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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03312335
• Date of registration: 29/09/2017
• Prospective Registration: Yes
• Primary sponsor: Onur Boyman, MD
• Public title: Low-dose Interleukin-2 for Treatment of Systemic Lupus Erythematosus Charact-IL-2
• Scientific title: Open-label, Monocentric, Phase II, Investigator-initiated Clinical Trial on Unbiased Characterization of Immunological Parameters in Interleukin-2-treated Systemic Lupus Erythematosus
• Date of first enrolment: August 8, 2018
• Target sample size: 16
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03312335
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Basic Science. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Switzerland

Contacts

• Name: Onur Boyman, MD
• Affiliation: Department of Immunology, University Hospital Zurich, University of Zurich

Key inclusion & exclusion criteria

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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Lupus Erythematosus, Systemic

Intervention(s)

Drug: Low-dose Aldesleukin (Proleukin®)

Primary Outcome(s)

Assessment of increase in percentage of Treg cells [Time Frame: Comparison between baseline (visit 2, day 0) and week 9 (visit 9, day 68).]

Secondary Outcome(s)

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 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).]

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 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).]

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).]

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).]

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 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 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).]

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).]

Secondary ID(s)

USZ-IM-001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors