OsteoporosisPhase 3NCT03293108
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
A Phase 3 study testing Denosumab, calcium and vitamin D in people with Osteoporosis, run by AryoGen Pharmed Co. at 1 site in Iran.
Trial 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… Read more about this study
- Who is it for?
- Ages 45 to 75 years, women only
- Conditions the study is for
- Osteoporosis
- What is being tested?
- Denosumab, calcium and vitamin D
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 190 participants
- Where
- 1 siteIran
- Study dates
- 29 Apr 2017to 30 Sep 2020
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 75 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.)
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- 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).
- Patients will be excluded if they have one severe or more than 2 moderate vertebral fractures. (Severe fracture is defined as more than 50 percent vertebral height loss and moderate fracture is defined as 25-50 percent vertebral height loss).
- Use of injectable bisphosphonates within the previous 12 months;
- Use of oral bisphosphonates within the previous 3 months;
- History of severe skeletal pain with bisphosphonates;
- Use of parathyroid hormone or its derivatives, systemic hormone-replacement therapy, selective estrogen-receptor modulator, calcitonin, or calcitriol within 6 weeks before study enrollment.
- Use of corticosteroids (>5 mg/prednisone daily or equivalent for ≥ 3months), in the past 3 months and more.
- Use of heparin (more than 20,000 international units/day for 6 months and longer), in the past 6 months and more.
- Patient that is possible to be administrated corticosteroids (>5 mg/prednisone daily or equivalent for ≥ 3months) or heparin (more than 20,000 international units/day for 6 months and longer) in the 18 month of the study, because of her chronic disease(s) such as allergy, asthma, coagulation disorders, should be excluded.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase III, Randomized, Two-armed, Parallel, Double-blind, Active-controlled, Non-inferiority Clinical Trial to Determine the Non-inferior Therapeutic Efficacy and Safety Between Arylia (60 mg, Denosumab, Produced by AryoGen Pharmed) Compared With Prolia® (60 mg, Denosumab, the Reference Drug, Produced by Amgen Company) in the Improvement of Bone Mineral Densitometry (BMD) Among Osteoporotic Postmenopausal Women
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.
Read more
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.
Read the detailed description
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) and 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. Visits are going to be conducted at screening, 0, 1, 3, 6, 9, 12, 15 and 18 months.
After signing the written informed consent, 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 percentage change from baseline in BMD at the lumbar spine (L1-L4), femoral neck and total hip by dual-energy x-ray absorptiometry to 18 months of the study, and compare it between two treatment groups.
The second objectives of this study are to assess the followings between treatment groups:
- The incidence of new vertebral fracture;
- Evolution of biochemical markers of bone metabolism at baseline, first month and afterward every 3 months from baseline.
- Comparing adverse events;
- Comparing immunogenicity of two products.
Before initiation, the trial is reviewed by food and drug administration of Iran. The protocol, electronic case report form (eCRF), information for patients and informed consent forms are submitted to the ethics committees responsible for review and approval purposes, according to national regulatory guidelines.
Sample size:
172 patients will be equally (1:1) divided into intervention arms for achieving 80% power in order to determine non-inferiority using a one-sided, independent sample t-test. Efficacy of Prolia® in comparison with placebo for lumbar spine BMD improvement in previous studies is reported 7.1%. The margin of non-inferiority is 1.78. The true difference between the means is assumed to be 0.000. The significance level (alpha) of the test is 0.025. The data are drawn from populations with standard deviations of 4.116 and 4.116. However, we have calculated that 190 patients should enter the study, by considering that there might be 10% drop-outs of participants during the trial.
Blinding:
To prevent the influence of knowing intervention group on study conclusion, the subjects and those who assess the study outcomes will be unaware of the state of the patient with regard to receiving the test drug or reference drug.
For this purpose, subjects and administrator of the drug will be blinded by using a similar masked prefilled syringes. All drugs packages will be identified by unique numbers.
- Conditions
- Osteoporosis
- Being tested
- Denosumab, calcium, vitamin D
- Keywords
- Osteoporosis, Denosumab
- Medical subject headings
- Osteoporosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DenosumabDrug
Denosumab 60 mg is subcutaneously administered to osteoporotic patients at baseline, month 6 and month 12.
calciumDietary 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.
vitamin DDietary supplement
All women will receive daily supplements containing at least 400 IU vitamin D daily during 18 month of the study.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Denosumab; Dietary Supplement: calcium; Dietary Supplement: vitamin D |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and at 18 months.
Secondary outcomes (4)
The incidence of new vertebral fracture.
The incidence of new vertebral fracture assessed by Lateral spine X-ray radiography (T4-L4) at baseline then at 18 months, and compare between two groups.
Measured: Baseline and at 18 months
Evolution of biochemical markers of bone metabolism.
Evolution of biochemical markers of bone metabolism at baseline, first month and afterwards every 3 months from baseline, and compare between two groups.
Measured: 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.
Evaluation of the following parameters at each visit including 0, 1, 3, 6, 9, 12, 15 and 18 months, and compare between two groups.
- Adverse events (AEs), Adverse drug reactions (ADR)
- Changes in physical examination findings
- Changes in vital signs
- Clinical laboratory testing for systemic safety, including liver function, renal function, complete blood count, and clinical chemistries.
Measured: 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.
Evaluation of immunogenicity at visit 0, 6, 12 and 18 months for both arms, and compare between two groups.
Measured: Baseline,at month 6,at month 12 and at month 18.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2017
- Study start29 Apr 2017
- Primary completion30 Sep 2020 (estimated)
- Study completion30 Sep 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for OsteoporosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 190 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AryoGen Pharmed Co.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03293108
- Sponsor's protocol ID
- DEN.ARY.AJ.95 (III)
- Status last verified
- Jul 2020
- First submitted
- 19 Sep 2017
- Last updated
- 10 Jul 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lim SY, Bolster MB. Current approaches to osteoporosis treatment. Curr Opin Rheumatol. 2015 May;27(3):216-24. doi: 10.1097/BOR.0000000000000169.
PubMed 25760281Drake MT, Clarke BL, Lewiecki EM. The Pathophysiology and Treatment of Osteoporosis. Clin Ther. 2015 Aug;37(8):1837-50. doi: 10.1016/j.clinthera.2015.06.006. Epub 2015 Jul 7.
PubMed 26163201Cosman F, de Beur SJ, LeBoff MS, Lewiecki EM, Tanner B, Randall S, Lindsay R; National Osteoporosis Foundation. Clinician's Guide to Prevention and Treatment of Osteoporosis. Osteoporos Int. 2014 Oct;25(10):2359-81. doi: 10.1007/s00198-014-2794-2. Epub 2014 Aug 15.
PubMed 25182228Cairoli E, Eller-Vainicher C, Chiodini I. Update on denosumab in the management of postmenopausal osteoporosis: patient preference and adherence. Int J Womens Health. 2015 Oct 13;7:833-9. doi: 10.2147/IJWH.S75681. eCollection 2015.
PubMed 26508890Diedhiou D, Cuny T, Sarr A, Norou Diop S, Klein M, Weryha G. Efficacy and safety of denosumab for the treatment of osteoporosis: A systematic review. Ann Endocrinol (Paris). 2015 Dec;76(6):650-7. doi: 10.1016/j.ando.2015.10.009. Epub 2015 Nov 27.
PubMed 26639186Herrero 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.
PubMed 26923729Black DM, Rosen CJ. Clinical Practice. Postmenopausal Osteoporosis. N Engl J Med. 2016 Jan 21;374(3):254-62. doi: 10.1056/NEJMcp1513724.
PubMed 26789873Cummings 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.
PubMed 19671655McClung 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.
PubMed 16495394Brown JP, Prince RL, Deal C, Recker RR, Kiel DP, de Gregorio LH, Hadji P, Hofbauer LC, Alvaro-Gracia JM, Wang H, Austin M, Wagman RB, Newmark R, Libanati C, San Martin J, Bone HG. Comparison of the effect of denosumab and alendronate on BMD and biochemical markers of bone turnover in postmenopausal women with low bone mass: a randomized, blinded, phase 3 trial. J Bone Miner Res. 2009 Jan;24(1):153-61. doi: 10.1359/jbmr.0809010.
PubMed 18767928Gu 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.
PubMed 26554766Bone 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.
PubMed 18381571Jamshidi 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.
PubMed 35773713
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Randomized, Two-armed, Parallel, Double-blind, Active-controlled, Non-inferiority Clinical Trial to Determine the Non-inferior Therapeutic Efficacy and Safety Between Arylia (60 mg, Denosumab, Produced by AryoGen Pharmed) Compared With Prolia® (60 mg, Denosumab, the Reference Drug, Produced by Amgen Company) in the Improvement of Bone Mineral Densitometry (BMD) Among Osteoporotic Postmenopausal Women
- ClinicalTrials.gov ID
- NCT03293108
- Acronym / sponsor ID
- DEN.ARY.AJ.95 (III)
- Conditions
- Osteoporosis
- Keywords
- Osteoporosis, Denosumab
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 190 participants (estimated)
- Lead sponsor
- AryoGen Pharmed Co.Industry (pharma, biotech, devices)
- Study start
- 29 Apr 2017 (actual)
- Primary completion
- 30 Sep 2020 (estimated)
- Study completion
- 30 Sep 2020 (estimated)
- First posted
- 26 Sep 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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) and 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. Visits are going to be conducted at screening, 0, 1, 3, 6, 9, 12, 15 and 18 months.
After signing the written informed consent, 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 percentage change from baseline in BMD at the lumbar spine (L1-L4), femoral neck and total hip by dual-energy x-ray absorptiometry to 18 months of the study, and compare it between two treatment groups.
The second objectives of this study are to assess the followings between treatment groups:
- The incidence of new vertebral fracture;
- Evolution of biochemical markers of bone metabolism at baseline, first month and afterward every 3 months from baseline.
- Comparing adverse events;
- Comparing immunogenicity of two products.
Before initiation, the trial is reviewed by food and drug administration of Iran. The protocol, electronic case report form (eCRF), information for patients and informed consent forms are submitted to the ethics committees responsible for review and approval purposes, according to national regulatory guidelines.
Sample size:
172 patients will be equally (1:1) divided into intervention arms for achieving 80% power in order to determine non-inferiority using a one-sided, independent sample t-test. Efficacy of Prolia® in comparison with placebo for lumbar spine BMD improvement in previous studies is reported 7.1%. The margin of non-inferiority is 1.78. The true difference between the means is assumed to be 0.000. The significance level (alpha) of the test is 0.025. The data are drawn from populations with standard deviations of 4.116 and 4.116. However, we have calculated that 190 patients should enter the study, by considering that there might be 10% drop-outs of participants during the trial.
Blinding:
To prevent the influence of knowing intervention group on study conclusion, the subjects and those who assess the study outcomes will be unaware of the state of the patient with regard to receiving the test drug or reference drug.
For this purpose, subjects and administrator of the drug will be blinded by using a similar masked prefilled syringes. All drugs packages will be identified by unique numbers.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AryoGen Pharmed Denosumab | Experimental | Drug: Denosumab, Dietary Supplement: calcium, Dietary Supplement: vitamin DArylia (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. |
| Amgen Denosumab | Active comparator | Drug: Denosumab, Dietary Supplement: calcium, Dietary Supplement: vitamin DProlia® (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. |
Who may qualify
- Ages
- 45 to 75 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (23 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DenosumabDenosumab 60 mg is subcutaneously administered to osteoporotic patients at baseline, month 6 and month 12. | Drug | Amgen Denosumab, AryoGen Pharmed Denosumab |
| calciumAll women will receive daily supplements containing at least 1000 mg of elemental calcium (divided in two doses), during 18 month of the study. | Dietary supplement | Amgen Denosumab, AryoGen Pharmed Denosumab |
| vitamin DAll women will receive daily supplements containing at least 400 IU vitamin D daily during 18 month of the study. | Dietary supplement | Amgen Denosumab, AryoGen Pharmed Denosumab |
Primary outcome
BMD percentage change from baseline at lumbar spine (L1-L4), femoral neck and total hip.
Time frame: Baseline and at 18 months.
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.
4 secondary outcomes
The incidence of new vertebral fracture.
Time frame: Baseline and at 18 months
Evolution of biochemical markers of bone metabolism.
Time frame: 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.
Time frame: 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.
Time frame: Baseline,at month 6,at month 12 and at month 18.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2020.
- Background: PubMed 25760281Lim SY, Bolster MB. Current approaches to osteoporosis treatment. Curr Opin Rheumatol. 2015 May;27(3):216-24. doi: 10.1097/BOR.0000000000000169.
- Background: PubMed 26163201Drake MT, Clarke BL, Lewiecki EM. The Pathophysiology and Treatment of Osteoporosis. Clin Ther. 2015 Aug;37(8):1837-50. doi: 10.1016/j.clinthera.2015.06.006. Epub 2015 Jul 7.
- Background: PubMed 25182228Cosman F, de Beur SJ, LeBoff MS, Lewiecki EM, Tanner B, Randall S, Lindsay R; National Osteoporosis Foundation. Clinician's Guide to Prevention and Treatment of Osteoporosis. Osteoporos Int. 2014 Oct;25(10):2359-81. doi: 10.1007/s00198-014-2794-2. Epub 2014 Aug 15.
- Background: PubMed 26508890Cairoli E, Eller-Vainicher C, Chiodini I. Update on denosumab in the management of postmenopausal osteoporosis: patient preference and adherence. Int J Womens Health. 2015 Oct 13;7:833-9. doi: 10.2147/IJWH.S75681. eCollection 2015.
- Background: PubMed 26639186Diedhiou D, Cuny T, Sarr A, Norou Diop S, Klein M, Weryha G. Efficacy and safety of denosumab for the treatment of osteoporosis: A systematic review. Ann Endocrinol (Paris). 2015 Dec;76(6):650-7. doi: 10.1016/j.ando.2015.10.009. Epub 2015 Nov 27.
- Background: PubMed 26923729Herrero 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.
- Background: PubMed 26789873Black 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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- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Denosumab, calcium and vitamin D in people with Osteoporosis, run by AryoGen Pharmed Co. at 1 site in Iran.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Iran. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
BMD percentage change from baseline at lumbar spine (L1-L4), femoral neck and total hip. (time frame: Baseline and at 18 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03293108, which also lists 13 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2020.