- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06059222
The Optimised Use of Romozosumab Study (OPTIMIST)
OPTIMIST is a two-year, randomised, active controlled, open-label, multicentre intervention trial. OPTIMIST includes 3 treatment groups each comprising combinations of romosozumab (ROMO) and zoledronate (ZOL) treatment used in standard doses (210 mg monthly (sc) and 5 mg yearly (iv), respectively).
The study will investigate if it is possible to maximize the effect of romosozumab by giving it in 2 periods of 6 months interrupted by zoledronate for 12 months compared to romosozumab for 12 months uninterrupted followed by zoledronate for 12 months. The investigators will also evaluate if 6 months of romosozumab followed by 18 months of zoledronate is non-inferior to the standard regimen of romosozumab for 12 months followed by zoledronate for 12 months.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Recent clinical trials have demonstrated the benefit of bone anabolic treatment over no treatment or antiresorptive treatment in terms of increasing bone mineral density (BMD) and reducing fracture risk for patients with osteoporosis. However, the bone anabolic treatment is expensive and therefore restricted to a limited group of patients.
This study is based on the hypothesis that treatment with romosozumab for 6 months, zoledronate for 12 months, and romosozumab for 6 months results in larger gains in bone mineral density than treatment regimens based on romosozumab treatment for 6 or 12 months followed by zoledronate for a total of 24 months of treatment due to reappearance of the bone anabolic effect of romosozumab upon retreatment.
The OPTIMIST study is a two-year, randomised, active controlled, open-label, intervention trial. The study includes 270 postmenopausal women who will be randomised to 3 groups. Group 1 (n=90) will receive romosozumab for 12 months followed by zoledronate for 12 months. Group 2 (n=90) will receive romosozumab for 6 months followed by zoledronate for 12 months and romosozumab for 6 months. Group 3 (n=90 ) will receive romosozumab for 6 months followed by zoledronate for 18 months.
The investigational drugs in this study are romosozumab 210 mg/2,34 mL and zoledronate 5 mg/100 mL
This study will include 270 treatment naïve postmenopausal women. When inclusion and exclusion criteria have been reviewed, and the participant meets the requirements for study participation and continues to participate in the study, the patients will be randomized 1:1:1 Data will be registered in RedCAP (eCRF) and site monitoring assessed by the local Good Clinical Practice unit (GCP-unit).
The patients will be recruited from the outpatient clinics and the Dual-Energy X-ray Absorptiometry (DXA) units to which patients are referred from their general practitioner or fracture liaison services (FLS) at:
Department of Endocrinology, Odense University Hospital Department of Endocrinology and Internal Medicine, Aarhus University Hospital Department of Endocrinology, Køge Hospital Department of Endocrinology, Hvidovre Hospital Department of Endocrinology, Bispebjerg Hospital
During the intervention phase, there will be obtained fasting blood test, high-resolution peripheral quantitative computed tomography (HR-pQCT),Oral Glucose Tolerance Test (OGTT), DXA, Vertebral fracture assessment (VFA) and biochemistry at different time stamps. From 105 patients there will be obtained bone marrow aspirates and performed jamshidi bone biopsies.
The study will therefore show if it would be possible to treat twice as many patients for the same prize but also if the treatment for 12 months can be optimized. The knowledge about the optimal use of romosozumab will be included in an update of osteoporosis treatment guidelines. This will lead to optimized treatment of patients with severe osteoporosis.
Study Type
Enrollment (Estimated)
Phase
- Phase 4
Contacts and Locations
Study Contact
- Name: Vivi Makinen, MD
- Phone Number: 78450000
- Email: vivmaa@rm.dk
Study Locations
-
-
-
Aarhus, Denmark, 8000
- Recruiting
- Department of Endrocinology and Internal Medicine
-
Contact:
- Vivi Mäkinen
- Phone Number: 78450000
- Email: vivmaa@rm.dk
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Postmenopausal women (postmenopausal for at least two years)
- BMD T-score < -2.5 at lumbar spine, total hip, or femoral neck
- Osteoporotic fracture within the last 3 years at the spine, hip, pelvis, humerus or forearm after the age of 50 years.
Exclusion Criteria:
- Osteoporosis treatment including hormone replacement therapy within the last 5 years
- Metabolic bone disease
- Known disorders affecting bone metabolism, e.g., uncontrolled thyrotoxicosis, liver dysfunction (baseline phosphatase higher than twice upper limit), rheumatism, severe COPD (chronic obstructive pulmonary disease), hypopituitarism, Cushing's disease
- Ongoing treatment with glucocorticoids (systemic)
- Estimated glomerular filtration rate (eGFR) < 35 mL/min
- Contraindications for zoledronate according to the Supplementary protection certificates (SPC)
- Contraindications for romosozumab according to the SPC
- For the subgroup with Jamshidi biopsies contraindications for local anaesthetics according to the SPC
- For the subgroup with Jamshidi biopsies contraindications for tetracycline or doxycykline according to the SPC
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Group 1 - ROMO 12 months, ZOL 12 months
90 patients 12 months of romosozumab (ROMO) followed by 12 months of zoledronate (ZOL)
|
Romosozumab 210 mg/2.34 ml from baseline to month 11
Other Names:
5 mg/100 ml at month 12
210 mg/2.34 ml from baseline to month 5 and from month 18 to month 23
Other Names:
5 mg/100 ml at month 6
210 mg/2.34 ml from baseline to month 5
Other Names:
5 mg/100 ml at month 5 and month 18
|
Active Comparator: Group 2 - ROMO 6 months, ZOL 12 months, ROMO 6 months
90 patients 6 months of romosozumab followed by 12 months of zoledronate and lastly 6 months of romosozumab.
|
Romosozumab 210 mg/2.34 ml from baseline to month 11
Other Names:
5 mg/100 ml at month 12
210 mg/2.34 ml from baseline to month 5 and from month 18 to month 23
Other Names:
5 mg/100 ml at month 6
210 mg/2.34 ml from baseline to month 5
Other Names:
5 mg/100 ml at month 5 and month 18
|
Active Comparator: Group 3 - ROMO 6 months, ZOL 18 months
90 patients 6 months of romosozumab followed by 18 months of zoledronate . |
Romosozumab 210 mg/2.34 ml from baseline to month 11
Other Names:
5 mg/100 ml at month 12
210 mg/2.34 ml from baseline to month 5 and from month 18 to month 23
Other Names:
5 mg/100 ml at month 6
210 mg/2.34 ml from baseline to month 5
Other Names:
5 mg/100 ml at month 5 and month 18
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in total hip BMD
Time Frame: 24 months
|
Change in total hip BMD
|
24 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in femoral neck BMD
Time Frame: 24 months
|
Change in femoral neck BMD
|
24 months
|
Changes in trabecular bone volume fraction (bone volume/tissue volume, BV/TV) and cortical porosity measured by high-resolution peripheral quantitative computed tomography (HR-pQCT)
Time Frame: 24 months
|
Mean percent change in trabecular bone volume fraction and cortical porosity measured by HR-pQCT at the radius and tibia
|
24 months
|
Change in spine BMD
Time Frame: 24 months
|
Change in spine BMD
|
24 months
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Bone resorption and formation -Changes in P1NP (procollagen type I N-terminal propeptide)
Time Frame: 1, 3, 6, 12, 18, 19, 21 and 24 months
|
Changes in P1NP (blood sample)
|
1, 3, 6, 12, 18, 19, 21 and 24 months
|
Bone resorption and formation - Changes in CTX
Time Frame: 1, 3, 6, 12, 18, 19, 21 and 24 months
|
Changes in cross-linked C-terminal telopeptide (CTX) (blood sample)
|
1, 3, 6, 12, 18, 19, 21 and 24 months
|
Bone resorption and formation - Changes in collagen
Time Frame: 1, 3, 6, 12, 18, 19, 21 and 24 months
|
Bone turnover marker (BTM) collagen (blood sample)
|
1, 3, 6, 12, 18, 19, 21 and 24 months
|
Bone remodelling and modelling assessed using bone histology (jamshidi biopsy)
Time Frame: Month 1, 6, 18, 19, 24
|
Investigate the activation of bone remodelling and modelling-based bone formation by ROMO assessed by bone histology (jamshidi biopsy) at 1 (any group), 6 (any group), 18 (group 3), 19 (group 2) and 24 (group 2) months.
Biopsies will be obtained from 15 participants at each timepoint.
Investigate the depletion of osteoprogenitor cells during ROMO treatment assessed by molecular bone histology and single-nucleic transcriptomics.
|
Month 1, 6, 18, 19, 24
|
Investigate the number and composition of osteoprogenitor cells in the bone marrow during the first and second romosozumab treatment.
Time Frame: Month 1 and 19
|
Investigate the number and composition of osteoprogenitor cells in the bone marrow during the first and second romosozumab treatment.
Bone marrow (BM) aspirates will be obtained by aspiration of the iliac crest (10-15 ml) during the jamshidi biopsy.
|
Month 1 and 19
|
Effect of romosozumab on glucose metabolism and insulin sensitivity (measurement of fasting glucose)
Time Frame: Month 1 and 3
|
Change in fasting glucose (mmol/l) Blood sample
|
Month 1 and 3
|
Effect of romosozumab on glucose metabolism and insulin sensitivity (measurement of Hba1c)
Time Frame: Month 1 and 3
|
Change in glycated haemoglobin (Hba1c) (mmol/mol) Blood sample
|
Month 1 and 3
|
Effect of romosozumab on glucose metabolism and insulin sensitivity (ogtt)
Time Frame: Month 1 and 3
|
Change in oral Glucose tolerance test (OGTT) Data is collected by giving glucose and blood samples are taken afterward to determine the patients blood sugar (mmol/l) how quickly it is cleared from the blood
|
Month 1 and 3
|
Effect of romosozumab on glucose metabolism and insulin sensitivity (HOMA-IR)
Time Frame: Month 1 and 3
|
Change in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) calculated from fasting blood sugar (blood sample) and insulin levels (blood sample) by following equation: ([insulin (μU/ml)] × [fasting glucose (mmol/l)]/22,5)
|
Month 1 and 3
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Bente Langdahl, MD, Professor, DMSc, PhD,, Department of Endocrinology and Internal medicin, Aarhus University Hospital
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CT-2023-505940-20-00
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Osteoporosis
-
Radius Health, Inc.CompletedOsteoporosis | Osteoporosis Risk | Osteoporosis, Postmenopausal | Osteoporosis Fracture | Osteoporosis, Age-Related | Osteoporosis Localized to Spine | Osteoporosis Senile | Osteoporosis of Vertebrae | Osteoporosis VertebralUnited States
-
Radius Health, Inc.CompletedOsteoporosis | Age Related Osteoporosis | Osteoporosis, Age-Related | Osteoporosis Localized to Spine | Osteoporosis Senile | Osteoporosis of VertebraeUnited States, Poland, Italy
-
Hoffmann-La RocheCompletedPostmenopausal OsteoporosisUnited States
-
Hoffmann-La RocheCompletedPost Menopausal OsteoporosisUnited States, Puerto Rico
-
Centre Hospitalier Universitaire de Saint EtienneMinistry of Health, FranceRecruitingPost Menopausal OsteoporosisFrance
-
AmgenCompletedPost Menopausal OsteoporosisFrance
-
Hoffmann-La RocheCompletedPost Menopausal OsteoporosisUnited States
-
Hoffmann-La RocheCompletedPost Menopausal OsteoporosisSpain, South Africa, Germany, Mexico, United States, Canada, France, United Kingdom, Italy, Belgium, Australia, Poland, Denmark, Hungary, Czech Republic, Norway
-
Hoffmann-La RocheGlaxoSmithKlineCompletedPost Menopausal OsteoporosisFrance
-
Novartis PharmaceuticalsCompletedPost-menopausal OsteoporosisColombia, Belgium, Sweden, Hong Kong, United States, Hungary, Switzerland, Australia, Germany, Italy, Canada, Poland, Argentina, Thailand, Norway, New Zealand, France, Finland
Clinical Trials on Romosozumab
-
AmgenRecruitingPostmenopausal OsteoporosisIndia
-
Memorial Sloan Kettering Cancer CenterRecruitingMultiple Myeloma | OsteoporosisUnited States
-
UCB Biopharma SRLCompleted
-
AmgenUCB PharmaCompletedFracture HealingCanada, Italy, United States, Russian Federation, France, Germany, Hong Kong, Hungary, Australia, Bulgaria, Poland, Romania, Greece, Denmark, Estonia, India, New Zealand, United Kingdom, Latvia, Slovakia, Lithuania, Mexico, Norway
-
AmgenCompletedPostmenopausal OsteoporosisKorea, Republic of
-
AmgenCompleted
-
AmgenCompleted
-
AmgenCompletedOsteoporosis in MenUnited States, Belgium, Colombia, Czechia, Denmark, Japan, Mexico, Poland, Russian Federation, Switzerland