Comparing Efficacy and Safety of AryoGen Pharmed Biosimilar Denosumab 60 mg (Arylia) Versus Prolia® in Improvement of Bone Mineral Densitometry (BMD) Among Osteoporotic Postmenopausal Women

NCT03293108 | Unknown Phase 3

• 1 other identifier: DEN.ARY.AJ.95 (III)
• Study Type: interventional
• Target: 190
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to compare the efficacy and safety of Denosumab 60 mg produced by AryoGen Pharmed and Amgen Denosumab 60 mg among osteoporotic postmenopausal women. Postmenopausal women diagnosed with osteoporosis according to their Bone mineral density result (BMD), aged between 45 to 75 are included in this trial. This is a Phase III, randomized, two armed, double-blind, parallel, active-controlled,non-inferiority clinical trial. The eligible patients are randomized in a 1:1 ratio to receive Arylia or Prolia® subcutaneous injections, at the beginning of the trial and every 6 months at month 6 and 12, in an 18-month study period. Along with, all women will receive daily supplements containing at least 1000 mg of elemental calcium (divided into two doses) and at least 400 IU vitamin D daily during 18 months of the study. The primary objective of this study is to assess non-inferiority of test- Denosumab 60 mg (Arylia) to the reference Denosumab 60 mg (Prolia®) in terms of efficacy among osteoporotic postmenopausal women. The secondary objectives of this study are: To further compare efficacy of test- Denosumab 60 mg to reference Denosumab 60 mg; To assess the safety of test- Denosumab 60 mg compared to reference Denosumab 60 mg.

Conditions

Osteoporosis

Keywords

Osteoporosis; Denosumab

Outcome Measures

Primary Outcomes (1)

• BMD percentage change from baseline at lumbar spine (L1-L4), femoral neck and total hip.

  Percentage change from baseline in BMD at lumbar spine (L1-L4), femoral neck and total hip by dual-energy x-ray absorptiometry to 18 months of the study, and compare between two groups.

  Baseline and at 18 months.

Secondary Outcomes (4)

• The incidence of new vertebral fracture.

  Baseline and at 18 months

• Evolution of biochemical markers of bone metabolism.

  Baseline,at month 1,at month 3,at month 6,at month 9, at month 12, at month 15 and at month 18.

• Comparing adverse events between two products.

  baseline,at month 1,at month 3,at month 6,at month 9,at month 12, at month 15 and at month 18.

• Comparing immunogenicity between two products.

  Baseline,at month 6,at month 12 and at month 18.

Study Arms (2)

AryoGen Pharmed Denosumab

EXPERIMENTAL

Arylia (Denosumab Prefilled Syringe produced by AryoGen Pharmed) 60 mg/1 ml in a prefilled syringe. Denosumab 60 mg is subcutaneously administered to osteoporotic patients at baseline, month 6 and month 12. Along with, all women will receive daily supplements containing at least 1000 mg of elemental calcium (divided into two doses) and at least 400 IU vitamin D daily during 18 months of the study.

Drug: Denosumab; Dietary Supplement: calcium; Dietary Supplement: vitamin D

Amgen Denosumab

ACTIVE COMPARATOR

Prolia® (Denosumab Prefilled Syringe produced by Amgen) 60 mg/1 ml in a prefilled syringe. Denosumab 60 mg is subcutaneously administered to osteoporotic patients at baseline, month 6 and month 12. Along with, all women will receive daily supplements containing at least 1000 mg of elemental calcium (divided into two doses) and at least 400 IU vitamin D daily during 18 months of the study.

Drug: Denosumab; Dietary Supplement: calcium; Dietary Supplement: vitamin D

Interventions

Denosumab DRUG

Denosumab 60 mg is subcutaneously administered to osteoporotic patients at baseline, month 6 and month 12.

Amgen Denosumab; AryoGen Pharmed Denosumab

calcium DIETARY_SUPPLEMENT

All women will receive daily supplements containing at least 1000 mg of elemental calcium (divided in two doses), during 18 month of the study.

Amgen Denosumab; AryoGen Pharmed Denosumab

vitamin D DIETARY_SUPPLEMENT

All women will receive daily supplements containing at least 400 IU vitamin D daily during 18 month of the study.

Amgen Denosumab; AryoGen Pharmed Denosumab

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Postmenopausal women aged between 45 up to 75;
• Bone mineral density T score at the lumbar spine (L1-L4), femoral neck or total hip should be equal or less than -2.5 and equal or more than -4. (-4 ≤ T score ≤-2.5); or patients with high risk of fracture on the basis of FRAX criteria which according to osteoporosis treatment guidelines, need medicinal treatment.
• Ability to comprehend and willingness to sign the Informed Consent Form for this study;
• Signed informed consent with full knowledge and mental health.

You may not qualify if:

• Lack of consent for being in the trial and not complying with an 18-months follow-up;
• Having hypersensitivity to denosumab or any component in the formulation (excipients include acetic acid, sorbitol, polysorbate 20, sodium hydroxide, water for injections);
• Malabsorption syndrome;
• History of thyroid surgery, parathyroid surgery or intestinal resection which has been caused malabsorption.
• Patient with CKD stage 4 and 5 should be exclude (GFR \<30cc/min)
• Level of serum 25-(OH) vitamin D less than 20 ng/ml; (If vitamin deficiency has been corrected, and two tests show the level above 20 ng/ml within a month, the patient can be enrolled.)
• Pre-existing hypocalcemia (Albumin-adjusted serum calcium level less than 8 mg/dl in fasting specimens) which is uncorrectable;
• Untreated hypercalciuria (\>250 mg/24h) and hypocalciuria (\<100 mg/24h). If urine calcium level of patient is less than 100 mg per 24 hours and by vitamin D treatment the problem has been solved or if urine calcium level of patient is greater than 250 mg per 24 hours, but PTH is normal, the patient can be enrolled.
• Presence of osteonecrosis of jaw (ONJ) risk factors including a diagnosis of cancer, poor oral hygiene, periodontal and/or dental diseases, having dentures; and comorbid disorders (anemia (hemoglobin level less than 11 g/dl, if it is corrected, patient can enter the study), history of diseases with coagulopathy, oral and dental infection);
• Malignancy;
• Having severe and active infections; (Severe infection is a difficult treated infection, like diabetic foot infection, but if the infection is treatable, after treatment, the patient can be enrolled.)
• Being bed rest (for 2 weeks during the past 3 months)
• A case in which the patient cannot take 1000 mg oral elemental calcium per day; (as supplement)
• A case in which bone mineral density could not be accurately measured;
• Conditions that influence bone metabolism, including hyperparathyroidism or hypoparathyroidism, hyperthyroidism or hypothyroidism, hypocalcemia, inflammatory rheumatologic diseases such as rheumatoid arthritis, Paget's disease of bone, osteomalacia that is resistant to therapy (definition of resistant to therapy: not being responder to 1-month administration of vitamin D).

Sponsors & Collaborators

• AryoGen Pharmed Co.: lead

Study Sites (1)

Rheumatology Center of Iran

Tehran, 021, Iran

Location

Related Publications (13)

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  PMID: 26639186 BACKGROUND

• Herrero S, Pico Y. Treatments for post-menopausal osteoporotic women, what's new? How can we manage long-term treatment? Eur J Pharmacol. 2016 May 15;779:8-21. doi: 10.1016/j.ejphar.2016.02.053. Epub 2016 Feb 26.

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• Black DM, Rosen CJ. Clinical Practice. Postmenopausal Osteoporosis. N Engl J Med. 2016 Jan 21;374(3):254-62. doi: 10.1056/NEJMcp1513724.

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• 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.

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• McClung MR, Lewiecki EM, Cohen SB, Bolognese MA, Woodson GC, Moffett AH, Peacock M, Miller PD, Lederman SN, Chesnut CH, Lain D, Kivitz AJ, Holloway DL, Zhang C, Peterson MC, Bekker PJ; AMG 162 Bone Loss Study Group. Denosumab in postmenopausal women with low bone mineral density. N Engl J Med. 2006 Feb 23;354(8):821-31. doi: 10.1056/NEJMoa044459.

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• Gu HF, Gu LJ, Wu Y, Zhao XH, Zhang Q, Xu ZR, Yang YM. Efficacy and Safety of Denosumab in Postmenopausal Women With Osteoporosis: A Meta-Analysis. Medicine (Baltimore). 2015 Nov;94(44):e1674. doi: 10.1097/MD.0000000000001674.

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• Bone HG, Bolognese MA, Yuen CK, Kendler DL, Wang H, Liu Y, San Martin J. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women. J Clin Endocrinol Metab. 2008 Jun;93(6):2149-57. doi: 10.1210/jc.2007-2814. Epub 2008 Apr 1.

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• Jamshidi A, Vojdanian M, Soroush M, Akbarian M, Aghaei M, Hajiabbasi A, Mirfeizi Z, Khabbazi A, Alishiri G, Haghighi A, Salimzadeh A, Karimzadeh H, Shirani F, Fard MRH, Nazarinia M, Soroosh S, Anjidani N, Gharibdoost F. Efficacy and safety of the biosimilar denosumab candidate (Arylia) compared to the reference product (Prolia(R)) in postmenopausal osteoporosis: a phase III, randomized, two-armed, double-blind, parallel, active-controlled, and noninferiority clinical trial. Arthritis Res Ther. 2022 Jun 30;24(1):161. doi: 10.1186/s13075-022-02840-8.

  PMID: 35773713 DERIVED

MeSH Terms

Conditions

Osteoporosis

Interventions

Denosumab; Calcium; Vitamin D

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal 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; Metals, Alkaline Earth; Elements; Inorganic Chemicals; Metals; Blood Coagulation Factors; Biological Factors; Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2017
• First Posted: September 26, 2017
• Study Start: April 29, 2017
• Primary Completion: September 30, 2020
• Study Completion: September 30, 2020
• Last Updated: July 10, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

IR (1)