Klinikai vizsgálatok Nct
Clinical Trial Results:
Single-Arm Study to Assess the Efficacy of UVADEX® (Methoxsalen) Sterile Solution in Conjunction With the THERAKOS® CELLEX® Photopheresis System in Pediatric Patients With Steroid-Refractory Acute Graft Versus Host Disease (aGvHD)
| Summary | |
EudraCT number | 2014-004806-14 |
Trial protocol | DE HU GB IT ES AT |
Global end of trial date | 16 Jul 2019 |
| Results information | |
Results version number | v2(current) |
This version publication date | 09 Sep 2020 |
First version publication date | 07 Aug 2020 |
Other versions | v1 |
Version creation reason |
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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 | |||
Sponsor protocol code | TKS-2014-001 | ||
| Additional study identifiers | |||
ISRCTN number | - | ||
US NCT number | NCT02524847 | ||
WHO universal trial number (UTN) | - | ||
| Sponsors | |||
Sponsor organisation name | Therakos, Inc., a Mallinckrodt Company | ||
Sponsor organisation address | 1425 U.S. Route 206, Bedminster, NJ, United States, 07921 | ||
Public contact | Medical Information Call Center, Therakos, Inc., a Mallinckrodt Company, 1 800-844-2830 Ext 5, ClinicalTrials@mnk.com | ||
Scientific contact | Medical Information Call Center, Therakos, Inc., a Mallinckrodt Company, 1 800-844-2830 Ext 5, ClinicalTrials@mnk.com | ||
| Paediatric regulatory details | |||
Is trial part of an agreed paediatric investigation plan (PIP) | No | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? | No | ||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? | No | ||
| Results analysis stage | |||
Analysis stage | Final | ||
Date of interim/final analysis | 23 Aug 2019 | ||
Is this the analysis of the primary completion data? | No | ||
Global end of trial reached? | Yes | ||
Global end of trial date | 16 Jul 2019 | ||
Was the trial ended prematurely? | Yes | ||
| General information about the trial | |||
Main objective of the trial | To evaluate the efficacy of extracorporeal photopheresis (ECP) in pediatric participants with steroid-refractory aGvHD. | ||
Protection of trial subjects | This trial was conducted in accordance with the ethical principles of Good Clinical Practice, according to the ICH Harmonized Tripartite Guideline, which has its foundation in the Declaration of Helsinki. | ||
Background therapy | - | ||
Evidence for comparator | - | ||
Actual start date of recruitment | 20 Jan 2016 | ||
Long term follow-up planned | No | ||
Independent data monitoring committee (IDMC) involvement? | Yes | ||
| Population of trial subjects | |||
Number of subjects enrolled per country | |||
Country: Number of subjects enrolled | Spain: 3 | ||
Country: Number of subjects enrolled | United Kingdom: 1 | ||
Country: Number of subjects enrolled | United States: 10 | ||
Country: Number of subjects enrolled | Austria: 2 | ||
Country: Number of subjects enrolled | France: 3 | ||
Country: Number of subjects enrolled | Germany: 2 | ||
Country: Number of subjects enrolled | Italy: 8 | ||
Worldwide total number of subjects | 29 | ||
EEA total number of subjects | 19 | ||
Number of subjects enrolled per age group | |||
In utero | 0 | ||
Preterm newborn - gestational age | 0 | ||
Newborns (0-27 days) | 0 | ||
Infants and toddlers (28 days-23 months) | 2 | ||
Children (2-11 years) | 17 | ||
Adolescents (12-17 years) | 9 | ||
Adults (18-64 years) | 1 | ||
From 65 to 84 years | 0 | ||
85 years and over | 0 | ||
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| Recruitment | |||||||||||||||||||
Recruitment details | - | ||||||||||||||||||
| Pre-assignment | |||||||||||||||||||
Screening details | Participants were recruited by multiple treatment centers in the United States and Europe. | ||||||||||||||||||
| Period 1 | |||||||||||||||||||
Period 1 title | Overall Study (overall period) | ||||||||||||||||||
Is this the baseline period? | Yes | ||||||||||||||||||
Allocation method | Not applicable | ||||||||||||||||||
Blinding used | Not blinded | ||||||||||||||||||
| Arms | |||||||||||||||||||
| Arm title | Methoxsalen with ECP | ||||||||||||||||||
Arm description | Participants received methoxsalen 20 μg/ml in conjunction with ECP procedure three times per week for Weeks 1 to 4, and two times per week for Weeks 5 to 12. | ||||||||||||||||||
Arm type | Experimental | ||||||||||||||||||
Investigational medicinal product name | Methoxsalen | ||||||||||||||||||
Investigational medicinal product code | 298-81-7 | ||||||||||||||||||
Other name | Methoxalen Sterile Solution | ||||||||||||||||||
Pharmaceutical forms | Solution for blood fraction modification | ||||||||||||||||||
Routes of administration | Extracorporeal use | ||||||||||||||||||
Dosage and administration details | Participants received methoxsalen 20 μg/ml in conjunction with extracorporeal (ECP) use procedure three times per week for Weeks 1 to 4, and two times per week for Weeks 5 to 12. | ||||||||||||||||||
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| Baseline characteristics reporting groups | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title | Overall Study | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description | - | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| End points reporting groups | |||
Reporting group title | Methoxsalen with ECP | ||
Reporting group description | Participants received methoxsalen 20 μg/ml in conjunction with ECP procedure three times per week for Weeks 1 to 4, and two times per week for Weeks 5 to 12. | ||
Subject analysis set title | Stage 0 = No GvHD rash | ||
Subject analysis set type | Full analysis | ||
Subject analysis set description | No GvHD rash | ||
Subject analysis set title | Stage 1 = Maculopapular rash on < 25% body surface area (BSA) | ||
Subject analysis set type | Full analysis | ||
Subject analysis set description | Maculopapular rash on < 25% body surface area (BSA) | ||
Subject analysis set title | Stage 2 = Maculopapular rash on 25-50% BSA | ||
Subject analysis set type | Full analysis | ||
Subject analysis set description | Maculopapular rash on 25-50% BSA | ||
Subject analysis set title | Stage 3 = Maculopapular rash on >50% BSA | ||
Subject analysis set type | Full analysis | ||
Subject analysis set description | Maculopapular rash on >50% BSA | ||
Subject analysis set title | Stage 4 = Generalized erythroderma plus bullous formation | ||
Subject analysis set type | Full analysis | ||
Subject analysis set description | Generalized erythroderma plus bullous formation, which are blisters bigger than 5 mm across | ||
Subject analysis set title | Stage 0 = Bilirubin < 2.0 mg/dL | ||
Subject analysis set type | Full analysis | ||
Subject analysis set description | Bilirubin < 2.0 mg/dL | ||
Subject analysis set title | Stage 1 = Bilirubin 2.0-3.0 mg/dL | ||
Subject analysis set type | Full analysis | ||
Subject analysis set description | Bilirubin 2.0-3.0 mg/dL | ||
Subject analysis set title | Stage 2 = Bilirubin 3.1-6.0 mg/dL | ||
Subject analysis set type | Full analysis | ||
Subject analysis set description | Bilirubin 3.1-6.0 mg/dL | ||
Subject analysis set title | Stage 3 = Bilirubin 6.1-15.0 mg/dL | ||
Subject analysis set type | Full analysis | ||
Subject analysis set description | Bilirubin 6.1-15.0 mg/dL | ||
Subject analysis set title | Stage 4 = Bilirubin > 15.0 mg/dL | ||
Subject analysis set type | Full analysis | ||
Subject analysis set description | Bilirubin > 15.0 mg/dL | ||
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End point title | Number of Participants Achieving Overall Response (OR) Using the Modified International Bone Marrow Transplant Registry (IBMTR) Severity Index at Week 4 [1] | ||||||
End point description | OR using the modified IBMTR Severity Index is defined as complete response (CR) + partial response (PR) as follows: • CR: complete resolution of all signs and symptoms of aGvHD in all evaluable organs without addition of next-line systemic treatment • PR: improvement of 1 stage in 1 or more aGvHD target organs without progression in others and without addition of next-line systemic treatment | ||||||
End point type | Primary | ||||||
End point timeframe | 4 weeks | ||||||
| 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: It was not possible to create an analysis module in this database because there was only one arm. | |||||||
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| No statistical analyses for this end point | |||||||
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End point title | Number of Participants With Adverse Events | ||||||||||||
End point description | Clinically significant changes in vital signs, laboratory values and investigations are reported as adverse events. Summary data are provided below, with details listed in the adverse events module. | ||||||||||||
End point type | Secondary | ||||||||||||
End point timeframe | 16 weeks | ||||||||||||
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| No statistical analyses for this end point | |||||||||||||
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End point title | Percentage of Participants Achieving Overall Response (OR) Using Modified IBMTR Severity Index at Week 8 | ||||||||
End point description | OR using the modified IBMTR Severity Index is defined as complete response (CR) + partial response (PR) as follows: • CR: complete resolution of all signs and symptoms of aGvHD in all evaluable organs without addition of next-line systemic treatment • PR: improvement of 1 stage in 1 or more aGvHD target organs without progression in others and without addition of next-line systemic treatment | ||||||||
End point type | Secondary | ||||||||
End point timeframe | 8 weeks | ||||||||
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| No statistical analyses for this end point | |||||||||
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End point title | Percentage of Participants Achieving Overall Response (OR) Using Modified IBMTR Severity Index at Week 12 | ||||||||
End point description | OR using the modified IBMTR Severity Index is defined as complete response (CR) + partial response (PR) as follows: • CR: complete resolution of all signs and symptoms of aGvHD in all evaluable organs without addition of next-line systemic treatment • PR: improvement of 1 stage in 1 or more aGvHD target organs without progression in others and without addition of next-line systemic treatment | ||||||||
End point type | Secondary | ||||||||
End point timeframe | 12 weeks | ||||||||
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| No statistical analyses for this end point | |||||||||
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End point title | Duration of Response (Days) Within 16 Weeks Using Modified IBMTR Severity Index | ||||||||
End point description | Duration of first response is presented for participants whose disease progressed. Duration of response is defined in the following way: Participants whose response failed: Date at which 1st disease progression occurs - date of 1st response +1. Participants whose response did not relapse: Date of 16-week follow-up or final assessment prior to week 16 (if participant withdrew early) - date of 1st response. | ||||||||
End point type | Secondary | ||||||||
End point timeframe | 16 weeks | ||||||||
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| No statistical analyses for this end point | |||||||||
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End point title | Overall Response Rate (ORR) According to the Modified Glucksberg Criteria | ||||||||||||||
End point description | ORR is defined as the percentage of participants who achieve an overall response after 4 weeks, 8 weeks, and 12 weeks of ECP treatment according to a scoring algorithm applied to calculate the grade of aGvHD using the modified Glucksberg Criteria. | ||||||||||||||
End point type | Secondary | ||||||||||||||
End point timeframe | 4 weeks, 8 weeks, and 12 weeks | ||||||||||||||
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| No statistical analyses for this end point | |||||||||||||||
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End point title | Cumulative Dose of Daily Steroids | ||||||||
End point description | Steroids administered from diagnosis of aGvHD to 12 weeks after initiation of ECP treatment. | ||||||||
End point type | Secondary | ||||||||
End point timeframe | 12 weeks | ||||||||
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| No statistical analyses for this end point | |||||||||
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End point title | Number of Participants With Skin Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria | ||||||||||||||||||||||||||||||||||||
End point description | Number of participants whose skin was rated as Stage 0 - 4 using the modified Glucksberg criteria based on the Graft versus Host Disease (GvHD) rash - Stages are defined in the reporting group titles shown in the table. | ||||||||||||||||||||||||||||||||||||
End point type | Secondary | ||||||||||||||||||||||||||||||||||||
End point timeframe | 4 weeks, 8 weeks, and 12 weeks | ||||||||||||||||||||||||||||||||||||
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||
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End point title | Number of Participants With Liver Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria | ||||||||||||||||||||||||||||||||||||
End point description | Number of participants whose liver was rated as Stage 0 - 4 on the modified Glucksberg criteria - Stages are based on level of bilirubin, as defined in the table's arm/group descriptions. | ||||||||||||||||||||||||||||||||||||
End point type | Secondary | ||||||||||||||||||||||||||||||||||||
End point timeframe | 4 weeks, 8 weeks, and 12 weeks | ||||||||||||||||||||||||||||||||||||
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||
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| Adverse events information | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events | Up to 16 weeks | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type | Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dictionary used for adverse event reporting | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name | MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version | 21.0 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Reporting groups | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title | Methoxsalen with ECP | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description | Participants received methoxsalen 20 μg/ml in conjunction with ECP procedure three times per week for Weeks 1 to 4, and two times per week for Weeks 5 to 12. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) | |||
| Were there any global substantial amendments to the protocol? Yes | |||
Date | Amendment | ||
15 Mar 2016 | Changes made to provide more detailed information for the investigators and ensure study success. Extended the duration of the trial, adding time points at which to collect measurements. Adjusted inclusion/exclusion criteria and recording requirements, and added a risk/benefit statement. | ||
27 Jul 2017 | Modified inclusion and exclusion criteria and extended the recording period for adverse events. | ||
Interruptions (globally) | |||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats | |||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| This study did have a notable limitation in its single-group study design. This may limit a more robust assessment vs standard of care alone for primary endpoint of overall response and secondary endpoints steroid sparing and disease progression. | |||