Clinical trial NCT05405725: 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
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Postmenopausal Osteoporosis
Lead sponsor: Enzene Biosciences Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Alkem Laboratories Ltd
First posted: 2022-06-06
Enrollment: 504
Sex: FEMALE
Minimum age (years): 55
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 360 days
measure: To compare the area under the effect curve (AUEC) of serum C-telopeptide of Type-1 collagen (sCTX) levels
timeFrame: 180 days
Secondary outcomes:
measure: To compare the immunogenicity potential of ENZ215 and Prolia
timeFrame: 540 days
measure: To compare the safety and tolerability of ENZ215 and Prolia
timeFrame: 540 days
measure: To compare the pharmacokinetics of ENZ215 and Prolia
timeFrame: 360 days
measure: To compare the pharmacokinetics of ENZ215 and Prolia
timeFrame: 360 days
measure: To compare the pharmacokinetics of ENZ215 and Prolia
timeFrame: 360 days
measure: To compare the change in serum procollagen type 1 N-terminal propeptide (sP1NP) levels
timeFrame: 180 days
measure: To compare the change in BMD at the lumbar spine
timeFrame: 180 days
measure: To compare the change in BMD at total hip and femoral neck
timeFrame: 360 days
Other outcomes:
Locations:
city: Uherské Hradiště
country: Czechia
facility: MEDICAL PLUS s.r.o.
Study officials:
References: