Clinical Trial Results:
A phase I/II study evaluating allogeneic mesenchymal stromal cells in adults with recessive dystrophic epidermolysis bullosa
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Summary
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EudraCT number |
2014-004500-30 |
Trial protocol |
GB |
Global end of trial date |
10 Oct 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
28 Feb 2019
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First version publication date |
28 Feb 2019
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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 |
ADSTEM001
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02323789 | ||
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, 44 207188 6409, john.mcgrath@kcl.ac.uk
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Scientific contact |
Professor John A. McGrath, King's College London, 44 207188 6409, 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 A. McGrath, Guy's and St Thomas NHS Foundation Trust, 44 207188 6409, john.mcgrath@kcl.ac.uk
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Scientific contact |
Professor John A. McGrath, Guy's and St Thomas NHS Foundation Trust, 44 207188 6409, 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 |
12 Jul 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
12 Jul 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
10 Oct 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 |
To evaluate the safety of allogeneic intravenously administered MSCs in adults with RDEB over a 12-month period
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Protection of trial subjects |
Study participants will be instructed that further information can be obtained at any time from the Investigator, and that they are free to withdraw their consent and to discontinue participation in the study at any time without prejudice
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Background therapy |
The study subjects can continue to receive their regular medication(s). | ||
Evidence for comparator |
n/a | ||
Actual start date of recruitment |
12 Jun 2015
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Long term follow-up planned |
No
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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 |
United Kingdom: 10
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Worldwide total number of subjects |
10
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EEA total number of subjects |
10
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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) |
10
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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 |
Guy‟s and St Thomas‟ NHS Trust is a local, regional and national referral centre for adults with EB with an extensive database. Trial participants were recruited from this one site during 2017-2017. | ||||||||||
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Pre-assignment
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Screening details |
The screening assessments (V1) will be conducted up to 200 days prior to Day 0. Inclusion Criteria 1) Individuals with a diagnosis of RDEB confirmed by DNA analysis. 2) Individuals 18 years of age or above, and under the age of 65, both male and female 3) Individuals that have voluntarily signed and dated an informed consent form (ICF) prior to | ||||||||||
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Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||
Blinding implementation details |
Phase I/II, non-randomised, open-label trial.
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Arms
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Arm title
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Full study | ||||||||||
Arm description |
8 visits over 12 months are planned for the first eight eligible patients, and over 8 months for the last two eligible patients. Each study subject will receive two intravenous infusions (day 0 and day 14). | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
TC-MSC (mesenchymal stem cells)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
TC-MSC (mesenchymal stem cells received two intravenous infusions (day 0 and day 14).
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Baseline characteristics reporting groups
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Reporting group title |
Overall Trial
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Reporting group description |
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End points reporting groups
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Reporting group title |
Full study
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Reporting group description |
8 visits over 12 months are planned for the first eight eligible patients, and over 8 months for the last two eligible patients. Each study subject will receive two intravenous infusions (day 0 and day 14). | ||
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End point title |
Safety [1] | ||||||
End point description |
Lack of serious and severe adverse events (SAEs) related to the administration of the investigational medicinal product over a 8 or a 12 month period. SAEs are defined as any occurrence related to the administration of the IMP that results in death, or is life threatening or requires hospitalization or prolongation of existing hospitalization.
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End point type |
Primary
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End point timeframe |
Up to 12 months post first infusion
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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: See attached document for all results and charts for both primary and secondary endpoints. |
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Attachments |
RESULTS |
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| No statistical analyses for this end point | |||||||
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End point title |
Secondary Endpoints | ||||||
End point description |
1. Presence of new type VII collagen at the dermal-epidermal junction post treatment on Day 28, Day 60, and Month 6.
2. Changes in general markers of inflammation at Day 14, Day 28, Day 60, Day 100, Month 6 (for all patients) and Month 12 (for the first eight eligible patients) or Month 8 (for the last two eligible patients) compared to baseline.
3. Changes in specific markers of inflammation on Day 14, Day 28, Day 60 and Month 6 compared to baseline using ELISA and LUMINEX platforms. Specific inflammatory markers include: HMGB-1, TNF α, IFN γ, IL-17A, IL1 β, IL-10, MMP-2, MMP-9, MMP-11 and TIMP-1.
4. Changes in the clinical appearance of the skin assessed with clinical photographs
5. Differences in quality of life data at Day 28, Day 60, Day 100, Month 6 (for all patients) and Month 12 (for the first eight eligible patients) or Month 8 (for the last two eligible patients) compared to baseline.
6 Changes in BEBSS & EBDASI scores at Day 28 60 100 & month 6 & 12 (8 for final 2 pts)
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End point type |
Secondary
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End point timeframe |
Up to 12 months post first infusion
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| No statistical analyses for this end point | |||||||
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End point title |
Secondary Endpoints continued | ||||||
End point description |
Change in pruritus score using the Leuven Itch Scale (LIS) at Day 28, Day 60, Day 100, Month 6 (for all patients) and Month 12 (for the first eight eligible patients) or Month 8 (for the last two eligible patients) compared to baseline.
8. Quantification of total blister numbers over the entire body surface area at Day 28, Day 60, Day 100, Month 6 (for all patients) and Month 12 (for the first eight eligible patients) or Month 8 (for the last two eligible patients) compared to baseline.
9. Increase in the skin strength measured by time to blister formation after negative pressure skin suction test at Day 28, Day 60, Day 100, Month 6 (for all patients) and Month 12 (for the first eight eligible patients) or Month 8 (for the last two eligible patients) compared to baseline
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End point type |
Secondary
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End point timeframe |
Up to 12 months post infustion
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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 |
12 months post first infustion for the first 8 participants and 8 months post first infusion for the final 2 participants.
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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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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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20 Nov 2015 |
• A change to the exclusion criteria, to exclude subjects with both a) positive C7 ELISA and b) a positive indirect immunofluorescence (IIF) with binding to the base of salt split skin.
• The removal of a secondary end point relating to quality of life data, which will now be captured as part of a nested study with an independent application to an Ethics Committee.
• A new secondary end point to perform flow cytometry to evaluate the cytotoxic T-cell signature at 24 to 48 hours post first infusion. This will involve an optional blood test and for all patients who partake in this an additional visit will be required, which has also been added to the protocol (visit 2a).
• The number of skin biopsies have also been reduced from 6 to 4, so the visit schedule has been updated accordingly to reflect these changes and a new table has been included in v3.0 to make the procedures per visit easier to see.
• The removal of the data monitoring committee section as this study only has a trial steering committee.
• The statistics section has been updated to explain that attempts will be made to replace patients that do not completed at least 6 months of the trial and No interim analysis will now be performed.
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27 Jan 2016 |
It includes a change to one of the inclusion criteria, as highlighted below:
Protocol v3.0 wording: ‘Individuals with a diagnosis of RDEB confirmed by DNA analysis and skin immunofluorescence for partial or complete absence of type VII collagen.’
Protocol v4.0 New wording: ‘Individuals with a diagnosis of RDEB confirmed by DNA analysis.’
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03 Apr 2017 |
The protocol has been amended to change the conduct and management of the trial by removing visit 2a and reducing the follow up for the final two patients in the trial from 12 to 8 months. |
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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 | |||
