Clinical trial NCT06059222: The Optimised Use of Romozosumab Study
Official title: The Optimised Use of Romozosumab Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Osteoporosis
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2023-09-28
Enrollment: 270
Sex: FEMALE
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in total hip BMD
timeFrame: 24 months
Secondary outcomes:
measure: Changes in femoral neck BMD
timeFrame: 24 months
measure: 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)
timeFrame: 24 months
measure: Change in spine BMD
timeFrame: 24 months
Other outcomes:
measure: Bone resorption and formation -Changes in P1NP (procollagen type I N-terminal propeptide)
timeFrame: 1, 3, 6, 12, 18, 19, 21 and 24 months
measure: Bone resorption and formation - Changes in CTX
timeFrame: 1, 3, 6, 12, 18, 19, 21 and 24 months
measure: Bone resorption and formation - Changes in collagen
timeFrame: 1, 3, 6, 12, 18, 19, 21 and 24 months
measure: Bone remodelling and modelling assessed using bone histology (jamshidi biopsy)
timeFrame: Month 1, 6, 18, 19, 24
measure: Investigate the number and composition of osteoprogenitor cells in the bone marrow during the first and second romosozumab treatment.
timeFrame: Month 1 and 19
measure: Effect of romosozumab on glucose metabolism and insulin sensitivity (measurement of fasting glucose)
timeFrame: Month 1 and 3
measure: Effect of romosozumab on glucose metabolism and insulin sensitivity (measurement of Hba1c)
timeFrame: Month 1 and 3
measure: Effect of romosozumab on glucose metabolism and insulin sensitivity (ogtt)
timeFrame: Month 1 and 3
measure: Effect of romosozumab on glucose metabolism and insulin sensitivity (HOMA-IR)
timeFrame: Month 1 and 3
Locations:
city: Aarhus
country: Denmark
facility: Department of Endrocinology and Internal Medicine
Study officials:
affiliation: Department of Endocrinology and Internal medicin, Aarhus University Hospital
name: Bente Langdahl, MD, Professor, DMSc, PhD,
role: STUDY_DIRECTOR
References: