Study of Safety and Efficacy of LNP023 in Patients With Kidney Disease Caused by Inflammation

NCT03373461 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: CLNP023X22032017-000891-27
• Study Type: interventional
• Target: 112
• Locations: 25 countries
• Sites: 56

Brief Summary

Efficacy and safety of LNP023 in IgAN patients

Conditions

IgA Nephropathy

Keywords

glomerunephritis, complement driven, chronic kidney disease

Outcome Measures

Primary Outcomes (1)

• MCP-Mod Estimates of the Ratio to Baseline of Urine Protein to Creatinine Ratio (UPCR) (g/Mol) - Parts 1 and 2 at Day 90

  The primary analysis of the dose-response effect of LNP023 versus placebo on the reduction in UPCR 24 hours at Day 90 was done using Multiple Comparison Procedure Modelling (MCP-Mod). The existence of a dose-response relationship was assessed at the MCP step at the one-sided 10% significance level vis a multiple contrasts test. In the Mod step, the mean predicted difference between each LNP023 dose and placebo were then estimated using parametric bootstrap model averaging. Results are presented on the original scale as geometric mean ratios. A ratio less than 1 indicates a reduction in proteinuria. Participants collected all urine over a 24 hour period for UPCR test.

  Baseline and Day 90

Secondary Outcomes (20)

• Mixed Model of Repeated Measures (MMRM) of the Change From Baseline for Estimated Glomerular Filtration Rate (eGFR) - Parts 1 and 2 at Day 90

  Baseline and Day 90

• Mixed Model of Repeated Measures (MMRM) of the Change From Baseline for Serum Creatinine - Parts 1 and 2 at Day 90

  Baseline and Day 90

• Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90

  Baseline and Day 90

• Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in 24hour Urine Protein (UP) - Parts 1 and 2 to Day 90

  Baseline and Day 90

• Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline of 24 Hour Urine Albumin (UA) - Parts 1 and 2 to Day 90

  Baseline and Day 90

Study Arms (5)

Placebo

PLACEBO COMPARATOR

Placebo identical to LNP023 twice a day

Other: Placebo

LNP023 10 mg BID

EXPERIMENTAL

10 mg taken twice a day.

Drug: LNP023

LNP023 50 mg BID

EXPERIMENTAL

50 mg taken twice a day.

Drug: LNP023

LNP023 100 mg BID - Part 2

EXPERIMENTAL

100 mg taken twice a day.

Drug: LNP023

LNP023 200 mg BID

EXPERIMENTAL

200 mg taken twice a day.

Drug: LNP023

Interventions

LNP023 DRUG

LNP023 5, 25, 100 mg capsles

LNP023 10 mg BID; LNP023 100 mg BID - Part 2; LNP023 200 mg BID; LNP023 50 mg BID

Placebo OTHER

Matching placebo to LNP023

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female and male patients above 18 years of age with a biopsy-verified IgA nephropathy and where the biopsy was performed within the prior three years.
• Patients must weigh at least 35 kg to participate in the study, and must have a body mass index (BMI) within the range of 15 - 38 kg/m2. BMI = Body weight (kg) / \[Height (m)\]2
• Measured Glomerular Filtration Rate (GFR) or estimated GFR (using the CKD-EPI formula) ≥30 mL/min per 1.73 m2
• Urine protein ≥1 g/24hr at screening and ≥0.75 g / 24h after the run- in period
• Vaccination against Neisseria meningitidis types A, C, Y and W-135 is required at least 30 days prior to first dosing with LNP023. Vaccination against N. meningitidis type B, S. pneumoniae and H. influenzae should be conducted if available and acceptable by local regulations, at least 30 days prior to first dosing with LNP023
• All patients must have been on supportive care including a maximally tolerated dose of ACEi or ARB therapy for the individual, antihypertensive therapy or diuretics for at least 90 days before dosing

You may not qualify if:

• Presence of crescent formation in ≥50% of glomeruli assessed on renal biopsy
• Patients previously treated with immunosuppressive agents such as cyclophosphamide or mycophenolate mofetil (MMF), or cyclosporine, systemic corticosteroids exposure within 90 days prior to start of LNP023/Placebo dosing
• Use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment, or within 30 days, whichever is longer; or longer if required by local regulations
• All transplanted patients (any organ, including bone marrow)
• History of immunodeficiency diseases, or a positive HIV (ELISA and Western blot) test result.
• Chronic infection with Hepatitis B (HBV) or Hepatitis C (HCV). A positive HBV surface antigen (HBsAg) test, or if standard local practice, a positive HBV core antigen test, excludes a patient. Patients with a positive HCV antibody test should have HCV RNA levels measured. Subjects with positive (detectable) HCV RNA should be excluded
• Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the subject in case of participation in the study. The Investigator should make this determination in consideration of the subject's medical history and/or clinical or laboratory evidence of any of the following:
• A history of invasive infections caused by encapsulated organisms, e.g. meningococcus or pneumococcus
• Splenectomy
• Inflammatory bowel disease, peptic ulcers, severe gastrointestinal disorder including rectal bleeding;
• Major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection;
• Pancreatic injury or pancreatitis;
• Liver disease or liver injury as indicated by abnormal liver function tests. ALT (SGPT), AST (SGOT), GGT, alkaline phosphatase and serum bilirubin will be tested.
• Any single parameter of ALT, AST, GGT, alkaline phosphatase or serum bilirubin must not exceed 3 x upper limit of normal (ULN)
• PT/INR must be within the reference range of normal individuals

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (56)

Novartis Investigative Site

Caba, Buenos Aires, C1280AEB, Argentina

Location

Novartis Investigative Site

Ciudad Autonoma de Bs As, Buenos Aires, C1015ABO, Argentina

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Westmead, New South Wales, 2145, Australia

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Parkville, Victoria, 3050, Australia

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Edegem, Antwerpen, 2650, Belgium

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Leuven, 3000, Belgium

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Roeselare, 8800, Belgium

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Curitiba, Paraná, 80440-020, Brazil

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Porto Alegre, Rio Grande do Sul, 90020-090, Brazil

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Guangzhou, Guangdong, 510080, China

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Beijing, 100034, China

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Guangzhou, 510080, China

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Shanghai, 200040, China

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Barranquilla, Colombia

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Prague, 12808, Czechia

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Aalborg, 9000, Denmark

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Arhus N, DK-8200, Denmark

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HUS, Finland, 00029, Finland

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Montpellier, 34295, France

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Berlin, 13353, Germany

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Heidelberg, 69120, Germany

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Hong Kong SAR, Hong Kong

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New Delhi, National Capital Territory of Delhi, 110 017, India

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New Delhi, 110029, India

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Ashkelon, 78278, Israel

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Jerusalem, 9112001, Israel

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Petah Tikva, 49100, Israel

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Toyoake, Aichi-ken, 470 1192, Japan

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Sapporo, Hokkaido, 006-8555, Japan

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Sendai, Miyagi, 981-3205, Japan

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Okayama, Okayama-ken, 700-8558, Japan

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Osaka, Osaka, 530-8480, Japan

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Kuala Lumpur, 50589, Malaysia

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Groningen, 9713 GZ, Netherlands

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Bergen, 5021, Norway

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Loerenskog, NO 1478, Norway

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Oslo, NO 0450, Norway

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Singapore, 119228, Singapore

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Singapore, 169608, Singapore

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Seoul, 03080, South Korea

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Lund, 221 85, Sweden

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Stockholm, 141 86, Sweden

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New Taipei City, 23561, Taiwan

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Taichung, 40705, Taiwan

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Taipei, 10048, Taiwan

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Bangkok, 10330, Thailand

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Bangkok, 10400, Thailand

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Istanbul, TUR, 34098, Turkey (Türkiye)

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Ankara, 06100, Turkey (Türkiye)

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Novartis Investigative Site

Kocaeli, 41380, Turkey (Türkiye)

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Novartis Investigative Site

Talas / Kayseri, 38039, Turkey (Türkiye)

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Novartis Investigative Site

Cambridge, Cambrigdeshire, CB2 0QQ, United Kingdom

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Novartis Investigative Site

Salford, Manchester, M6 8HD, United Kingdom

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Novartis Investigative Site

Leicester, LE5 4PW, United Kingdom

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Novartis Investigative Site

London, SE5 9RS, United Kingdom

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Novartis Investigative Site

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Related Links

• A Plain Language Trial Summary is available on novctrd.com

MeSH Terms

Conditions

Glomerulonephritis, IGA; Renal Insufficiency, Chronic

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Autoimmune Diseases; Immune System Diseases; Renal Insufficiency; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+ 1 862 778 8300

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2017
• First Posted: December 14, 2017
• Study Start: February 7, 2018
• Primary Completion: December 29, 2020
• Study Completion: June 22, 2021
• Last Updated: January 30, 2023
• Results First Posted: October 7, 2022

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share

Locations

TU (4); CZ (1); IL (3); BE (3); GB (5); KR (1); NL (1); TW (3); AU (2); DE (2); BR (2); FR (1); CO (1); AR (2); DK (2); FI (1); HK (1); MY (1); NO (3); SE (2); SG (2); TH (2); IN (2); CN (4); JP (5)