Glucocorticoid-induced OsteoporosisPhase 4NCT04091243
Romosozumab Versus Denosumab for Osteoporosis in Long-term Glucocorticoid Users
A Phase 4 study testing Romosozumab in people with Glucocorticoid-induced Osteoporosis, run by Tuen Mun Hospital at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glucocorticoid-induced Osteoporosis
- What is being tested?
- Romosozumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 1 siteChina
- Study dates
- 15 Jan 2021to 15 Nov 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- 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
Who cannot join
- Patients with previous use of denosumab, teriparatide, intravenous bisphosphonates, strontium or other experimental anti-osteoporotic agents within 24 months of study entry.
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Romosozumab Versus Denosumab for Osteoporosis in Long-term Glucocorticoid Users: an Open Randomized Controlled Trial
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.
Read the 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.
- Conditions
- Glucocorticoid-induced Osteoporosis
- Being tested
- Romosozumab
- Keywords
- glucocorticoid, osteoporosis, rheumatic diseases
- Medical subject headings
- Osteoporosis, Rheumatic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RomosozumabDrug
Experimental drug for the treatment of glucocorticoid induced osteoporosis
| Study group | Role | What they receive |
|---|---|---|
| Romosozumab | Experimental | Romosozumab (210mg) subcutaneously every month for 12 doses Receives: Drug: Romosozumab |
| Denosumab | Active comparator | Denosumab subcutaneously (60mg) every 6 months for 2 doses Receives: Drug: Romosozumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bone mineral density (BMD)
Changes in BMD at lumbar spine from baseline
Measured: month 12
Secondary outcomes (2)
Bone mineral density (BMD)
Changes in BMD at the hip and femoral neck from baseline
Measured: month 12
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
Measured: months 6,12,18 and 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2019
- Study start15 Jan 2021
- Primary completion15 Oct 2023
- Study completion15 Nov 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Glucocorticoid-induced OsteoporosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- An open randomized parallel group controlled trial
- Masking
- None (open label)
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tuen Mun Hospital
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Chi Chiu Mok, Tuen Mun Hospital
- Investigators
- Chi Chiu Mok, MD, FRCP, Principal investigator, Tuen Mun Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04091243
- Sponsor's protocol ID
- NTWC/REC/19074
- Status last verified
- Sep 2024
- First submitted
- 12 Sep 2019
- Last updated
- 4 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Romosozumab Versus Denosumab for Osteoporosis in Long-term Glucocorticoid Users: an Open Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT04091243
- Acronym / sponsor ID
- NTWC/REC/19074
- Conditions
- Glucocorticoid-induced Osteoporosis
- Keywords
- glucocorticoid, osteoporosis, rheumatic diseases
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Tuen Mun HospitalOther government
- Study start
- 15 Jan 2021 (actual)
- Primary completion
- 15 Oct 2023 (actual)
- Study completion
- 15 Nov 2023 (actual)
- First posted
- 16 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- An open randomized parallel group controlled trial
| Arm | Type | Receives |
|---|---|---|
| Romosozumab | Experimental | Drug: RomosozumabRomosozumab (210mg) subcutaneously every month for 12 doses |
| Denosumab | Active comparator | Drug: RomosozumabDenosumab subcutaneously (60mg) every 6 months for 2 doses |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
- 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
Key exclusion criteria (6 listed)
- Patients with previous use of denosumab, teriparatide, intravenous bisphosphonates, strontium or other experimental anti-osteoporotic agents within 24 months of study entry.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RomosozumabExperimental drug for the treatment of glucocorticoid induced osteoporosis | Drug | Denosumab, Romosozumab |
Primary outcome
Bone mineral density (BMD)
Time frame: month 12
Changes in BMD at lumbar spine from baseline
2 secondary outcomes
Bone mineral density (BMD)
Time frame: month 12
bone turnover markers
Time frame: months 6,12,18 and 24
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chi Chiu Mok, MD, FRCP principal investigator
Tuen Mun Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Romosozumab in people with Glucocorticoid-induced Osteoporosis, run by Tuen Mun Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Bone mineral density (BMD) (time frame: month 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Sep 2024.