The Optimised Use of Romozosumab Study

Osteoporosis Clinical Trial

— OPTIMIST  

Official title:

The Optimised Use of Romozosumab Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06059222
• Other study ID #: CT-2023-505940-20-00
• Status: Recruiting
• Phase: Phase 4
• Start date: October 2, 2023
• Est. completion date: August 2026

Study information

• Verified date: September 2023
• Source: University of Aarhus
• Contact: Vivi Makinen, MD
• Phone: 78450000
• Email: vivmaa[@]rm.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 270
• Est. completion date: August 2026
• Est. primary completion date: August 2026
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 50 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Osteoporosis

Intervention

Drug:
• Romosozumab
Romosozumab 210 mg/2.34 ml from baseline to month 11
• Zoledronate
5 mg/100 ml at month 12
• Romosozumab
210 mg/2.34 ml from baseline to month 5 and from month 18 to month 23
• Zoledronate
5 mg/100 ml at month 6
• Romosozumab
210 mg/2.34 ml from baseline to month 5
• Zoledronate
5 mg/100 ml at month 5 and month 18

Locations

Country	Name	City	State
Denmark	Department of Endrocinology and Internal Medicine	Aarhus

Sponsors (1)

Lead Sponsor	Collaborator
University of Aarhus

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Bone resorption and formation -Changes in P1NP (procollagen type I N-terminal propeptide)	Changes in P1NP (blood sample)	1, 3, 6, 12, 18, 19, 21 and 24 months
Other	Bone resorption and formation - Changes in CTX	Changes in cross-linked C-terminal telopeptide (CTX) (blood sample)	1, 3, 6, 12, 18, 19, 21 and 24 months
Other	Bone resorption and formation - Changes in collagen	Bone turnover marker (BTM) collagen (blood sample)	1, 3, 6, 12, 18, 19, 21 and 24 months
Other	Bone remodelling and modelling assessed using bone histology (jamshidi biopsy)	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
Other	Investigate the number and composition of osteoprogenitor cells in the bone marrow during the first and second romosozumab treatment.	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
Other	Effect of romosozumab on glucose metabolism and insulin sensitivity (measurement of fasting glucose)	Change in fasting glucose (mmol/l) Blood sample	Month 1 and 3
Other	Effect of romosozumab on glucose metabolism and insulin sensitivity (measurement of Hba1c)	Change in glycated haemoglobin (Hba1c) (mmol/mol) Blood sample	Month 1 and 3
Other	Effect of romosozumab on glucose metabolism and insulin sensitivity (ogtt)	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
Other	Effect of romosozumab on glucose metabolism and insulin sensitivity (HOMA-IR)	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
Primary	Change in total hip BMD	Change in total hip BMD	24 months
Secondary	Changes in femoral neck BMD	Change in femoral neck BMD	24 months
Secondary	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)	Mean percent change in trabecular bone volume fraction and cortical porosity measured by HR-pQCT at the radius and tibia	24 months
Secondary	Change in spine BMD	Change in spine BMD	24 months