Clinical Trial Details
— Status: Active, not recruiting
Administrative data
NCT number |
NCT03571191 |
Other study ID # |
180114 |
Secondary ID |
18-D-0114 |
Status |
Active, not recruiting |
Phase |
Phase 2
|
First received |
|
Last updated |
|
Start date |
June 13, 2019 |
Est. completion date |
March 15, 2030 |
Study information
Verified date |
February 15, 2022 |
Source |
National Institutes of Health Clinical Center (CC) |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
Objectives:
The primary objective of this study is to evaluate the effect of denosumab on bone turnover
in individuals with fibrous dysplasia (FD). Secondary objectives are to determine the effect
of denosumab on bone pain, FD lesion intensity as revealed in 18F-sodium fluoride PET/CT bone
scan, and to determine the effect of denosumab discontinuation on bone turnover re-bound
after discontinuation.
Study Population:
Up to 14 adult subjects with FD may be enrolled to ensure complete study data on 9 subjects.
Design:
This study is a single center, open label pilot study of once-monthly dosing of denosumab.
Subjects will be treated for 6 months, after which they will be followed by an 8-month
observation period. A final visit will occur 21 months after denosumab discontinuation.
Dosing will be adopted from studies in adults on treatment for giant cell tumors, with
denosumab administered at 120 mg per dose every 4 weeks, with loading doses on days 7 and 14
of month 1.
Outcome Measures:
Primary:
Assessment of the effects of denosumab on:
1. Markers of bone turnover:
Beta-crosslaps C-telopeptides (bone resorption marker)
Procollagen-1-propeptide (bone formation marker)
Secondary:
Assessment of the effects of denosumab on:
1. Bone histomorphometric indices:
Mineralized perimeter
Bone formation rate
Cortical width
Cortical area
Osteoid width
Osteoid perimeter
Mineral apposition rate
2. Surrogate markers of a direct therapeutic effect of denosumab on FD lesions:
Semi-quantitative changes in RANKL, Ki67 (marker of cell proliferation), p16 (marker of
cell senescence), and/or apoptosis index before and after treatment, as assessed by
immunohistochemistry
Changes in sentinel lesion intensity, measured quantitatively by uptake on 18Fsodium
fluoride PET/CT bone scan.
3. FD-related bone pain assessed by the Brief Pain Inventory (Short Form) , a validated
self-reporting tool for assessment of pain.
Exploratory Endpoints:
1. Effect of denosumab initiation and discontinuation on
Serum calcium, phosphorus and parathyroid hormone
Serum RANKL and osteoprotegerin (OPG), and RANKL/OPG levels
2. Effect of denosumab discontinuation, as measured by the following outcomes:
Biochemical markers of bone metabolism: beta-crosslaps C-telopeptides, procollagen-1
propeptide, bone specific alkaline phosphatase, osteocalcin, NTX-telopeptides
3. Effect measured by change in other outcome measures, such as:
Bone density assessed by DXA
Physical Medicine and Rehabilitation evaluation
Description:
Objectives:
The primary objective of this study is to evaluate the effect of denosumab on bone turnover
in individuals with fibrous dysplasia (FD). Secondary objectives are to determine the effect
of denosumab on bone pain, FD lesion intensity as revealed in 18F-sodium fluoride PET/CT bone
scan, and to determine the effect of denosumab discontinuation on bone turnover re-bound
after discontinuation.
Study Population:
Up to 14 adult subjects with FD may be enrolled to ensure complete study data on 9 subjects.
Design:
This study is a single center, open label pilot study of once-monthly dosing of denosumab.
Subjects will be treated for 6 months, after which they will be followed by an 8-month
observation period. A final visit will occur 21 months after denosumab discontinuation.
Dosing will be adopted from studies in adults on treatment for giant cell tumors, with
denosumab administered at 120 mg per dose every 4 weeks, with loading doses on days 7 and 14
of month 1.
Outcome Measures:
Primary:
Assessment of the effects of denosumab on:
1. Markers of bone turnover:
- Beta-crosslaps C-telopeptides (bone resorption marker)
- Procollagen-1-propeptide (bone formation marker)
Secondary:
Assessment of the effects of denosumab on:
1. Bone histomorphometric indices:
- Mineralized perimeter
- Bone formation rate
- Cortical width
- Cortical area
- Osteoid width
- Osteoid perimeter
- Mineral apposition rate
2. Surrogate markers of a direct therapeutic effect of denosumab on FD lesions:
- Semi-quantitative changes in RANKL, Ki67 (marker of cell proliferation), p16
(marker of cell senescence), and/or apoptosis index before and after treatment, as
assessed by immunohistochemistry
- Changes in sentinel lesion intensity, measured quantitatively by uptake on
18Fsodium fluoride PET/CT bone scan.
3. FD-related bone pain assessed by the Brief Pain Inventory (Short Form), a validated
self-reporting tool for assessment of pain.
Exploratory Endpoints:
1. Effect of denosumab initiation and discontinuation on
- Serum calcium, phosphorus and parathyroid hormone
- Serum RANKL and osteoprotegerin (OPG), and RANKL/OPG levels
2. Effect of denosumab discontinuation, as measured by the following outcomes:
-Biochemical markers of bone metabolism: beta-crosslaps C-telopeptides, procollagen-1
propeptide, bone specific alkaline phosphatase, osteocalcin, NTX-telopeptides
3. Effect measured by change in other outcome measures, such as:
- Bone density assessed by DXA
- Physical Medicine and Rehabilitation evaluation