Clinical Trial Results:
Multicenter, Double-Blind, Randomized, Comparative Efficacy and Safety Study of MYL 1401H and European Sourced Neulasta® in Stage II/III Breast Cancer Patients Receiving Neoadjuvant or Adjuvant Chemotherapy
Summary
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EudraCT number |
2014-002324-27 |
Trial protocol |
HU DE BG PL |
Global end of trial date |
09 Feb 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
12 Jan 2024
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First version publication date |
12 Jan 2024
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Other versions |
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 |
MYL-1401H-3001
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Mylan GmbH
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Sponsor organisation address |
Thurgauerstrasse 40, 8050 Zürich, Switzerland, Switzerland, 8010
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Public contact |
Eduardo J. Pennella, Mylan GmbH, 724 514-2369, Eduardo.Pennella@mylan.com
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Scientific contact |
Eduardo J. Pennella, Mylan GmbH, 724 514-2369, Eduardo.Pennella@mylan.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 |
15 Sep 2016
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
09 Feb 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
09 Feb 2016
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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 the study is to compare the efficacy of MYL-1401H versus Neulasta® for the prophylactic treatment of chemotherapy-induced neutropenia in patients with stage II/III breast cancer receiving TAC anti-cancer chemotherapy.
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Protection of trial subjects |
Informed consent was obtained before a patient was enrolled in the study and prior to the
commencement of any protocol-driven activities. The investigator (or designated staff member)
met with the patient and explained the study in sufficient detail to permit an informed decision to
participate. The investigator (or designated staff member), patient, and a witness signed an ICF.
The original signed and dated ICF for each patient was kept with the patient’s chart, and a copy
was provided to the patient.
The ICF was written in compliance with ICH guidelines and other national regulations as
appropriate.
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Background therapy |
- | ||
Evidence for comparator |
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Actual start date of recruitment |
05 Jan 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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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 |
Bulgaria: 15
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Country: Number of subjects enrolled |
Georgia: 56
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Country: Number of subjects enrolled |
Hungary: 13
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Country: Number of subjects enrolled |
Ukraine: 110
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Worldwide total number of subjects |
194
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EEA total number of subjects |
28
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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) |
194
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
This was a multicenter, randomized, double-blind, parallel-group study with 2 treatment arms. Patients underwent 6 chemotherapy cycles planned every 3 weeks (Cycle 1 through Cycle 6), each cycle beginning on Day 1, when the chemotherapy dose was administered, with the administration of either MYL-1401H or EU-Neulasta® on Day 2 of each cycle. | ||||||||||||||
Pre-assignment
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Screening details |
The planned duration for the entire study was approximately 28 weeks (from Screening to follow-up [24 weeks from the first dose of study drug]), assuming no delays in dosing. The planned duration of patient treatment during the entire study was approximately 18 weeks (from the first day of chemotherapy [Day 1 Cycle 1] to the last scheduled asses | ||||||||||||||
Period 1
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Period 1 title |
Test product- MYL-1401H
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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 | ||||||||||||||
Blinding implementation details |
The oncology pharmacist who prepared the doses and the person administering the drug (eg,
study nurse, physician [other than the principal investigator or sub-principal investigator]) were
the only individuals who had access or knowledge of the actual drug delivered.
Other unblinded personnel in the study included the clinical research associate (CRA) who
audited the drug dispensation log and drug accountability. There were 2 CRAs assigned to each
site: with the CRA monitoring the study
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Arms
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Arm title
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Test arm | ||||||||||||||
Arm description |
- | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
Test Product
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Investigational medicinal product code |
MYL-1401H
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Test Product, Dose, Mode of Administration, and Batch Number: MYL-1401H 6 mg injection administered
as a single sc dose, on Day 2 of each cycle, ie, 24 h (+ 2 h after) after the end of chemotherapy. Each prefilled
syringe (PFS) contained 6 mg of MYL-1401H in 0.6 mL solution for injection. The concentration was 10 mg/mL
based on protein only. Batch S14DBPEGI-0003 of MYL-1401H was used.
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Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: Number of Patients (Planned and Analyzed): Planned: Approximately 189 patients were planned for enrolment into the study in a 2:1 ratio of the 2 treatment groups (126:63 in the MYL-1401H and EU-Neulasta® arm, respectively). Actual: 194 patients were randomized and received study treatment; 127 patients were randomized to receive MYL-1401H and 67 patients were randomized to receive EU-Neulasta®. Completed: 186 patients completed the study. Analyzed: 194 patients were included in the data an |
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Period 2
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Period 2 title |
Reference product, US-Neulasta®
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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 | ||||||||||||||
Blinding implementation details |
The oncology pharmacist who prepared the doses and the person administering the drug (eg,
study nurse, physician [other than the principal investigator or sub-principal investigator]) were
the only individuals who had access or knowledge of the actual drug delivered.
Other unblinded personnel in the study included the clinical research associate (CRA) who
audited the drug dispensation log and drug accountability. There were 2 CRAs assigned to each
site: with the CRA monitoring the study bei
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Arms
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Arm title
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Reference Product- EU-Neulasta® | ||||||||||||||
Arm description |
- | ||||||||||||||
Arm type |
Active comparator | ||||||||||||||
Investigational medicinal product name |
Reference
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Investigational medicinal product code |
EU-Neulasta®
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Reference Product, Dose, Mode of Administration, and Batch Numbers: EU-Neulasta® 6 mg injection
administered as a single sc dose, on Day 2 of each cycle, ie, 24 h (+ 2 h) after the end of chemotherapy. Each PFS
contained 6 mg of pegfilgrastim in 0.6 mL solution for injection. The concentration was 10 mg/mL based on
protein only. Batches 1048603D and 1053573B of EU-Neulasta® were used.
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Notes [2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period. Justification: Number of Patients (Planned and Analyzed): Planned: Approximately 189 patients were planned for enrolment into the study in a 2:1 ratio of the 2 treatment groups (126:63 in the MYL-1401H and EU-Neulasta® arm, respectively). Actual: 194 patients were randomized and received study treatment; 127 patients were randomized to receive MYL-1401H and 67 patients were randomized to receive EU-Neulasta®. Completed: 186 patients completed the study. Analyzed: 194 patients were included in the data an |
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End points reporting groups
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Reporting group title |
Test arm
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Reporting group description |
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Reporting group title |
Reference Product- EU-Neulasta®
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Reporting group description |
- |
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End point title |
Primary Efficacy Endpoint: [1] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Primary Efficacy Endpoint:
The primary efficacy endpoint was the duration of severe neutropenia (DSN) in Cycle 1, defined as days with
ANC <0.5 × 109/L.
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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: Primary Efficacy Analysis: An analysis of variance (ANOVA) model, with treatment as an independent variable, and a 2-sided 95% confidence interval (CI) for the difference in least squares mean (LS Mean) of the DSN for the 2 treatments, was employed. Equivalence between the 2 treatments was declared if the CI was completely within the range of ± 1 day. |
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
A total of 1220 TEAEs were reported in the safety population. A total of 806 TEAEs were
reported in 114 (89.8%) patients in the MYL-1401H group and 414 TEAEs were reported in
58 (86.6%) patients in the EU-Neulasta® group (Table 14.3.1.1.2). Refer to Tab
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.0
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Reporting groups
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Reporting group title |
Test- MYL-1401H
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Reporting group description |
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Reporting group title |
Reference arm- EU-Neulasta®
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Reporting group description |
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Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
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 |