Clinical Trial Results:
A Phase I-IIa trial on low-dose IL-2 (Aldesleukin) treatment for immunological dysregulation in common variable immunodeficiency (CVID)
Summary
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EudraCT number |
2015-003369-27 |
Trial protocol |
DE |
Global end of trial date |
05 Jun 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
04 Nov 2020
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First version publication date |
04 Nov 2020
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Other versions |
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 |
REGAIN
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
DRKS: DRKS00010424 | ||
Sponsors
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Sponsor organisation name |
Medical Center - University of Freiburg
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Sponsor organisation address |
Breisacher Str. 153, Freiburg, Germany, 79110
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Public contact |
Dr. rer. nat. Annette Uhlmann , Clinical Trials Unit, Medical Center - University of Freiburg, +49 761 270 77771, annette.uhlmann@uniklinik-freiburg.de
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Scientific contact |
Prof. Dr. med. Klaus Warnatz, Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, +49 761 270 77640, klaus.warnatz@uniklinik-freiburg.de
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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 |
06 Jun 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
15 May 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
05 Jun 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 assess the safety (esp. with respect to autoimmunity) of different doses of low-dose s.c. Aldesleukin treatment in in common variable immunodeficiency (CVID) patients with autoimmune enteropathy (AIE)
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Protection of trial subjects |
Risk-based monitoring done according to ICH-GCP E6 and standard operating procedures (SOP) to verify that patients’ rights and wellbeing are protected.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Jul 2016
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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 |
Germany: 2
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Worldwide total number of subjects |
2
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EEA total number of subjects |
2
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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) |
2
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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 |
- | ||||||
Pre-assignment
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Screening details |
- | ||||||
Pre-assignment period milestones
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Number of subjects started |
2 | ||||||
Number of subjects completed |
2 | ||||||
Period 1
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Period 1 title |
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 |
Single arm trial, no blinding possible
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Arms
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Arm title
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Aldesleukin | ||||||
Arm description |
Patients with autoimmune enteropathy occurring in the context of common variable immunodeficiency were treated with a cyclic, subcutaneous application of IL-2 (Aldesleukin) at different dose levels (0.5-2.0 MIO IE/day) during a period of 4 - 6 months. Each patient started with an induction cycle (1 MIO IE Aldesleukin/day on five consecutive days followed by nine days without treatment). The following maintenance cycles had a duration of three days followed by 11 days without treatment. IL-2 dosage was adjusted according to adverse events, frequency of Treg cells and clinical efficacy. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Aldesleukin
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Investigational medicinal product code |
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Other name |
Interleukin-2, IL-2, Proleukin
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Pharmaceutical forms |
Powder for solution for injection/infusion
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Different dose levels (0.5-2.0 MIO IE/day) during a period of 4 - 6 months. Each patient started with an induction cycle (1 MIO IE Aldesleukin/day on five consecutive days followed by nine days without treatment). The following maintenance cycles had a duration of three days followed by 11 days without treatment. IL-2 dosage was adjusted according to adverse events, frequency of Treg cells and clinical efficacy. Treatment duration was intended to be six months /per patient.
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Baseline characteristics reporting groups
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Reporting group title |
Overall period
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Aldesleukin
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Reporting group description |
Patients with autoimmune enteropathy occurring in the context of common variable immunodeficiency were treated with a cyclic, subcutaneous application of IL-2 (Aldesleukin) at different dose levels (0.5-2.0 MIO IE/day) during a period of 4 - 6 months. Each patient started with an induction cycle (1 MIO IE Aldesleukin/day on five consecutive days followed by nine days without treatment). The following maintenance cycles had a duration of three days followed by 11 days without treatment. IL-2 dosage was adjusted according to adverse events, frequency of Treg cells and clinical efficacy. |
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End point title |
Safety (combined primary endpoint) [1] | ||||||
End point description |
Safety (combined primary endpoint):
- Any adverse event with CTCAE grade ≥ 3 if not defined otherwise below (except injection site reaction grade 3)
- Increasing lymphocytic infiltration or villous atrophy on histopathological analysis/ gastroduodenoscopy
- Flare of pre-existing, previously silent, immune dysregulatory disorder (e.g. lymphocytic lung infiltration) requiring immunosuppressive treatment with > 20mg prednisolone equivalent
- Percentage of Foxp3+CD127lo Treg among CD3+CD4+ T cells > 50%
- Severe impairment of heart, liver or kidney function (CTCAE grade ≥ 3)
- Cytopenia: - leukocyte count: < 2.000/ µl or - neutropenia < 1000/ µl or - platelets: < 50.000/ µl or - haemoglobin <8g/dl
- Development of autoantibodies (ANA, RF) during the treatment phase
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End point type |
Primary
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End point timeframe |
during the trial
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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: Only two participants were included in trial. Descriptive statistics were used to evaluate the results of the study. |
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No statistical analyses for this end point |
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End point title |
IBDQ score | ||||||
End point description |
Increase of IBDQ score by at least 16 points compared to baseline according to the different dose levels.
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End point type |
Secondary
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End point timeframe |
during the trial
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No statistical analyses for this end point |
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End point title |
Stool frequency | ||||||
End point description |
Reduction of daily stool frequency by 3 stools compared to baseline according to the different dose levels
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End point type |
Secondary
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End point timeframe |
during the trial
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No statistical analyses for this end point |
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End point title |
Weight gain | ||||||
End point description |
Weight gain of ≥ 2kg at EOT visit compared to baseline in each patient.
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End point type |
Secondary
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End point timeframe |
end of trial
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No statistical analyses for this end point |
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End point title |
Norovirus infection | ||||||
End point description |
Clearance of (chronic) norovirus infection during treatment was analysed at 2, 4 and 6 months after initiation of treatment in each norovirus-positive patient at baseline. Patient 001 was negative for norovirus infection and therefore not included in this analysis (reporting group). Patient 002 was a norovirus carrier at baseline level and at all control measurements throughout the treatment.
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End point type |
Secondary
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End point timeframe |
2, 4 and 6 months after initiation of treatment
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No statistical analyses for this end point |
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End point title |
Resolution of lymphocytic infiltration and villous atrophy | ||||||
End point description |
Resolution of lymphocytic infiltration and villous atrophy in gastroduodenoscopy + histopathology will be analyzed in each patient at follow-up compared to baseline.
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End point type |
Secondary
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End point timeframe |
after the low-dose IL-2 treatment
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No statistical analyses for this end point |
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End point title |
Expansion of Tregs | ||||||
End point description |
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End point type |
Secondary
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End point timeframe |
% of Tregs measured before each cycle and on day 4 of every cycle and on day 6 of the induction cycle(s).
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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 |
During the treatment and follow-up
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
21
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Reporting groups
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Reporting group title |
Overall
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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? No | |||
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. | |||
Despite intensive efforts no further eligible patients could be recruited |