Lupus Erythematosus, SystemicPhase 2Charact-IL-2NCT03312335
Low-dose Interleukin-2 for Treatment of Systemic Lupus Erythematosus
A Phase 2 study testing Low-dose Aldesleukin (Proleukin®) in people with Lupus Erythematosus, Systemic, run by Onur Boyman, MD at 1 site in Switzerland.
Trial summary
Systemic lupus erythematosus (SLE) is an autoimmune disease with multifactorial genesis. Recent research suggests a numerical and functional deficit of regulatory T (Treg) cells as an important contributing factor to the pathology seen in SLE. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lupus Erythematosus, Systemic
- What is being tested?
- Low-dose Aldesleukin (Proleukin®)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteSwitzerland
- Study dates
- 8 Aug 2018to 23 Dec 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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):
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Open-label, Monocentric, Phase II, Investigator-initiated Clinical Trial on Unbiased Characterization of Immunological Parameters in Interleukin-2-treated Systemic Lupus Erythematosus
Systemic lupus erythematosus (SLE) is an autoimmune disease with multifactorial genesis. Recent research suggests a numerical and functional deficit of regulatory T (Treg) cells as an important contributing factor to the pathology seen in SLE. Treg cells play important roles in dampening overt stimulation of effector cells, as seen in many autoimmune diseases. As Treg cells are highly dependent on interleukin-2 (IL-2), application of low doses of IL-2 leads to markedly increased numbers and improved functionality of Treg cells in mice and humans. Several clinical trials investigated the safety of low-dose IL-2 treatment in different autoimmune diseases, including SLE. The trials conducted so far mainly focused on an increase in Treg cells after IL-2 treatment, not evaluating in detail the effects on other immune cells, presumably also playing important roles in the pathogenesis of SLE. For this reason, the investigators of this trial aim to conduct a complete phenotyping of cellular and soluble components in the blood of SLE patients treated with low-dose IL-2. Furthermore, the investigators want to offer this promising treatment to SLE patients in a controlled framework of an investigator initiated clinical trial.
- Conditions
- Lupus Erythematosus, Systemic
- Being tested
- Low-dose Aldesleukin (Proleukin®)
- Keywords
- Lupus Erythematosus, Systemic, SLE, Interleukin-2, IL-2, T-Lymphocytes, Regulatory, Treg
- Medical subject headings
- Lupus Erythematosus, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low-dose Aldesleukin (Proleukin®)Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| Low-dose Aldesleukin (Proleukin®) | Experimental | Not described Receives: Drug: Low-dose Aldesleukin (Proleukin®) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of increase in percentage of Treg cells
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+.
Measured: Comparison between baseline (visit 2, day 0) and week 9 (visit 9, day 68).
Secondary outcomes (11)
Exploratory assessment of cellular immune cell subsets in the blood of SLE patients.
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.
Measured: 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).
Exploratory assessment of soluble cytokines in the blood of SLE patients.
Quantification of cytokines in the blood will include: common gamma chain cytokines, pro-inflammatory cytokines and anti-inflammatory cytokines.
Measured: 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).
Exploratory assessment of soluble CD25 in the blood of SLE patients.
Soluble CD25 will be quantified in the serum of SLE patients.
Measured: 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).
Exploratory assessment of antibodies in the blood of SLE patients.
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.
Measured: 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).
Exploratory assessment of complement activity in SLE patients.
Activity of complete and classical complement pathways will be determined.
Measured: 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).
Assessment of immune cells with immunohistochemistry and immunofluorescence in skin biopsies (optional outcome)
Skin biopsies will be optional and only taken from patients signing a separate consent form.
Measured: Comparison between baseline (visit 2, day 0) and week 9 (visit 9, day 68).
Clinical response measured by the SELENA-SLEDAI score.
Measured: Comparison between baseline (visit 2, day 0), visit 5 (day 26), visit 9 (day 68) and visit 11 (day 124).
Clinical response measured by the BILAG-2004 score.
Measured: Comparison between baseline (visit 2, day 0), visit 5 (day 26), visit 9 (day 68) and visit 11 (day 124).
Clinical response measured by the Physician's Global Assessment (PGA) score.
Measured: Comparison between baseline (visit 2, day 0), visit 5 (day 26), visit 9 (day 68) and visit 11 (day 124).
Clinical response measured by the SLE Responder Index (SRI).
Measured: Comparison between baseline (visit 2, day 0), visit 5 (day 26), visit 9 (day 68) and visit 11 (day 124).
Reduction in dosing of concomitant medication.
Measured: 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).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2017
- Study start8 Aug 2018
- Primary completion23 Dec 2019
- Study completion23 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lupus Erythematosus, SystemicStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Onur Boyman, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Onur Boyman, MD, University of Zurich
- Investigators
- Onur Boyman, MD, Principal investigator, Department of Immunology, University Hospital Zurich, University of Zurich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03312335
- Sponsor's protocol ID
- USZ-IM-001
- Acronym
- Charact-IL-2
- Status last verified
- Aug 2020
- First submitted
- 29 Sep 2017
- Last updated
- 19 Aug 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-label, Monocentric, Phase II, Investigator-initiated Clinical Trial on Unbiased Characterization of Immunological Parameters in Interleukin-2-treated Systemic Lupus Erythematosus
- ClinicalTrials.gov ID
- NCT03312335
- Acronym / sponsor ID
- Charact-IL-2 / USZ-IM-001
- Conditions
- Lupus Erythematosus, Systemic
- Keywords
- Lupus Erythematosus, Systemic, SLE, Interleukin-2, IL-2, T-Lymphocytes, Regulatory, Treg
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Onur Boyman, MDUniversity, hospital or other
- Study start
- 8 Aug 2018 (actual)
- Primary completion
- 23 Dec 2019 (actual)
- Study completion
- 23 Dec 2019 (actual)
- First posted
- 17 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Systemic lupus erythematosus (SLE) is an autoimmune disease with multifactorial genesis. Recent research suggests a numerical and functional deficit of regulatory T (Treg) cells as an important contributing factor to the pathology seen in SLE. Treg cells play important roles in dampening overt stimulation of effector cells, as seen in many autoimmune diseases. As Treg cells are highly dependent on interleukin-2 (IL-2), application of low doses of IL-2 leads to markedly increased numbers and improved functionality of Treg cells in mice and humans. Several clinical trials investigated the safety of low-dose IL-2 treatment in different autoimmune diseases, including SLE. The trials conducted so far mainly focused on an increase in Treg cells after IL-2 treatment, not evaluating in detail the effects on other immune cells, presumably also playing important roles in the pathogenesis of SLE. For this reason, the investigators of this trial aim to conduct a complete phenotyping of cellular and soluble components in the blood of SLE patients treated with low-dose IL-2. Furthermore, the investigators want to offer this promising treatment to SLE patients in a controlled framework of an investigator initiated clinical trial.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Low-dose Aldesleukin (Proleukin®) | Experimental | Drug: Low-dose Aldesleukin (Proleukin®) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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).
Key exclusion criteria (26 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Low-dose Aldesleukin (Proleukin®)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. | Drug | Low-dose Aldesleukin (Proleukin®) |
Primary outcome
Assessment of increase in percentage of Treg cells
Time frame: Comparison between baseline (visit 2, day 0) and week 9 (visit 9, day 68).
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+.
11 secondary outcomes
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2020.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Onur Boyman, MD principal investigator
Department of Immunology, University Hospital Zurich, University of Zurich
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Low-dose Aldesleukin (Proleukin®) in people with Lupus Erythematosus, Systemic, run by Onur Boyman, MD at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of increase in percentage of Treg cells (time frame: Comparison between baseline (visit 2, day 0) and week 9 (visit 9, day 68).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2020.