Treating Idiopathic Inflammatory Myopathies Related Reduced Bone Mineral Density With Denosumab or Zoledronic Acid

NCT04034199 | Unknown Phase 3

• 1 other identifier: kwh_rheumat_tyk_01
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Idiopathic inflammatory myopathies (IIM) patients are at high risk of development of reduced bone mineral density due to impairment of functional status due to the disease and a relatively high dose of glucocorticoid use for the treatment. Reduced bone mineral density is prevalent in local IIMs patients. Denosumab and zoledronic acid are established treatments for osteoporosis in postmenopausal women and glucocorticoid-induced osteoporosis. However, the role of these treatments in reduced bone mineral density including osteoporosis and osteopenia related to IIMs are lacking. There is also no evidence on comparing the efficacy of the two agents. Therefore, the investigators conducted this prospective randomized controlled study to compare the efficacies of denosumab and zoledronic acid in treating reduced bone mineral density in IIMs patients. The hypothesis in this study is that treatment by denosumab or zoledronic acid would improve bone mineral density in IIMs patients with reduced bone mineral density.

Conditions

Idiopathic Inflammatory Myopathies; Osteoporosis, Osteopenia

Keywords

denosumab; zoledronic acid

Outcome Measures

Primary Outcomes (1)

• Change in bone mineral density at 12 months in denosumab and zoledronic acid group

  The primary outcome is change in bone mineral density at lumbar spine and hip measured by DEXA between the denosumab and zoledronic acid groups compared to control group at 12 months. Differences in BMD between two groups is compared with paired t-test.

  12 months

Secondary Outcomes (20)

• Prevalence of osteoporosis and osteopenia in idiopathic inflammatory myopathies patients

  at baseline

• Comparison of Change in Bone Mineral Density at lumbar spine and hip between the two treatment groups (denosumab and zoledronic acid)

  12 months

• Gender as a risk factor for osteoporosis and osteopenia in IIMs patients

  at baseline

• Smoking status as a risk factor for osteoporosis and osteopenia in IIMs patients

  at baseline

• Drinking status as a risk factor for osteoporosis and osteopenia in IIMs patients

  at baseline

Study Arms (2)

Denosumab group

EXPERIMENTAL

Patients randomized into the denosumab group will receive denosumab 60mg subcutaneously every 6 months, for a total duration of 1 year. DEXA scan would be repeated at 1 year.

Drug: Denosumab

Zoledronic acid

ACTIVE COMPARATOR

Patients randomized into the denosumab group will receive one dose of zoledronic acid at 5mg intravenously. DEXA scan would be repeated at 1 year.

Drug: Zoledronic Acid

Interventions

Denosumab DRUG

Denosumab is a human monoclonal antibody against receptor activator of nuclear factor kappa-B ligand (RANKL) and its use is associated with a reduced risk of vertebral, non-vertebral and hip fracture in post-menopausal women. RANKL plays a crucial role in the pathogenesis of glucocorticoid-induced osteoporosis (GIOP). Its production is increased by GC, resulting in stimulated osteoprotegerin ligand production and increased bone resorption. Recent randomized controlled trial from Saag et al have shown that denosumab is more efficacious than risedronate in the improvement of BMD in GIOP patients. Denosumab has been confirmed efficacious in GIOP patients but its efficacy in high-risk osteopenia patients are not well studied. It is given subcutaneously at 60mg every 6 months.

Also known as: Prolia

Denosumab group

Zoledronic Acid DRUG

Zoledronic acid belongs to bisphosphonates and is licensed for the treatment of GIOP and 2 RCTs found zoledronic acid has superior efficacy in improvement in BMD at lumbar spine or femoral neck at 12 months when compared to risedronate. It is given intravenously every year at a dosage of 5mg.

Also known as: Aclasta

Zoledronic acid

Eligibility Criteria

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

You may qualify if:

• Adult patients of at least 18 years of age and
• Evidence of reduced BMD in osteopenia (defined by T-score of -0.1 to -2.5) or osteoporosis range (defined by T-score of \< -2.5) at baseline by dual-energy X-ray absorptiometry (DEXA) scan.

You may not qualify if:

• Pregnant patients
• Patients with juvenile onset of disease (\<18 years of age)
• Patients with pre-existing metabolic bone conditions
• Patients who are already on osteoporotic treatment other than calcium and vitamin D (including bisphosphonates, denosumab, teriparatide, raloxifene or strontium)
• Patients who are contraindicated to denosumab or zoledronic acid including severe renal impairment and hypersensitivity
• Patients who are not able to give informed consent

Sponsors & Collaborators

• Kwong Wah Hospital: lead
• Tung Wah Group of Hospitals: collaborator

Study Sites (1)

Kwong Wah Hospital

Hong Kong, 00000, Hong Kong

Location

Related Publications (12)

• Curtis JR, Westfall AO, Allison J, Bijlsma JW, Freeman A, George V, Kovac SH, Spettell CM, Saag KG. Population-based assessment of adverse events associated with long-term glucocorticoid use. Arthritis Rheum. 2006 Jun 15;55(3):420-6. doi: 10.1002/art.21984.

  PMID: 16739208 BACKGROUND

• Angeli A, Guglielmi G, Dovio A, Capelli G, de Feo D, Giannini S, Giorgino R, Moro L, Giustina A. High prevalence of asymptomatic vertebral fractures in post-menopausal women receiving chronic glucocorticoid therapy: a cross-sectional outpatient study. Bone. 2006 Aug;39(2):253-9. doi: 10.1016/j.bone.2006.02.005. Epub 2006 Mar 30.

  PMID: 16574519 BACKGROUND

• Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). N Engl J Med. 1975 Feb 13;292(7):344-7. doi: 10.1056/NEJM197502132920706. No abstract available.

  PMID: 1090839 BACKGROUND

• Bohan A, Peter JB. Polymyositis and dermatomyositis (second of two parts). N Engl J Med. 1975 Feb 20;292(8):403-7. doi: 10.1056/NEJM197502202920807. No abstract available.

  PMID: 1089199 BACKGROUND

• Isenberg DA, Allen E, Farewell V, Ehrenstein MR, Hanna MG, Lundberg IE, Oddis C, Pilkington C, Plotz P, Scott D, Vencovsky J, Cooper R, Rider L, Miller F; International Myositis and Clinical Studies Group (IMACS). International consensus outcome measures for patients with idiopathic inflammatory myopathies. Development and initial validation of myositis activity and damage indices in patients with adult onset disease. Rheumatology (Oxford). 2004 Jan;43(1):49-54. doi: 10.1093/rheumatology/keg427. Epub 2003 Jul 16.

  PMID: 12867580 BACKGROUND

• Mok CC, Ying KY, To CH, Ho LY, Yu KL, Lee HK, Ma KM. Raloxifene for prevention of glucocorticoid-induced bone loss: a 12-month randomised double-blinded placebo-controlled trial. Ann Rheum Dis. 2011 May;70(5):778-84. doi: 10.1136/ard.2010.143453. Epub 2010 Dec 27.

  PMID: 21187295 BACKGROUND

• Mok CC, Ho LY, Ma KM. Switching of oral bisphosphonates to denosumab in chronic glucocorticoid users: a 12-month randomized controlled trial. Bone. 2015 Jun;75:222-8. doi: 10.1016/j.bone.2015.03.002. Epub 2015 Mar 8.

  PMID: 25761434 BACKGROUND

• Liu M, Guo L, Pei Y, Li N, Jin M, Ma L, Liu Y, Sun B, Li C. Efficacy of zoledronic acid in treatment of osteoporosis in men and women-a meta-analysis. Int J Clin Exp Med. 2015 Mar 15;8(3):3855-61. eCollection 2015.

  PMID: 26064284 BACKGROUND

• Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, Zoog HB, Austin M, Wang A, Kutilek S, Adami S, Zanchetta J, Libanati C, Siddhanti S, Christiansen C; FREEDOM Trial. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009 Aug 20;361(8):756-65. doi: 10.1056/NEJMoa0809493. Epub 2009 Aug 11.

  PMID: 19671655 BACKGROUND

• So H, Yip ML, Wong AK. Prevalence and associated factors of reduced bone mineral density in patients with idiopathic inflammatory myopathies. Int J Rheum Dis. 2016 May;19(5):521-8. doi: 10.1111/1756-185X.12405. Epub 2014 May 21.

  PMID: 24848429 RESULT

• Saag KG, Wagman RB, Geusens P, Adachi JD, Messina OD, Emkey R, Chapurlat R, Wang A, Pannacciulli N, Lems WF. Denosumab versus risedronate in glucocorticoid-induced osteoporosis: a multicentre, randomised, double-blind, active-controlled, double-dummy, non-inferiority study. Lancet Diabetes Endocrinol. 2018 Jun;6(6):445-454. doi: 10.1016/S2213-8587(18)30075-5. Epub 2018 Apr 6.

  PMID: 29631782 RESULT

• Reid DM, Devogelaer JP, Saag K, Roux C, Lau CS, Reginster JY, Papanastasiou P, Ferreira A, Hartl F, Fashola T, Mesenbrink P, Sambrook PN; HORIZON investigators. Zoledronic acid and risedronate in the prevention and treatment of glucocorticoid-induced osteoporosis (HORIZON): a multicentre, double-blind, double-dummy, randomised controlled trial. Lancet. 2009 Apr 11;373(9671):1253-63. doi: 10.1016/S0140-6736(09)60250-6.

  PMID: 19362675 RESULT

MeSH Terms

Conditions

Myositis; Osteoporosis; Bone Diseases, Metabolic

Interventions

Denosumab; Zoledronic Acid

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Bone Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

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

Central Study Contacts

Yan Ki Tang

CONTACT

+852 35178320; tyk155@ha.org.hk

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Model Details: This is a prospective open-label controlled trial. All patients will continue calcium (1000mg daily) and vitamin D supplementation (at least 800 international unit daily). Patients with osteopenia or osteoporosis in a baseline DEXA scan will be randomized by computer-generated blocks in 1:1 ratio into receiving denosumab (treatment group) or zoledronic acid (controlled group). Denosumab is given at 60mg subcutaneously every 6 months, following the FDA approved dosage. Zoledronic acid is administered intravenously at 5mg yearly. DEXA scan will be repeated after 12 months of treatment.

Study Record Dates

• First Submitted: July 4, 2019
• First Posted: July 26, 2019
• Study Start: August 15, 2019
• Primary Completion: December 31, 2020
• Study Completion: March 31, 2021
• Last Updated: July 26, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)