ATRIO Study: Effect of Romosozumab vs. Denosumab on Coronary Atherosclerotic Damage in Postmenopausal Osteoporosis: A Phase IV, Low-Risk Intervention Study.

2025-522592-29-00 Protocol ATRIO (L4204) Therapeutic use (Phase IV) Authorised, recruitment pending

Status Authorised, recruitment pending · 1 EU/EEA countries · 2 sites · Protocol ATRIO (L4204)

Overview

Sponsor-declared trial summary

Phase Therapeutic use (Phase IV)
Status Authorised, recruitment pending
Participants planned 60
Countries 1
Sites 2

Coronary atherosclerotic status in women with postmenopausal osteoporosis

The primary objective of the study is to evaluate the impact of treatment with Romosozumab carried out according to the standard of care, compared to that with Denosumab, on the progression of coronary atherosclerotic damage in a cohort of female patients affected by post-menopausal osteoporosis, through the variation …

Key facts

Sponsor
Ospedale Galeazzi S.p.A.
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Female
Therapeutic area
Diseases [C] - Musculoskeletal Diseases [C05]
Decision date (initial)
2026-02-23
Transition trial
No
Low-intervention
Yes
Rare-disease indication
No
Vulnerable population
No
Funding sources
Fondazione POLIZZOTTO, Pegoraro Paolo Amedeo and IRCCS Ospedale Galeazzi Sant’Ambrogio

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others

The primary objective of the study is to evaluate the impact of treatment with Romosozumab carried out according to the standard of care, compared to that with Denosumab, on the progression of coronary atherosclerotic damage in a cohort of female patients affected by post-menopausal osteoporosis, through the variation of the coronary CT score adapted according to the CCTA-Leaman method, after 12 months of therapy.

Secondary objectives 2

  1. To assess the progression of coronary atherosclerotic damage by measuring additional scores at V1 and V3: the Segment Involvement Score (SIS) and the Segment Stenosis Score (SSS).
  2. To assess the patient’s pathological condition through the measurement of bone and cardiovascular biomarkers at V1: Sclerostin, Lipoprotein-Associated Phospholipase A2, Myeloid-Related Protein 8 and 14, and Monocyte Chemoattractant Protein 1 (MCP-1). Any potential correlation between these biomarkers and changes in coronary scores will be evaluated.

Conditions and MedDRA coding

Coronary atherosclerotic status in women with postmenopausal osteoporosis

VersionLevelCodeTermSystem organ class
20.0 PT 10031285 Osteoporosis postmenopausal 100000004859

Study design 3 periods

#TitleAllocationBlindingRoles blindedArms
1 Enrollment
The study includes an initial phase of patient enrollment, which will continue until the number necessary to obtain the sample size is reached, with an estimated time of 18 months.
 2 None Romosozumab Group: Patients to be treated with Romosozumab for clinical indication.

After enrollment, patients will have to continue taking Romosozumab as prescribed.

Patients will then undergo the following evaluations:
• collection of demographic and clinical data (V1)
• blood sampling for osteometabolics according to clinical practice (V1 and V2 and V3)
• blood sampling for glycemic, lipid and blood count profile (V1)
• blood sampling for biomarkers performed for research (V1)
• cardiac CT scan (V1 and V3)
• collection of vital parameters, weight and height (V1, V2 and V3)
Denosumab Group: Patients to be treated with Denosumab for clinical indication.

After enrollment, patients will have to continue taking Denosumab as prescribed.

Patients will then undergo the following evaluations:
• collection of demographic and clinical data (V1)
• blood sampling for osteometabolics according to clinical practice (V1 and V2 and V3)
• blood sampling for glycemic, lipid and blood count profile (V1)
• blood sampling for biomarkers performed for research (V1)
• cardiac CT scan (V1 and V3)
• collection of vital parameters, weight and height (V1, V2 and V3)
2 Treatment and monitoring
Each patient will be monitored for a period of 12 months, in accordance with the maximum permitted duration of treatment with Romosozumab (12 months). Treatment with Denosumab is longer than Romosozumab (approximately 3 years), patients treated with Denosumab will continue therapy after the end of the study, according to standard of care.
 2 None
3 Follow-up visits
The clinical evaluations for the study will be scheduled for eatch patient at: - an initial baseline visit (V1), - a follow-up check-up at 6 months (V2) - a final evaluation at 12 months (V3) Additionally, patients will be contacted by telephone at 3 and 9 months to assess their health status and the occurrence of any adverse events or side effects.
 Not Applicable None

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

  1. female patients
  2. Patients who need to initiate treatment with Romosozumab or Denosumab in accordance with the prescribing criteria for each drug as established by AIFA Note 79.
  3. patients on secondary prophylaxis
  4. patients with postmenopausal osteoporosis (i.e., no menstruation for 12 months without an alternative medical cause. An elevated follicle-stimulating hormone level in the postmenopausal interval may be used to confirm a postmenopausal status in women not using hormonal contraceptives or hormone replacement therapy. However, in the absence of 12 months of amenorrhea, a single elevated follicle-stimulating hormone measurement is insufficient)
  5. Patients who sign the Informed Consent Form for participation in the study

Exclusion criteria 17

  1. Diabetes mellitus
  2. Concomitant steroid or immunosuppressive therapy or other drugs known to interfere with bone metabolism
  3. Women ≤ 69 years: cardiovascular risk ≥ 20% at 10 years according to the Heart Project risk charts
  4. Women ≥ 70 years: 2OP score (ESC 2021) with risk > 15% at 10 years
  5. Uncontrolled hypercholesterolemia without therapy or uncontrolled despite ongoing cholesterol-lowering therapy (LDL ≥ 116 mg/dl)
  6. Uncontrolled hypertension without therapy or uncontrolled despite ongoing antihypertensive therapy (blood pressure ≥ 140/90 mmHg)
  7. Active endocrinopathies (except subclinical hypothyroidism)
  8. Chronic renal failure stages IIIb-IV-V (eGFR < 45 ml/min according to CKD-EPI)
  9. Chronic liver disease (Child classifications B and C )
  10. History of bone disease other than osteoporosis (e.g. Paget's disease)
  11. Active neoplasms (including patients in remission for more than 5 years)
  12. Previous acute myocardial infarction (AMI) and/or stroke, regardless of age of onset
  13. Alcohol consumption (more than 2 units of alcohol/day)
  14. Active smoking
  15. 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
  16. Patients with hypocalcemia, defined as plasma calcium corrected for albumin < 8.8 mg/dL.
  17. Previous allergic reaction to iodinated contrast media or allergy or hypersensitivity to the study drugs (active substance and excipients)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Change in the coronary CT score adapted according to the CCTA-Leaman method after 12 months of therapy.

Secondary endpoints 2

  1. Change in scores: Segment Involvement Score (SIS) and Segment Stenosis Score (SSS) between V1 and V3
  2. Measurement of biomarkers at V1 and their correlation with changes in coronary scores: Sclerostin, Lipoprotein-Associated Phospholipase A2, Myeloid-Related Protein 8 and 14, and Monocyte Chemoattractant Protein 1 (MCP-1).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 8

EVENITY 105 mg solution for injection in pre-filled pen

PRD7764607 · Product

Active substance
Romosozumab
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
SUBCUTANEOUS
Max daily dose
210 mg milligram(s)
Max total dose
2520 mg milligram(s)
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
M05BX06 — -
Marketing authorisation
EU/1/19/1411/002
MA holder
UCB PHARMA S.A.
MA country
Liechtenstein
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

EVENITY 105 mg solution for injection in pre-filled pen

PRD7764048 · Product

Active substance
Romosozumab
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
SUBCUTANEOUS
Max daily dose
210 mg milligram(s)
Max total dose
2520 mg milligram(s)
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
M05BX06 — -
Marketing authorisation
EU/1/19/1411/002
MA holder
UCB PHARMA S.A.
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

EVENITY 105 mg solution for injection in pre-filled pen

PRD7764314 · Product

Active substance
Romosozumab
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
SUBCUTANEOUS
Max daily dose
210 mg milligram(s)
Max total dose
2520 mg milligram(s)
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
M05BX06 — -
Marketing authorisation
EU/1/19/1411/001
MA holder
UCB PHARMA S.A.
MA country
Iceland
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

EVENITY 105 mg solution for injection in pre-filled pen

PRD7764424 · Product

Active substance
Romosozumab
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
SUBCUTANEOUS
Max daily dose
210 mg milligram(s)
Max total dose
2520 mg milligram(s)
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
M05BX06 — -
Marketing authorisation
EU/1/19/1411/002
MA holder
UCB PHARMA S.A.
MA country
Norway
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

EVENITY 105 mg solution for injection in pre-filled pen

PRD7764543 · Product

Active substance
Romosozumab
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
SUBCUTANEOUS
Max daily dose
210 mg milligram(s)
Max total dose
2520 mg milligram(s)
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
M05BX06 — -
Marketing authorisation
EU/1/19/1411/001
MA holder
UCB PHARMA S.A.
MA country
Liechtenstein
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

EVENITY 105 mg solution for injection in pre-filled pen

PRD7764416 · Product

Active substance
Romosozumab
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
SUBCUTANEOUS
Max daily dose
210 mg milligram(s)
Max total dose
2520 mg milligram(s)
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
M05BX06 — -
Marketing authorisation
EU/1/19/1411/001
MA holder
UCB PHARMA S.A.
MA country
Norway
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

EVENITY 105 mg solution for injection in pre-filled pen

PRD7764348 · Product

Active substance
Romosozumab
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
SUBCUTANEOUS
Max daily dose
210 mg milligram(s)
Max total dose
2520 mg milligram(s)
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
M05BX06 — -
Marketing authorisation
EU/1/19/1411/002
MA holder
UCB PHARMA S.A.
MA country
Iceland
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

EVENITY 105 mg solution for injection in pre-filled pen

PRD7764042 · Product

Active substance
Romosozumab
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
SUBCUTANEOUS
Max daily dose
210 mg milligram(s)
Max total dose
2520 mg milligram(s)
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
M05BX06 — -
Marketing authorisation
EU/1/19/1411/001
MA holder
UCB PHARMA S.A.
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Comparator 9

Prolia 60 mg solution for injection in pre-filled syringe

PRD3618670 · Product

Active substance
Denosumab
Substance synonyms
AMG 162, HLX14, TVB-009, MAB-22
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
SUBCUTANEOUS
Max daily dose
60 mg milligram(s)
Max total dose
360 mg milligram(s)
Max treatment duration
36 Month(s)
Authorisation status
Authorised
ATC code
M05BX04 — -
Marketing authorisation
EU/1/10/618/002
MA holder
AMGEN EUROPE B.V.
MA country
Iceland
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Prolia 60 mg solution for injection in pre-filled syringe

PRD3618669 · Product

Active substance
Denosumab
Substance synonyms
AMG 162, HLX14, TVB-009, MAB-22
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
SUBCUTANEOUS
Max daily dose
60 mg milligram(s)
Max total dose
360 mg milligram(s)
Max treatment duration
36 Month(s)
Authorisation status
Authorised
ATC code
M05BX04 — -
Marketing authorisation
EU/1/10/618/001
MA holder
AMGEN EUROPE B.V.
MA country
Iceland
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Prolia 60 mg solution for injection in pre-filled syringe

PRD385446 · Product

Active substance
Denosumab
Substance synonyms
AMG 162, HLX14, TVB-009, MAB-22
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
SUBCUTANEOUS
Max daily dose
60 mg milligram(s)
Max total dose
360 mg milligram(s)
Max treatment duration
36 Month(s)
Authorisation status
Authorised
ATC code
M05BX04 — -
Marketing authorisation
EU/1/10/618/002
MA holder
AMGEN EUROPE B.V.
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Prolia 60 mg solution for injection in pre-filled syringe

PRD3618879 · Product

Active substance
Denosumab
Substance synonyms
AMG 162, HLX14, TVB-009, MAB-22
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
SUBCUTANEOUS
Max daily dose
60 mg milligram(s)
Max total dose
360 mg milligram(s)
Max treatment duration
36 Month(s)
Authorisation status
Authorised
ATC code
M05BX04 — -
Marketing authorisation
EU/1/10/618/001
MA holder
AMGEN EUROPE B.V.
MA country
Norway
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Prolia 60 mg solution for injection in pre-filled syringe

PRD385447 · Product

Active substance
Denosumab
Substance synonyms
AMG 162, HLX14, TVB-009, MAB-22
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
SUBCUTANEOUS
Max daily dose
60 mg milligram(s)
Max total dose
360 mg milligram(s)
Max treatment duration
36 Month(s)
Authorisation status
Authorised
ATC code
M05BX04 — -
Marketing authorisation
EU/1/10/618/003
MA holder
AMGEN EUROPE B.V.
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Prolia 60 mg solution for injection in pre-filled syringe

PRD3618671 · Product

Active substance
Denosumab
Substance synonyms
AMG 162, HLX14, TVB-009, MAB-22
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
SUBCUTANEOUS
Max daily dose
60 mg milligram(s)
Max total dose
360 mg milligram(s)
Max treatment duration
36 Month(s)
Authorisation status
Authorised
ATC code
M05BX04 — -
Marketing authorisation
EU/1/10/618/003
MA holder
AMGEN EUROPE B.V.
MA country
Iceland
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Prolia 60 mg solution for injection in pre-filled syringe

PRD3618881 · Product

Active substance
Denosumab
Substance synonyms
AMG 162, HLX14, TVB-009, MAB-22
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
SUBCUTANEOUS
Max daily dose
60 mg milligram(s)
Max total dose
360 mg milligram(s)
Max treatment duration
36 Month(s)
Authorisation status
Authorised
ATC code
M05BX04 — -
Marketing authorisation
EU/1/10/618/003
MA holder
AMGEN EUROPE B.V.
MA country
Norway
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Prolia 60 mg solution for injection in pre-filled syringe

PRD385437 · Product

Active substance
Denosumab
Substance synonyms
AMG 162, HLX14, TVB-009, MAB-22
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
SUBCUTANEOUS
Max daily dose
60 mg milligram(s)
Max total dose
360 mg milligram(s)
Max treatment duration
36 Month(s)
Authorisation status
Authorised
ATC code
M05BX04 — -
Marketing authorisation
EU/1/10/618/001
MA holder
AMGEN EUROPE B.V.
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Prolia 60 mg solution for injection in pre-filled syringe

PRD3618880 · Product

Active substance
Denosumab
Substance synonyms
AMG 162, HLX14, TVB-009, MAB-22
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
SUBCUTANEOUS
Max daily dose
60 mg milligram(s)
Max total dose
360 mg milligram(s)
Max treatment duration
36 Month(s)
Authorisation status
Authorised
ATC code
M05BX04 — -
Marketing authorisation
EU/1/10/618/002
MA holder
AMGEN EUROPE B.V.
MA country
Norway
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ospedale Galeazzi S.p.A.

2 Total trials 1 Recruiting
Academic / Non-commercial
Sponsor organisation
Ospedale Galeazzi S.p.A.
Address
Via Cristina Belgioioso 173
City
Milan
Postcode
20157
Country
Italy

Scientific contact point

Organisation
Ospedale Galeazzi S.p.A.
Contact name
Dr. Antonio Rossi

Public contact point

Organisation
Ospedale Galeazzi S.p.A.
Contact name
Dr. Antonio Rossi

Locations

1 EU/EEA country · 2 investigational sites

By country

CountryMS statusPlanned subjectsSites
Italy Authorised, recruitment pending 60 2
Rest of world — 0 —

Investigational sites

Italy

2 sites · Authorised, recruitment pending
Ospedale Galeazzi S.p.A.
U.O. Medicina ad Indirizzo Endocrino-Metabolico, Via Cristina Belgioioso 173, 20157, Milan
Asst Centro Specialistico Ortopedico Traumatologico Gaetano Pini Cto
UOC Osteoporosi e Malattie Metaboliche dell’Osso, Piazza Cardinale Andrea Ferrari 1, 20122, Milan

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 16 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_Protocol_2025-522592-29-00_EN_Red 1.0
Protocol (for publication) D1_Protocol_2025-522592-29-00_IT_V3Red 3.0
Protocol (for publication) D1_Protocol_EN_2025-522592-29-00_v3_Clean_Red 3.0
Protocol (for publication) D4_Scores_EN 1.0
Recruitment arrangements (for publication) K1_Recruitment arrangements 1.0
Subject information and informed consent form (for publication) L1_SIS and ICF adults patients_Red 1.0
Subject information and informed consent form (for publication) L2_Other subject information material_Letter to physician_Red 1.0
Subject information and informed consent form (for publication) L2_Other subject information material_Privacy_Red 1.0
Summary of Product Characteristics (SmPC) (for publication) E2_FI_Denosumab PROLIA 1
Summary of Product Characteristics (SmPC) (for publication) E2_FI_Romosozumab EVENITY 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_Denosumab PROLIA 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_Romosozumab EVENITY 1
Synopsis of the protocol (for publication) D1_Layperson synopsis_IT_2025-522592-29-00 2.0
Synopsis of the protocol (for publication) D1_Protocol Synopsis_EN_2025-522592-29-00 1.0
Synopsis of the protocol (for publication) D1_Protocol Synopsis_EN_2025-522592-29-00_V2_Clean 2.0
Synopsis of the protocol (for publication) D1_Protocol Synopsis_IT_2025-522592-29-00_TC 2.0

Application history

1 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2025-10-16 Italy Acceptable with conditions
2026-02-16
 2026-02-23