- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03312335
Low-dose Interleukin-2 for Treatment of Systemic Lupus Erythematosus (Charact-IL-2)
Open-label, Monocentric, Phase II, Investigator-initiated Clinical Trial on Unbiased Characterization of Immunological Parameters in Interleukin-2-treated Systemic Lupus Erythematosus
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Zurich, Switzerland
- University Hospital Zurich
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Informed consent forms as documented by signature.
- Diagnosis of SLE according to the criteria issued by the American College of Rheumatology.
- Female and male patients older than 18 years.
- Corticosteroids given at a stable dose for at least 4 weeks prior to enrollment.
- Immunosuppressive medication must be unchanged for at least 4 weeks prior to enrollment (e.g. mycophenolate-mofetil and/or methotrexate, see exclusion criteria).
- Participants must present with the following organ functions as defined below:
- Cardiac: No myocardial infarction prior to enrollment. No symptoms of heart failure New York Heart Association (NYHA) Class II or higher. No severe uncontrolled ventricular arrhythmias. No clinical signs of angina pectoris. No acute ischemia or active conduction system abnormalities additionally documented by an electrocardiogram prior to study enrollment.
- Pulmonary: forced expiratory volume 1 (FEV1) ≥50% (CTCAE grade 3 or lower) or diffusing capacity of the lungs for carbon monoxide (DLCO) ≥40% of predicted values.
- Renal: Glomerular filtration rate (GFR) ≥30 ml/min/1.73m2.
- Hepatic: Adequate hepatic function (aspartate aminotransferase [AST, also termed GOT] and alanine aminotransferase [ALT, also termed GPT] ≤2-fold upper limit of normal; total bilirubin <2.0 mg/dl, except for Gilbert-Meulengracht syndrome.
- The life expectancy of the patients should be greater than 12 months.
Exclusion Criteria:
- Contraindication to IL-2, e.g. known hypersensitivity or allergy.
- Solid organ transplant (allograft) recipient.
- Exposure to any new additional immunosuppressive medication within 4 weeks prior to enrollment.
- Exposure to rituximab 3 months prior to enrollment.
- Exposure to cyclophosphamide 3 months prior to enrollment.
Following concomitant medications above the indicated maximal dose (given orally unless otherwise stated):
g) Hydroxychloroquine, >400 mg/day h) Prednisone, >20 mg/day (or equivalent) i) Azathioprine, >2.5 mg/kg/day j) Mycophenolate-mofetil, >3 g/day k) Methotrexate, injected subcutaneously, >20 mg applied once weekly l) Belimumab, given intravenously, after induction >10 mg/kg every 4 weeks (only 4 participants with Belimumab treatment will be recruited, after this recruitment goal is achieved, Belimumab at any dose becomes an exclusion criteria)
- Simultaneous use of Sirolimus and Tacrolimus at the same time. Either agent alone is allowed. (Risk of thrombotic microangiopathy in chronic graft-versus-host disease patients)
- Participation in another study with investigational drug within 100 days preceding and during the present study.
- History of thrombotic thrombocytopenic purpura, hemolytic-uremic syndrome or thrombotic microangiopathy.
- Any active uncontrolled infection.
- Women who are pregnant or breast feeding.
- Intention to become pregnant during the course of the study.
- Lack of safe contraception, defined as:
Female participants of childbearing potential, not using, not willing to use, and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices in addition to the use of condoms. Note that female participants who are surgically sterilized / hysterectomized or post-menopausal for longer than 2 years are not considered as being of childbearing potential.
Male participants are obliged to use condoms as well to inform their partner about the participation in this trial. In addition, the partner must use a save method of contraception as described above.
- Other clinically significant concomitant disease states (e.g. renal failure, hepatic dysfunction, cardiovascular disease, etc.).
- Known or suspected non-compliance, drug or alcohol abuse.
- Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders or dementia of the participant.
- Previous enrolment in the current study.
- Enrolment of the investigator, his/her family members, employees and other dependent persons.
Chronic infections:
- HIV-positive individuals (increased risk of severe infections).
- Patients suffering from active hepatitis B or C are ineligible.
- Patients suffering from active tuberculosis are ineligible. Patients with latent tuberculosis may be eligible if patient received adequate tuberculostatic treatment.
- Any reason at the discretion of the treating physician where treatment with the investigational drug could indicate a risk for the patient.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Low-dose Aldesleukin (Proleukin®)
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Subcutaneous injection of 1.5 million international units (MIU) of Aldesleukin (Proleukin®, Interleukin-2) once daily in 5-day courses every three weeks for a total of 4 cycles.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Assessment of increase in percentage of Treg cells
Time Frame: Comparison between baseline (visit 2, day 0) and week 9 (visit 9, day 68).
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The primary outcome of this study is an increase in percentage of Treg cells of total CD4+ T cells between visit 2 (baseline) and week 9 (visit 9) measured in the blood of SLE patients not receiving Belimumab treatment.
Treg cells are defined as CD3+CD4+CD127loCD25hiFoxp3+ and total CD4+ T cells are defined as CD3+CD4+.
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Comparison between baseline (visit 2, day 0) and week 9 (visit 9, day 68).
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Exploratory assessment of cellular immune cell subsets in the blood of SLE patients.
Time Frame: Comparison between baseline (visit 2, day 0), visit 3 (day 5), visit 4 (day 21), visit 5 (day 26), visit 6 (day 42), visit 7 (day 47), visit 8 (day 63), visit 9 (day 68), visit 10 (day 96) and visit 11 (day 124).
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Different immune cell subsets isolated from whole blood will be quantified.
Immune cells of interest will include: T cell subsets, including effector and regulatory CD4 and CD8 T cells, B cells, natural killer cells, innate lymphoid cells, dendritic cells, monocytes/macrophages, as well as eosinophil, basophil and neutrophil granulocytes and their respective subtypes including premature stages.
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Comparison between baseline (visit 2, day 0), visit 3 (day 5), visit 4 (day 21), visit 5 (day 26), visit 6 (day 42), visit 7 (day 47), visit 8 (day 63), visit 9 (day 68), visit 10 (day 96) and visit 11 (day 124).
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Exploratory assessment of soluble cytokines in the blood of SLE patients.
Time Frame: Comparison between baseline (visit 2, day 0), visit 3 (day 5), visit 4 (day 21), visit 5 (day 26), visit 6 (day 42), visit 7 (day 47), visit 8 (day 63), visit 9 (day 68), visit 10 (day 96) and visit 11 (day 124).
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Quantification of cytokines in the blood will include: common gamma chain cytokines, pro-inflammatory cytokines and anti-inflammatory cytokines.
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Comparison between baseline (visit 2, day 0), visit 3 (day 5), visit 4 (day 21), visit 5 (day 26), visit 6 (day 42), visit 7 (day 47), visit 8 (day 63), visit 9 (day 68), visit 10 (day 96) and visit 11 (day 124).
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Exploratory assessment of soluble CD25 in the blood of SLE patients.
Time Frame: Comparison between baseline (visit 2, day 0), visit 3 (day 5), visit 4 (day 21), visit 5 (day 26), visit 6 (day 42), visit 7 (day 47), visit 8 (day 63), visit 9 (day 68), visit 10 (day 96) and visit 11 (day 124).
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Soluble CD25 will be quantified in the serum of SLE patients.
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Comparison between baseline (visit 2, day 0), visit 3 (day 5), visit 4 (day 21), visit 5 (day 26), visit 6 (day 42), visit 7 (day 47), visit 8 (day 63), visit 9 (day 68), visit 10 (day 96) and visit 11 (day 124).
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Exploratory assessment of antibodies in the blood of SLE patients.
Time Frame: Comparison between baseline (visit 2, day 0), visit 3 (day 5), visit 4 (day 21), visit 5 (day 26), visit 6 (day 42), visit 7 (day 47), visit 8 (day 63), visit 9 (day 68), visit 10 (day 96) and visit 11 (day 124).
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Specific and unspecific antibodies will be quantified.
This measurement will include Immunglobulin subclasses (IgA, IgG, IgD, IgM and IgE), anti-dsDNA, antinuclear, anti-Sm and anti-C1q antibodies.
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Comparison between baseline (visit 2, day 0), visit 3 (day 5), visit 4 (day 21), visit 5 (day 26), visit 6 (day 42), visit 7 (day 47), visit 8 (day 63), visit 9 (day 68), visit 10 (day 96) and visit 11 (day 124).
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Exploratory assessment of complement activity in SLE patients.
Time Frame: Comparison between baseline (visit 2, day 0), visit 3 (day 5), visit 4 (day 21), visit 5 (day 26), visit 6 (day 42), visit 7 (day 47), visit 8 (day 63), visit 9 (day 68), visit 10 (day 96) and visit 11 (day 124).
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Activity of complete and classical complement pathways will be determined.
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Comparison between baseline (visit 2, day 0), visit 3 (day 5), visit 4 (day 21), visit 5 (day 26), visit 6 (day 42), visit 7 (day 47), visit 8 (day 63), visit 9 (day 68), visit 10 (day 96) and visit 11 (day 124).
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Assessment of immune cells with immunohistochemistry and immunofluorescence in skin biopsies (optional outcome)
Time Frame: Comparison between baseline (visit 2, day 0) and week 9 (visit 9, day 68).
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Skin biopsies will be optional and only taken from patients signing a separate consent form.
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Comparison between baseline (visit 2, day 0) and week 9 (visit 9, day 68).
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Clinical response measured by the SELENA-SLEDAI score.
Time Frame: Comparison between baseline (visit 2, day 0), visit 5 (day 26), visit 9 (day 68) and visit 11 (day 124).
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Comparison between baseline (visit 2, day 0), visit 5 (day 26), visit 9 (day 68) and visit 11 (day 124).
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Clinical response measured by the BILAG-2004 score.
Time Frame: Comparison between baseline (visit 2, day 0), visit 5 (day 26), visit 9 (day 68) and visit 11 (day 124).
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Comparison between baseline (visit 2, day 0), visit 5 (day 26), visit 9 (day 68) and visit 11 (day 124).
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Clinical response measured by the Physician's Global Assessment (PGA) score.
Time Frame: Comparison between baseline (visit 2, day 0), visit 5 (day 26), visit 9 (day 68) and visit 11 (day 124).
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Comparison between baseline (visit 2, day 0), visit 5 (day 26), visit 9 (day 68) and visit 11 (day 124).
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Clinical response measured by the SLE Responder Index (SRI).
Time Frame: Comparison between baseline (visit 2, day 0), visit 5 (day 26), visit 9 (day 68) and visit 11 (day 124).
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Comparison between baseline (visit 2, day 0), visit 5 (day 26), visit 9 (day 68) and visit 11 (day 124).
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Reduction in dosing of concomitant medication.
Time Frame: Comparison between baseline (visit 2, day 0), visit 3 (day 5), visit 4 (day 21), visit 5 (day 26), visit 6 (day 42), visit 7 (day 47), visit 8 (day 63), visit 9 (day 68), visit 10 (day 96) and visit 11 (day 124).
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Comparison between baseline (visit 2, day 0), visit 3 (day 5), visit 4 (day 21), visit 5 (day 26), visit 6 (day 42), visit 7 (day 47), visit 8 (day 63), visit 9 (day 68), visit 10 (day 96) and visit 11 (day 124).
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of adverse events (safety and tolerability)
Time Frame: Visit 2 (day 0), visit 3 (day 5), visit 4 (day 21), visit 5 (day 26), visit 6 (day 42), visit 7 (day 47), visit 8 (day 63), visit 9 (day 68), visit 10 (day 96) and visit 11 (day 124).
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Assessment of safety will be conducted by reporting adverse events.
Frequency, severity and relation to IL-2 treatment will be evaluated and thoroughly described in the final report.
Reporting will follow the Common Terminology Criteria for Adverse Events (CTCAE).
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Visit 2 (day 0), visit 3 (day 5), visit 4 (day 21), visit 5 (day 26), visit 6 (day 42), visit 7 (day 47), visit 8 (day 63), visit 9 (day 68), visit 10 (day 96) and visit 11 (day 124).
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Onur Boyman, MD, Department of Immunology, University Hospital Zurich, University of Zurich
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- USZ-IM-001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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