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Postmenopausal OsteoporosisPhase 3NCT05405725

A Phase 3 Study to Compare Biosimilar Denosumab With Prolia®

A Phase 3 study testing ENZ215 and Prolia in people with Postmenopausal Osteoporosis, run by Enzene Biosciences Ltd. at 48 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 55 to 85 years, women only
Conditions the study is for
Postmenopausal Osteoporosis
What is being tested?
ENZ215 and Prolia
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
504 participants
Where
48 sitesin 7 countries
Study dates
4 Jul 2022to 18 Jul 2024
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 55 to 85 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
  • Postmenopausal women aged ≥ 65 and < 75 years with LS T-score is ≤ -2.5 and a prior fragility fracture (except for hip fracture), including non-exclusionary vertebral fractures
  • 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
Show all 10Show fewer
  • 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

Who cannot join

  • 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
Show all 48Show fewer
  • 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.
  • Use of parathyroid hormone or its derivatives, hormone replacement therapy, romosozumab, selective estrogen-receptor modulators, or tibolone or calcitonin within 12 months prior to enrollment Note: occasional use of intravaginal estrogen treatment is not exclusionary
  • 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
  • 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 (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] > 3 times upper limit of normal)
  • 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 (determined by glomerular filtration rate of < 45 mL/min/1.73 m2 by the Modification of Diet in Renal Disease (MDRD) formula, as calculated by the central laboratory) or receiving dialysis
  • Oral or dental conditions:
  • Osteomyelitis or history and/or presence of osteonecrosis of the jaw (ONJ)
  • Presence of risk factors for ONJ (e.g., periodontal disease, poorly fitting dentures, poor oral hygiene, invasive dental procedures such as tooth extractions within 6 months prior to screening)
  • Active dental or jaw condition which requires oral surgery
  • Planned invasive dental procedure
  • 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 Note: In case of an abnormal laboratory result which in the opinion of the investigator may be an error, is borderline, or indeterminate for inclusion in the study, the investigator may consider repeating the test once in order to rule out laboratory error.
  • Patient with an active infection or history of infection as follows:
  • Any active infection for which systemic anti-infectives were used within 4 weeks prior to randomization
  • A serious infection defined as requiring hospitalization or intravenous anti infectives within 8 weeks prior to randomization
  • Recurrent or chronic infections or other active infection that, in the opinion of the Investigator, might compromise the safety of the patient
  • Evidence of any of the following conditions per laboratory test results, medical history, electrocardiogram (ECG), DXA, or X-ray review:
  • Uncontrolled hyperthyroidism or hypothyroidism Note: Clinical significance of abnormal TSH values in patients on stable replacement therapy due to hypothyroidism or on anti-thyroid medication should be assessed and discussed with the Medical Monitor.
  • History or current hyperparathyroidism or hypoparathyroidism (intact parathyroid hormone levels not within normal range) Note: Mild secondary hyperparathyroidism in the context of vitamin D deficiency may be acceptable upon discussion with the Medical Monitor.
  • Vitamin D deficiency defined as 25 (OH) vitamin D level < 20 ng/mL (< 50 nmol/L) Note: Patients can be enrolled if a repeat test (post supplementation) prior to enrollment shows corrected 25 (OH) vitamin D level ≥ 20 ng/mL (≥ 50 nmol/L).
  • Current hypocalcemia (albumin-adjusted serum calcium < 8.0 mg/dL [< 2.0 mmol/L]) or hypercalcemia (albumin-adjusted serum calcium > 10.6 mg/dL [> 2.62 mmol/L])
  • History of parathyroid surgery
  • Any bone or metabolic disease which may affect BMD or interfere with the interpretation of the findings, e.g., osteomalacia, osteogenesis imperfecta, osteopetrosis, achondroplasia, Paget's disease, rheumatoid arthritis, ankylosing spondylitis, Cushing's disease, hyperprolactinemia, or malabsorption syndrome
  • Any malignancy, including solid tumors, and hematologic malignancies (except basal cell carcinoma and squamous cell carcinomas of the skin, cervical, or breast ductal carcinoma in situ, that have been completely excised and are considered cured) within the last 5 years
  • Known or suspected history of alcoholism (including heavy drinking defined as consuming more than 3 drinks on one day or more than 7 drinks per week) or substance abuse within the past 12 months prior to the first dosing that the Investigator believes would interfere with understanding or completing the study
  • Current heavy smoking, defined as smoking 20 or more cigarettes per day.
  • Participated in any other clinical study in last 30 days prior to screening
  • History and/or presence of significant cardiac disease as per Investigator's discretion, including but not restricted to:
  • History of cardiac arrhythmia or long QT syndrome or ECG abnormalities at screening indicating significant risk for safety (e.g., that required hospitalization, emergency cardioversion, or defibrillation) ii. History and/or presence of myocardial infarction within 6 months before screening iii. History and/or presence of New York Heart Association (NYHA) class III or IV heart failure
  • 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

Trial locations and contacts

48 sites in 7 countries.

48 sites in 7 countries

Poland23 sites

  • Osteo-Medic S.C. A Racewicz

    Bialystok

  • Szpital Uniwersytecki

    Bydgoszcz

  • Centrum Medyczne Pratia Czestochowa

    Częstochowa

  • Synexus Polska

    Częstochowa

  • Synexus Polska

    Gdansk

  • Centrum Medyczne Pratia Gdynia

    Gdynia

  • Synexus Polska

    Gdynia

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

    Katowice

  • Synexus Polska

    Katowice

  • ETG Kielce, ul. Zagorska

    Kielce

  • Krakowskie Centrum Medyczne

    Krakow

  • ETG Lodz, ul. Pilota Stanislawa Wigury

    Lodz

  • Synexus Polska

    Lodz

  • ETG Lublin, ul. Kunickiego

    Lublin

  • Twoja Przychodnia Nowosolskie Centrum Medyczne,

    Nowa Sól

  • Prywatna Praktyka Lekarska

    Poznan

  • Synexus Polska

    Poznan

  • Twoja Przychodnia PCM

    Poznan

  • ETG Siedlce

    Siedlce

  • Twoja Przychodnia - Szczecinskie Centrum Medyczne

    Szczecin

  • Synexus Polska

    Warsaw

  • Synexus Polska

    Wroclaw

  • Centrum Medyczne Kuba- Med

    Zamość

Other trials in Poland

Czechia8 sites

  • Research Center

    Brno, 60200

  • G-CENTRUM Olomouc

    Horní Město

  • Research Center

    Pardubice

  • University Hospital.

    Pilsen

  • Synexus Czech

    Prague, 12000

  • Clinic

    Prague, 14800

  • Fakultni nemocnice v Motole

    Prague

  • MEDICAL PLUS s.r.o.

    Uherské Hradiště

Other trials in Czechia

Lithuania7 sites

  • JSC Saules seimos medicinos ce

    Kaunas, 49449

  • Hospital of Lithuanian University of Health Sciences Kauno klinikos

    Kaunas, 50161

  • Kaunas City Polyclinic

    Kaunas, 51270

  • Lithuanian University of Health Sciences Hospital

    Kaunas

  • Republican Siauliai Hospital

    Šiauliai

  • Vilnius University Hospital Santaros Klinikos

    Vilnius, 08661

  • National Osteoporosis Center

    Vilnius, 09310

Other trials in Lithuania

Bulgaria4 sites

  • University Hospital

    Plovdiv, 4027

  • Medical Center Teodora,

    Rousse, 7000

  • DCC XVII-Sofia EOOD

    Sofia, 1505

  • Research Center(Medical Center Synexus Sofia EOOD)

    Sofia, 1784

Other trials in Bulgaria

Serbia4 sites

  • Institute for Rheumatology

    Belgrade

  • Zvezdara University Medical Center

    Belgrade

  • Institute for Treatment and Rehabilitation Niska Banja

    Niška Banja

  • Clinical Hospital Centre Bezanijska Kosa

    Zemun

Other trials in Serbia

Denmark1 site

  • Sydvestjysk Sygehus Esbjerg

    Esbjerg, 6700

Other trials in Denmark

Spain1 site

  • Hospital de La Santa Creu i Sant Pau

    Barcelona

Other trials in Spain

About this study

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

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. 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. To compare the AUEC of sCTX levels from baseline to Month 6
Read the detailed description

The study will be divided into three periods: Screening period: up to 35 days; Double-blind treatment period of 12 months; and Open-label, switch-over period of six months.

Five hundred four (504) patients (252 patients in each treatment arm) will be enrolled in this study. All eligible patients will be randomized in the double blind treatment period in a 1:1 ratio to receive either ENZ215 or Prolia® (60 mg) subcutaneously (SC) on Day 1 and Month 6. These participants will complete study at 12 months. A PK sub-study will be conducted in a subset of 120 participants with 60 participants in each arm.

A subset of 120 participants randomised to Prolia arm and who completed 12 months of the double-blind treatment period without any significant safety concerns per the Investigator's discretion will be offered to enroll in the open-label, switch-over extension period. After re-consenting for the open-label, switch-over study, the participants will be re-randomised in a 1:1 ratio to receive either ENZ215 or Prolia® (60 mg) SC at Month 12. These participants will complete the study at Month 18.

Being tested
ENZ215, Prolia
Medical subject headings
Osteoporosis, Postmenopausal

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ENZ215Biological

    Enrolled women with postmenopausal osteoporosis receive ENZ215 (60mg)

  • ProliaBiological

    Enrolled women with postmenopausal osteoporosis receive Prolia

Study groups in NCT05405725
Study groupRoleWhat they receive
ENZ215ExperimentalENZ215 Injection: - 60 mg denosumab administered as a single subcutaneous injection at day 1 and at month 6
Receives: Biological: ENZ215
ProliaActive comparatorProlia Injection: - 60 mg denosumab administered as a single subcutaneous injection at day 1 and at month 6
Receives: Biological: Prolia

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Month 12

  2. 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

    Measured: Month 6

Secondary outcomes (5)

  1. To Compare the Immunogenicity Potential of ENZ215 and Prolia

    ADAs incidence such as ADA positive, ADA negative, NAB positive, NAB negative assessed at baseline and different timepoints from 1 month to 12 months and during open-label switch over period assessed. Subjects were considered as post-treatment ADA and NAb positive if they had at least one "Positive" ADA and NAb result after the first drug exposure. Post-treatment ADA and NAb status was determined regardless of the results at pre-dose.

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

  2. To Compare the Pharmacokinetics of ENZ215 and Prolia

    Comparison of PK parameters of ENZ215 and Prolia over 12 months

    Measured: 12 months

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

    Percent change from baseline in type 1 N-terminal propeptide (sP1NP) levels at 6 months

    Measured: Month 6

  4. To Compare the Change in BMD at the Lumbar Spine at Month 6

    Percentage change in BMD at lumbar spine measured by DXA from baseline at month 6

    Measured: Baseline to Month 6

  5. 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

    Measured: Baseline to Month 6 and Month 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Jun 2022
  2. Study start4 Jul 2022
  3. Primary completion18 Jul 2024
  4. Study completion18 Jul 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
The study is having two periods, in first period its parallel assignment, second period is switch over design.
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
504 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05405725
Sponsor's protocol ID
ALK22/ENZ215-DEN2
Other IDs
2021-004811-26
Status last verified
Jan 2026
First submitted
12 May 2022
Last updated
10 Feb 2026
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing ENZ215 and Prolia in people with Postmenopausal Osteoporosis, run by Enzene Biosciences Ltd. at 48 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 48 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 48 sites in Poland, Czechia, Lithuania, Bulgaria, Serbia and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Feb 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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. (time frame: Month 12). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05405725.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2026.

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