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Romosozumab Versus Denosumab for Osteoporosis in Long-term Glucocorticoid Users

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ClinicalTrials.gov Identifier: NCT04091243
Recruitment Status : Not yet recruiting
First Posted : September 16, 2019
Last Update Posted : September 16, 2019
Sponsor:
Information provided by (Responsible Party):
Chi Chiu Mok, Tuen Mun Hospital

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.


Condition or disease Intervention/treatment Phase
Glucocorticoid-induced Osteoporosis Drug: Romosozumab Phase 4

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: An open randomized parallel group controlled trial
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Romosozumab Versus Denosumab for Osteoporosis in Long-term Glucocorticoid Users: an Open Randomized Controlled Trial
Estimated Study Start Date : April 1, 2020
Estimated Primary Completion Date : April 1, 2023
Estimated Study Completion Date : December 1, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Denosumab

Arm Intervention/treatment
Experimental: Romosozumab
Romosozumab (210mg) subcutaneously every month for 12 doses
Drug: Romosozumab
Experimental drug for the treatment of glucocorticoid induced osteoporosis

Active Comparator: Denosumab
Denosumab subcutaneously (60mg) every 6 months for 2 doses
Drug: Romosozumab
Experimental drug for the treatment of glucocorticoid induced osteoporosis




Primary Outcome Measures :
  1. Bone mineral density (BMD) [ Time Frame: month 12 ]
    Changes in BMD at lumbar spine from baseline


Secondary Outcome Measures :
  1. Bone mineral density (BMD) [ Time Frame: month 12 ]
    Changes in BMD at the hip and femoral neck from baseline

  2. bone turnover markers [ Time Frame: months 6,12,18 and 24 ]
    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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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. Having received oral bisphosphonates for ≥ 12 months.
  4. Severe osteoporosis (bone mineral density [BMD] Z score ≤ -2.0 in subjects aged <50 years or T score ≤ -2.5 in subjects aged ≥ 50 years; or personal history of fragility fractures; or loss of spinal / hip BMD by more than 10% despite bisphosphonate treatment for 2 years or more).
  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04091243


Contacts
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Contact: Chi Chiu MOK, MD, FRCP 852-24685389 ccmok2005@yahoo.com
Contact: Becky Fong 852-24686118 becky_fongls@yahoo.com.hk

Locations
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China
Tuen Mun Hospital
Hong Kong, China
Sponsors and Collaborators
Tuen Mun Hospital
Investigators
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Principal Investigator: Chi Chiu Mok, MD, FRCP Tuen Mun Hospital

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Responsible Party: Chi Chiu Mok, Consultant, Tuen Mun Hospital
ClinicalTrials.gov Identifier: NCT04091243     History of Changes
Other Study ID Numbers: NTWC/REC/19074
First Posted: September 16, 2019    Key Record Dates
Last Update Posted: September 16, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Chi Chiu Mok, Tuen Mun Hospital:
glucocorticoid
osteoporosis
rheumatic diseases
Additional relevant MeSH terms:
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Osteoporosis
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Metabolic Diseases
Denosumab
Glucocorticoids
Bone Density Conservation Agents
Physiological Effects of Drugs
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists