Study of Efficacy and Safety of LNP023 in Participants With Active Lupus Nephritis Class III-IV, +/- V
- Conditions
- Lupus Nephritis
- Interventions
- Drug: Placebo + standard of careDrug: Iptacopan (part 1)Drug: Iptacopan (part 2)Drug: Iptacopan + placebo
- Registration Number
- NCT05268289
- Lead Sponsor
- Novartis Pharmaceuticals
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 240
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.
Induction treatment with cyclophosphamide within 3 months of planned treatment for this study; treatment with calcineurin inhibitors within the previous 3 months prior to screening 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 10 mg/day prednisone (or equivalent) in the previous 4 weeks and more than an average of 20 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/exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Placebo matching iptacopan + standard of care (part 2) Placebo + standard of care Placebo matching iptacopan + standard of care Iptacopan + standard of care (part 1) Iptacopan (part 1) Iptacopan + standard of care Iptacopan + standard of care (part 2) Iptacopan (part 2) Iptacopan + standard of care Iptacopan + placebo (part 2) Iptacopan + placebo Iptacopan + placebo standard of care Placebo matching iptacopan + standard of care (part 1) Placebo + standard of care Placebo matching iptacopan standard of care
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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
Change from baseline in SLEDAI-2K score at weeks 24 and 52 Weeks 24 and 52 Measure disease activity in SLE
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
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 in BILAG-2004 score at weeks 24 and 52 Weeks 24 and 52 Measure disease activity
Change from baseline FACIT-Fatigue Score Weeks 24 and 52 Measure fatigue in patients
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
Trial Locations
- Locations (1)
Novartis Investigative Site
🇹🇷Talas / Kayseri, Turkey