A Phase 3 Study to Compare Biosimilar Denosumab With Prolia®
Study Details
Study Description
Brief Summary
This is a phase 3 Randomized, Double-blind, Parallel-group, Active-controlled Study to Compare the Efficacy, Safety, Pharmacodynamics, Pharmacokinetics, and Immunogenicity of Enzene Denosumab (ENZ215) and Prolia® in Postmenopausal Women with Osteoporosis
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: ENZ215 ENZ215 Injection:- 60 mg Denosumab (ENZ215) will be administered subcutaneously on day 1. |
Biological: ENZ215
Enrolled women with postmenopausal osteoporosis will receive ENZ215 (60mg)
|
| Active Comparator: Prolia Prolia Injection:- 60 mg Denosumab (Prolia) will be administered subcutaneously on day 1. |
Biological: Prolia
Enrolled women with postmenopausal osteoporosis will receive Prolia
|
Outcome Measures
Primary Outcome Measures
- To evaluate the efficacy of ENZ215 when compared to Prolia in patients with postmenopausal osteoporosis, in terms of change in bone mineral density (BMD) at lumbar spine [360 days]
Percentage change in BMD at lumbar spine (L1-L4 region) measured by dual-energy X-ray absorptiometry (DXA)
- To compare the area under the effect curve (AUEC) of serum C-telopeptide of Type-1 collagen (sCTX) levels [180 days]
AUEC of sCTX over the initial 6 months (from Day 1 pre-dose to Month 6 pre-dose) will be assessed.
Secondary Outcome Measures
- To compare the immunogenicity potential of ENZ215 and Prolia [540 days]
ADAs incidence at baseline and different timepoints from 1 month to 12 months and during open-label switch over period will be assessed.
- To compare the safety and tolerability of ENZ215 and Prolia [540 days]
Treatment-emergent serious and non-serious adverse events (TEAEs) during main treatment period and open-label switch-over period will be assessed
- To compare the pharmacokinetics of ENZ215 and Prolia [360 days]
Cmax of denosumab measured at predefined timepoints.
- To compare the pharmacokinetics of ENZ215 and Prolia [360 days]
Tmax of denosumab measured at predefined timepoints.
- To compare the pharmacokinetics of ENZ215 and Prolia [360 days]
partial AUC of denosumab measured at predefined timepoints.
- To compare the change in serum procollagen type 1 N-terminal propeptide (sP1NP) levels [180 days]
- To compare the change in BMD at the lumbar spine [180 days]
Percentage change in BMD at lumbar spine measured by DXA from baseline to predefined timepoint
- To compare the change in BMD at total hip and femoral neck [360 days]
Percentage change in BMD at total hip and femoral neck measured by DXA from baseline to Month to predefined timepoint
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Willing to provide voluntary written informed consent and able to comply with the protocol requirements
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Postmenopausal women aged ≥ 55 and ≤ 85 years
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Body weight ≥ 50 kg and ≤ 90 kg
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Diagnosed with osteoporosis, with absolute BMD at the lumbar spine (L1-L4 region) as measured by dual-energy X ray absorptiometry (DXA) at screening
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At least 5 years of postmenopausal status confirmed by follicle-stimulating hormone (FSH) levels at screening
-
At least one hip joint and two vertebrae in L1-L4 region evaluable by DXA
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No other clinically significant medical history, vital signs, physical examination, laboratory profiles as deemed by the Investigator or designee
Exclusion Criteria:
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Known hypersensitivity to denosumab or any of the excipients of the study drug
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Known intolerance to, or malabsorption of calcium or vitamin D supplements
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Previous exposure to Prolia® or any other denosumab biosimilar
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Previous use of oral bisphosphonates
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Use of intravenous bisphosphonates within the past 5 years prior to screening
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Use of parathyroid hormone or its derivatives, systemic hormone replacement therapy, selective estrogen-receptor modulators, or tibolone or calcitonin within 12 months prior to enrollment
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Any prior use of fluoride or strontium
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Systemic glucocorticoids (≥ 5 mg prednisone equivalent per day or cumulative dose ≥ 50 mg) for more than 10 days within 3 months prior to enrollment (topical and inhaled corticosteroids are allowed)
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Other bone active drugs (i.e. drugs affecting bone metabolism) including heparin, anti-epileptics (except for benzodiazepines and pregabalin), systemic ketoconazole, adrenocorticotrophic hormone (ACTH), lithium, protease inhibitors, gonadotropin-releasing hormone (GnRH) agonists, or anabolic steroids within the past 3 months prior to screening
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Known sensitivity to drug products derived from mammalian cell lines
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History of one severe or more than two moderate vertebral fractures per Genant classification as determined by the central reading center
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History of hip fracture or bilateral hip replacement
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Total hip or femoral neck T-score <-4.0
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History and/or presence of atypical femoral fracture
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Presence of any active healing fracture according to the Investigator's assessment
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History of any transplant or chronic immunosuppression (including patients on immunosuppressive therapy)
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Severe liver dysfunction
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Positive testing for hepatitis B (hepatitis B virus surface antigen [HbsAg]) or hepatitis C (hepatitis C virus antibody [HCV Ab]) virology
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Known history of human immunodeficiency virus (HIV) infection or positive serology for HIV at screening
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Significantly impaired renal function or receiving dialysis
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Oral or dental conditions
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Major surgery within 8 weeks prior to screening or anticipated major surgery during the study
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Clinically significant leukopenia, neutropenia, or anemia as determined by the Investigator or any other clinically significant medical condition or laboratory abnormality that, in the opinion of the Investigator, would pose a risk to patient safety or interfere with adherence to study procedures, study completion, or the interpretation of study results
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Patient with an active infection or history of infection
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Suspected signs and symptoms of COVID-19/confirmed COVID-19 or with recent history of travel/contact (less than 2 weeks from screening) with any COVID-19 positive patient/isolation/quarantine
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | MEDICAL PLUS s.r.o. | Uherské Hradiště | Czechia |
Sponsors and Collaborators
- Enzene Biosciences Ltd.
- Alkem Laboratories Ltd
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ALK22/ENZ215-DEN2