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

Lupus Nephritis Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05268289
• Other study ID #: CLNP023K12201
• Secondary ID: 2021-002046-33
• Status: Recruiting
• Phase: Phase 2
• Start date: August 10, 2022
• Est. completion date: March 13, 2028

Study information

• Verified date: May 2024
• Source: Novartis
• Contact: Novartis Pharmaceuticals
• Phone: 1-888-669-6682
• Email: novartis.email[@]novartis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: March 13, 2028
• Est. primary completion date: October 24, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 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

Related Conditions & MeSH terms

• Lupus Nephritis
• Nephritis

Intervention

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

Locations

Country	Name	City	State
Brazil	Novartis Investigative Site	Sao Paulo	SP
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Wuhan
France	Novartis Investigative Site	Marseille
France	Novartis Investigative Site	Nantes Cedex 1
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Strasbourg Cedex
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Muenchen
Hong Kong	Novartis Investigative Site	Pokfulam
Hungary	Novartis Investigative Site	Debrecen
India	Novartis Investigative Site	New Delhi
India	Novartis Investigative Site	Puducherry
India	Novartis Investigative Site	Vellore	Tamil Nadu
Israel	Novartis Investigative Site	Ashkelon
Israel	Novartis Investigative Site	Jerusalem
Israel	Novartis Investigative Site	Ramat Gan
Malaysia	Novartis Investigative Site	Kuantan	Pahang
Malaysia	Novartis Investigative Site	Selangor Darul Ehsan
Malaysia	Novartis Investigative Site	Taiping	Perak
Mexico	Novartis Investigative Site	Merida	Yucatan
Mexico	Novartis Investigative Site	Tampico	Tamaulipas
Mexico	Novartis Investigative Site	Veracruz
Portugal	Novartis Investigative Site	Carnaxide - Linda-A-Velha	Lisboa
Portugal	Novartis Investigative Site	Lisboa
Portugal	Novartis Investigative Site	Vila Nova de Gaia
Puerto Rico	Novartis Investigative Site	San Juan
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Sevilla	Andalucia
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Bursa	Gorukle
Turkey	Novartis Investigative Site	Istanbul
Turkey	Novartis Investigative Site	Talas / Kayseri
United States	Novartis Investigative Site	Baltimore	Maryland
United States	Novartis Investigative Site	Hinsdale	Illinois
United States	Novartis Investigative Site	Phoenix	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Brazil,  China,  France,  Germany,  Hong Kong,  Hungary,  India,  Israel,  Malaysia,  Mexico,  Portugal,  Puerto Rico,  Singapore,  Spain,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1 and 2: Proportion of patients achieving Complete Renal Response (CRR) at week 24 in the absence of renal flares	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.	Baseline and week 24
Secondary	Parts 1 and 2: Proportion of patients achieving CRR or PRR in the absence of renal flares	Proportion of patients achieving complete renal response or partial renal response	Baseline, week 24, week 52
Secondary	Proportion of patients achieving =25% UPCR reduction in the absence of renal flares compared to baseline at week 24	Frequency of renal flares between weeks 24 and 52	Baseline, week 24 week 52
Secondary	Log-transformed ratio to baseline of 24h UPCR at 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)	Baseline week 24
Secondary	Change from baseline FACIT-Fatigue Score	Measure fatigue in patients	Weeks 24 and 52
Secondary	Change from baseline in SLEDAI-2K score at weeks 24 and 52	Measure disease activity in SLE	Weeks 24 and 52
Secondary	Change from baseline in BILAG-2004 score at weeks 24 and 52	Measure disease activity	Weeks 24 and 52
Secondary	Time-to-Complete Renal Response (CRR) based on first morning void(FMV) urine samples	Measurement of time to complete renal response based on urine samples	Week 24 and Week 52