A Phase 3 Study to Compare Biosimilar Denosumab With Prolia®
Primary Purpose
Postmenopausal Osteoporosis
Status
Recruiting
Phase
Phase 3
Locations
Czechia
Study Type
Interventional
Intervention
ENZ215
Prolia
Sponsored by
About this trial
This is an interventional treatment trial for Postmenopausal Osteoporosis
Eligibility Criteria
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
Sites / Locations
- MEDICAL PLUS s.r.o.Recruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
ENZ215
Prolia
Arm Description
ENZ215 Injection:- 60 mg Denosumab (ENZ215) will be administered subcutaneously on day 1.
Prolia Injection:- 60 mg Denosumab (Prolia) will be administered subcutaneously on day 1.
Outcomes
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
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
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
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
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
Cmax of denosumab measured at predefined timepoints.
To compare the pharmacokinetics of ENZ215 and Prolia
Tmax of denosumab measured at predefined timepoints.
To compare the pharmacokinetics of ENZ215 and Prolia
partial AUC of denosumab measured at predefined timepoints.
To compare the change in serum procollagen type 1 N-terminal propeptide (sP1NP) levels
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
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
Full Information
NCT ID
NCT05405725
First Posted
May 12, 2022
Last Updated
July 30, 2022
Sponsor
Enzene Biosciences Ltd.
Collaborators
Alkem Laboratories Ltd
1. Study Identification
Unique Protocol Identification Number
NCT05405725
Brief Title
A Phase 3 Study to Compare Biosimilar Denosumab With Prolia®
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Recruiting
Study Start Date
July 4, 2022 (Actual)
Primary Completion Date
February 2024 (Anticipated)
Study Completion Date
August 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Enzene Biosciences Ltd.
Collaborators
Alkem Laboratories Ltd
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Postmenopausal Osteoporosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
504 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
ENZ215
Arm Type
Experimental
Arm Description
ENZ215 Injection:- 60 mg Denosumab (ENZ215) will be administered subcutaneously on day 1.
Arm Title
Prolia
Arm Type
Active Comparator
Arm Description
Prolia Injection:- 60 mg Denosumab (Prolia) will be administered subcutaneously on day 1.
Intervention Type
Biological
Intervention Name(s)
ENZ215
Intervention Description
Enrolled women with postmenopausal osteoporosis will receive ENZ215 (60mg)
Intervention Type
Biological
Intervention Name(s)
Prolia
Intervention Description
Enrolled women with postmenopausal osteoporosis will receive Prolia
Primary Outcome Measure Information:
Title
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
Description
Percentage change in BMD at lumbar spine (L1-L4 region) measured by dual-energy X-ray absorptiometry (DXA)
Time Frame
360 days
Title
To compare the area under the effect curve (AUEC) of serum C-telopeptide of Type-1 collagen (sCTX) levels
Description
AUEC of sCTX over the initial 6 months (from Day 1 pre-dose to Month 6 pre-dose) will be assessed.
Time Frame
180 days
Secondary Outcome Measure Information:
Title
To compare the immunogenicity potential of ENZ215 and Prolia
Description
ADAs incidence at baseline and different timepoints from 1 month to 12 months and during open-label switch over period will be assessed.
Time Frame
540 days
Title
To compare the safety and tolerability of ENZ215 and Prolia
Description
Treatment-emergent serious and non-serious adverse events (TEAEs) during main treatment period and open-label switch-over period will be assessed
Time Frame
540 days
Title
To compare the pharmacokinetics of ENZ215 and Prolia
Description
Cmax of denosumab measured at predefined timepoints.
Time Frame
360 days
Title
To compare the pharmacokinetics of ENZ215 and Prolia
Description
Tmax of denosumab measured at predefined timepoints.
Time Frame
360 days
Title
To compare the pharmacokinetics of ENZ215 and Prolia
Description
partial AUC of denosumab measured at predefined timepoints.
Time Frame
360 days
Title
To compare the change in serum procollagen type 1 N-terminal propeptide (sP1NP) levels
Time Frame
180 days
Title
To compare the change in BMD at the lumbar spine
Description
Percentage change in BMD at lumbar spine measured by DXA from baseline to predefined timepoint
Time Frame
180 days
Title
To compare the change in BMD at total hip and femoral neck
Description
Percentage change in BMD at total hip and femoral neck measured by DXA from baseline to Month to predefined timepoint
Time Frame
360 days
10. Eligibility
Sex
Female
Gender Based
Yes
Gender Eligibility Description
Patients with postmenopausal osteoporosis is required for the study
Minimum Age & Unit of Time
55 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Dr. Harish Shandilya
Phone
+9102067184202
Ext
4202
Email
harish.shandilya@enzene.com
Facility Information:
Facility Name
MEDICAL PLUS s.r.o.
City
Uherské Hradiště
Country
Czechia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eva Dokoupilova
12. IPD Sharing Statement
Learn more about this trial
A Phase 3 Study to Compare Biosimilar Denosumab With Prolia®
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