Matrix-Directed Therapy In Older Adolescents And Adults With Osteogenesis Imperfecta

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Istituto Ortopedico Rizzoli

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

18 Sep 2025 → ongoing

Decision date (initial)

2025-03-13

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Horizon Europe Topic HORIZON-HLTH-2021-DISEASE-04-02

External identifiers

EU CT number

2024-515516-50-00

ISRCTN

ISRCTN13317811

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Dose response

To establish the effective dose of losartan in patients aged 16 years and above with Osteogenisis Imperfecta, based on maximal reduction in the bone resorption marker carboxy-terminal crosslink of type I collagen telopeptide (CTX)

Secondary objectives 2

1. To determine the changes in proxy efficacy outcomes for bone (turn over, mass, architecture and strength) using blood test, High Resolution peripheral Quantitative CT (HRpQCT), Dual Energy X-ray Absorptiometry (DXA) and muscle (strength) using the “Timed Up and Go” test
2. To determine changes in quality of life using a disease-specific tool (OI-QOL) & a validated generic tool (EQ-5D-5L-VAS)

Conditions and MedDRA coding

Osteogenesis Imperfecta

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Age 16 years and above
2. Prior treatment with more than a single dose of denosumab is allowed provided there has been a 1-year washout period since the last dose of treatment.
3. Diagnosed with osteogenesis imperfecta (any type)
4. Prior treatment with up to and including 6 weeks of oral bisphosphonate therapy is allowed provided there has been a 12 month washout period since the last dose of treatment.
5. Prior treatment with a single dose of an intravenous bisphosphonate is allowed provided there has been an 18 month washout period since the treatment was given
6. A women of childbearing potential (WOCBP) who agrees to use an effective method of contraception from point of signing the informed consent throughout the study.
7. Agreed not to participate in another interventional research project during their involvement in this study.
8. Not taking prohibited concomitant medications, listed in exclusion criteria
9. Does not have any other contraindication that makes the patient unsuitable to take part in the study in the opinion of the investigator.
10. Prior treatment with more than 6 weeks of oral or more than one single intravenous bisphosphonate therapy is allowed provided there has been a 10-year washout period since the last dose of treatment.
11. Subjects not eligible (i.e., safety, tolerability and/or compliance issues, investigator’s judgement, etc.) or do not have access to the authorized products (i.e., neridronate in Italy).

Exclusion criteria 20

1. Current use of losartan
2. Prior treatment with more than 6 weeks oral bisphosphonates treatment within 10 years of the consent
3. Prior treatment with more than one dose of denosumab within 1 year of the consent
4. Recent (last 12 months) or current treatment likely to affect bone – this does not include inhaled or intermittent oral therapy with steroids for asthma (no more than three months of oral steroids in previous 12 months)
5. Severe Hepatic impairment (AST ≥ 144U/L, ALT ≥ 165U/L, GGT ≥ 183 U/L)
6. Renal impairment (GFR <60ml/min/m2; GFR in children will be assessed using the Bedside Schwartz equation) if treated with aliskiren-containing products.
7. Diabetes mellitus if treated with aliskiren-containing products
8. Cardiac failure if treated with diuretics (excluding grade 1 according to the NYHA Functional Classification)
9. Pregnancy or lactation
10. Known hypersensitivity to losartan or any of the excipients
11. Prior use of losartan within preceding 6 month to enrolment
12. Recent fracture in the prior 6 months to enrolment
13. Presence of other chronic illnesses including renal failure likely to affect bone metabolism or structure. GFR in children will be assessed using the Bedside Schwartz equation
14. Known severe hypotension resulting in dizziness, fainting or headaches
15. Hyperkalaemia
16. Current medication that increases potassium retention, or may increase potassium levels, such as potassium-retaining diuretics
17. Current medication with lithium
18. Current medication with other substances which may induce hypotension
19. Currently taking oral bisphosphonates or intravenous bisphosphonates
20. Prior treatment with more than a single dose of intravenous bisphosphonate within 10 years of the consent

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percentage change in CTX from baseline to week 24

Secondary endpoints 6

1. Percentage change in CTX from baseline to week 8
2. Percentage change in TGFβ & P1NP from baseline to week 8 and w24
3. Change in DXA LSaBMD from baseline to w24
4. Change in radial and tibial total vBMD by HRpQCT from baseline to w24
5. Change in Timed Up and Go test from baseline to w24
6. Change in QoL using OI-QOL & EQ-5D-5L-VAS from baseline to w24

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Istituto Ortopedico Rizzoli

Sponsor organisation

Istituto Ortopedico Rizzoli

Address

Via Di Barbiano 1/10

City

Bologna

Postcode

40136

Country

Italy

Scientific contact point

Organisation

Istituto Ortopedico Rizzoli

Contact name

Luca Sangiorgi

Public contact point

Organisation

Istituto Ortopedico Rizzoli

Contact name

Martina Piccinni Leopardi

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 35 files

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

Application history

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