Denosumab (DMAB) Discontinuation And Switching In Glucocorticoid-Induced Osteoporosis (GIOP): A Pilot Study

NCT04177940 | Completed Phase 4 Results FDA Drug

• 2 other identifiers: IRB-300004179Protocol Number: 20187528
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

Investigators will test the hypothesis that an increase in bone turnover markers (e.g. carboxy-terminal collagen crosslinks (CTX) and P1NP) in patients currently taking chronic glucocorticoids will be attenuated more in those who switch from denosumab to "late" zoledronic acid (9 months after last denosumab dose) compared to participants randomized to "early" zoledronic acid (6 months after last denosumab dose) or weekly alendronate (6 months after last denosumab dose).

Conditions

Osteoporosis

Outcome Measures

Primary Outcomes (1)

• Absolute Difference in the Log-transformed CTX Values Between V4 vs. V6

  Absolute difference in the log-transformed CTX Values between randomization (V4) and 6 months after randomization (V6)

  from randomization (V4) through 6 months post randomization (V6)

Study Arms (3)

Denosumab (DMAB) to Alendronate (ALN)

ACTIVE COMPARATOR

Switch from Denosumab 60 mg administered subcutaneously (SC) to weekly oral alendronate (70 mg; started 6 months after last denosumab dose)

Drug: DMAB Discontinuation and Switching

DMAB to "Early" Zoledronic Acid (ZA)

ACTIVE COMPARATOR

Switch from Denosumab 60 mg administered subcutaneously (SC) to one "early" zoledronic acid infusion (5 mg; 6 months after last denosumab dose)

Drug: DMAB Discontinuation and Switching

DMAB to "Late" ZA

ACTIVE COMPARATOR

Switch from Denosumab 60 mg administered subcutaneously (SC) to one "late" zoledronic acid infusion (5 mg; 9 months after last denosumab dose)

Interventions

DMAB Discontinuation and Switching DRUG

Investigators will test the hypothesis that an increase in bone turnover markers (e.g. CTX and P1NP) in patients currently taking chronic glucocorticoids will be attenuated more in those who switch from denosumab to "late" zoledronic acid (9 months after last denosumab dose) compared to participants randomized to "early" zoledronic acid (6 months after last denosumab dose) or weekly alendronate (6 months after last denosumab dose

DMAB to "Early" Zoledronic Acid (ZA); Denosumab (DMAB) to Alendronate (ALN)

Eligibility Criteria

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

You may qualify if:

• Women and men, age 18 years or older and able to provide informed consent (IC)
• ≥ 3 months of glucocorticoid use at \> 7.5 mg /day (prednisone equivalent dose) and anticipated to remain on glucocorticoids for at least six months
• A baseline BMD T-score of ≤ -2.0 at the lumbar spine, total hip, or femoral neck; OR
• A BMD T-score ≤ -1.0 at the lumbar spine, total hip, or femoral neck and a history of an osteoporotic fracture.

You may not qualify if:

• Patients with fewer than three lumbar vertebrae that could be evaluated on dual energy x-ray absorptiometry (DXA)
• Treatment with bisphosphonates in the preceding 2 years
• Greater than 24 months (\>4 injections) of prior treatment with denosumab
• Women of childbearing potential, who are not currently using birth control, are pregnant, planning to become pregnant, or are breastfeeding. For women of childbearing potential: refusal to use 2 highly effective forms of contraception and to continue this practice for 7 months after last injection of study medication\*
• Men planning to conceive in the next 12 months
• Unstable systemic medical condition
• Uncontrolled hyperthyroidism
• Uncontrolled hypothyroidism
• History of Addison disease
• History of osteomalacia
• History of osteonecrosis of the jaw (ONJ)
• History of atypical femur fracture
• History of tooth extraction, jaw surgery, dental implants, or other dental surgery within the prior 6 months
• History of anorexia nervosa, bulimia (by history or physical) or obvious malnutrition.
• Invasive dental work(implants/surgery) planned in the next 2 years

Sponsors & Collaborators

• Maastricht University: collaborator
• Vrije Universiteit Brussel: collaborator
• University of Alabama at Birmingham: lead
• Amgen: collaborator

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

MeSH Terms

Conditions

Osteoporosis

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Kenneth Saag, MD, MSc
• Organization: University of Alabama at Birmingham Division of Clinical Immunology and Rheumatology

ksaag@uabmc.edu

205-996-9784

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: November 22, 2019
• First Posted: November 26, 2019
• Study Start: August 17, 2020
• Primary Completion: July 22, 2024
• Study Completion: January 14, 2025
• Last Updated: April 23, 2026
• Results First Posted: April 23, 2026

Record last verified: 2026-03

Locations

US (1)