Denosumab Sequential Therapy

NCT03868033 | Completed Phase 4 DMC FDA Drug

• 1 other identifier: 201811067MIPC
• Study Type: interventional
• Target: 101
• Locations: 1 country
• Sites: 1

Brief Summary

Denosumab is a potent anti-resorptive agent and is now widely used in the treatment of osteoporosis. Although denosumab has excellent effect to increase bone mass and prevent fracture in FREEDOM study with very low complications, even up to ten years, it's effect is reversible. After holding the drug, circulating denosumab levels fall rapidly, and bone resorption reaching twice baseline levels for about 6 months. How to prevent bone loss after denosumab therapy is an important issue, especially when considering the compliance, persistence, or other comorbidities of the patient. We want to verify if zoledronic acid could be used as a sequential therapy after denosumab to prevent rapid bone loss by randomized clinical trial.

Conditions

Osteoporosis

Keywords

Osteoporosis; Denosumab; Zoledronate; Bone mineral density

Outcome Measures

Primary Outcomes (1)

• Changes of lumbar spine, total hip and femoral neck bone mineral density

  Changes of lumbar spine, total hip and femoral neck bone mineral density from baseline

  baseline, 1 year, 2 year

Secondary Outcomes (2)

• Change of bone turnover marker

  baseline, 6 months, 12 months, 15 months, 18 months, 24 months

• Clinical osteoporotic fracture

  baseline, 1 year, 2 year

Study Arms (4)

Continuous Denosumab

EXPERIMENTAL

Continuous anti-resorptive therapy by Denosumab for 2 years

Drug: Denosumab

Zoledronic acid to Denosumab

EXPERIMENTAL

treat with Zoledronic acid for one year and then shift to Denosumab for another one year

Drug: Zoledronic Acid; Drug: Denosumab

Continuous Zoledronic acid

EXPERIMENTAL

Continuous anti-resorptive therapy by Zoledronic acid for 2 years

Drug: Zoledronic Acid

Zoledronic acid to observation

EXPERIMENTAL

treat with Zoledronic acid for one year and then close follow up by bone turn over marker. resume another dose of Zoledronic acid if elevated CTX level above normal range

Drug: Zoledronic Acid

Interventions

Zoledronic Acid DRUG

Use Zoledronic acid as a sequential therapy after denosumab treatment for more than 2 years

Also known as: Aclasta

Continuous Zoledronic acid; Zoledronic acid to Denosumab; Zoledronic acid to observation

Denosumab DRUG

Continuous Denosumab treatment in arm 1 for two years or as a 2nd year treatment in arm 2 for one year

Also known as: Prolia

Continuous Denosumab; Zoledronic acid to Denosumab

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Postmenopausal women
• Men \>50-year-old
• After Denosumab treatment ≥ 2 years due to osteoporosis

You may not qualify if:

• Patientshadeverusedantiosteoporosismedications other than Dmab
• Estimated glomerular filtration rate \<35 ml/min.
• Malignancy
• Continuous steroid treatment, hormone therapy or other medical treatment affecting bone metabolism
• Secondary osteoporosis
• Metabolic bone diseases
• Contraindications to ZOL
• Patients older than 80 years old
• Hypocalcemia

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (1)

Department of Orthopedics, National Taiwan University Hospital

Taipei, N/A = Not Applicable, 64041, Taiwan

Location

Related Publications (2)

• Lee CC, Wang CY, Yen HK, Hung CC, Lai CY, Hu MH, Wang TM, Li CY, Fu SH. Zoledronate Sequential Therapy After Denosumab Discontinuation to Prevent Bone Mineral Density Reduction: A Randomized Clinical Trial. JAMA Netw Open. 2024 Nov 4;7(11):e2443899. doi: 10.1001/jamanetworkopen.2024.43899.

  PMID: 39527056 DERIVED

• Lee CC, Wang CY, Hung CC, Huang CC, Li CY, Chen HY, Chang YL, Tseng WJ, Wang TM, Yang RS, Wong TH, Fu SH. A Multi-Institutional Randomized Controlled Trial to Investigate Whether Zoledronate Prevents Bone Loss After Discontinuation of Denosumab: The Study Protocol of Denosumab Sequential Therapy (DST) Trial. Front Med (Lausanne). 2021 Sep 8;8:717168. doi: 10.3389/fmed.2021.717168. eCollection 2021.

  PMID: 34568375 DERIVED

MeSH Terms

Conditions

Osteoporosis

Interventions

Zoledronic Acid; Denosumab

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Shau-Huai Fu, doctor

  Department of Orthopedics, National Taiwan University Hospital Yunlin Branch

  PRINCIPAL INVESTIGATOR

• Chia-Che Lee

  Department of Orthopedics, National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2019
• First Posted: March 8, 2019
• Study Start: April 12, 2019
• Primary Completion: July 1, 2023
• Study Completion: December 31, 2023
• Last Updated: April 23, 2024

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)