Study of Efficacy and Safety of LNP023 in Participants With Active Lupus Nephritis Class III-IV, +/- V

Official title

An Adaptive, Randomized, Double-blind, Dose Exploration, Parallel Group, Placebo Controlled, Multicenter Phase 2 Trial to Evaluate the Efficacy, Safety and Tolerability of LNP023 in Combination With Standard-of-care With and Without Oral Corticosteroids in Patients With Active Lupus Nephritis Class III-IV, +/- V

Overview

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

• Drug Iptacopan (part 1)
  Taken for 52 Weeks
• Drug Iptacopan (part 2)
  Taken for 52 Weeks
• Drug Placebo + standard of care
  Taken for 52 Weeks
• Drug Iptacopan + placebo
  Taken for 52 Weeks

Primary outcome measures

• Part 1 and 2: Proportion of patients achieving Complete Renal Response (CRR) at week 24 in the absence of renal flares [Time frame: Baseline and week 24]

Secondary outcome measures (7)

• Parts 1 and 2: Proportion of patients achieving CRR or PRR in the absence of renal flares [Time frame: Baseline, week 24, week 52]
• Proportion of patients achieving ≥25% UPCR reduction in the absence of renal flares compared to baseline at week 24 [Time frame: Baseline, week 24 week 52]
• Log-transformed ratio to baseline of 24h UPCR at week 24 [Time frame: Baseline week 24]
• Change from baseline FACIT-Fatigue Score [Time frame: Weeks 24 and 52]
• Change from baseline in SLEDAI-2K score at weeks 24 and 52 [Time frame: Weeks 24 and 52]
• Change from baseline in BILAG-2004 score at weeks 24 and 52 [Time frame: Weeks 24 and 52]
• Time-to-Complete Renal Response (CRR) based on first morning void(FMV) urine samples [Time frame: Week 24 and Week 52]

Eligibility criteria

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/exclusion criteria may apply

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 26 centers

• AKDHC Medical Research ServicesLLC — Phoenix
• Kaiser Permanente Fontana — Fontana
• Univ Calif Irvine — Irvine
• Ronald Reagan UCLA Medical Center — Los Angeles
• Loma Linda University — San Bernardino
• Olive View UCLA Medical Center — Sylmar
• University of Colorado Denver — Aurora
• Royal Research Corp — Hollywood
• … and 18 more centers

Brazil · 8 centers

• Novartis Investigative Site — Salvador
• Novartis Investigative Site — Belo Horizonte
• Novartis Investigative Site — Juiz de Fora
• Novartis Investigative Site — Barretos
• Novartis Investigative Site — São Paulo
• Novartis Investigative Site — São Paulo
• Novartis Investigative Site — São Paulo
• Novartis Investigative Site — Salvador

Germany · 7 centers

• Novartis Investigative Site — Munich
• Novartis Investigative Site — Ludwigshafen
• Novartis Investigative Site — Frankfurt am Main
• Novartis Investigative Site — Braunschweig
• Novartis Investigative Site — Cologne
• Novartis Investigative Site — Berlin
• Novartis Investigative Site — Mainz

India · 7 centers

• Novartis Investigative Site — Ahmedabad
• Novartis Investigative Site — Kozhikode
• Novartis Investigative Site — New Delhi
• Novartis Investigative Site — Vellore
• Novartis Investigative Site — Hyderabad
• Novartis Investigative Site — Lucknow
• Novartis Investigative Site — Puducherry

China · 6 centers

• Novartis Investigative Site — Nanning
• Novartis Investigative Site — Wuhan
• Novartis Investigative Site — Shenyang
• Novartis Investigative Site — Yinchuan
• Novartis Investigative Site — Beijing
• Novartis Investigative Site — Shenzhen

Spain · 6 centers

Center list to be confirmed — check the primary protocol.

Turkey (Türkiye) · 6 centers

Center list to be confirmed — check the primary protocol.

Portugal · 5 centers

Center list to be confirmed — check the primary protocol.

Colombia · 4 centers

• Novartis Investigative Site — Barranquilla
• Novartis Investigative Site — Bogota
• Novartis Investigative Site — Bucaramanga
• Novartis Investigative Site — Montería

France · 4 centers

• Novartis Investigative Site — Marseille
• Novartis Investigative Site — Nantes
• Novartis Investigative Site — Paris
• Novartis Investigative Site — Strasbourg

Mexico · 4 centers

• Novartis Investigative Site — Tampico
• Novartis Investigative Site — Mérida
• Novartis Investigative Site — Aguascalientes
• Novartis Investigative Site — Veracruz

Argentina · 3 centers

• Novartis Investigative Site — Rosario
• Novartis Investigative Site — San Luis
• Novartis Investigative Site — Santa Fe

Hungary · 3 centers

• Novartis Investigative Site — Debrecen
• Novartis Investigative Site — Budapest
• Novartis Investigative Site — Szeged

Israel · 3 centers

• Novartis Investigative Site — Ashkelon
• Novartis Investigative Site — Jerusalem
• Novartis Investigative Site — Ramat Gan

Malaysia · 3 centers

• Novartis Investigative Site — Kuantan
• Novartis Investigative Site — Taiping
• Novartis Investigative Site — Selangor Darul Ehsan

Philippines · 3 centers

• Novartis Investigative Site — Makati City
• … and 2 more centers

United Kingdom · 2 centers

Center list to be confirmed — check the primary protocol.

Hong Kong · 1 center

• Novartis Investigative Site — Hong Kong

Puerto Rico · 1 center

Center list to be confirmed — check the primary protocol.

Singapore · 1 center

Center list to be confirmed — check the primary protocol.

Publications

• Avasare R, Drexler Y, Caster DJ, Mitrofanova A, Jefferson JA. Management of Lupus Nephritis: New Treatments and Updated Guidelines. Kidney360. 2023 Oct 1;4(10):1503-1511. doi: 10.34067/KID.0000000000000230. PMID 37528520

Identifiers

NCT: NCT05268289 · CLNP023K12201 · 2021-002046-33

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗