Study on Efficacy and Safety of LNP023 in C3 Glomerulopathy Patients Transplanted and Not Transplanted

NCT03832114 | Completed Phase 2 Results FDA Drug

• 1 other identifier: CLNP023X2202
• Study Type: interventional
• Target: 27
• Locations: 6 countries
• Sites: 9

Brief Summary

The study is an open-label, two cohort non-randomized study evaluating the efficacy, safety, and pharmacokinetics of LNP023 in patients with C3G (Cohort A) and patients who have undergone kidney transplant and have C3G recurrence (Cohort B).

Conditions

Glomerulonephritis

Outcome Measures

Primary Outcomes (2)

• Cohort A: Change From Baseline in Urine Protein to Creatinine Concentration Ratio (UPCR)

  Change in proteinuria assessed by ratio to baseline of UPCR derived from 24h urine collection

  Week 12

• Cohort B: Change From Baseline in C3 Deposit

  Histopathological changes in kidney biopsies as assessed by change from baseline in C3 Deposit Score (based on immunofluorescence microscopy)

  Week 12

Secondary Outcomes (17)

• Change From Baseline in Urine Protein Creatinine Concentration Ratio (UPCR)

  Week 12: Day 84

• Change From Baseline in Urine Protein (UP) Excretion

  Week 12: Day 84

• Change From Baseline in Urine Albumin Creatinine Concentration Ratio (UACR) Excretion

  Week 12: Day 84

• Change From Baseline Change in Urinary Albumin (UA) Excretion

  Week 12: Day 84

• Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)

  Day 84

Study Arms (2)

Cohort A - no kidney transplant

EXPERIMENTAL

C3G patients who have not received a kidney transplant and have reduced C3 blood levels.

Drug: LNP023

Cohort B - kidney transplant

EXPERIMENTAL

C3G patients who have received a kidney transplant and have C3G recurrence.

Drug: LNP023

Interventions

LNP023 DRUG

Increasing doses of LNP023 up to 200 mg.

Cohort A - no kidney transplant; Cohort B - kidney transplant

Eligibility Criteria

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

You may qualify if:

• Written informed consent must be obtained before any assessment is performed
• Male and female patients between the ages of 18 to 65 (inclusive) at screening
• C3G patients wit proteinuria
• Able to communicate well with the investigator, to understand and comply with the requirements of the study
• At screening and baseline visits, patients must weigh at least 35 kg
• Supine vital signs should be within the following ranges :
• oral body temperature between 35.0-37.5 °C systolic blood pressure, 80-170 mm Hg diastolic blood pressure, 50-105 mm Hg pulse rate, 45 - 100 bpm
• Estimated GFR (using the CKD-EPI formula) or measured GFR ≥30 mL/min per 1.73 m2 for patients on a maximum recommended or maximum tolerated dose of an angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB)
• UPCR ≥ 100 mg/mmol (equivalent to ≥ 1 g/24h total urinary protein excretion)
• Prior to entry, all patients must have been on supportive care including a maximally tolerated dose of ACEi or ARB for at least 30 days.
• No histological/laboratory/clinical signs of allorejection

You may not qualify if:

• Use of other investigational drugs at the time of enrollment, or within 5 half-lives of randomization, or within 30 days, whichever is longer; or longer if required by local regulations
• A history of clinically significant ECG abnormalities,
• Known family history or known presence of long QT syndrome or Torsades de Pointes
• Use of agents known to prolong the QT interval unless they can be permanently discontinued for the duration of the study
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
• Women of child bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 1 week after stopping of investigational drug.
• History of immunodeficiency diseases, or a positive HIV test result.
• Chronic infection with Hepatitis B (HBV) or Hepatitis C (HCV).
• Patients who cannot receive vaccinations against N. meningitidis, S. pneumoniae, or H. influenzae

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (9)

Novartis Investigative Site

Iowa City, Iowa, 52242, United States

Location

Novartis Investigative Site

Montpellier, 34295, France

Location

Novartis Investigative Site

Paris, 75015, France

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Ranica, BG, 24020, Italy

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Madrid, 28041, Spain

Location

Novartis Investigative Site

London, W12 0NN, United Kingdom

Location

Novartis Investigative Site

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Related Publications (1)

• Wong E, Nester C, Cavero T, Karras A, Le Quintrec M, Lightstone L, Eisenberger U, Soler MJ, Kavanagh D, Daina E, Praga M, Medjeral-Thomas NR, Gackler A, Garcia-Carro C, Biondani A, Chaperon F, Kulmatycki K, Milojevic J, Webb NJA, Nidamarthy PK, Junge G, Remuzzi G. Efficacy and Safety of Iptacopan in Patients With C3 Glomerulopathy. Kidney Int Rep. 2023 Sep 22;8(12):2754-2764. doi: 10.1016/j.ekir.2023.09.017. eCollection 2023 Dec.

  PMID: 38106570 DERIVED

Related Links

• Link to plain language trial summary

MeSH Terms

Conditions

Glomerulonephritis

Condition Hierarchy (Ancestors)

Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

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: NON RANDOMIZED
• Masking: NONE
• Masking Details: Open label study
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study is an open-label, two cohort non-randomized study evaluating the efficacy, safety, and pharmacokinetics of LNP023 in patients with C3G (Cohort A) and patients who have undergone kidney transplant and have C3G recurrence (Cohort B).

Study Record Dates

• First Submitted: January 28, 2019
• First Posted: February 6, 2019
• Study Start: February 20, 2019
• Primary Completion: April 23, 2021
• Study Completion: April 23, 2021
• Last Updated: January 30, 2024
• Results First Posted: July 8, 2022

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share

Locations

US (1); GB (2); DE (1); ES (2); FR (2); IT (1)