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Trial record 1 of 1 for:    NCT04578834
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Study of Efficacy and Safety of LNP023 in Primary IgA Nephropathy Patients (APPLAUSE-IgAN)

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ClinicalTrials.gov Identifier: NCT04578834
Recruitment Status : Recruiting
First Posted : October 8, 2020
Last Update Posted : May 10, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
The study is designed as a multicenter, randomized, double-blind, placebo controlled study to demonstrate the superiority of LNP023 at a dose of 200 mg b.i.d. compared to placebo on top of maximally tolerated ACEi or ARB on reduction of proteinuria and slowing renal disease progression in primary IgA Nephropathy patients.

Condition or disease Intervention/treatment Phase
IgA Nephropathy Drug: Placebo Drug: LNP023 Phase 3

Detailed Description:
This trial is a multicenter, randomized, double-blind, placebo controlled parallel group study. The purpose of the study is to evaluate the efficacy and safety of LNP023 compared to placebo on proteinuria reduction and slowing disease progression in primary IgAN patients. The study will be the pivotal trial for registration of LNP023 in IgA Nephropathy patients with the aim to demonstrate a clinically meaningful reduction in proteinuria by LNP023 vs. placebo as assessed by reduction in urine protein to creatinine ratio (UPCR) sampled from a 24 hour urine collection at an IA at 9 months. The trial will continue in a blinded fashion to confirm long-term efficacy based on annualized total slope of eGFR decline over 24 months to provide confirmatory evidence of LNP023 efficacy and safety in treating patients with IgAN. The trial will enroll approximately 450 participants; 430 biopsy-proven IgAN participants with eGFR ≥30 mL /min/1.73m2 (main study population) and approximately 20 participants with eGFR 20 to <30 mL/min/1.73m2 (severe renal impairment (SRI) population). Estimated GFR decline will be calculated using the CKD-EPI formula. The SRI population will not be included in the efficacy analyses of the main study population; it will primarily provide additional PK and safety information for SRI participants.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 450 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel Group, Phase III Study to Evaluate the Efficacy and Safety of LNP023 in Primary IgA Nephropathy Patients
Actual Study Start Date : January 25, 2021
Estimated Primary Completion Date : January 7, 2025
Estimated Study Completion Date : January 14, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Diseases

Arm Intervention/treatment
Experimental: LNP023 200mg b.i.d Drug: LNP023
LNP023 200mg b.i.d

Placebo Comparator: Placebo to LNP023 200mg b.i.d Drug: Placebo
Placebo to LNP023 200mg b.i.d




Primary Outcome Measures :
  1. Ratio to baseline in Urine Protein to Creatinine Ratio (sampled from 24h urine collection) at 9 months [ Time Frame: Baseline and 9 months ]
    Evaluated at interim analysis - To demonstrate superiority of LNP023 vs. placebo in the change of proteinuria at 9 months by measuring Urine Protein to Creatinine Ratio sampled from a 24h urine collection.

  2. Annualized total estimated Glomerular Filtration Rate (eGFR) slope over 24 months). [ Time Frame: Baseline and 24 months ]
    Evaluated at the final analysis - to demonstrate superiority of LNP023 vs. placebo in slowing IgAN progression measured by the annualized total slope of Estimated Glomerular Filtration Rate (eGFR) change over 24 months.


Secondary Outcome Measures :
  1. Proportion of participants reaching Urine Protein To Creatinine Ratio <1g/g without receiving Corticosteroids/Immunosuppressant or other newly approved drugs or initiating new background therapy for treatment of IgAN or Kidney Replacement Therapy (KRT) [ Time Frame: Baseline and 9 months ]
    Evaluated at interim analysis - To assess the effect of LNP023 vs. placebo on the proportion of study participants reaching proteinuria below 1g/g of Urine Protein To Creatinine Ratio (sampled from 24h urine collection) at 9 months.

  2. Annualized total Estimated Glomerular Filtration Rate slope estimated over 12 months [ Time Frame: Baseline and 12 months ]
    Evaluated at interim analysis - To evaluate the effect of LNP023 vs. placebo on slowing IgAN progression measured by the annualized total slope of Estimated Glomerular Filtration Rate change over 1 year.

  3. Change from baseline to 9 months in the fatigue scale measured by the Functional Assessment Of Chronic Illness Therapy-Fatigue questionnaire [ Time Frame: Baseline and 9 months ]
    Evaluated at interim analysis - To assess the effect of LNP023 vs. placebo on the change from baseline to 9 months in fatigue scale measured by the Functional Assessment Of Chronic Illness Therapy-Fatigue questionnaire.

  4. Time from randomization to first occurrence of composite kidney failure endpoint event [ Time Frame: Up to 24 months ]
    Evaluated at final analysis - demonstrate the superiority of LNP023 vs. placebo on delaying the time to first occurrence of a composite kidney failure endpoint, defined as reaching either sustained ≥30% decline in Estimated Glomerular Filtration Rate (eGFR) relative to baseline or sustained eGFR <15 mL/min/1.73m2 or maintenance dialysis or receipt of kidney transplant or death from kidney failure.

  5. Ratio to baseline in Urine Protein-To-Creatinine Ratio (sampled from 24h urine collection) at 9 months [ Time Frame: Baseline and 9 months ]
    Evaluated at final analysis - To demonstrate superiority of LNP023 vs. placebo in the change of proteinuria at 9 months by measuring Urine Protein To Creatinine Ratio sampled from a 24h urine collection.

  6. Proportion of participants reaching Urine Protein-To-Creatinine Ratio <1g/g without receiving Corticosteroids/Immunosuppressant Therapy or other newly approved drugs or initiating new background therapy for treatment of IgAN or initiating KRT [ Time Frame: Baseline and 9 months ]
    Evaluated at final analysis - To demonstrate the superiority of LNP023 vs. placebo on the proportion of study participants reaching proteinuria below 1g/g of Urine Protein To Creatinine Ratio (sampled from 24h urine collection) at 9 months.

  7. Change from baseline to 9 months in the fatigue scale measured by the Functional Assessment Of Chronic Illness Therapy-Fatigue questionnaire. [ Time Frame: Baseline and 9 months ]
    Evaluated at final analysis - To demonstrate the superiority of LNP023 vs. placebo on the change from baseline to 9 months in the fatigue scale measured by Functional Assessment Of Chronic Illness Therapy-Fatigue questionnaire.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female patients ≥ 18 years of age with an eGFR level and biopsy-confirmed IgA nephropathy as follows:
  • For patients eGFR* ≥ 45ml/min/1.73m2, a qualifying biopsy performed within the last 5 years is required.
  • For patients with eGFR* 30 to <45ml/min/1.73m2, a qualifying biopsy performed within 2 years with < 50% tubulointerstitial fibrosis is required.
  • For patients with eGFR* 20 to <30ml/min/1.73m2, a qualifying biopsy performed at any time.

In all cases, if a historical biopsy is not available, one may be performed during screening. *eGFR calculated using the CKD-EPI formula (or modified MDRD formula according to specific ethnic groups and local practice guidelines)

  • Proteinuria due to primary diagnosis of IgA nephropathy as assessed at screening by UPCR ≥1 g/g (113 mg/mmol) sampled from FMV or 24h urine collection, as well as at the completion of the run-in period by UPCR ≥1 g/g (113 mg/mmol) calculated as the (geometric) mean of two 24h urine collections obtained within 14 days of each other at baseline.
  • Vaccination against Neisseria meningitidis infection is required prior to the start of study treatment. If the patient has not been previously vaccinated, or if a booster is required, vaccine should be given according to local regulations at least 2 weeks prior to first study drug administration. If study treatment has to start earlier than 2 weeks post vaccination, prophylactic antibiotic treatment should be initiated.
  • If not previously vaccinated, vaccination against Streptococcus pneumoniae and Haemophilus influenzae infections should be given, if available and according to local regulations, at least 2 weeks prior to first study drug administration. If study treatment has to start earlier than 2 weeks post vaccination, prophylactic antibiotic treatment should be initiated.
  • All patients must have been on supportive care including stable dose regimen of ACEi or ARB at either the locally approved maximal daily dose or the maximally tolerated dose (per investigators' judgment) for at least 90 days before first study drug administration. In addition, if patients are taking diuretics, other antihypertensive medication, or other background medication for IgAN, the doses should also be stabilized for at least 90 days prior to the first dosing of study treatment.

Exclusion Criteria:

  • Any secondary IgAN as defined by the investigator; secondary IgAN can be associated with cirrhosis, celiac disease, Human Immunodeficiency Virus (HIV) infection, dermatitis herpetiformis, seronegative arthritis, small-cell carcinoma, lymphoma, disseminated tuberculosis, bronchiolitis obliterans, and inflammatory bowel disease, familial mediterranean fever, etc.
  • Sitting office SBP >140 mmHg or DBP >90 mmHg at the randomization visit
  • Patients previously treated with immunosuppressive or other immunmodulatory agents such as but not limited to cyclophosphamide, rituximab, infliximab, eculizumab, canakinumab, mycophenolate mofetil (MMF) or mycophenolate sodium (MPS), cyclosporine, tacrolimus, sirolimus, everolimus, or systemic corticosteroids exposure (>7.5 mg/d prednisone/prednisolone equivalent) within 90 days (or 180 days for rituximab) prior to first study drug administration
  • Prior use of LNP023 or prior enrollment in any other LNP023 clinical trial where study drug was taken, including matching placebo
  • History of recurrent invasive infections caused by encapsulated organisms, such as meningococcus and pneumococcus.
  • Active systemic bacterial, viral (including COVID-19) or fungal infection within 14 days prior to study drug administration.

Other protocol-defined inclusion/exclusion criteria may apply.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04578834


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
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Sponsors and Collaborators
Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04578834    
Other Study ID Numbers: CLNP023A2301
First Posted: October 8, 2020    Key Record Dates
Last Update Posted: May 10, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
LNP023
IgA nephropathy
IgAN, proteinuria
UPCR
eGFR
eGFR slope
kidney function decline
Additional relevant MeSH terms:
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Kidney Diseases
Glomerulonephritis, IGA
Urologic Diseases
Glomerulonephritis
Nephritis
Autoimmune Diseases
Immune System Diseases