A study to evaluate the effectiveness and safety of the study drug, when patients are given dosage of ILT-101 with active moderate to severe systemic lupus erythematosus(SLE)

• Register: EUCTR
• Last refreshed on: 30 April 2019
• Main ID: EUCTR2016-000488-17-AT
• Date of registration: 21/07/2016
• Prospective Registration: Yes
• Primary sponsor: ILTOO PHARMA
• Public title: A study to evaluate the effectiveness and safety of the study drug, when patients are given dosage of ILT-101 with active moderate to severe systemic lupus erythematosus(SLE)
• Scientific title: A Phase II, multi-centre, randomized, double blind, placebo-controlled study to evaluate the efficacy, safety and pharmacokinetics of ILT-101 in patients with active moderate to severe systemic lupus erythematosus (SLE)
• Date of first enrolment: 08/08/2016
• Target sample size: 100
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-000488-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Bulgaria, France, Germany, Italy, Mauritius, Mexico, Portugal, Romania, Spain

Contacts

• Name: Jérémie MARIAU
• Affiliation: ILTOO PHARMA

• Name: Jérémie MARIAU
• Affiliation: ILTOO PHARMA

Key inclusion & exclusion 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:
- 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 <60ml/min) OR (urinary protein = 2g/24h with normal albuminemia)
> 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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Body processes [G] - Immune system processes [G12]

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

Intervention(s)

Product Name: ILT-101
Product Code: ILT-101
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Aldesleukin
CAS Number: 110942-02-4
Other descriptive name: INTERLEUKIN-2
Concentration unit: million IU million international units
Concentration type: equal
Concentration number: 1.2-
Pharmaceutical form of the placebo: Powder for solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

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

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.

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 Outcome(s)

Timepoint(s) of evaluation of this end point: Please refer to E.5.2

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 of biological and clinical response at week 36
• Number and percentage of W12 and W24 SRI-4 responder patients who sustain SRI-4 response at week 36
• Number and percentage of W12 and W24 SRI-4 responder patients with mild/moderate or severe flares according to SFI at week 36
• Time to flare between week 24 and week 36 in W24 SRI-4 responder patients
• Percentage of W12 and W24 SRI-4 responder patients fulfilling SRI-6, SRI-8, BICLA criteria at week 36 as compared to week 24
• Change in anti-dsDNA at week 36 as compared to week 24
• Change in blood Tregs (expressed as percentage of CD4 and absolute numbers) at week 36 as compared to week 24

Early clinical response
- Number and percentage of patients responding to treatment according to SRI-4 at week 4 and 8 as compared to baseline
- Number and percentage of patients fulfilling SRI-6, SRI-8, BICLA criteria at week 4, 8 and 12 as compared to baseline
- Time to first SRI-4, -6, -8 response during the first three months
- Time to flare during the first three months
- Number and percentage of patients with mild/moderate or severe flares according to SFI at week 4, 8 and 12

Other clinical assessments
- Absolute and relative change in SELENA-SLEDAI at week 4, 8, 12, 16, 20 24 and 36 as compared to baseline
- Absolute and relative change in BILAG at week 4, 8, 12, 16, 20, 24 and 36 as compared to baseline
- Absolute and relative change in PGA at week 4, 8, 12, 16, 20, 24 and 36 as compared to baseline
- Percentage of patients in remission (SLEDAI=2) at week 4, 8, 12, 16, 20, 24 and 36
- Quality of life index: Lupus QoL at week 4, 12, 24 and 36 as compared to baseline
- Fatigue by VAS and fatigue severity scale at week 4, 8, 12, 24 and 36 as compared to baseline
Biological response
- Change in C3/C4 at week 4, 8, 12, 20, 24 and 36 as compared to baseline
- Quantification of anti-ILT-101 antibodies and of their neutralising effect at baseline, week 12 and 24

Secondary ID(s)

LUPIL-2

Source(s) of Monetary Support

ILTOO PHARMA

Ethics review

Status: Approved
Approval date:
Contact: