Study of safety, efficacy and tolerability of ianalumab versus placebo, in combination with SOC therapy, in participants with active lupus nephritis
- Conditions
- upus nephritisMedDRA version: 21.1Level: PTClassification code 10025140Term: Lupus nephritisSystem Organ Class: 10038359 - Renal and urinary disordersTherapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2020-005830-14-DE
- Lead Sponsor
- ovartis Pharma AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 420
Participants eligible for inclusion in this study must meet all of the following criteria:
1. Adult male and female patients aged 18 years or older at the time of screening
2. Signed informed consent must be obtained prior to participation in the study.
3. Have a confirmed clinical diagnosis of SLE according to EULAR/ACR SLE classification criteria (Aringer et al 2019; see Section 16.3)
4.Have a positive anti-nuclear antibody (ANA) test result defined as an ANA titer =1:80 at screening based on central laboratory results or a documented, positive historical result.
5. Presence of active LN at screening requiring induction therapy, as defined by meeting the 3 following criteria, requiring:
• Renal Biopsy within 6 months prior to screening period indicating ISN/RPS class III or IV active glomerulonephritis with or without co-existing class V features, or pure class V membranous LN. If no biopsy was performed within 6 months prior to screening period, a biopsy will need to be performed during the screening period after having met all other inclusion/exclusion criteria.
• Urine protein creatinine ratio (UPCR) =1.0 g/g on 24-hour urine collection at Screening
• Threshold renal function requirement or eGFR =25 mL/min/1.73 m2 (Patients with eGFR <30 mL/min/1.73 m2 require renal biopsy during the screening period showing sclerosis in =50% of glomeruli)Induction therapy, as defined by starting high dose corticosteroids and MPA, may begin before Screening but should be initiated upon or within 60 days prior to randomization. Participants who have been on MPA for SLE including LN may be eligible if they have received, or will receive, the induction therapy within 60 days prior to or on Day 0. This is comprised of initiation of high dose corticosteroids with MPA dose increased to reach the target dose for induction in the participant.
6. Newly diagnosed patients, as well as pre-treated LN participants (including refractory cases) can be included as long as they are currently on, or willing to initiate SoC induction therapy for LN using MPA.
-Induction therapy, as defined by treatment including both high dose corticosteroids and MPA, should be initiated prior to or on the day of randomization;
-Anti-malarial treatment at stable dosing prior to randomization is strongly recommended, in the absence of contraindications
- Participants on azathioprine treatment at Screening must be switched to MPA prior to randomization.
7. Receipt of at least one dose of pulse methylprednisolone i.v. (500-1000 mg) or equivalent for treatment of current episode of active LN during the past 60 days prior to or at screening/randomization
8. Within 60 days prior to randomization, participants who cannot take pulse i.v corticosteroid therapy should directly start on 0.8 - 1.0 mg/kg/day (max 80 mg/day) oral predniso(lo)ne
9. Ability to communicate well with the Investigator to understand and comply with the requirements of the study
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 378
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 42
Participants meeting any of the following criteria are not eligible for inclusion in this study.
1. Severe renal impairment as defined by: i) presence of oliguria
(defined as a documented urine volume <400 mL/24 hrs), or ii.) End-Stage Renal Disease (ESRD) requiring dialysis or transplantation.
2. Sclerosis in >50% of glomeruli on renal biopsy.
3. Use of other investigational drugs within 5 half-lives of enrollment, or within 30 days or until the expected pharmacodynamic effect has returned to baseline, whichever is longer, or longer if required by local regulations
4. Prior use of any B cell depleting therapy (e.g., ianalumab, rituximab or other anti-CD20 mAb, anti-CD22 mAb, or anti-CD52 mAb) administered within 36 weeks prior to randomization or if therapy was administered < 36 weeks prior to randomization B cell count less than the lower limit of
normal or patients own baseline value prior to having received B cell depleting therapy
5. Prior treatment with any of the following within 12 weeks prior to randomization:
• belimumab (anti-BAFF mAb), telitacicept, abatacept (CTLA4-Fc Ig), anti-tumor necrosis factor-alpha (TNF-a) mAb, immunoglobulins (i.v./s.c.) plasmapheresis
• any other immuno-suppressants (e.g., i.v. or oral cyclophosphamide), calcineurin inhibitors (e.g., cyclosporine, voclosporin, tacrolimus), JAK inhibitors or other kinase inhibitors
• thalidomide treatment and/or one of the following DMARDs:
methotrexate or an imidazole derivative (e.g. mizoribine)
• Use of anti-malarials permitted if stable dosing regimen prior to randomization. Combination of other DMARDs is not permitted.
6. Receipt of more than 3000 mg i.v. pulse methylprednisolone
(cumulative dose) within 12 weeks prior to randomization
7. History of major organ transplant or hematopoietic stem cell/bone marrow transplant or are due to receive transplantation
8. Any one of the following laboratory values at screening:
• Hemoglobin levels <8.0 g/dL (one re-test is allowed during the
screening period)
• Platelet count <25 x 103/µL
• Absolute neutrophil count (ANC) <0.8 x 103/µL (one re-test is allowed during the screening period)
9. Active viral, bacterial or other infections requiring systemic treatment at the time of screening , or history of recurrent clinically significant infection
10. History of known intolerance/hypersensitivity to MPA, or oral corticosteroids, or any component of the study drug(s) or its excipients or to drugs of similar chemical classes (e.g., mAb of IgG1 class) or to any of the constituents of the study drug
(sucrose, L-arginine hydrochloride, L-histidine, polysorbate 80,
hydrochloric acid)
11. Receipt of live/attenuated vaccine within a 4-week period prior to randomization
12. History of primary or secondary immunodeficiency, including a positive human immunodeficiency virus (Enzyme-linked immunosorbent assay [ELISA] and Western blot) test result
13. History of malignancy of any organ system (other than localized basal cell carcinoma or squamous cell carcinoma of the skin or in-situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
14. Any surgical, medical (e.g., uncontrolled hypertension, heart failure or diabetes), psychiatric or additional physical condition that the Investigator feels may jeopardize the patient in case of participation in this study.
15.Chronic infection with hepatitis B or hepatitis C. Positive serology for HBsAg excludes th
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method