Prospective Biomarkers of Bone Metabolism in Hemophilia A

Phase 3

Completed

• Conditions: Hemophilia; Bone Disease
• Interventions: Drug: Advate

• Registration Number: NCT02306694
• Lead Sponsor: Oregon Health and Science University

Brief Summary

One of the major shortcomings in studying bone disease in hemophilia is the lack of fracture outcome data demonstrating the clinical significance of decreased BMD and altered bone biomarkers in the hemophilia population. This study demonstrates that PwH have an increased risk of fracture compared to the general population and that the issue of bone health will increase in importance as the PwH population ages.

Detailed Description

This is a pilot study to determine the impact of factor replacement on bone biomarkers in up to 20 hemophilia A subjects. Subjects will be recruited over 1 year for the 5-day protocol.

Following a 72-hour washout period, factor levels and bone biomarkers will be followed before and after 50 units/kg replacement on Day 1 and 20 units/kg replacement on Day 3. Each subject can serve as their Figure 4. Fracture rates in PwH compared to historic controls.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2014-11-25
• Study Start: 2014-12
• Study First Submitted QC: 2014-12-01
• Study First Posted: 2014-12-03
• Primary Completion: 2018-04-16
• Study Completion: 2018-04-16
• Results First Submitted: 2019-05-28
• Status Verified: 2020-03
• Results First Submitted QC: 2020-03-10
• Last Update Submitted: 2020-03-23
• Results First Posted: 2020-03-24
• Last Update Posted: 2020-04-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 16

Inclusion Criteria

1. Males with a diagnosis of hemophilia A with a historic baseline FVIII level ≤ 2%.
2. Age > 16 years old
3. Currently using ADVATE as FVIII replacement therapy

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Exclusion Criteria

1. Subject or guardian is unwilling or unable to give written informed consent and/or assent
2. Joint or muscle bleeding within 2 weeks of Study Day 1
3. Presence of a current factor inhibitor (>0.6 BU/mL via Nijmegan-modified Bethesda assay)
4. Known collagen vascular bone disease.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Open label	Advate	Everyone receives Advate (antihemophilic factor) on Day 1 and 3.

Primary Outcome Measures

Name	Time	Method
Bone Biomarker Density (BMD)	5 days	BMD was measured as Z-scores/T-scores using Dual-Energy X-ray Absorptiometry (DEXA) scanning; specifically looking at Spine, Hip/Neck, and Hip total scores. BMD Z-scores compare what would be expected in someone your age and body size. A Z-score, is a unit of standard deviation, where above 0 would indicate the bones are more dense than expected, while a Z-score below 0 would indicate the bones were less dense.
Joint Health	5 days	Hemophilia Joint Health Score (HJHS); with a higher score representing worst outcomes, scores could range from 0 (no problems) to a max score of 120 (severe problems).
Quality of Life Using the VAS and EQ-5D-3L	5 days	Visual Analog Scale (VAS) via the EQ-5D-3L was used to report participants self-rated health. EQ-5D-3L total score ranges from 5 (no problems) to 15 (significant problems). VAS scores could range from 0 (worst health ever) to 100 (best health ever).
Plasma Cytokine Concentration Differences From 0-hour to 24-hour	24 hours	cytokines were measured using ELISA/magnetic bead multiplex kits. We calculated concentration change from hour 0 to hour 24. Cytokines: FGF, C-Terminal telopeptide (CTX-1), Dickkopf WNT signaling pathway inhibitor 1(DKK1), Eotaxin, fibroblast growth factor 23(FGF23), interferon gamma, interleukin 13, interleukin 1 beta, interleukin receptor 1 antagonist, interleukin 2, interleukin 4, interleukin 6, interleukin 17, interleukin 8, interleukin 9 Insulin, interferon gamma induced protein 10 (IP10), Leptin, monocyte chemoattractant protein1, monocyte chemoattractant protein1, macrophage inflammatory protein 1a (MIP1a), osteoclasts, Osteoprotegerin, osteopontin, platelet derived growth factors, parathyroid horomone, Recepter activator of nuclear factor kappa-B ligand (RANKL), chemokine ligand 5, sclerostin, transforming growth factor-beta 1, transforming growth factor beta 2, transforming growth factor beta 3, tumor necrosis factor alpha, vascular endothelial growth factor, MIP1b.

Trial Locations

Locations (1)

Oregon Health and Science University; 🇺🇸 Portland, Oregon, United States