Clinical Trial Results:
A Phase III Randomised, Double-blind, Multicentre Study to Compare the Efficacy, Safety, Pharmacokinetics, and Immunogenicity between SB12 (proposed eculizumab biosimilar) and Soliris® in Subjects with Paroxysmal Nocturnal Haemoglobinuria
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Summary
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EudraCT number |
2018-002857-31 |
Trial protocol |
RO |
Global end of trial date |
21 Oct 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
20 Apr 2024
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First version publication date |
20 Apr 2024
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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 |
SB12-3003
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04058158 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Samsung Bioepis Co., Ltd.
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Sponsor organisation address |
76, Songdogyoyuk-ro, Yeonsu-gu, Incheon, Korea, Republic of, 21987
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Public contact |
Information Desk, Samsung Bioepis Co., Ltd., +82 032 728 0114, bioepisinfo@samsung.com
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Scientific contact |
Information Desk, Samsung Bioepis Co., Ltd., +82 032 728 0114, bioepisinfo@samsung.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 |
21 Oct 2021
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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 |
21 Oct 2021
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of this study is to demonstrate comparable clinical efficacy of SB12 and Soliris®, by evaluating the lactate dehydrogenase (LDH) in subjects with paroxysmal nocturnal haemoglobinuria (PNH).
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Protection of trial subjects |
Subjects should be monitored and documented for at least one hour following completion of the infusion for signs or symptoms of an infusion reaction. If an adverse reaction occurs during the administration of IPs, the infusion may be slowed or stopped at the discretion of the Investigator. If the infusion is slowed, the total infusion time may not exceed 2 hours.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
07 Aug 2019
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Ethical reason | ||
Long term follow-up duration |
2 Years | ||
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 |
India: 6
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Country: Number of subjects enrolled |
Korea, Republic of: 3
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Country: Number of subjects enrolled |
Mexico: 5
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Country: Number of subjects enrolled |
Malaysia: 8
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Country: Number of subjects enrolled |
Romania: 9
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Country: Number of subjects enrolled |
Thailand: 4
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Country: Number of subjects enrolled |
Taiwan: 6
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Country: Number of subjects enrolled |
Ukraine: 9
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Worldwide total number of subjects |
50
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EEA total number of subjects |
9
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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) |
48
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From 65 to 84 years |
2
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85 years and over |
0
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Recruitment
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Recruitment details |
This study was conducted at a total of 24 study centres in 8 countries: 4 centres in India, 1 centre in Republic of Korea, 5 centres in Malaysia, 1 centre in Mexico, 4 centres in Romania, 3 centres in Taiwan, 2 centres in Thailand, and 4 centres in Ukraine. | |||||||||||||||||||||
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Pre-assignment
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Screening details |
Subjects who meet the eligibility criteria were randomly assigned in a 1:1 ratio to treatment sequence I (SB12 to Soliris) or treatment sequence II (Soliris to SB12). | |||||||||||||||||||||
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Period 1
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Period 1 title |
Period 1
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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 | |||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Soliris to SB12 | |||||||||||||||||||||
Arm description |
Subjects randomly assigned to treatment with Soliris received 600 mg of eculizumab intravenous (IV) infusion every week for first 4 weeks (initial phase) and 900 mg for the fifth week, followed by 900 mg every 2 weeks thereafter. Subjects who were randomised to initially receive Soliris were switched to receive SB12 at Week 26. | |||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||
Investigational medicinal product name |
Soliris
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Soliris was administered 600 mg every 7 days for the first 4 weeks and 900 mg for the fifth week, followed by 900 mg every 14 ± 2 days via 25-45 minutes IV infusion until Week 24.
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Arm title
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SB12 to Soliris | |||||||||||||||||||||
Arm description |
Subjects randomly assigned to treatment with SB12 received 600 mg of eculizumab intravenous (IV) infusion every week for first 4 weeks (initial phase) and 900 mg for the fifth week, followed by 900 mg every 2 weeks thereafter. Subjects who were randomised to initially receive SB12 were switched to receive Soliris at Week 26. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
SB12
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
SB12 was administered 600 mg every 7 days for the first 4 weeks and 900 mg for the fifth week, followed by 900 mg every 14 ± 2 days via 25-45 minutes IV infusion until Week 24.
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Period 2
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Period 2 title |
Period 2
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Is this the baseline period? |
No | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer, Assessor | |||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Soliris to SB12 | |||||||||||||||||||||
Arm description |
Subjects randomly assigned to treatment with Soliris received 600 mg of eculizumab intravenous (IV) infusion every week for first 4 weeks (initial phase) and 900 mg for the fifth week, followed by 900 mg every 2 weeks thereafter. Subjects who were randomised to initially receive Soliris were switched to receive SB12 at Week 26. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
SB12
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
SB12 was administered 900 mg every 14 ± 2 days via 25-45 minutes IV infusion until Week 50.
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Arm title
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SB12 to Soliris | |||||||||||||||||||||
Arm description |
Subjects randomly assigned to treatment with SB12 received 600 mg of eculizumab intravenous (IV) infusion every week for first 4 weeks (initial phase) and 900 mg for the fifth week, followed by 900 mg every 2 weeks thereafter. Subjects who were randomised to initially receive SB12 were switched to receive Soliris at Week 26. | |||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||
Investigational medicinal product name |
Soliris
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Soliris was administered 900 mg every 14 ± 2 days via 25-45 minutes IV infusion until Week 50.
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Baseline characteristics reporting groups
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Reporting group title |
Soliris to SB12
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Reporting group description |
Subjects randomly assigned to treatment with Soliris received 600 mg of eculizumab intravenous (IV) infusion every week for first 4 weeks (initial phase) and 900 mg for the fifth week, followed by 900 mg every 2 weeks thereafter. Subjects who were randomised to initially receive Soliris were switched to receive SB12 at Week 26. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
SB12 to Soliris
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Reporting group description |
Subjects randomly assigned to treatment with SB12 received 600 mg of eculizumab intravenous (IV) infusion every week for first 4 weeks (initial phase) and 900 mg for the fifth week, followed by 900 mg every 2 weeks thereafter. Subjects who were randomised to initially receive SB12 were switched to receive Soliris at Week 26. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Soliris to SB12
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Reporting group description |
Subjects randomly assigned to treatment with Soliris received 600 mg of eculizumab intravenous (IV) infusion every week for first 4 weeks (initial phase) and 900 mg for the fifth week, followed by 900 mg every 2 weeks thereafter. Subjects who were randomised to initially receive Soliris were switched to receive SB12 at Week 26. | ||
Reporting group title |
SB12 to Soliris
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Reporting group description |
Subjects randomly assigned to treatment with SB12 received 600 mg of eculizumab intravenous (IV) infusion every week for first 4 weeks (initial phase) and 900 mg for the fifth week, followed by 900 mg every 2 weeks thereafter. Subjects who were randomised to initially receive SB12 were switched to receive Soliris at Week 26. | ||
Reporting group title |
Soliris to SB12
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Reporting group description |
Subjects randomly assigned to treatment with Soliris received 600 mg of eculizumab intravenous (IV) infusion every week for first 4 weeks (initial phase) and 900 mg for the fifth week, followed by 900 mg every 2 weeks thereafter. Subjects who were randomised to initially receive Soliris were switched to receive SB12 at Week 26. | ||
Reporting group title |
SB12 to Soliris
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Reporting group description |
Subjects randomly assigned to treatment with SB12 received 600 mg of eculizumab intravenous (IV) infusion every week for first 4 weeks (initial phase) and 900 mg for the fifth week, followed by 900 mg every 2 weeks thereafter. Subjects who were randomised to initially receive SB12 were switched to receive Soliris at Week 26. | ||
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End point title |
LDH (U/L) at Week 26 | |||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
At Week 26
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Statistical analysis title |
Equivalence test | |||||||||||||||
Comparison groups |
Soliris to SB12 v SB12 to Soliris
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Number of subjects included in analysis |
46
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | |||||||||||||||
Method |
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Parameter type |
Least squares mean difference | |||||||||||||||
Point estimate |
34.48
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Confidence interval |
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level |
95% | |||||||||||||||
sides |
2-sided
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lower limit |
-47.66 | |||||||||||||||
upper limit |
116.62 | |||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events (AEs) were collected from the time of signing the informed consent form until the end of study (EOS).
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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 |
21.0
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Reporting groups
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Reporting group title |
SB12
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Reporting group description |
N for SB12 represents the total number of pooled subjects who had been treated with SB12 in either Periods 1 or 2. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Soliris
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Reporting group description |
N for Soliris represents the total number of pooled subjects who had been treated with Soliris in either Periods 1 or 2. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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08 Oct 2018 |
This amendment considered clarifications on:
•To extend the period from randomization to initiation of study drug taking account of IP shipment
•To change platelet count criteria
•To remove several hematology parameters
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12 Dec 2018 |
This amendment considered clarifications on:
•To add the additional information for SB12 provision (in case of serious hemolysis after completion of study treatment, up to 1 year)
•To add exclusion criteria (to exclude the subjects with history of serious thrombotic events) |
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29 Nov 2019 |
This amendment considered clarifications on:
•To implement the changes due to 2-year extension period (to all patients, up to 2 years)
•To clarify dosing and treatment schedule
•To add several hematology parameters
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21 Aug 2020 |
This amendment considered clarifications on:
•To update study design/process in order to minimize the risk of COVID-19 pandemic
•To add clarification of dosing interval adjustment DSMB feedback
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27 Nov 2020 |
This amendment considered clarifications on:
•To update safety design/process in order to address a special circumstances of a shortage of the comparator
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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 | |||
