Lupus Nephritis
Conditions
Keywords
LNP023, Iptacopan, Lupus Nephritis, proteinuria, Urine Protein-to-Creatinine Ratio, complete renal response, estimated glomerular filtration rate, renal flares, Systemic Lupus Erythematosus
Brief summary
The overall purpose of this two-part study is to evaluate the efficacy, safety and tolerability of iptacopan (LNP023) in addition to standard of care treatment.
Detailed description
The overall purpose of this two-part study is to evaluate the efficacy, safety and tolerability of iptacopan (LNP023) in addition to standard of care treatment.
Interventions
DRUGIptacopan (part 1)
Taken for 52 Weeks
DRUGIptacopan (part 2)
Taken for 52 Weeks
Taken for 52 Weeks
DRUGIptacopan + placebo
Taken for 52 Weeks
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
Unequivocally positive ANA test result and/or a positive anti dsDNA at screening Active biopsy-proven lupus nephritis within 3 months of screening demonstrating Class III or IV lupus nephritis with or without co-existing features of Class V lupus nephritis. Documentation of active renal disease at the time of screening necessitating the commencement of therapy with corticosteroids in combination with MMF/MPS. eGFR ≥ 30 ml/min/1.73 m2 Vaccination against Neisseria meningitidis and Streptococcus pneumoniae infections Vaccination against Haemophilus influenzae infection Supportive care including stable dose regimen of anti-malarials (e.g. hydroxychloroquine) unless contraindicated, ACEi or ARB at either locally approved maximal daily dose or the maximally tolerated dose (per investigators' judgement) at screening, as per the local clinical practice. Doses should remain stable throughout the study. First presentation or flare of lupus nephritis.
Exclusion criteria
Induction treatment with cyclophosphamide within 3 months of planned treatment for this study; treatment with calcineurin inhibitors within the previous 3 months prior to randomization. Presence of rapidly progressive glomerulonephritis (RPGN) as defined by 50% decline in eGFR within 3 months prior to screening. Renal biopsy presenting with interstitial fibrosis/tubular atrophy (IF/TA) or glomerulosclerosis of more than 50%, or which in the opinion of the investigator is such that it precludes likely response to immunosuppressive therapy. Participants being treated with systemic corticosteroids (\>5 mg/day prednisone or equivalent) for indications other than SLE or LN e.g. acute asthma, inflammatory bowel disease. Participants being treated with systemic corticosteroids for SLE or LN will be excluded if they have taken more than an average of 15 mg/day prednisone (or equivalent) in the previous 4 weeks and more than an average of 30 mg/day in the previous 1 week Receipt of more than a total dose of 1000 mg equivalent i.v. pulse methylprednisolone (cumulative dose) within 2 weeks prior to enrollment (and at enrollment) Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1 and 2: Proportion of patients achieving Complete Renal Response (CRR) at week 24 in the absence of renal flares | Baseline and week 24 | Part 1: To evaluate the proportion of patients achieving complete renal response with iptacopan treatment "A" plus standard of care, compared to treatment alone Part 2: To evaluate the proportion of patients achieving complete renal response with Iptacopan treatment "B" plus standard of care, compared to treatment "D" alone Part 2: To evaluate the proportion of patients achieving complete renal response with Iptacopan treatment "C" plus standard of care, compared to treatment "D" alone Complete Renal Response is defined as meeting the following criteria: estimated glomerular filtration rate (eGFR) ≥ 90 mL/min/1.73 m2 or no less than 85% of baseline value, and 24h urine protein-to-creatinine ratio (UPCR) ≤ 0.5 g/g. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Parts 1 and 2: Proportion of patients achieving CRR or PRR in the absence of renal flares | Baseline, week 24, week 52 | Proportion of patients achieving complete renal response or partial renal response |
| Proportion of patients achieving ≥25% UPCR reduction in the absence of renal flares compared to baseline at week 24 | Baseline, week 24 week 52 | Frequency of renal flares between weeks 24 and 52 |
| Log-transformed ratio to baseline of 24h UPCR at week 24 | Baseline week 24 | Dose exposure response for reduction in proteinurea. (each 24h urine protein-to-creatinine ratio value will based on two 24 urine collections sampled within 10 days before the respective study visit) |
| Change from baseline FACIT-Fatigue Score | Weeks 24 and 52 | Measure fatigue in patients |
| Change from baseline in SLEDAI-2K score at weeks 24 and 52 | Weeks 24 and 52 | Measure disease activity in SLE |
| Change from baseline in BILAG-2004 score at weeks 24 and 52 | Weeks 24 and 52 | Measure disease activity |
| Time-to-Complete Renal Response (CRR) based on first morning void(FMV) urine samples | Week 24 and Week 52 | Measurement of time to complete renal response based on urine samples |
Countries
Argentina, Brazil, China, Colombia, France, Germany, Hong Kong, Hungary, India, Israel, Malaysia, Mexico, Philippines, Portugal, Puerto Rico, Singapore, Spain, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTNovartis Pharmaceuticals
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed