Effects of Emicizumab vs. Factor VIII Prophylaxis on Joint and Bone Health in Severe Hemophilia A

Hemophilia A Clinical Trial

— EmiMSK  

Official title:

Effects of Emicizumab vs. Factor VIII Prophylaxis on Joint and Bone Health in Severe Hemophilia A

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04131036
• Other study ID #: ML40714
• Status: Recruiting
• Start date: April 4, 2019
• Est. completion date: August 2026

Study information

• Verified date: August 2023
• Source: Washington Institute for Coagulation
• Contact: Rebecca Kruse-Jarres, MD, MPH
• Phone: 206-614-1200
• Email: RKJ[@]WACBD.org
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: August 2026
• Est. primary completion date: August 2026
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 16 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Hemophilia A

Intervention

Other:
• assessment of joint health and bone density
We propose to study longitudinal joint and bone density changes in patients with severe Hemophilia A.

Locations

Country	Name	City	State
United States	Orthopedic Hemophilia Treatment Center	Los Angeles	California
United States	The University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Hemophilia and Thrombosis Treatment Center, University of California, San Diego	San Diego	California
United States	Washington Center for Bleeding Disorders at Washington Institute for Coagulation	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Washington Institute for Coagulation	Genentech, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (15)

Aznar JA, Perez-Alenda S, Jaca M, Garcia-Dasi M, Vila C, Moret A, Querol F, Bonanad S. Home-delivered ultrasound monitoring for home treatment of haemarthrosis in haemophilia A. Haemophilia. 2015 Mar;21(2):e147-e150. doi: 10.1111/hae.12622. Epub 2015 Jan 27. No abstract available. — View Citation

Boban A, Zupancic Salek S, Kastelan D, Nemet D. Quantitative ultrasound and dual energy X-ray absorptiometry in the assessment of osteoporosis in patients with haemophilia. Haemophilia. 2014 Nov;20(6):e420-2. doi: 10.1111/hae.12529. No abstract available. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Kempton CL, Antoniucci DM, Rodriguez-Merchan EC. Bone health in persons with haemophilia. Haemophilia. 2015 Sep;21(5):568-77. doi: 10.1111/hae.12736. Epub 2015 Jul 14. — View Citation

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. — View Citation

Lau AG, Sun J, Hannah WB, Livingston EW, Heymann D, Bateman TA, Monahan PE. Joint bleeding in factor VIII deficient mice causes an acute loss of trabecular bone and calcification of joint soft tissues which is prevented with aggressive factor replacement. Haemophilia. 2014 Sep;20(5):716-22. doi: 10.1111/hae.12399. Epub 2014 Apr 8. — View Citation

Liel MS, Greenberg DL, Recht M, Vanek C, Klein RF, Taylor JA. Decreased bone density and bone strength in a mouse model of severe factor VIII deficiency. Br J Haematol. 2012 Jul;158(1):140-3. doi: 10.1111/j.1365-2141.2012.09101.x. Epub 2012 Apr 2. No abstract available. — View Citation

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 in boys with severe hemophilia. N Engl J Med. 2007 Aug 9;357(6):535-44. doi: 10.1056/NEJMoa067659. — View Citation

Martinoli C, Della Casa Alberighi O, Di Minno G, Graziano E, Molinari AC, Pasta G, Russo G, Santagostino E, Tagliaferri A, Tagliafico A, Morfini M. Development and definition of a simplified scanning procedure and scoring method for Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US). Thromb Haemost. 2013 Jun;109(6):1170-9. doi: 10.1160/TH12-11-0874. Epub 2013 Apr 4. — View Citation

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. — View Citation

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. — View Citation

Paschou SA, Anagnostis P, Karras S, Annweiler C, Vakalopoulou S, Garipidou V, Goulis DG. Bone mineral density in men and children with haemophilia A and B: a systematic review and meta-analysis. Osteoporos Int. 2014 Oct;25(10):2399-407. doi: 10.1007/s00198-014-2773-7. Epub 2014 Jul 8. — View Citation

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. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	joint health comparison	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.	3 years
Secondary	bone density comparison	Bone density changes over 3 years compared between group A (factor prophylaxis) vs. group B (emicizumab prophylaxis) as assessed by DEXA scan at baseline and after 3 years.	3 years
Secondary	comparative assessment of joint and overall health	Observational comparative assessment of joint and overall health status evaluated by activity level, functional assessment, pain assessment, joint examination, and adherence.	3 years
Secondary	mid-point assessment of joint health and bone density	Observational assessment of joint health and bone density at 1 and 2 years in the different groups.	2 years
Secondary	biomarkers for joint and bone health	Exploration of potential biomarkers for joint and bone health.	through completion of study, average 3 years