Systematic Lupus Erythematosus MedDRA version: 20.0 Level: PT Classification code 10042945 Term: Systemic lupus erythematosus System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Sponsors
ILTOO PHARMA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age>=18 years - Male or female - Having a confirmed diagnosis of SLE assessed by the presence of at least 4 of the criteria of American College of Rheumatology (ACR) list or of the Systemic Lupus International Collaborating Clinics (SLICC) list at least at diagnosis. - Having an active SLE characterised by: > SELENA-SLEDAI score >= 6 > Positive for Anti-nuclear antibody (ANA) (equivalent to titre =1:160) AND > positive either for anti-dsDNA-Abs OR for anti-Sm-Abs OR for anti-Ro- Abs OR for anti-Phospholipid-Abs (anti-Cardiolipin-Abs, anti-beta-2- Glycoprotein-Abs or lupus anticoagulant) OR for any combination of these antibodies - Being on stable background therapy (dose and type) before inclusion including any corticotherapy at dose lower than 30mg/day or 0.5mg/kg/day whichever is the lowest. Corticosteroids and antimalarial drug should be stable for 1 month prior to first dosing, immunosuppressant must be stable for 2 months prior to inclusion. - Normal thyroid function (evaluated by both TSH and T4) with or without treatment - Normal thyroid function (evaluated by both TSH and T4) with or without treatment - Using highly effective methods of contraception during the duration of the study, including oral, or injectable hormonal contraceptives or intrauterine device or systems, vasectomised partner, bilateral tubal occlusion, combined with condom - Having freely provided informed consent to participate in the study preceding any study procedure Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 85 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: - A known contraindication to treatment with IL-2: > Hypersensitivity to the active substance or to any of its excipients > Ongoing infection (requiring antibiotic treatment or fever=38°C) at the time of inclusion > Blood oxygen saturation = 90% in resting position > A previous organ allograft - Serious organ failure: > Renal functional impairment (glomerular Filtration Rate Severe central nervous system manifestations > Heart failure of grade 3 or greater by the NYHA classification > Liver disease with transaminases more than 5 times the upper limit of normal - Any clinical evidence of acute or chronic infection, and/or HIV infection (positive serum antibodies against HIV1/2), and/or acute or chronic hepatitis B infection (positive for HBs-Ag in serum), and/or acute or chronic hepatitis C infection (positive for serum HCV RNA). - Patient with clinical significant pleuritis with pleural effusion and/or pericarditis - Patient with mesenteric vasculitis or peritonitis or recent thrombosis (less than 3 months) - Patient diagnosed with type 1 diabetes and/or Crohn’s disease - Use of Benlysta (belimumab) in the past 4 weeks - Use of or Rituximab in the past 24 weeks (6 months) prior to inclusion - Use of cyclosporine, interferon alpha and antimitotic agents in the past 4 weeks - Use of any prohibited drug prior to the study participation as described in section 9.3 and 9.4 - Vaccination with live attenuated virus in the last month - Necessity for application of radiographic iodinated contrast media during and 2 weeks after the completion of the treatment - A white blood cell count <2000/ mm 3, platelets <50 000/ mm or Anemia with Hb=0.8 g/dl - Elevated TSH and T4 - Existing cancer or a history of cancer treated within the past five years, except cervical carcinoma in situ or basal cell carcinoma - Veins in a poor state unsuitable for venepuncture - Major surgery in the previous two months or anticipated during the course of the Study period - In women, pregnancy or lactation - Psychiatric pathology or any other chronic illness or addiction that might interfere with the ability to provide informed consent or to comply with the requirements of the Protocol - A patient under legal protection - Having received any investigational product (small molecule or biologic) or commercially available biologic agent within 4 weeks or 5 half-lives prior to signing of the ICF, whichever is greater
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is the evaluation of the clinical efficacy of ILT-101 (1.5 MUI of IL-2 daily for 5 days and then weekly from day 8 to day 162) at week 12 in active SLE patients with moderate to severe disease activity.; Secondary Objective: To assess: 1/ Maintenance of clinical efficacy (at week 24) within responders (i.e. those with SRI-4 at week 12) 2/ Maintenance of clinical efficacy at week 36 within responders 3/ Safety of ILT-101 during the treatment period 4/ Relationship between immunological cell subsets (Tregs) and clinical endpoints ;Primary end point(s): Percentage of patients with a SLE responder index of 4 (SRI-4) at week 12, SRI-4 response being defined as (1) a = 4-point reduction in SELENA-SLEDAI score as compared to baseline, and (2) no new BILAG A score or = 1 new BILAG B score, and (3) no deterioration from baseline in the physician's global assessment by = 0.3 points;Timepoint(s) of evaluation of this end point: 12 weeks after baseline | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Maintenance of clinical response - Number and percentage of W12 SRI-4 responder patients who sustain SRI-4 response at week 24 - Percentage of W12 SRI-4 responder patients with mild/moderate or severe flares according to SFI at week 24 Corticosteroids tapering • Prednisone-equivalent CS daily dose at week 12 as compared with baseline, at week 24 compared with week 12 and at week 36 as compared with week 24 - Percentage of patients able to reduce oral steroid dose to 15mg daily at week 12, and to 7.5 mg daily prednisone at week 24 - Percentage of patients able to reduce oral steroid dose by 25 and 50% at week 12, 16, 20 and 24 as compared to baseline Biological response - Change in anti-dsDNA at week 4, 8, 12, 20, 24 and 36 as compared to baseline - Change in blood Tregs (expressed as percentage of CD4 and absolute numbers) at day 5, week 4, 12, 24 and 36 as compared to baseline Safety - Safety parameters assessed by clinical examination, routine laboratory tests, recording of adverse events and vital signs preceding any study procedure Maintenance of clinical response from week 12 to 24 Number and percentage of W12 SRI-4 responder patients who sustain SRI-4 response at week 16 and 20 - Number and percentage of W12 SRI-4 responder patients with mild/moderate or severe flares according to SFI at week 16 and 20 - Time to flare between week 12 and week 24 in W12 SRI-4 responder patients - Percentage of patients having a SRI-4 response at week 4, 8 or 12 and who sustain it for 3 months - Percentage of W12 SRI-4 responder patients fulfilling SRI-6, SRI-8, BICLA criteria at week 16, 20 and 24 as compared to baseline Maintenance | — |
Countries
Austria, Bulgaria, France, Germany, Italy, Mauritius, Mexico, Portugal, Romania, Spain
Contacts
Public ContactJérémie MARIAU
ILTOO PHARMA
Outcome results
None listed