Clinical Trial Results:
A Phase Ib/IIa multi-centric study to determine the safety and efficacy of a combination of anti-CD3 & anti-CD7 ricin A immunotoxins (T-Guard) for the treatment of steroid-resistant acute Graft-versus-Host Disease.
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Summary
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EudraCT number |
2013-000068-27 |
Trial protocol |
NL DE |
Global end of trial date |
03 Nov 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
19 Oct 2020
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First version publication date |
19 Oct 2020
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Other versions |
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Summary report(s) |
Publication T-Guard Ph1/2 study XEN/TG-001 |
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 |
XEN/TG-001
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02027805 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Xenikos BV
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Sponsor organisation address |
Wilhelminasingel 14, Nijmegen , Netherlands, 6524 AL
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Public contact |
Ypke van Oosterhout, Ypke van Oosterhout, +31 243000100, y.vanoosterhout@xenikos.com
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Scientific contact |
Ypke van Oosterhout, Ypke van Oosterhout, +31 243000100, y.vanoosterhout@xenikos.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 |
Final
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Date of interim/final analysis |
20 Apr 2017
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
03 Nov 2016
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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 determine the efficacy with which T-Guard, four weeks after the first infusion (study Day 28) induces an objective clinical response in patients with steroid-resistant acute GVHD.
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Protection of trial subjects |
This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research. The following additional measure(s) defined for this individual study was (were) in place for the protection of trial subjects:
- Patients were closely followed for symptoms which might have been indicative for the occurrence of esophagus or gastrointestinal toxicity.
- The occurrence of an anaphylactic reaction to T-Guard formed a contraindication for subsequent doses.
- No further doses should have been given when albumin levels decreased to 10.0 g/l or below. It was also recommended to consider an adjustment or halting of further doses if albumin levels dropped more than 5.0 g/l as compared to baseline, which decision was left to the Investigator's discretion.
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Background therapy |
High dose steroids, which started at a level of 1-2 mg/kg | ||
Evidence for comparator |
No comparator was used | ||
Actual start date of recruitment |
20 Dec 2013
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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 |
Netherlands: 12
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Country: Number of subjects enrolled |
Germany: 8
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Worldwide total number of subjects |
20
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EEA total number of subjects |
20
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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) |
17
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From 65 to 84 years |
3
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was performed at 2 transplantation sites, one in The Netherlands and one in Germany. In total, 20 evaluable patients were included over 29 months. First patient screened was 2014-03-04. Last patient last visit was 2016-11-03. | ||||||
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Pre-assignment
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Screening details |
The study population consisted of patients who were treated for aGVHD that had developed following HSCT or DLI, and who did not respond to standard first-line therapy of 2 mg/kg methylprednisolone daily. | ||||||
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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 | ||||||
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Arms
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Arm title
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T-Guard treated patients | ||||||
Arm description |
Subjects with steroid refractory acute Graft-vs-Host Disease who were treated with T-Guard | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
T-Guard
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Investigational medicinal product code |
combination of anti-CD3/ CD7 ricin A immunotoxins
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Other name |
combination of SPV-T3a-RTA and WT1-RTA
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
T-Guard will be administered as an infusion at a dose of 4mg/m2 (actual body weight) over 4 hours
every 2 calendar days on Days 0, 2, 4, and 6.
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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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Subject analysis sets
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Subject analysis set title |
All Subjects Treated
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Subject analysis set type |
Full analysis | |||||||||||||||||||||||||||||||||
Subject analysis set description |
All patients that received at least one dose of T-Guard
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End points reporting groups
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Reporting group title |
T-Guard treated patients
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Reporting group description |
Subjects with steroid refractory acute Graft-vs-Host Disease who were treated with T-Guard | ||
Subject analysis set title |
All Subjects Treated
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
All patients that received at least one dose of T-Guard
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End point title |
Overall Response Rate at 4 weeks after the first infusion of TGuard (Day 28) [1] | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
28 days after administration of the first dose of T-Guard
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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: This was a non comparative single arm study; only descriptive statistics was performed. The estimated aGVHD response rates along with the 95% Clopper-Pearson exact CI were calculated. |
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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 |
6 months
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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 |
19.1E
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Reporting groups
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Reporting group title |
All Subjects Treated
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Reporting group description |
All subjects who received at least one dose of T-Guard | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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? Yes | |||
Date |
Amendment |
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01 Sep 2013 |
On request of the ethics committee, a provision has been added to the protocol that for reasons of risk mitigation first 8 patients should be treated sequentially, meaning that treatment should not be started until the previous patient has been observed for at least 48 hours after the last infusion. Furthermore, the collected personal demographic information of the study participants was restricted to ‘month and year of birth’,
‘gender’ and ‘patient study number’. |
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08 Apr 2014 |
The following main changes were made to the protocol:
- language regarding the potential cross-reactivity of SVP-T3a-RTA with esophagus epithelium was added and adequate safety measures were implemented
- the severity of VLS was now scored according to the CTCAE V4.0 criteria for Capillary Leakage
- 24 hours-delay of the dosage was recommended if Grade II or III toxicity occurred after the previous dosage, with the next dose given
if toxicity improved to < grade II or ≤ grade II, respectively. Given the potentially life-threatening consequences of leaving steroid-resistant acute GVHD under-treated, the final decision to postpone the next dosage is left to the investigators discretion depending on the clinical status of the individual patient. Also, halving of the dosage could be considered
- language was added regarding the consideration for adjustment or halting of further T-Guard doses if albumin levels decreased to 12.0 g/l or below, or dropped more than 5.0 g/l as compared to baseline, though in the end it was still left to the investigator's discretion. |
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13 Nov 2014 |
- No further T-Guard doses should be administered when the serum albumin level decrease to 10 g/l or lower. Furthermore it was also recommended to consider an adjustment or halting of further doses if albumin levels drop more than 5.0 g/l as compared to baseline,
which decision was left to the Investigator's discretion. |
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01 Dec 2014 |
The German Arzneimittelgesetz (AMG) prohibited the mixing of the two drug products SPV-T3a-RTA and WT1-RTA by a Hospital Pharmacist without a manufacturing license. As a consequence, the preparation of the infusions and subsequent administration procedure of T-Guard differed slightly between the Radboudumc in The Netherlands and the University Hospital Münster in Germany. Of not, this had no effect on the composition, amount, or administration rate of the T-Guard IMP actually administered to the patient via the central intravenous catheter. |
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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. | |||
| The samplesize was small, and no randomized comparator arm was included. In addition, the study population was heterogeneous with respect to e.g. age, donor type, and GVHD prophylaxis regimens used. Nonetheless the population was representative. | |||
