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

Inclusion Criteria:

• Informed consent forms as documented by signature.

• Diagnosis of SLE according to the criteria issued by the American College ofRheumatology.

• 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 toenrollment (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 failureNew York Heart Association (NYHA) Class II or higher. No severe uncontrolledventricular arrhythmias. No clinical signs of angina pectoris. No acute ischemia oractive conduction system abnormalities additionally documented by an electrocardiogramprior to study enrollment.

• Pulmonary: forced expiratory volume 1 (FEV1) ≥50% (CTCAE grade 3 or lower) ordiffusing 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 toenrollment.

• 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 orallyunless 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 treatmentwill be recruited, after this recruitment goal is achieved, Belimumab at any dosebecomes an exclusion criteria)

• Simultaneous use of Sirolimus and Tacrolimus at the same time. Either agent alone isallowed. (Risk of thrombotic microangiopathy in chronic graft-versus-host diseasepatients)

• Participation in another study with investigational drug within 100 days preceding andduring the present study.

• History of thrombotic thrombocytopenic purpura, hemolytic-uremic syndrome orthrombotic 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 notwilling to continue using a medically reliable method of contraception for the entire studyduration, such as oral, injectable, or implantable contraceptives, or intrauterinecontraceptive devices in addition to the use of condoms. Note that female participants whoare surgically sterilized / hysterectomized or post-menopausal for longer than 2 years arenot considered as being of childbearing potential. Male participants are obliged to use condoms as well to inform their partner about theparticipation in this trial. In addition, the partner must use a save method ofcontraception as described above.

• Other clinically significant concomitant disease states (e.g. renal failure, hepaticdysfunction, 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 dependentpersons.

• 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 latenttuberculosis may be eligible if patient received adequate tuberculostatictreatment.

• Any reason at the discretion of the treating physician where treatment with theinvestigational drug could indicate a risk for the patient.