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

NCT ID: NCT04131036

Last Updated: 2023-09-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

40 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-04-04

Study Completion Date

2026-08-31

Brief Summary

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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

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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.

Conditions

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Hemophilia A

Study Design

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Observational Model Type

COHORT

Study Time Perspective

OTHER

Study Groups

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Arm A

Male patients with severe Hemophilia A who use prophylaxis with IV factor VIII concentrate with intended trough \>1%.

assessment of joint health and bone density

Intervention Type OTHER

We propose to study longitudinal joint and bone density changes in patients with severe Hemophilia A.

Arm B

Male patients with severe Hemophilia A who use prophylaxis with SQ emicizumab.

assessment of joint health and bone density

Intervention Type OTHER

We propose to study longitudinal joint and bone density changes in patients with severe Hemophilia A.

Interventions

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assessment of joint health and bone density

We propose to study longitudinal joint and bone density changes in patients with severe Hemophilia A.

Intervention Type OTHER

Eligibility Criteria

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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)
Minimum Eligible Age

16 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Genentech, Inc.

INDUSTRY

Sponsor Role collaborator

Washington Institute for Coagulation

OTHER

Sponsor Role lead

Responsible Party

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Rebecca Kruse-Jarres, MD, MPH

Executive/Medical Director, Washington Center for Bleeding Disorders at Washington Institute for Coagulation

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Rebecca Kruse-Jarres, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Washington Institute for Coagulation

Locations

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Orthopedic Hemophilia Treatment Center

Los Angeles, California, United States

Site Status NOT_YET_RECRUITING

Hemophilia and Thrombosis Treatment Center, University of California, San Diego

San Diego, California, United States

Site Status RECRUITING

The University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status RECRUITING

Washington Center for Bleeding Disorders at Washington Institute for Coagulation

Seattle, Washington, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Rebecca Kruse-Jarres, MD, MPH

Role: CONTACT

206-614-1200

Cassandra Bryan

Role: CONTACT

206-681-9072

Facility Contacts

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Isabel Chang

Role: primary

Jeffrey Kallberg, DPT

Role: primary

Rebecca Kruse-Jarres, MD, MPH

Role: primary

206-614-1200

References

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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.

Reference Type BACKGROUND
PMID: 22757683 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17687129 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25712992 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21904998 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22964536 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23230091 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23672827 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25623830 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25623041 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23571706 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25001982 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26172840 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22469061 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24712867 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25354773 (View on PubMed)

Other Identifiers

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ML40714

Identifier Type: -

Identifier Source: org_study_id

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