Clinical Trial Results:
A pilot Phase I/IIa, multicentre, open proof-of-concept study on the efficacy and safety of allogeneic osteoblastic cells (ALLOB®) implantation in non-infected delayed-union fractures
Summary
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EudraCT number |
2012-005333-36 |
Trial protocol |
BE GB DE |
Global end of trial date |
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Results information
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Results version number |
v1(current) |
This version publication date |
15 Mar 2020
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First version publication date |
15 Mar 2020
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Other versions |
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Summary report(s) |
ALLOB-DU1 synopsis 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 |
ALLOB-DU1
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02020590 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Bone Therapeutics S.A.
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Sponsor organisation address |
Auguste Piccard 37, Gosselies, Belgium, 6041
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Public contact |
Clinical Trial Information, Bone Therapeutics S.A., allob.du1@bonetherapeutics.com
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Scientific contact |
Clinical Trial Information, Bone Therapeutics S.A., allob.du1@bonetherapeutics.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 |
Interim
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Date of interim/final analysis |
11 Sep 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
30 Jan 2018
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Global end of trial reached? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of the main study is to assess the safety and efficacy of ALLOB® single percutaneous implantation in healing delayed-union fractures at the end of the study period (Month 6).
Safety:
Subjects will be systematically assessed for the potential occurrence of any AE or SAE, related to the product or related to the procedure, using patient open questionnaires, physical examination, (including vital signs), and laboratory measurements.
Efficacy:
The success will be based on the percentage of treated patients (ALLOB®) not failing under treatment.
A patient will be considered as failed under a treatment if, at the end of the study period (Month 6), the patient had required a rescue surgery or the Global Disease Evaluation score (VAS) as perceived by the patient has not improved by at least 25% and the TUS as assessed by CT scan has not increased by at least two points (versus baseline).
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Protection of trial subjects |
For the first 16 patients, the patient recruitment was proceeded stepwise by blocks of 4. Full first 2 weeks safety data of the first block of 4 patients was analysed before the first patient of the second block of 4 patients was treated. First 48 hours safety data of the second block of 4 patients was analysed before treating the first patient of the next block. This latter scheme was repeated until the first 16 patients was treated.
A Data Safety Monitoring Board (DSMB) was established to assess the safety and efficacy when 6-month post treatment results for the first 16 assessable patients was available (i.e., interim analysis). This Board recommended to the Sponsor whether to stop the trial for efficacy.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
17 Feb 2014
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
24 Months | ||
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 |
Belgium: 15
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Country: Number of subjects enrolled |
Germany: 10
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Worldwide total number of subjects |
25
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EEA total number of subjects |
25
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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) |
21
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From 65 to 84 years |
4
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85 years and over |
0
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Recruitment
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Recruitment details |
recruitment period: 17 February 2014 - 30 January 2018 countries: Belgium and Germany | ||||||||||||
Pre-assignment
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Screening details |
Patient diagnosed with a non-infected delayed-union fracture of a long bone of minimum 3 months and maximum 7 months (± 2 weeks)without signs of healing over the last 4 weeks at the time of screening Modified Radiographic Union Score (mRUS) < 10 Global Disease Evaluation Score as assessed by the patients. | ||||||||||||
Period 1
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Period 1 title |
baseline
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Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||
Arms
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Arm title
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active treatment | ||||||||||||
Arm description |
active treatment with ALLOB single injection | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
ALLOB
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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 syringe
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Routes of administration |
Percutaneous use
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Dosage and administration details |
25X10^6 cell/ml (2-4 ml) administered percoutaneously into the delayed union site
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Period 2
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Period 2 title |
final efficacy analysis
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Is this the baseline period? |
No | ||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||
Arms
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Arm title
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active treatment | ||||||||||||
Arm description |
active treatment with ALLOB | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
ALLOB
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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 syringe
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Routes of administration |
Percutaneous use
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Dosage and administration details |
25X10^6 cell/ml (2-4 ml) administered percoutaneously into the delayed union site
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Baseline characteristics reporting groups
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Reporting group title |
active treatment
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Reporting group description |
active treatment with ALLOB single injection | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
per protocol
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
21 subjects were included in the per protocol population
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Subject analysis set title |
safety population
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Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
22 subjects were included in the safety analysis
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End points reporting groups
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Reporting group title |
active treatment
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Reporting group description |
active treatment with ALLOB single injection | ||
Reporting group title |
active treatment
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Reporting group description |
active treatment with ALLOB | ||
Subject analysis set title |
per protocol
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
21 subjects were included in the per protocol population
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Subject analysis set title |
safety population
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
22 subjects were included in the safety analysis
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End point title |
Percentage of responders at 6 months (efficacy of ALLOB) | |||||||||
End point description |
The efficacy of ALLOB® will be evaluated at Month 6. The success of the study will be based on the percentage of treated patients (ALLOB®) not failing under treatment.
A patient will be considered as failed under treatment if, at Month 6:
- He/she had a rescue surgery
Or
- The Global Disease Evaluation score (VAS) as perceived by the patient has not improved by at least 25% and the TUS as assessed by CT scan has not increased by at least two points (versus baseline).
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End point type |
Primary
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End point timeframe |
At 6-months after treatment
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Statistical analysis title |
2-stage fleming method design | |||||||||
Statistical analysis description |
According to the Schoenfeld approach (Schoenfeld et al., 1980), for the efficacy analysis, the type I error rate will be increased from the usual 5% to the 10% rate. Indeed, in this pilot single arm “proof of concept” study, it is appropriate to maintain the power and increase the type I error rate. This increases the risk of erroneously concluding that the treatment is worthy of further investigation, but does not increase the risk of missing an efficacious treatment. So in this phase II study,
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Comparison groups |
active treatment v per protocol
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Number of subjects included in analysis |
42
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Analysis specification |
Pre-specified
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Analysis type |
other | |||||||||
P-value |
< 5 | |||||||||
Method |
Wilcoxon (Mann-Whitney) | |||||||||
Parameter type |
One single treatment arm | |||||||||
Confidence interval |
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level |
90% |
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Adverse events information [1]
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Timeframe for reporting adverse events |
From ICF signature till end of long-term safety follow-up (24 months after the end of the study)
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Adverse event reporting additional description |
questionnaire submitted to subjects during on site visits and phone calls
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.1
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Reporting groups
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Reporting group title |
active treatment
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Reporting group description |
active treatment with ALLOB single injection | ||||||||||||||||||||||||||||||||||||||
Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: Display of non-serious AEs will be encoded at a later stage |
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||||||
Interruptions (globally) |
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Were there any global interruptions to the trial? Yes | |||||||
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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 |