Comparison of Romosozumab and Denosumab on Coronary Atherosclerotic Damage in Postmenopausal Women with Osteoporosis
- Trial ID
- 2025-522592-29-00
- Protocol
- ATRIO (L4204)
- Sponsor
- Ospedale Galeazzi S.p.A.
Trial statistics
Diseases & Conditions
Objectives
The primary objective is to evaluate the effect of romosozumab compared to denosumab on the progression of coronary atherosclerotic damage in postmenopausal women with osteoporosis. This is assessed through changes in the coronary CT score, adapted via the CCTA-Leaman method, following 12 months of therapy.
Secondary objectives include:
- Assessment of coronary atherosclerotic progression using the Segment Involvement Score (SIS) and the Segment Stenosis Score (SSS).
- Evaluation of the pathological condition through the measurement of bone and cardiovascular biomarkers, specifically sclerostin, lipoprotein-associated phospholipase A2, myeloid-related protein 8 and 14, and monocyte chemoattractant protein 1 (MCP-1), including the analysis of potential correlations between these markers and coronary score variations.
Participants
The sponsor did not provide information regarding the total number of participants. The study population consists of female patients diagnosed with postmenopausal osteoporosis. Included individuals are those requiring the initiation of treatment with Romosozumab or Denosumab according to established prescribing criteria. Participants must be undergoing secondary prophylaxis. The age range for the cohort corresponds to specific clinical classifications. The study focuses on the progression of coronary atherosclerotic damage through the assessment of the coronary CT score using the CCTA-Leaman method.
Plans and Procedures
This Phase IV pharmacological intervention study evaluates the effect of romosozumab compared to denosumab on the progression of coronary atherosclerotic damage in women with postmenopausal osteoporosis. The study design focuses on assessing changes in the coronary CT score adapted according to the CCTA-Leaman method after 12 months of therapy. The primary objective is to measure the variation in this score, while secondary endpoints include evaluating the Segment Involvement Score, the Segment Stenosis Score, and specific biomarkers such as sclerostin, lipoprotein-associated phospholipase A2, myeloid-related protein 8 and 14, and monocyte chemoattractant protein 1. Participants undergo a screening process to confirm eligibility based on prescribing criteria and postmenopausal status. Following the initial assessments, therapy is administered via subcutaneous injection for a 12-month duration. The total trial period is estimated to span from December 2025 to June 2028.
Treatment
The experimental medication is romosozumab, provided as a solution for injection in a pre-filled pen. The administered dose is 210 mg via a subcutaneous route.
The comparator treatment consists of denosumab, administered as a 60 mg solution for injection in a pre-filled syringe through a subcutaneous route.
Efficacy
The primary efficacy endpoint is the change in the coronary CT score adapted according to the CCTA-Leaman method following 12 months of therapy. This assessment is used to evaluate the progression of coronary atherosclerotic damage in women with postmenopausal osteoporosis.
Secondary efficacy assessments include:
- Changes in the Segment Involvement Score (SIS) and the Segment Stenosis Score (SSS) between the first (V1) and third (V3) visits.
- Measurement of specific biomarkers at V1 to determine correlation with changes in coronary scores, including Sclerostin, Lipoprotein-Associated Phospholipase A2, Myeloid-Related Protein 8 and 14, and Monocyte Chemoattractant Protein 1 (MCP-1).
Inclusion and Exclusion Criteria
Inclusion Criteria
- Postmenopausal women with osteoporosis (defined as the absence of menstruation for at least 12 consecutive months without an alternative medical cause. An elevated follicle-stimulating hormone [FSH] level within the postmenopausal range may be used to confirm postmenopausal status in women not using hormonal contraceptives or hormone replacement therapy; however, in the absence of 12 months of amenorrhea, a single elevated FSH measurement is insufficient for diagnosis)
- Patients requiring initiation of anti-osteoporotic therapy for secondary fracture prevention
- Patients eligible for randomization to either treatment group according to AIFA note 79 as follows: Spine or femur T-score <-2.5 (<-2.0 if patient with ‚≥2 moderate or severe vertebral fractures or if femoral fracture in the previous 2 years) AND history of ‚≥1 moderate or severe vertebral fracture or ‚≥2 mild vertebral fractures or femoral fracture or at least 2 non-vertebral fractures AND high 10-year fracture risk (determined with a validated calculator) ‚≥20% AND inability to follow other effective treatments (intolerance, ineffectiveness, or expiration of the authorized use period)
- Patients who provide written informed consent to participate in the study
Exclusion Criteria
- Diabetes mellitus
- Concomitant steroid or immunosuppressive therapy or other drugs known to interfere with bone metabolism
- Women ≤ 69 years: cardiovascular risk ≥ 20% at 10 years according to the Heart Project risk charts
- Women ≥ 70 years: 2OP score (ESC 2021) with risk > 15% at 10 years
- Uncontrolled hypercholesterolemia without therapy or uncontrolled despite ongoing cholesterol-lowering therapy (LDL ≥ 116 mg/dl)
- Uncontrolled hypertension without therapy or uncontrolled despite ongoing antihypertensive therapy (blood pressure ≥ 140/90 mmHg)
- Active endocrinopathies (except subclinical hypothyroidism)
- Chronic renal failure stages IIIb-IV-V (eGFR < 45 ml/min according to CKD-EPI)
- Chronic liver disease (Child classifications B and C )
- History of bone disease other than osteoporosis (e.g. Paget's disease)
- Active neoplasms (including patients in remission for more than 5 years)
- Previous acute myocardial infarction (AMI) and/or stroke, regardless of age of onset
- Alcohol consumption (more than 2 units of alcohol/day)
- Active smoking
- Participation in a clinical study in which an investigational medicinal product was administered within 30 days prior to screening or within five half-lives of the study drug, whichever is longer
- Patients with hypocalcemia, defined as plasma calcium corrected for albumin < 8.8 mg/dL.
- Previous allergic reaction to iodinated contrast media or allergy or hypersensitivity to the study drugs (active substance and excipients)
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Italy | Not Yet Recruiting | 31 Jul 2026 | 60 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
EVENITY 105 mg solution for injection in pre-filled pen | Test | SOLUTION FOR INJECTION IN PRE-FILLED PEN | SUBCUTANEOUS | 210 | 12 | PRD7764543 |
EVENITY 105 mg solution for injection in pre-filled pen | Test | SOLUTION FOR INJECTION IN PRE-FILLED PEN | SUBCUTANEOUS | 210 | 12 | PRD7764424 |
Prolia 60 mg solution for injection in pre-filled syringe | Comparator | SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE | SUBCUTANEOUS | 60 | 36 | PRD3618881 |
EVENITY 105 mg solution for injection in pre-filled pen | Test | SOLUTION FOR INJECTION IN PRE-FILLED PEN | SUBCUTANEOUS | 210 | 12 | PRD7764607 |
Prolia 60 mg solution for injection in pre-filled syringe | Comparator | SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE | SUBCUTANEOUS | 60 | 36 | PRD3618671 |
EVENITY 105 mg solution for injection in pre-filled pen | Test | SOLUTION FOR INJECTION IN PRE-FILLED PEN | SUBCUTANEOUS | 210 | 12 | PRD7764048 |
Prolia 60 mg solution for injection in pre-filled syringe | Comparator | SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE | SUBCUTANEOUS | 60 | 36 | PRD385446 |
Prolia 60 mg solution for injection in pre-filled syringe | Comparator | SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE | SUBCUTANEOUS | 60 | 36 | PRD3618880 |
EVENITY 105 mg solution for injection in pre-filled pen | Test | SOLUTION FOR INJECTION IN PRE-FILLED PEN | SUBCUTANEOUS | 210 | 12 | PRD7764314 |
Prolia 60 mg solution for injection in pre-filled syringe | Comparator | SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE | SUBCUTANEOUS | 60 | 36 | PRD3618669 |