A Phase 3 Study to Compare Biosimilar Denosumab With Prolia®

Study Overview
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Brief Summary
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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

Official Title
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A 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

Conditions
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Postmenopausal Osteoporosis

Intervention / Treatment
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* Biological: ENZ215
* Biological: Prolia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing to provide voluntary written informed consent and able to comply with the protocol requirements Postmenopausal women aged ≥ 55 and ≤ 85 years Body weight ≥ 50 kg and ≤ 90 kg Diagnosed with osteoporosis, with absolute BMD at the lumbar spine (L1-L4 region) as measured by dual-energy X ray absorptiometry (DXA) at screening 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 No other clinically significant medical history, vital signs, physical examination, laboratory profiles as deemed by the Investigator or designee Exclusion Criteria: Known hypersensitivity to denosumab or any of the excipients of the study drug Known intolerance to, or malabsorption of calcium or vitamin D supplements Previous exposure to Prolia® or any other denosumab biosimilar Previous use of oral bisphosphonates Use of intravenous bisphosphonates within the past 5 years prior to screening 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 Any prior use of fluoride or strontium 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) 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 Known sensitivity to drug products derived from mammalian cell lines History of one severe or more than two moderate vertebral fractures per Genant classification as determined by the central reading center History of hip fracture or bilateral hip replacement Total hip or femoral neck T-score <-4.0 History and/or presence of atypical femoral fracture Presence of any active healing fracture according to the Investigator's assessment History of any transplant or chronic immunosuppression (including patients on immunosuppressive therapy) Severe liver dysfunction Positive testing for hepatitis B (hepatitis B virus surface antigen [HbsAg]) or hepatitis C (hepatitis C virus antibody [HCV Ab]) virology Known history of human immunodeficiency virus (HIV) infection or positive serology for HIV at screening Significantly impaired renal function or receiving dialysis Oral or dental conditions Major surgery within 8 weeks prior to screening or anticipated major surgery during the study 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 Patient with an active infection or history of infection 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

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ENZ215<br>ENZ215 Injection:- 60 mg Denosumab (ENZ215) will be administered subcutaneously on day 1. | Biological: ENZ215<br>* Enrolled women with postmenopausal osteoporosis will receive ENZ215 (60mg)<br>|
| Active Comparator: Prolia<br>Prolia Injection:- 60 mg Denosumab (Prolia) will be administered subcutaneously on day 1. | Biological: Prolia<br>* Enrolled women with postmenopausal osteoporosis will receive Prolia<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Percentage change in BMD at lumbar spine (L1-L4 region) measured by dual-energy X-ray absorptiometry (DXA) | 360 days | 
| To compare the area under the effect curve (AUEC) of serum C-telopeptide of Type-1 collagen (sCTX) levels | AUEC of sCTX over the initial 6 months (from Day 1 pre-dose to Month 6 pre-dose) will be assessed. | 180 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the immunogenicity potential of ENZ215 and Prolia | ADAs incidence at baseline and different timepoints from 1 month to 12 months and during open-label switch over period will be assessed. | 540 days | 
| To compare the safety and tolerability of ENZ215 and Prolia | Treatment-emergent serious and non-serious adverse events (TEAEs) during main treatment period and open-label switch-over period will be assessed | 540 days | 
| To compare the pharmacokinetics of ENZ215 and Prolia | Cmax of denosumab measured at predefined timepoints. | 360 days | 
| To compare the pharmacokinetics of ENZ215 and Prolia | Tmax of denosumab measured at predefined timepoints. | 360 days | 
| To compare the pharmacokinetics of ENZ215 and Prolia | partial AUC of denosumab measured at predefined timepoints. | 360 days | 
| 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 | Percentage change in BMD at lumbar spine measured by DXA from baseline to predefined timepoint | 180 days | 
| To compare the change in BMD at total hip and femoral neck | Percentage change in BMD at total hip and femoral neck measured by DXA from baseline to Month to predefined timepoint | 360 days |