A Phase 3 Study to Compare Biosimilar Denosumab With Prolia®

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

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

Study Overview

• Status: Recruiting
• Conditions: Postmenopausal Osteoporosis
• Intervention / Treatment: Biological: ENZ215; Biological: Prolia

• Study Type: Interventional
• Enrollment (Anticipated): 504
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Dr. Harish Shandilya; Phone Number: 4202 +9102067184202; Email: harish.shandilya@enzene.com

Study Locations

• Czechia
  • Uherské Hradiště, Czechia
    • Recruiting
    • Medical Plus S.R.O.
    • Contact: Eva Dokoupilova

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Willing to provide voluntary written informed consent and able to comply with the protocol requirements
2. Postmenopausal women aged ≥ 55 and ≤ 85 years
3. Body weight ≥ 50 kg and ≤ 90 kg
4. Diagnosed with osteoporosis, with absolute BMD at the lumbar spine (L1-L4 region) as measured by dual-energy X ray absorptiometry (DXA) at screening
5. At least 5 years of postmenopausal status confirmed by follicle-stimulating hormone (FSH) levels at screening
6. At least one hip joint and two vertebrae in L1-L4 region evaluable by DXA
7. No other clinically significant medical history, vital signs, physical examination, laboratory profiles as deemed by the Investigator or designee

Exclusion Criteria:

1. Known hypersensitivity to denosumab or any of the excipients of the study drug
2. Known intolerance to, or malabsorption of calcium or vitamin D supplements
3. Previous exposure to Prolia® or any other denosumab biosimilar
4. Previous use of oral bisphosphonates
5. Use of intravenous bisphosphonates within the past 5 years prior to screening
6. 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
7. Any prior use of fluoride or strontium
8. 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)
9. 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
10. Known sensitivity to drug products derived from mammalian cell lines
11. History of one severe or more than two moderate vertebral fractures per Genant classification as determined by the central reading center
12. History of hip fracture or bilateral hip replacement
13. Total hip or femoral neck T-score <-4.0
14. History and/or presence of atypical femoral fracture
15. Presence of any active healing fracture according to the Investigator's assessment
16. History of any transplant or chronic immunosuppression (including patients on immunosuppressive therapy)
17. Severe liver dysfunction
18. Positive testing for hepatitis B (hepatitis B virus surface antigen [HbsAg]) or hepatitis C (hepatitis C virus antibody [HCV Ab]) virology
19. Known history of human immunodeficiency virus (HIV) infection or positive serology for HIV at screening
20. Significantly impaired renal function or receiving dialysis
21. Oral or dental conditions
22. Major surgery within 8 weeks prior to screening or anticipated major surgery during the study
23. 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
24. Patient with an active infection or history of infection
25. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Enzene Biosciences Ltd.
• Collaborators: Alkem Laboratories Ltd

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 4, 2022
• Primary Completion (ANTICIPATED): February 1, 2024
• Study Completion (ANTICIPATED): August 1, 2024

Study Registration Dates

• First Submitted: May 12, 2022
• First Submitted That Met QC Criteria: June 2, 2022
• First Posted (ACTUAL): June 6, 2022

Study Record Updates

• Last Update Posted (ACTUAL): August 2, 2022
• Last Update Submitted That Met QC Criteria: July 30, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Osteoporosis; Osteoporosis, Postmenopausal; Physiological Effects of Drugs; Bone Density Conservation Agents; Denosumab
• Other Study ID Numbers: ALK22/ENZ215-DEN2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No