Denosumab Treatment for Fibrous Dysplasia
- Registration Number
- NCT03571191
- Lead Sponsor
- National Institute of Dental and Craniofacial Research (NIDCR)
- Brief 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
- Detailed 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
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 9
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description 1 Denosumab Denosumab will be administered at 120 mg per dose every 4 weeks for six months, with loading doses on days 8 and 15 of month 1.
- Primary Outcome Measures
Name Time Method Primary:1. Assessment of markers of bone turnover: Beta-crosslaps, C-telopeptides (bone resorption marker,Procollagen-1-propeptide (bone formation marker) every 3 months 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 Outcome Measures
Name Time Method Secondary endpoint #3 - Pain assessments utilizing the Brief Pain Inventory scores 2 time points Exploratory endpoint #3 - Effect measured by change in other outcome measures(SqrRoot) Bone density assessed by DXA(SqrRoot) Physical Medicine and Rehabilitation evaluation Q 3 mths/Q 6 mths Secondary Endpoint #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 od cell senescence), and/or apoptosis index-Sen... 2-4 timepoints Exploratory Endpoint # 1. Effect of denosumab initiation and discontinuation on(SqrRoot) Serum calcium, phosphorus and parathyroid hormone (SqrRoot) Serum circulating RANKL and osteoprotegerin (OPG), and RANKL/OPG level... up to12 timepoints Secondary outcome #1- Bone histomorphometric indices: (SqrRoot) Mineralized perimeter, (SqrRoot) Bone formation rate (SqrRoot) Cortical width (SqrRoot) Cortical area (SqrRoot) Osteoid width... 2 time points Exploratory endpoint #2 - Denosumab discontinuation effect on:(SqrRoot) Biochemical markers of bone metabolism: beta-crosslaps C-telopeptides, procollagen-1 propeptide, bone specific alkaline phosphatase, osteocalcin, NTX-telopeptides every 3 months
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States