Effects of Emicizumab vs. Factor VIII Prophylaxis on Joint and Bone Health in Severe Hemophilia A
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: assessment of joint health and bone density.
- Who it may be relevant to
- Registry conditions: Hemophilia A. Basic parameters: from 16 years · Male.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
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.
Interventions
- Other assessment of joint health and bone density
We propose to study longitudinal joint and bone density changes in patients with severe Hemophilia A.
Primary outcome measures
- joint health comparison [Time frame: 3 years]
Secondary outcome measures (4)
- bone density comparison [Time frame: 3 years]
- comparative assessment of joint and overall health [Time frame: 3 years]
- mid-point assessment of joint health and bone density [Time frame: 2 years]
- biomarkers for joint and bone health [Time frame: through completion of study, average 3 years]
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)
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Cohort
Study locations
United States · 4 centers
- Orthopedic Hemophilia Treatment Center — Los Angeles
- Hemophilia and Thrombosis Treatment Center, University of California, San Diego — San Diego
- The University of Texas Health Science Center at San Antonio — San Antonio
- Washington Center for Bleeding Disorders at Washington Institute for Coagulation — Seattle
Publications
- Forsyth AL, Giangrande P, Hay CR, Kenet G, Kessler CM, Knobl PN, Llinas A, Santagostino E, Young G. Difficult clinical challenges in haemophilia: international experiential perspectives. Haemophilia. 2012 Jul;18 Suppl 5:39-45. doi: 10.1111/j.1365-2516.2012.02887.x. PMID 22757683
- Manco-Johnson MJ, Abshire TC, Shapiro AD, Riske B, Hacker MR, Kilcoyne R, Ingram JD, Manco-Johnson ML, Funk S, Jacobson L, Valentino LA, Hoots WK, Buchanan GR, DiMichele D, Recht M, Brown D, Leissinger C, Bleak S, Cohen A, Mathew P, Matsunaga A, Medeiros D, Nugent D, Thomas GA, Thompson AA, McRedmond K, Soucie JM, Austin H, Evatt BL. Prophylaxis versus episodic treatment to prevent joint disease i PMID 17687129
- Oldenburg J. Optimal treatment strategies for hemophilia: achievements and limitations of current prophylactic regimens. Blood. 2015 Mar 26;125(13):2038-44. doi: 10.1182/blood-2015-01-528414. Epub 2015 Feb 23. PMID 25712992
- Foltz V, Gandjbakhch F, Etchepare F, Rosenberg C, Tanguy ML, Rozenberg S, Bourgeois P, Fautrel B. Power Doppler ultrasound, but not low-field magnetic resonance imaging, predicts relapse and radiographic disease progression in rheumatoid arthritis patients with low levels of disease activity. Arthritis Rheum. 2012 Jan;64(1):67-76. doi: 10.1002/art.33312. PMID 21904998
- McAlindon TE, Bannuru RR. Osteoarthritis: Is viscosupplementation really so unsafe for knee OA? Nat Rev Rheumatol. 2012 Nov;8(11):635-6. doi: 10.1038/nrrheum.2012.152. Epub 2012 Sep 11. No abstract available. PMID 22964536
- Porta F, Gargani L, Kaloudi O, Schmidt WA, Picano E, Damjanov N, Matucci-Cerinic M. The new frontiers of ultrasound in the complex world of vasculitides and scleroderma. Rheumatology (Oxford). 2012 Dec;51 Suppl 7:vii26-30. doi: 10.1093/rheumatology/kes336. PMID 23230091
- Ceponis A, Wong-Sefidan I, Glass CS, von Drygalski A. Rapid musculoskeletal ultrasound for painful episodes in adult haemophilia patients. Haemophilia. 2013 Sep;19(5):790-8. doi: 10.1111/hae.12175. Epub 2013 May 15. PMID 23672827
- Kidder W, Nguyen S, Larios J, Bergstrom J, Ceponis A, von Drygalski A. Point-of-care musculoskeletal ultrasound is critical for the diagnosis of hemarthroses, inflammation and soft tissue abnormalities in adult patients with painful haemophilic arthropathy. Haemophilia. 2015 Jul;21(4):530-7. doi: 10.1111/hae.12637. Epub 2015 Jan 27. PMID 25623830
Identifiers
NCT: NCT04131036 · ML40714