophilia Treatment Center
state: California
city: San Diego
country: United States
facility: Hemophilia and Thrombosis Treatment Center, University of California, San Diego
state: California
city: San Antonio
country: United States
facility: The University of Texas Health Science Center at San Antonio
state: Texas
city: Seattle
country: United States
facility: Washington Center for Bleeding Disorders at Washington Institute for Coagulation
state: Washington
Study officials:
affiliation: Washington Institute for Coagulation
name: Rebecca Kruse-Jarres, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
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