Clinical Trial Results:
A Phase 3b, Multicenter, Open-label, Single-arm, Expanded Access Protocol of Talimogene Laherparepvec for the Treatment of Subjects in Europe With Unresected Stage IIIB to IVM1c Melanoma
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Summary
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EudraCT number |
2014-002834-30 |
Trial protocol |
AT |
Global end of trial date |
08 Aug 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
18 Aug 2018
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First version publication date |
18 Aug 2018
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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 |
20120328
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02297529 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Amgen Inc.
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Sponsor organisation address |
One Amgen Center Drive, Thousand Oaks, CA, United States, 91320
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Public contact |
IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.com
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Scientific contact |
IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.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 |
08 Aug 2017
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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 |
08 Aug 2017
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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 was to provide access of talimogene laherparepvec for subjects with unresected stage IIIB to IVM1c melanoma in select countries in Europe until marketing authorization approval by the European Commission for the treatment of melanoma.
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Protection of trial subjects |
This study was conducted in accordance with International Council on Harmonisation (ICH) Good Clinical Practice (GCP) regulations/guidelines.
The protocol, informed consent form, other written subject information, and any advertising material were submitted to the Independent Ethics Committee (IEC) for written approval. A copy of the written approval of the protocol and informed consent form must have been received by Amgen before recruitment of subjects into the protocol and shipment of Amgen investigational product.
Before a subject’s participation in the expanded access protocol, the investigator was responsible for obtaining written informed consent from the subject after adequate explanation of the aims, methods, anticipated benefits, and potential hazards of the protocol and before any protocol-specific screening procedures or any investigational product(s) were administered.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
12 Aug 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 |
Switzerland: 11
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Worldwide total number of subjects |
11
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EEA total number of subjects |
0
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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) |
5
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From 65 to 84 years |
4
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85 years and over |
2
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Recruitment
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Recruitment details |
This study was conducted at 3 centers in Switzerland from 12 August 2015 (first subject enrolled) to 08 August 2017 (date last subject completed study). | ||||||||||
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Pre-assignment
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Screening details |
Eligible subjects were men and women ≥18 years of age with a histologically confirmed diagnosis of melanoma and unresected stage IIIB to IVM1c disease, regardless of prior line of therapy. | ||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
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Arms
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Arm title
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Talimogene Laherparepvec | ||||||||||
Arm description |
Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL followed by a dose of 10⁸ PFU/mL 21 days after the initial dose and every 14 days thereafter. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Talimogene laherparepvec
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Investigational medicinal product code |
AMG 678
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Other name |
IMLYGIC®
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intralesional use
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Dosage and administration details |
The initial dose of talimogene laherparepvec was up to 4 mL at a concentration of 10⁶ plaque-forming units (PFU)/mL administered by intralesional injection. The initial cycle was 21 days. Subsequent doses consisted of up to 4.0 mL of talimogene laherparepvec at a concentration of 10⁸ PFU/mL every 14 days.
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Baseline characteristics reporting groups
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Reporting group title |
Overall Study
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Reporting group description |
Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10 plaque-forming units (PFU) per mL followed by a dose of 10. PFU/mL 21 days after the initial dose and every 14 days thereafter. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Talimogene Laherparepvec
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Reporting group description |
Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL followed by a dose of 10⁸ PFU/mL 21 days after the initial dose and every 14 days thereafter. | ||
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End point title |
Number of Participants with Adverse Events (AEs) [1] | ||||||||||||||||||||||||||||||||||
End point description |
Treatment-related adverse events refer to treatment-emergent AEs that have possible or probable relation to study treatment as assessed by investigator.
The Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was used to grade severity of AEs.
The Safety Analysis Set included all subjects who are enrolled and receive at least one dose of talimogene laherparepvec.
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End point type |
Primary
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End point timeframe |
From first dose of study drug until 30 days after the last dose, the median duration of treatment was 13.3 weeks.
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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: Statistical reporting was descriptive (summary statistics), with no formal statistical testing performed. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||
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End point title |
Number of Participants with Detectable Talimogene Laherparepvec DNA in Swab Samples Taken From Cold Sores, Vesicles, and Other Lesions Suspected to be Herpetic in Origin [2] | ||||||
End point description |
Swab samples were to be taken from any cold sore, vesicles, and other lesions suspected to be herpetic in origin (if any) to test for the presence of talimogene laherparepvec deoxyribonucleic acid (DNA).
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End point type |
Primary
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End point timeframe |
From first dose of study drug until 30 days after the last dose, the median duration of treatment was 13.3 weeks.
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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: Statistical reporting was descriptive (summary statistics), with no formal statistical testing performed. |
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| Notes [3] - No events were reported for DNA analysis |
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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 |
From first dose of study drug until 30 days after the last dose, the median duration of treatment was 13.3 weeks.
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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 |
20.0
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Reporting groups
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Reporting group title |
Talimogene Laherparepvec
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Reporting group description |
Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL followed by a dose of 10⁸ PFU/mL 21 days after the initial dose and every 14 days thereafter. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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Date |
Amendment |
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09 Feb 2015 |
A superseding protocol was required to address UK regulatory agency requirements. The administrative changes in the superseding protocol consisted of adding a note (Section 4.1.2, exclusion criteria # 220) and throughout protocol as appropriate stating that acceptable methods of effective contraception are defined in the Informed Consent and where required by local laws and regulations country-specific requirements are outlined in country-specific protocol supplements.
Administration, typographical and formatting changes were made throughout the protocol. |
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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 | |||
