Clinical Trial Results:
A Multinational, Randomized, Double-Blind, Active-Controlled Phase 3 Study to Compare the Clinical Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of EB1001 Biosimilar With EU-Licensed Prolia® in Postmenopausal Women With Osteoporosis
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Summary
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EudraCT number |
2021-002187-49 |
Trial protocol |
HU EE BG |
Global end of trial date |
28 Jul 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
06 Apr 2025
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First version publication date |
06 Apr 2025
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
EB-CLIN-1001-03
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Eden Biologics, Inc.
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Sponsor organisation address |
5F. No. 18, Sec 2., Shengyi Rd. Zhubei City, Hsinchu County 302, Zhubei, Taiwan,
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Public contact |
Stephen B. Shrewsbury, Eden Biologics, Inc., +1415 2501169, sshrewsbury@edenbiologics.com
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Scientific contact |
Stephen B. Shrewsbury, Eden Biologics, Inc., +1415 2501169, sshrewsbury@edenbiologics.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
12 Feb 2025
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
28 Jul 2023
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
- To demonstrate the equivalence between EB1001 and EU-licensed Prolia in terms of change in bone marrow density (BMD) at the lumbar spine from baseline to Month 12 in postmenopausal women with osteoporosis.
- To demonstrate the pharmacodynamic similarity between EB1001 and EU-licensed Prolia for the area under the effect curve (AUEC) of s-CTX (serum carboxy-terminal cross-linking telopeptide of type I collagen) from baseline to Month 6 in postmenopausal women with osteoporosis.
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Protection of trial subjects |
The study was conducted accordance with the ethical principles that have their origin in the Declaration of Helsinki, ICH GCP, and all applicable regulations.
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Background therapy |
Calcium and vitamin D were co-administered to prevent low serum calcium level while taking study drugs. All patients were to receive daily supplementation containing 1000 mg of elemental calcium and 400 IU vitamin D from randomization until the EoS visit (Month 12). | ||
Evidence for comparator |
The EU-Licensed Prolia® is used as active comparator. | ||
Actual start date of recruitment |
24 Sep 2021
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Poland: 52
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Country: Number of subjects enrolled |
Estonia: 9
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Worldwide total number of subjects |
61
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EEA total number of subjects |
61
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
19
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From 65 to 84 years |
42
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85 years and over |
0
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Recruitment
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Recruitment details |
A total of 203 patients were screened for the study. Of these, a total of 61 patients were randomly assigned - 29 patients in EB1001 group and 32 in EU-licensed Prolia group. All patients in EB1001 group and 30 patients in EU-licensed Prolia group completed the study treatment. 2 patients in EU-licensed Prolia group discontinued the study treatment | ||||||||||||||||||
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Pre-assignment
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Screening details |
The study comprised of screening evaluations which were to be completed within 28 days prior to randomization. After the screening period, patients were to undergo 12-months treatment period. Eligible patients were to be randomized (1:1) to receive either EB1001(60 mg) or EU-licensed Prolia (60 mg) via SC injection on Day 1 and at Month 6. | ||||||||||||||||||
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Period 1
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Period 1 title |
Treatment period (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer, Assessor | ||||||||||||||||||
Blinding implementation details |
Treatment period was double-blinded.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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EB1001 Group | ||||||||||||||||||
Arm description |
EB1001 60 mg on Day 1 and Month 6 | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
EB1001
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Investigational medicinal product code |
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Other name |
JHL1266
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
EB1001 (60 mg) was administered using a PFS of 60 mg/1 mL solution on Day 1 (Week 0, the same date as randomization) and at Month 6. The EoS visit was to occur at Month 12.
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Arm title
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EU-licensed Prolia Group | ||||||||||||||||||
Arm description |
Prolia 60 mg on Day 1 and Month 6 | ||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||
Investigational medicinal product name |
EU-licensed Prolia
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Investigational medicinal product code |
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Other name |
Denosumab
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
EU-licensed Prolia (60 mg) was administered using a PFS of 60 mg/1 mL solution on Day 1 (Week 0, the same date as randomization) and at Month 6. The EoS visit was to occur at Month 12.
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Baseline characteristics reporting groups
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Reporting group title |
EB1001 Group
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Reporting group description |
EB1001 60 mg on Day 1 and Month 6 | ||||||||||||||||||||||||||||||||||||||||
Reporting group title |
EU-licensed Prolia Group
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Reporting group description |
Prolia 60 mg on Day 1 and Month 6 | ||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
EB1001 Group
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Reporting group description |
EB1001 60 mg on Day 1 and Month 6 | ||
Reporting group title |
EU-licensed Prolia Group
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Reporting group description |
Prolia 60 mg on Day 1 and Month 6 | ||
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End point title |
Primary Efficacy Endpoint: Percent change in BMD at the lumbar spine (L1 to L4) by DXA from baseline to Month 12 [1] | ||||||||||||
End point description |
The "0" in the below table is dummy value - not result.
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End point type |
Primary
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End point timeframe |
Due to the early termination of this study, the primary efficacy endpoint was not evaluated in the study.
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Due to the early termination of this study, the primary efficacy endpoint was not evaluated in the study and, therefore no statistical analyses for this primary end point. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Primary PD Endpoint: The AUEC of s-CTX from Day 1 predose to Month 6 predose [2] | ||||||||||||
End point description |
The "0" in the below table is dummy value - not result.
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End point type |
Primary
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End point timeframe |
Due to the early termination of this study, the primary PD endpoint was not evaluated in the study.
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Due to the early termination of this study, the primary efficacy endpoint was not evaluated in the study and, therefore no statistical analyses for this primary end point. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Safety Endpoints | |||||||||||||||||||||||||||||||||
End point description |
All safety analyses were conducted on the Safety Set (patients received 1 full or partial dose). All summary tables were based on TEAEs. No clinical safety labs, vital signs, ECG, or physical examination endpoints were derived for the final analysis.
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End point type |
Secondary
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End point timeframe |
During study treatment
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||
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End point title |
Local Injection Site Pain (Visual Analogue Scale) | |||||||||||||||||||||
End point description |
Local injection site pain (visual analogue scale) was analysed in the Safety Set (patients received 1 full or partial dose).
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End point type |
Secondary
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End point timeframe |
On Baseline and Day 183
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Adverse events information
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Timeframe for reporting adverse events |
All safety analyses were conducted on the Safety Set during the treatment period. The Safety Set was defined as all randomly assigned patients who receive at least 1 dose (full or partial) of the study drug (EB1001 or EU-licensed Prolia).
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.0
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Reporting groups
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Reporting group title |
EB1001
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Reporting group description |
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Reporting group title |
EU-licensed Prolia
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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24 May 2021 |
Protocol Version 1.0 dated 24 May 2021 - Original protocol |
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22 Jul 2021 |
Protocol Version 2.0 dated 22 Jul 2021 - Amendment 1
The amendment is considered minor because it does not significantly impact the safety or physical/mental integrity of participants. No patients have been enrolled as of the date of this amendment.
Per the recommendations of Committee for Medicinal Products for Human Use (CHMP) regarding the overall study design, a restricted weight range of 50 to 100 kg for study participants is endorsed, as this would increase homogeneity of the participant population. To address this recommendation, inclusion criterion #4 concerning a body weight range has been added in Section 4.1.1 Inclusion Criteria:
''Inserted inclusion criterion #4 “Body weight between 40.0 and 99.9 kg, both inclusive, when rounded to the nearest tenth.” |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
