Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04131036
Other study ID # ML40714
Secondary ID
Status Recruiting
Phase
First received
Last updated
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
Health authority
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)

Study Design


Related Conditions & MeSH terms


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 allClick 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
See also
  Status Clinical Trial Phase
Completed NCT03834727 - Characterizing the Impact and Treatment of Reproductive Tract Bleeding on Women and Post-menarchal Girls With Bleeding Disorders
Completed NCT03191799 - A Study to Evaluate the Safety and Tolerability of Prophylactic Emicizumab in Hemophilia A Patients With Inhibitors Phase 3
Completed NCT01599819 - BAX 855 Dose-Escalation Safety Study Phase 1
Terminated NCT04541628 - Safety & Efficacy of Encapsulated Allogeneic FVIII Cell Therapy in Haemophilia A Phase 1/Phase 2
Completed NCT02847637 - A Clinical Trial to Evaluate Prophylactic Emicizumab Versus no Prophylaxis in Hemophilia A Participants Without Inhibitors Phase 3
Completed NCT04072237 - Study of Coagulation Faction VIIa Variant Marzeptacog Alfa (Activated) in Adult Subjects With Hemophilia Phase 1
Completed NCT04085458 - Study to Gain More Information on How Safe and Effective Jivi Works in Patients With Severe Hemophilia A (Post-marketing Investigation) Phase 4
Completed NCT04565236 - A Post Approval Commitment Study to Gain More Information on How Safe and Effective KOVALTRY is in Chinese Children, Adolescents /Adults With Severe Hemophilia A Phase 4
Recruiting NCT05987449 - A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of NXT007 in Persons With Severe or Moderate Hemophilia A Phase 1/Phase 2
Active, not recruiting NCT04621916 - Preventing Inhibitor Recurrence Indefinitely Phase 4
Not yet recruiting NCT02888223 - Pharmacokinetic Study of SCT800 in Previously Treated Patients With Hemophilia A Phase 1
Completed NCT02528968 - National Study of a Pharmacokinetic-Focused Educational Package for Patients With Severe Haemophilia A N/A
Completed NCT02225483 - Phenotypic Heterogeneity in Hemophilia A: An Investigation of the Role of Platelet Function N/A
Completed NCT02199717 - An Institutional Pilot Study to Investigate Physical Activity Patterns in Boys With Hemophilia N/A
Completed NCT01217255 - Comparing the Burden of Illness of Hemophilia in the Developing and the Developed World
Completed NCT00969319 - Effekt-2 - Efficacy and Safety of Long-term Treatment With KOGENATE® FS in Latin America N/A
Terminated NCT00995046 - Individually Tailored Prophylaxis in Patients With Severe Hemophilia A N/A
Completed NCT00868530 - Study Evaluating On-Demand Treatment Of Xyntha In Chinese Subjects Phase 3
Completed NCT00839202 - Activity and Content of Factor VIII (FVIII) in Human Plasma: The Assessment of a Novel Immunoassay N/A
Completed NCT00629837 - Pharmacokinetics and Safety of a Single Intravenous Infusion of BAY 79-4980 Phase 1