Clinical Trial Results:
Phase I study of lentiviral-mediated COL7A1 gene-modified autologous fibroblasts in adults with recessive dystrophic epidermolysis bullosa (RDEB)
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Summary
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EudraCT number |
2014-004884-19 |
Trial protocol |
GB |
Global end of trial date |
13 Mar 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
27 Mar 2019
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First version publication date |
27 Mar 2019
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Other versions |
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Summary report(s) |
FINAL STUDY REPORT |
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 |
LENTICOL-F
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02493816 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
King's College London
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Sponsor organisation address |
The Strand, London, United Kingdom, WC2R 2LS
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Public contact |
Professor John A McGrath, King's College London and Guy's and St Thomas' NHS Foundation Trust, 44 2071886409, john.mcgrath@kcl.ac.uk
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Scientific contact |
Professor John A McGrath, King's College London and Guy's and St Thomas' NHS Foundation Trust, 44 2071886409, john.mcgrath@kcl.ac.uk
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Sponsor organisation name |
Guy's and St Thomas' NHS Foundation Trust
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Sponsor organisation address |
Great Maze Pond, London, United Kingdom, SE19RT
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Public contact |
Professor John McGrath, Guy's and St Thomas' NHS Foundation Trust and King's College London, 44 2071886409, john.mcgrath@kcl.ac.uk
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Scientific contact |
Professor John McGrath, Guy's and St Thomas' NHS Foundation Trust and King's College London, 44 2071886409, john.mcgrath@kcl.ac.uk
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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 |
13 Mar 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
13 Mar 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
13 Mar 2018
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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 |
To evaluate the safety of intradermal injections of SIN LV-mediated COL7A1 gene-modified autologous fibroblasts in adults with RDEB.
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Protection of trial subjects |
Each study participant will receive three intradermal injections of ex vivo transduced autologous fibroblasts expressing codon-optimised COL7A1 as the IMP on Day 0 only. Each injection of the IMP containing 0.8–1.2x106 cells suspended in 0.25ml of 0.9% saline, will be administered intradermally into 1cm2 area of intact skin (x3). Participants will be followed up with study interventions for a 12-month period at various time points. All followups, where possible, will be co-ordinated to try to coincide with the individuals’ routine clinic reviews.
Each subject will undergo an initial screening including a physical examination and assessment of disease severity. Blood analyses and skin biopsies will be performed at various time points throughout the trial. The second participant will be treated only if there is no safety concern 4 weeks after the first participant’s IMP injections. All patients with RDEB are followed up on a lifelong basis, and we will therefore be able to capture any long-term possible adverse effects related to the IMP.
Subjects with positive results for HIV, Hepatitis B, Hepatitis C, HTLV or Syphilis will be excluded.
Subjects will not be included who are pregnant or of child-bearing potential who are neither abstinent nor practising an acceptable means of contraception when this is in line with the usual and preferred lifestyle of the subject, as determined by the Investigator, for 12 months after the cell injections.
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Background therapy |
- | ||
Evidence for comparator |
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Actual start date of recruitment |
18 Sep 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 |
United Kingdom: 4
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Worldwide total number of subjects |
4
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EEA total number of subjects |
4
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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) |
4
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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 |
The participants were recruited by St John’s Institute of Dermatology at Guy's and St Thomas NHS Foundation Trust. | ||||||
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Pre-assignment
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Screening details |
Thirty-nine RDEB adults with confirmed biallelic COL7A1 mutations by Sanger sequencing were invited to participate in the study, of which 35 patients were excluded due to failing screening. | ||||||
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Period 1
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Period 1 title |
Overall Trial Period (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
Blinding implementation details |
Open label SIN LV-mediated ex vivo transduced autologous fibroblasts expressing codon-optimised COL7A1 will be given to patients at a does of 0.8–1.2 million cells suspended in 0.25ml of 0.9% saline per injection over 1 cm2 of intact skin (3 intradermal injections of IMP at a single timepoint). Patients were followed up for 12 months post injection.
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Arms
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Arm title
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Treatment | ||||||
Arm description |
Patients treated with SIN LV-mediated ex vivo transduced autologous fibroblasts expressing codon-optimised COL7A1. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
SIN LV Mediated ex vivo transduced autologous fibroblasts expressing codon-optimised COL7A1
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection in pre-filled injector
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Routes of administration |
Intradermal use
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Dosage and administration details |
0.8 - 1.2 million cells in 0.25ml of 0.9% saline per injection; 2.4 - 3.6 million cells total dose
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Baseline characteristics reporting groups
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Reporting group title |
Overall Trial Period
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Reporting group description |
- | ||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Treatment
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Reporting group description |
Patients treated with SIN LV-mediated ex vivo transduced autologous fibroblasts expressing codon-optimised COL7A1. | ||
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End point title |
Adverse Events [1] | ||||||
End point description |
Adverse events (AEs) at each visit after screening over a 12month follow-up period
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End point type |
Primary
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End point timeframe |
From screening to 12 months after injection
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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: Please see attached report for full results and trial outcomes, including full list of adverse events |
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| Notes [2] - There were 45 AEs (including SAEs) in total |
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| No statistical analyses for this end point | |||||||
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End point title |
Adverse reactions [3] | ||||||
End point description |
The incidence of Adverse Reactions (ARs) and Serious Adverse Reactions (SARs) at each visit after screening over a 12-month follow-up period.
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End point type |
Primary
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End point timeframe |
Screening over a 12-month follow-up period.
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| Notes [3] - 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: Please see attached report for full results and trial outcomes, including full list of adverse reactions |
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| Notes [4] - There were 7 adverse reactions and no serious adverse reactions |
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End point title |
Serious Adverse Evemts [5] | ||||||
End point description |
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End point type |
Primary
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End point timeframe |
From screening to 12 months post dose.
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| Notes [5] - 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: Please see attached report for full results and trial outcomes, including full list of serious adverse events |
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| Notes [6] - Number of serious adverse events |
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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 |
Screening to 12 months post dose of IMP
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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 |
17.1
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Reporting groups
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Reporting group title |
Whole trial
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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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Date |
Amendment |
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10 Jul 2015 |
• To decrease the duration of follow up from 36mths to 12mths
• To amend the exclusion criteria such that persons with positive serology for HIV, Hepatitis B and C, HTLV and Syphilis are excluded from the study
• To amend the total number of skin biopsies to be taken at baseline (V1B) from 2 (1x6mm and 1x4mm punch) to 2-3 (1x6mm and 1-2x4mm punch).
• To include two additional investigations on the skin biopsies; histology and RT-PCR to demonstrate the difference in COL7A1 gene expression between fibroblasts from treated versus untreated skin.
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25 Apr 2016 |
The purpose of this amendment secondary endpoints.
Amend inclusion/exclusion criteria.
Amend IMP administration details to minimise the amount of tattooing to mark the injected sites. |
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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 | |||
