Clinical Trial Results:
A phase I-IIa safety and efficacy pilot clinical trial of intraarticular administration of autologous mesenchymal stem cells in meniscus injury
|
Summary
|
|
EudraCT number |
2011-006270-13 |
Trial protocol |
ES |
Global end of trial date |
04 Mar 2017
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
29 Mar 2022
|
First version publication date |
29 Mar 2022
|
Other versions |
|
Summary report(s) |
A Phase I-IIa Safety and Efficacy Pilot Clinical Trial of Intraarticular Administration of Autologous Mesenchymal Cells for Meniscus Injury |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
XCEL-MEN-01
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT02033525 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Banc de Sang i Teixits
|
||
Sponsor organisation address |
Passeig Taulat 116, Barcelona, Spain,
|
||
Public contact |
Ruth Coll, Banc de Sang i Teixits, +34 935573500, rucoll@bst.cat
|
||
Scientific contact |
Ruth Coll, Banc de Sang i Teixits, +34 935573500, rucoll@bst.cat
|
||
|
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 |
04 Mar 2017
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
04 Mar 2017
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
04 Mar 2017
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
- To assess the efficacy of intraarticular administration of XCEL-M-ALPHA by VAS for pain at 12 month follow-up.
|
||
Protection of trial subjects |
Patients were able to contact the investigator whenever needed, in order to proceed with the most adequate approach to the reported issue.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Dec 2012
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Spain: 21
|
||
Worldwide total number of subjects |
21
|
||
EEA total number of subjects |
21
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
21
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
||
|
||||||||||
|
Recruitment
|
||||||||||
Recruitment details |
Patients were recruited between January 2014 and May 2016 , from those patients visited at ICATME (Dexeus Hospital), in Barcelona, Spain. | |||||||||
|
Pre-assignment
|
||||||||||
Screening details |
All screened patients entered the study. There were no screening failure. | |||||||||
|
Pre-assignment period milestones
|
||||||||||
Number of subjects started |
21 | |||||||||
Number of subjects completed |
21 | |||||||||
|
Period 1
|
||||||||||
Period 1 title |
overall trial (overall period)
|
|||||||||
Is this the baseline period? |
Yes | |||||||||
Allocation method |
Non-randomised - controlled
|
|||||||||
Blinding used |
Not blinded | |||||||||
|
Arms
|
||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||
|
Arm title
|
BM-MSC | |||||||||
Arm description |
The patients assigned to the experimental treatment were scheduled for the previous extraction of BM and, after the days necessary for cell expansion, the mesenchymal cells were infiltrated in the knee by intra-articular puncture. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
BM-MSC
|
|||||||||
Investigational medicinal product code |
||||||||||
Other name |
Autologous mesenchymal stromal cells from bone marrow
|
|||||||||
Pharmaceutical forms |
Injection/infusion
|
|||||||||
Routes of administration |
Intraarticular use
|
|||||||||
Dosage and administration details |
Dose: 40x106 ± 10x106 mesenchymal cells in approximately 6 ml suspension.
Pharmaceutical form: Suspension for intraarticular infiltration in a prefilled syringe
Administration route: Intraarticular
Treatment administration schedule: Single dose
Lot number: Autologous product with a unique lot number for each one of the 10 productions
|
|||||||||
|
Arm title
|
Rehabilitation | |||||||||
Arm description |
The control group followed conservative treatment through the same rehabilitation program | |||||||||
Arm type |
Rehabilitation | |||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
|
|||||||||
|
||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
BM-MSC
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
The patients assigned to the experimental treatment were scheduled for the previous extraction of BM and, after the days necessary for cell expansion, the mesenchymal cells were infiltrated in the knee by intra-articular puncture. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Rehabilitation
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
The control group followed conservative treatment through the same rehabilitation program | ||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
BM-MSC
|
||
Reporting group description |
The patients assigned to the experimental treatment were scheduled for the previous extraction of BM and, after the days necessary for cell expansion, the mesenchymal cells were infiltrated in the knee by intra-articular puncture. | ||
Reporting group title |
Rehabilitation
|
||
Reporting group description |
The control group followed conservative treatment through the same rehabilitation program | ||
|
|||||||||||||
End point title |
VAS for pain | ||||||||||||
End point description |
Visual analogue scale (VAS) for pain at 12 month follow-up
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
12 month follow-up
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Main variable for efficacy (VAS for pain at 12m) | ||||||||||||
Statistical analysis description |
Efficacy analysis was performed by intention to treat, using the FAS analysis set. In case of missing values (missings), these were replaced by the last available value (Last Observation Carried Forward or LOCF), even if this was the baseline. In this case, as well as in the case of important protocol violations, the convenience of conducting sensitivity analysis without imputation of missing data, or excluding said violations, was assessed.
|
||||||||||||
Comparison groups |
BM-MSC v Rehabilitation
|
||||||||||||
Number of subjects included in analysis |
20
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other [1] | ||||||||||||
P-value |
= 0.19 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
|||||||||||||
| Notes [1] - Greater percentage changes were observed in the BM-MSC group than in the group of rhb, but were not statistically significant, which could be attributed to the low sample size, to the dispersion of results obtained or to the high number of missing data. For changes in the VAS for pain at 12 m, the adjusted mean estimates (least-squares) showed a slightly greater percentage reduction in the BM-MSC group (-67.46) than in the rhb group (-44.33) (not statistically significant) |
|||||||||||||
|
|||||||||||||
End point title |
Efficacy by MRI | ||||||||||||
End point description |
Efficacy will be assessed by qualitative and quantitative changes of the meniscus and articular cartilage by imaging procedures (MRI) T2 mapping at 6 and 12 month follow-up.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
6 and 12 month follow-up.
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Clinical efficacy by clinical questionnaires | ||||||||||||
End point description |
IKDC, KOOS and Lysholm functionality test and SF-36 quality of life at 3, 6 and 12 month follow-up
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
3, 6 and 12 month follow-up
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Safety | ||||||||||||
End point description |
Safety will be assessed by collecting adverse events, physical exam, laboratory tests, and vital signs
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
12 month follow-up
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
From the iIC signature to the 12-months follow-up
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.0
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
BM-MSC
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Rehabilitation
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 3% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? No | |||
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. | |||
| Limited sample size. Premature study discontinuations were significantly more frequent in the rehabilitation group than in the experimental group (7/10 vs 1/10 patients respectively, p = 0.022), most of them due to therapeutic ineffectiveness. | |||
