Strategies for zoledronic acid post-denosumab discontinuation in postmenopausal osteoporosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Toulouse

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

2 Oct 2025 → ongoing

Decision date (initial)

2024-11-15

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

To compare the 1-year lumbar clinical and densitometric efficacy of biomarkers-driven ZOL treatment vs standardized ZOL treatment after denosumab withdrawal in post-menopausal osteoporosis

Secondary objectives 6

1. To compare the 1-year hip densitometric efficacy of biomarkers-driven ZOL treatment vs standardized ZOL treatment after denosumab withdrawal in post-menopausal osteoporosis
2. To compare the 2-years densitometric efficacy of biomarkers-driven ZOL treatment vs standardized ZOL treatment, after denosumab withdrawal in post-menopausal osteoporosis
3. To compare the 1-year and 2-years biological efficacy of biomarkers-driven ZOL treatment vs standardized ZOL treatment, after denosumab withdrawal in post-menopausal osteoporosis
4. To compare the 1-year and 2-years anti-fracture efficacy of biomarkers-driven ZOL treatment vs standardized ZOL treatment, after denosumab withdrawal in post-menopausal osteoporosis
5. To compare the 1-year and 2-years tolerance of biomarkers-driven ZOL treatment vs standardized ZOL treatment, after denosumab withdrawal in post-menopausal osteoporosis
6. To compare the use of second ZOL infusion in biomarkers-driven ZOL infusion vs standardized ZOL treatment, after denosumab withdrawal in post-menopausal osteoporosis

Conditions and MedDRA coding

Postmenopausal osteoporosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Women aged ≥ 18 years
2. With post-menopausal osteoporosis AND treated with denosumab for at least 2 years
3. With post-menopausal osteoporosis - AND reaching decision of denosumab withdrawal because of achieved therapeutic target defined as no fracture during treatment; no new risk factors; no BMD decrease > 0.03 g/cm² at the spine or hip
4. With post-menopausal osteoporosis - AND with a history of severe fracture OR a femoral or a lumbar T-score ≤ −2.5 prior denosumab initiation.
5. Free, informed and written consent signed by the participant and the investigator (at the latest on the day of inclusion and before any examination required by the research).
6. Person affiliated or beneficiary of the French social security scheme.

Exclusion criteria 12

1. Bone disease other than post-menopausal osteoporosis, including metabolic bone disease
2. Uncontrolled endocrine diseases
3. Liver failure
4. Cancer not in remission for at least 5 years
5. Patients with non-healed jaw injury
6. Ongoing treatment with systemic glucocorticoids
7. Daily systemic glucocorticoids ≥ 7.5 mg prednisone-equivalent used for at least 3 months, and stopped less than 3 months prior inclusion.
8. Use of medication affecting bone metabolism during the last year: bisphosphonates, teriparatide, romosozumab, hormone replacement therapy
9. Contra-indication to bisphosphonates according to license recommendation including: o Chronic kidney disease with Glomerular filtration rate stage > or = G3b (<35 mL/min) o Prior allergy to zoledronic acid or another bisphosphonate o Hypocalcemia
10. Subjects unable to give an informed consent or to fill the case report form
11. Subjects under law protection
12. Foreseeable poor compliance with the strategy, alcoholism, toxicomania.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. the proportion of patients who failed: - to maintain lumbar BMD, assessed by dual-energy x-ray absorptiometry (DXA) after 1 year of ZOL. The least significant change in BMD being 0.03 g/cm²; - or presenting an additional vertebral fracture during 1st year.

Secondary endpoints 6

1. the proportion of patients who failed to maintain hip BMD after 1 year of ZOL (least significant change: 0.03 g/cm²)
2. the changes in hip and lumbar BMD from baseline to 1 year after ZOL, and from year 1 to year 2
3. the changes from baseline in bone turnover markers (crosslaps, bone alkalin phosphatase, osteocalcin, amino-terminal propeptide of type 1 procollagen, TRAP5b, dickkopf 1, sclerostin), at year 1 and year 2
4. the number of morphometric vertebral fractures (by vertebral fracture assessment – VFA or X-rays), of clinical vertebral fractures and of clinical peripheral fractures, at year 1 and year 2
5. the number of adverse events and serious adverse events at year 1 and year 2
6. the proportion of patients requiring a second ZOL infusion across groups.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Toulouse

Sponsor organisation

Centre Hospitalier Universitaire De Toulouse

Address

2 Rue Viguerie

City

Toulouse

Postcode

31300

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Toulouse

Contact name

principal investigator

Public contact point

Organisation

Centre Hospitalier Universitaire De Toulouse

Contact name

clinical research project manager

Locations

1 EU/EEA country · 18 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 6 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