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

NCT04131036 | Recruiting DMC

• 1 other identifier: ML40714
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 4

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.

Conditions

Hemophilia A

Keywords

Hemophilia A; Joint Health; Bone Density; Emicizumab; factor VIII prophylaxis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• bone density comparison

  3 years

• comparative assessment of joint and overall health

  3 years

• mid-point assessment of joint health and bone density

  2 years

• biomarkers for joint and bone health

  through completion of study, average 3 years

Study Arms (2)

Arm A

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

Other: assessment of joint health and bone density

Arm B

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

Other: assessment of joint health and bone density

Interventions

assessment of joint health and bone density OTHER

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

Arm A; Arm B

Eligibility Criteria

• Age: 16 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Washington Institute for Coagulation: lead
• Genentech, Inc.: collaborator

Study Sites (4)

Orthopedic Hemophilia Treatment Center

Los Angeles, California, 90007, United States

NOT YET RECRUITING

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

San Diego, California, 92092, United States

RECRUITING

The University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

Washington Center for Bleeding Disorders at Washington Institute for Coagulation

Seattle, Washington, 98101, United States

RECRUITING

Related Publications (15)

• 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 BACKGROUND

• 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.

  PMID: 17687129 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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.

  PMID: 25623041 BACKGROUND

• 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.

  PMID: 23571706 BACKGROUND

• 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.

  PMID: 25001982 BACKGROUND

• 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.

  PMID: 26172840 BACKGROUND

• 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.

  PMID: 22469061 BACKGROUND

• 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.

  PMID: 24712867 BACKGROUND

• 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.

  PMID: 25354773 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Plasma samples for biomarkers for storage in the data and sample research repository at Washington Institute for Coagulation

MeSH Terms

Conditions

Hemophilia A

Interventions

Bone Density

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Rebecca Kruse-Jarres, MD, MPH

  Washington Institute for Coagulation

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rebecca Kruse-Jarres, MD, MPH

CONTACT

206-614-1200; RKJ@WACBD.org

Cassandra Bryan

CONTACT

206-681-9072; cassandra.bryan@wacbd.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Executive/Medical Director, Washington Center for Bleeding Disorders at Washington Institute for Coagulation

Study Record Dates

• First Submitted: October 14, 2019
• First Posted: October 18, 2019
• Study Start: April 4, 2019
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: September 5, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)