A Phase 3 Study to Compare Biosimilar Denosumab With Prolia®

NCT05405725 | Completed Phase 3 Results DMC

• 2 other identifiers: ALK22/ENZ215-DEN22021-004811-26
• Study Type: interventional
• Target: 504
• Locations: 7 countries
• Sites: 48

Brief Summary

The Study will be conducted to Compare the Efficacy, Safety, Pharmacodynamics, Pharmacokinetics, and Immunogenicity of Enzene Denosumab (ENZ215) and Prolia® in Postmenopausal Women with Osteoporosis. The primary goal for the study is

1. 1.To evaluate the efficacy of ENZ215 when compared to Prolia® in patients with postmenopausal osteoporosis, in terms of change in BMD at the lumbar spine from baseline to Month 12 and
2. 2.To compare the AUEC of sCTX levels from baseline to Month 6

Conditions

Postmenopausal Osteoporosis

Outcome Measures

Primary Outcomes (2)

• 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.

  The percentage change in BMD at lumbar spine (L1-L4 region) measured by DXA from baseline to month 12 and the mean (±SD) percentage change over time is displayed for the ITT set. The ITT analysis set consisted of all randomised participants who received at least one dose of study intervention in the double-blind treatment period. In the ITT analysis set, treatment was assigned based on the study intervention to which participants were randomised, regardless of which treatment they actually received.

  Month 12

• Area Under the Effect Curve (AUEC) of % Change From Baseline (%CfB) of Serum C-telopeptide of Type-1 Collagen (sCTX) Levels

  The AUEC of %CfB in sCTX of ENZ215 was assessed as part of pharmacodynamics assessment to compare with Prolia® in female participants with postmenopausal osteoporosis. This outcome measure was assessed for initial 6 months

  Month 6

Secondary Outcomes (5)

• To Compare the Immunogenicity Potential of ENZ215 and Prolia

  From Baseline to Month 12 for Double blind treatment period and to month 18 for Open label switchover treatment period

• To Compare the Pharmacokinetics of ENZ215 and Prolia

  12 months

• Serum Procollagen Type 1 N-terminal Propeptide (sP1NP) Levels

  Month 6

• To Compare the Change in BMD at the Lumbar Spine at Month 6

  Baseline to Month 6

• To Compare the Change in BMD at Total Hip and Femoral Neck

  Baseline to Month 6 and Month 12

Study Arms (2)

ENZ215

EXPERIMENTAL

ENZ215 Injection: - 60 mg denosumab administered as a single subcutaneous injection at day 1 and at month 6

Biological: ENZ215

Prolia

ACTIVE COMPARATOR

Prolia Injection: - 60 mg denosumab administered as a single subcutaneous injection at day 1 and at month 6

Biological: Prolia

Interventions

ENZ215 BIOLOGICAL

Enrolled women with postmenopausal osteoporosis receive ENZ215 (60mg)

ENZ215

Prolia BIOLOGICAL

Enrolled women with postmenopausal osteoporosis receive Prolia

Prolia

Eligibility Criteria

• Age: 55 Years - 85 Years
• Gender Eligibility Details: Female Patients with postmenopausal osteoporosis
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing to provide voluntary written informed consent and able to comply with the protocol requirements
• Postmenopausal women aged ≥ 55 and ≤ 85 years globally, except for Spain. In Spain specifically refer to the below criteria:
• Postmenopausal women aged ≥ 75 and ≤ 85 years with LS T-score ≤ -2.5 or
• In both cases (i.e. criteria a and b), it must also be that these are women who present a contraindication for the use of bisphosphonates or who do not tolerate the oral route.
• Body weight ≥ 50 kg and ≤ 90 kg
• Diagnosed with osteoporosis, with absolute BMD consistent with T-scores of ≤ 2.5 and ≥ - 4.0 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 that would pose a risk to participant safety or interfere with the study evaluation, procedures or completion

You may not qualify if:

• 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:
• Used for 3 or more years cumulatively
• If used for \< 3 years, use within the past 12 months prior to screening
• Use of intravenous bisphosphonates within the past 5 years prior to screening. If used more than 5 years prior, patients will be excluded if cumulative use was \> 3 years.
• 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), antidepressants such as SSRIs, SNRIs, antipsychotics, systemic ketoconazole, adrenocorticotrophic hormone (ACTH), lithium, protease inhibitors, gonadotropin releasing hormone (GnRH) agonists, or anabolic steroids within the past 3 months prior to screening or requiring treatment with these agents during the study.
• Note: Please refer to Section 6.11 for a comprehensive list of prohibited medications
• Known sensitivity to drug products derived from mammalian cell lines such as hormones, enzymes, cytokines, bone morphogenic proteins, clotting factors, antibodies, and fusion protein therapeutics. Patients with any known hypersensitivity to complex proteins such as monoclonal antibodies will be excluded.
• 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

Sponsors & Collaborators

• Enzene Biosciences Ltd.: lead
• Alkem Laboratories Ltd: collaborator

Study Sites (48)

University Hospital

Plovdiv, 4027, Bulgaria

Location

Medical Center Teodora,

Rousse, 7000, Bulgaria

Location

DCC XVII-Sofia EOOD

Sofia, 1505, Bulgaria

Location

Research Center(Medical Center Synexus Sofia EOOD)

Sofia, 1784, Bulgaria

Location

Research Center

Brno, 60200, Czechia

Location

G-CENTRUM Olomouc

Horní Město, Czechia

Location

Research Center

Pardubice, Czechia

Location

University Hospital.

Pilsen, Czechia

Location

Synexus Czech

Prague, 12000, Czechia

Location

Clinic

Prague, 14800, Czechia

Location

Fakultni nemocnice v Motole

Prague, Czechia

Location

MEDICAL PLUS s.r.o.

Uherské Hradiště, Czechia

Location

Sydvestjysk Sygehus Esbjerg

Esbjerg, 6700, Denmark

Location

JSC Saules seimos medicinos ce

Kaunas, 49449, Lithuania

Location

Hospital of Lithuanian University of Health Sciences Kauno klinikos

Kaunas, 50161, Lithuania

Location

Kaunas City Polyclinic

Kaunas, 51270, Lithuania

Location

Lithuanian University of Health Sciences Hospital

Kaunas, Lithuania

Location

Republican Siauliai Hospital

Šiauliai, Lithuania

Location

Vilnius University Hospital Santaros Klinikos

Vilnius, 08661, Lithuania

Location

National Osteoporosis Center

Vilnius, 09310, Lithuania

Location

Osteo-Medic S.C. A Racewicz

Bialystok, Poland

Location

Szpital Uniwersytecki

Bydgoszcz, Poland

Location

Centrum Medyczne Pratia Czestochowa

Częstochowa, Poland

Location

Synexus Polska

Częstochowa, Poland

Location

Synexus Polska

Gdansk, Poland

Location

Centrum Medyczne Pratia Gdynia

Gdynia, Poland

Location

Synexus Polska

Gdynia, Poland

Location

Silmedic sp. z o.o.,ul. Gen. Wladyslawa Sikorskiego

Katowice, Poland

Location

Synexus Polska

Katowice, Poland

Location

ETG Kielce, ul. Zagorska

Kielce, Poland

Location

Krakowskie Centrum Medyczne

Krakow, Poland

Location

ETG Lodz, ul. Pilota Stanislawa Wigury

Lodz, Poland

Location

Synexus Polska

Lodz, Poland

Location

ETG Lublin, ul. Kunickiego

Lublin, Poland

Location

Twoja Przychodnia Nowosolskie Centrum Medyczne,

Nowa Sól, Poland

Location

Prywatna Praktyka Lekarska

Poznan, Poland

Location

Synexus Polska

Poznan, Poland

Location

Twoja Przychodnia PCM

Poznan, Poland

Location

ETG Siedlce

Siedlce, Poland

Location

Twoja Przychodnia - Szczecinskie Centrum Medyczne

Szczecin, Poland

Location

Synexus Polska

Warsaw, Poland

Location

Synexus Polska

Wroclaw, Poland

Location

Centrum Medyczne Kuba- Med

Zamość, Poland

Location

Institute for Rheumatology

Belgrade, Serbia

Location

Zvezdara University Medical Center

Belgrade, Serbia

Location

Institute for Treatment and Rehabilitation Niska Banja

Niška Banja, Serbia

Location

Clinical Hospital Centre Bezanijska Kosa

Zemun, Serbia

Location

Hospital de La Santa Creu i Sant Pau

Barcelona, Spain

Location

MeSH Terms

Conditions

Osteoporosis, Postmenopausal

Interventions

Denosumab

Condition Hierarchy (Ancestors)

Osteoporosis; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Akhilesh Sharma
• Organization: Alkem Laboratories Limited

akhilesh.sharma@alkem.com

+91- 9701346369

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The study is having two periods, in first period its double-blind treatment period for 12 months, second period is open label switchover period
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study is having two periods, in first period its parallel assignment, second period is switch over design.

Study Record Dates

• First Submitted: May 12, 2022
• First Posted: June 6, 2022
• Study Start: July 4, 2022
• Primary Completion: July 18, 2024
• Study Completion: July 18, 2024
• Last Updated: February 10, 2026
• Results First Posted: February 10, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1); SE (4); BU (4); LI (7); DK (1); PL (23); CZ (8)