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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

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

Вторичные конечные точки (7)

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

Критерии участия

Критерии включения

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.

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 26 центров

• 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
• … и ещё 18 центров

Бразилия · 8 центров

• 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

Германия · 7 центров

• 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

Индия · 7 центров

• 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

Китай · 6 центров

• Novartis Investigative Site — Nanning
• Novartis Investigative Site — Ухань
• Novartis Investigative Site — Шэньян
• Novartis Investigative Site — Иньчуань
• Novartis Investigative Site — Пекин
• Novartis Investigative Site — Шэньчжэнь

Испания · 6 центров

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Turkey (Türkiye) · 6 центров

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Португалия · 5 центров

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Колумбия · 4 центра

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

Франция · 4 центра

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

Мексика · 4 центра

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

Аргентина · 3 центра

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

Венгрия · 3 центра

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

Израиль · 3 центра

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

Малайзия · 3 центра

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

Филиппины · 3 центра

• Novartis Investigative Site — Makati City
• … и ещё 2 центра

Великобритания · 2 центра

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Гонконг · 1 центр

• Novartis Investigative Site — Гонконг

Пуэрто-Рико · 1 центр

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Сингапур · 1 центр

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Публикации

• 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

Идентификаторы

NCT: NCT05268289 · CLNP023K12201 · 2021-002046-33

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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