Low-dose Interleukin-2 for Treatment of Systemic Lupus Erythematosus

NCT03312335 | Completed Phase 2

• 1 other identifier: USZ-IM-001
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief 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. 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

Keywords

Lupus Erythematosus, Systemic; SLE; Interleukin-2; IL-2; T-Lymphocytes, Regulatory; Treg

Outcome Measures

Primary Outcomes (1)

• 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+.

  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.

  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.

  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.

  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.

  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.

  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).

Other Outcomes (1)

• Incidence of adverse events (safety and tolerability)

  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).

Study Arms (1)

Low-dose Aldesleukin (Proleukin®)

EXPERIMENTAL

Drug: Low-dose Aldesleukin (Proleukin®)

Interventions

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.

Low-dose Aldesleukin (Proleukin®)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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):
• 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.

Sponsors & Collaborators

• Onur Boyman, MD: lead

Study Sites (1)

University Hospital Zurich

Zurich, Switzerland

Location

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

aldesleukin

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Onur Boyman, MD

  Department of Immunology, University Hospital Zurich, University of Zurich

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor and Chair

Study Record Dates

• First Submitted: September 29, 2017
• First Posted: October 17, 2017
• Study Start: August 8, 2018
• Primary Completion: December 23, 2019
• Study Completion: December 23, 2019
• Last Updated: August 19, 2020

Record last verified: 2020-08

Locations

CH (1)