A Phase 3 Study to Compare Biosimilar Denosumab With Prolia®

Postmenopausal Osteoporosis Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05405725
• Other study ID #: ALK22/ENZ215-DEN2
• Status: Recruiting
• Phase: Phase 3
• Start date: July 4, 2022
• Est. completion date: August 2024

Study information

• Verified date: July 2022
• Source: Enzene Biosciences Ltd.
• Contact: Dr. Harish Shandilya
• Phone: +9102067184202
• Email: harish.shandilya[@]enzene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 504
• Est. completion date: August 2024
• Est. primary completion date: February 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 55 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Osteoporosis
• Osteoporosis, Postmenopausal
• Postmenopausal Osteoporosis

Intervention

Biological:
• ENZ215
Enrolled women with postmenopausal osteoporosis will receive ENZ215 (60mg)
• Prolia
Enrolled women with postmenopausal osteoporosis will receive Prolia

Locations

Country	Name	City	State
Czechia	MEDICAL PLUS s.r.o.	Uherské Hradište

Sponsors (2)

Lead Sponsor	Collaborator
Enzene Biosciences Ltd.	Alkem Laboratories Ltd

Country where clinical trial is conducted

Czechia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	To compare the pharmacokinetics of ENZ215 and Prolia	Cmax of denosumab measured at predefined timepoints.	360 days
Secondary	To compare the pharmacokinetics of ENZ215 and Prolia	Tmax of denosumab measured at predefined timepoints.	360 days
Secondary	To compare the pharmacokinetics of ENZ215 and Prolia	partial AUC of denosumab measured at predefined timepoints.	360 days
Secondary	To compare the change in serum procollagen type 1 N-terminal propeptide (sP1NP) levels		180 days
Secondary	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
Secondary	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