Clinical trial NCT05268289: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Lupus Nephritis
Keywords: LNP023
Iptacopan
Lupus Nephritis
proteinuria
Urine Protein-to-Creatinine Ratio
complete renal response
estimated glomerular filtration rate
renal flares
Systemic Lupus Erythematosus
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2022-03-07
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Part 1 and 2: Proportion of patients achieving Complete Renal Response (CRR) at week 24 in the absence of renal flares
timeFrame: Baseline and week 24
Secondary outcomes:
measure: Parts 1 and 2: Proportion of patients achieving CRR or PRR in the absence of renal flares
timeFrame: Baseline, week 24, week 52
measure: Proportion of patients achieving ≥25% UPCR reduction in the absence of renal flares compared to baseline at week 24
timeFrame: Baseline, week 24 week 52
measure: Log-transformed ratio to baseline of 24h UPCR at week 24
timeFrame: Baseline week 24
measure: Change from baseline FACIT-Fatigue Score
timeFrame: Weeks 24 and 52
measure: Change from baseline in SLEDAI-2K score at weeks 24 and 52
timeFrame: Weeks 24 and 52
measure: Change from baseline in BILAG-2004 score at weeks 24 and 52
timeFrame: Weeks 24 and 52
measure: Time-to-Complete Renal Response (CRR) based on first morning void(FMV) urine samples
timeFrame: Week 24 and Week 52
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: AKDHC Medical Research ServicesLLC
state: Arizona
city: Fontana
country: United States
facility: Kaiser Permanente Fontana
state: California
city: Irvine
country: United States
facility: Univ Calif Irvine
state: California
city: Loma Linda
country: United States
facility: Loma Linda University
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
city: Sylmar
country: United States
facility: Olive View UCLA Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
city: Hollywood
country: United States
facility: Royal Research Corp
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville
state: Florida
city: Orlando
country: United States
facility: Nephrology Associates Of Central FL
state: Florida
city: Riverview
country: United States
facility: Florida Kidney Physicians
state: Florida
city: Riverview
country: United States
facility: Florida Kidney Physicians
state: Florida
city: Hinsdale
country: United States
facility: Nep Assoc of Northern Illinois
state: Illinois
city: Wichita
country: United States
facility: Wichita Community Clcl Onco Program
state: Kansas
city: New Orleans
country: United States
facility: Ochsner Health System
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Brigham and Womens Hosp Harvard Med School
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: East Setauket
country: United States
facility: Stony Brook Internists PC
state: New York
city: Philadelphia
country: United States
facility: Temple University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny Health Network
state: Pennsylvania
city: Dallas
country: United States
facility: Dallas Nephrology Associates
state: Texas
city: Houston
country: United States
facility: Prolato Clinical Research Center
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Rosario
country: Argentina
facility: Novartis Investigative Site
state: Santa Fe
city: San Luis
country: Argentina
facility: Novartis Investigative Site
city: Santa Fe
country: Argentina
facility: Novartis Investigative Site
city: Salvador
country: Brazil
facility: Novartis Investigative Site
state: BA
city: Belo Horizonte
country: Brazil
facility: Novartis Investigative Site
state: MG
city: Juiz de Fora
country: Brazil
facility: Novartis Investigative Site
state: MG
city: Barretos
country: Brazil
facility: Novartis Investigative Site
state: Sao Paulo
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Salvador
country: Brazil
facility: Novartis Investigative Site
city: Nanning
country: China
facility: Novartis Investigative Site
state: Guangxi
city: Shenyang
country: China
facility: Novartis Investigative Site
state: Liaoning
city: Yinchuan
country: China
facility: Novartis Investigative Site
state: Ningxia
city: Beijing
country: China
facility: Novartis Investigative Site
city: Shenzhen
country: China
facility: Novartis Investigative Site
city: Wuhan
country: China
facility: Novartis Investigative Site
city: Bogota
country: Colombia
facility: Novartis Investigative Site
state: Cundinamarca
city: Bucaramanga
country: Colombia
facility: Novartis Investigative Site
state: Santander
city: Barranquilla
country: Colombia
facility: Novartis Investigative Site
city: Monteria
country: Colombia
facility: Novartis Investigative Site
city: Marseille
country: France
facility: Novartis Investigative Site
city: Nantes
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Strasbourg Cedex
country: France
facility: Novartis Investigative Site
city: Frankfurt am Main
country: Germany
facility: Novartis Investigative Site
state: Hessen
city: Braunschweig
country: Germany
facility: Novartis Investigative Site
state: Niedersachsen
city: Koeln
country: Germany
facility: Novartis Investigative Site
state: Nordrhein-Westfalen
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Ludwigshafen
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Pokfulam
country: Hong Kong
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Szeged
country: Hungary
facility: Novartis Investigative Site
city: Ahmedabad
country: India
facility: Novartis Investigative Site
state: Gujarat
city: Kozhikode
country: India
facility: Novartis Investigative Site
state: Kerala
city: Vellore
country: India
facility: Novartis Investigative Site
state: Tamil Nadu
city: Hyderabad
country: India
facility: Novartis Investigative Site
state: Telangana
city: Lucknow
country: India
facility: Novartis Investigative Site
state: Uttar Pradesh
city: New Delhi
country: India
facility: Novartis Investigative Site
city: Puducherry
country: India
facility: Novartis Investigative Site
city: Ashkelon
country: Israel
facility: Novartis Investigative Site
city: Jerusalem
country: Israel
facility: Novartis Investigative Site
city: Ramat Gan
country: Israel
facility: Novartis Investigative Site
city: Kuantan
country: Malaysia
facility: Novartis Investigative Site
state: Pahang
city: Taiping
country: Malaysia
facility: Novartis Investigative Site
state: Perak
city: Selangor Darul Ehsan
country: Malaysia
facility: Novartis Investigative Site
city: Tampico
country: Mexico
facility: Novartis Investigative Site
state: Tamaulipas
city: Merida
country: Mexico
facility: Novartis Investigative Site
state: Yucatan
city: Aguascalientes
country: Mexico
facility: Novartis Investigative Site
city: Veracruz
country: Mexico
facility: Novartis Investigative Site
city: Makati
country: Philippines
facility: Novartis Investigative Site
state: Metro Manila
city: Iloilo
country: Philippines
facility: Novartis Investigative Site
city: Quezon
country: Philippines
facility: Novartis Investigative Site
city: Carnaxide
country: Portugal
facility: Novartis Investigative Site
state: Lisboa
city: Coimbra
country: Portugal
facility: Novartis Investigative Site
city: Lisboa
country: Portugal
facility: Novartis Investigative Site
city: Porto
country: Portugal
facility: Novartis Investigative Site
city: Vila Nova De Gaia
country: Portugal
facility: Novartis Investigative Site
city: San Juan
country: Puerto Rico
facility: FDI Clinical Research
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Puerto De Sagunto
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Ciudad Real
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
state: Cankaya
city: Bursa
country: Turkey
facility: Novartis Investigative Site
state: Gorukle
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Mersin
country: Turkey
facility: Novartis Investigative Site
city: Talas Kayseri
country: Turkey
facility: Novartis Investigative Site
city: Cambridge
country: United Kingdom
facility: Novartis Investigative Site
city: Leicester
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: