search
Back to results

Romosozumab Versus Denosumab for Osteoporosis in Long-term Glucocorticoid Users

Primary Purpose

Glucocorticoid-induced Osteoporosis

Status
Active
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Romosozumab
Sponsored by
Tuen Mun Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glucocorticoid-induced Osteoporosis focused on measuring glucocorticoid, osteoporosis, rheumatic diseases

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Adults (women or men) >18 years of age
  2. Receiving long-term prednisolone treatment for various medical illnesses, defined as a daily prednisolone dose of ≥5mg/day for ≥12 months.
  3. Moderate to high risk of osteoporotic fracture (in subjects <40 years, personal history of fragility/vertebral fracture, bone mineral density [BMD] of the hip/spine Z score ≤ -3.0, loss of BMD >10% per year or new fracture; in subjects aged ≥40 years, personal history of fragility/vertebral fracture, BMD of the hip/spine T score ≤ -2.5, GC-adjusted 10-year major osteoporotic fracture risk ≥20% or hip fracture risk ≥3% by FRAX [ie. multiplying risk by 1.15 for the former and 1.20 for the latter when prednisolone ≥7.5mg/day], or new fracture development).

5. Informed consent from patients. 6. Willing to comply with all study procedures

Exclusion Criteria:

  1. Patients with previous use of denosumab, teriparatide, intravenous bisphosphonates, strontium or other experimental anti-osteoporotic agents.
  2. Premenopausal women who plan for pregnancy within 24 months of study entry.
  3. Patients with a known past history of atherosclerotic cardiovascular or cerebrovascular disease.
  4. Patients with known bone disorders such as osteomalacia, renal osteodystrophy, and hyperparathyroidism.
  5. Patients with unexplained hypocalcemia.
  6. Patients with serum creatinine level of >=200umol/L.

Sites / Locations

  • Tuen Mun Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Romosozumab

Denosumab

Arm Description

Romosozumab (210mg) subcutaneously every month for 12 doses

Denosumab subcutaneously (60mg) every 6 months for 2 doses

Outcomes

Primary Outcome Measures

Bone mineral density (BMD)
Changes in BMD at lumbar spine from baseline

Secondary Outcome Measures

Bone mineral density (BMD)
Changes in BMD at the hip and femoral neck from baseline
bone turnover markers
Changes in serum procollagen type 1 N-terminal propeptide (P1NP) and C-terminal telopeptide collagen degradation product of type 1 collagen (beta-CTX) from baseline

Full Information

First Posted
September 12, 2019
Last Updated
February 20, 2023
Sponsor
Tuen Mun Hospital
search

1. Study Identification

Unique Protocol Identification Number
NCT04091243
Brief Title
Romosozumab Versus Denosumab for Osteoporosis in Long-term Glucocorticoid Users
Official Title
Romosozumab Versus Denosumab for Osteoporosis in Long-term Glucocorticoid Users: an Open Randomized Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 15, 2021 (Actual)
Primary Completion Date
October 15, 2023 (Anticipated)
Study Completion Date
April 15, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Tuen Mun Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Glucocorticoid (GC) is the main stay of treatment of many rheumatic diseases but is also an important cause of secondary osteoporosis. The long-term use of GCs increases the risk of fragility fracture at a much higher bone mineral density (BMD) than postmenopausal osteoporosis, indicating an additional deleterious effect of GC on bone quality. An increased relative risk of vertebral and hip fractures is demonstrated in chronic GC users, with fracture risk proportional to the daily dose of GC. Other studies have also confirmed that intermittent use of high-dose GC and the cumulative GC dose was associated with an augmented risk of osteoporotic fracture. Romosozumab (ROMO) is a humanized monoclonal antibody against sclerostin. The landmark RCT has demonstrated efficacy of ROMO (210mg subcutaneously monthly) over placebo in reducing vertebral fractures by 73% at 12 months in 7180 postmenopausal women with osteoporosis of the hip at entry. Another RCT has demonstrated efficacy of ROMO in reducing vertebral and hip fractures in 4093 post-menopausal women at month 24. There are no data regarding the efficacy of ROMO in GC-induced osteoporosis. Comparative study on the efficacy of ROMO and denosumab in post-menopausal osteoporosis is also not yet available in the literature. This prompts the current pilot study to compare the efficacy of ROMO with denosumab in high-risk patients receiving long-term GCs.
Detailed Description
Glucocorticoid (GC) is the main stay of treatment of many rheumatic diseases but is also an important cause of secondary osteoporosis. The long-term use of GCs increases the risk of fragility fracture at a much higher bone mineral density (BMD) than postmenopausal osteoporosis, indicating an additional deleterious effect of GC on bone quality. More than one-third of postmenopausal women receiving GC therapy developed asymptomatic vertebral fractures. A study in general practice reported an increased relative risk of vertebral and hip fractures in chronic GC users, with fracture risk proportional to the daily dose of GC. Another study also confirmed that intermittent use of high-dose GC and the cumulative GC dose was associated with an augmented risk of osteoporotic fracture. The glycoprotein sclerostin, secreted by the osteocytes under the influence of mechanical loading, inhibits activation of the canonical Wnt pathway involved in osteoblastogenesis and hence suppresses bone formation. Moreover, sclerostin enhances resorption of the bone by stimulating the production of (RANKL) by the osteocytes. Romosozumab (ROMO) is a humanized monoclonal antibody against sclerostin. The landmark RCT has demonstrated efficacy of ROMO (210mg subcutaneously monthly) over placebo in reducing vertebral fractures by 73% at 12 months in 7180 postmenopausal women with osteoporosis of the hip at entry. The suppression of markers of bone resorption and enhancement of markers of bone formation indicates that ROMO has a dual mode of action on the bones. The efficacy of ROMO has also been tested against oral bisphosphonates. A RCT was conducted in 4093 post-menopausal women who were assigned to receive either ROMO (201mg subcutaneously monthly) or oral alendronate (70mg weekly) for 12 months, followed by open-label alendronate for another 12 months. At month 24, a 48% lower risk of new vertebral fractures was observed in the ROMO (6.2%) than the alendronate group (11.9%; p<0.001). The risk of incident hip fractures was also significantly lower in the ROMO (2%) than alendronate treated patients (3.2%; p=0.02). The frequencies of adverse events and serious adverse events, however, were similar in the two treatment arms. There are no data regarding the efficacy of ROMO in GC-induced osteoporosis. Comparative study on the efficacy of ROMO and denosumab in post-menopausal osteoporosis is also not yet available in the literature. This prompts the current pilot study to compare the efficacy of ROMO with denosumab in high-risk patients receiving long-term GCs.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glucocorticoid-induced Osteoporosis
Keywords
glucocorticoid, osteoporosis, rheumatic diseases

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
An open randomized parallel group controlled trial
Masking
None (Open Label)
Allocation
Randomized
Enrollment
72 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Romosozumab
Arm Type
Experimental
Arm Description
Romosozumab (210mg) subcutaneously every month for 12 doses
Arm Title
Denosumab
Arm Type
Active Comparator
Arm Description
Denosumab subcutaneously (60mg) every 6 months for 2 doses
Intervention Type
Drug
Intervention Name(s)
Romosozumab
Intervention Description
Experimental drug for the treatment of glucocorticoid induced osteoporosis
Primary Outcome Measure Information:
Title
Bone mineral density (BMD)
Description
Changes in BMD at lumbar spine from baseline
Time Frame
month 12
Secondary Outcome Measure Information:
Title
Bone mineral density (BMD)
Description
Changes in BMD at the hip and femoral neck from baseline
Time Frame
month 12
Title
bone turnover markers
Description
Changes in serum procollagen type 1 N-terminal propeptide (P1NP) and C-terminal telopeptide collagen degradation product of type 1 collagen (beta-CTX) from baseline
Time Frame
months 6,12,18 and 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Adults (women or men) >18 years of age Receiving long-term prednisolone treatment for various medical illnesses, defined as a daily prednisolone dose of ≥5mg/day for ≥12 months. Moderate to high risk of osteoporotic fracture (in subjects <40 years, personal history of fragility/vertebral fracture, bone mineral density [BMD] of the hip/spine Z score ≤ -3.0, loss of BMD >10% per year or new fracture; in subjects aged ≥40 years, personal history of fragility/vertebral fracture, BMD of the hip/spine T score ≤ -2.5, GC-adjusted 10-year major osteoporotic fracture risk ≥20% or hip fracture risk ≥3% by FRAX [ie. multiplying risk by 1.15 for the former and 1.20 for the latter when prednisolone ≥7.5mg/day], or new fracture development). 5. Informed consent from patients. 6. Willing to comply with all study procedures Exclusion Criteria: Patients with previous use of denosumab, teriparatide, intravenous bisphosphonates, strontium or other experimental anti-osteoporotic agents. Premenopausal women who plan for pregnancy within 24 months of study entry. Patients with a known past history of atherosclerotic cardiovascular or cerebrovascular disease. Patients with known bone disorders such as osteomalacia, renal osteodystrophy, and hyperparathyroidism. Patients with unexplained hypocalcemia. Patients with serum creatinine level of >=200umol/L.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chi Chiu Mok, MD, FRCP
Organizational Affiliation
Tuen Mun Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Tuen Mun Hospital
City
Hong Kong
Country
China

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Romosozumab Versus Denosumab for Osteoporosis in Long-term Glucocorticoid Users

We'll reach out to this number within 24 hrs