This study is designed as a multicenter, randomized, double-blind, parallel group, placebo-controlled study to evaluate the efficacy and safety of iptacopan (LNP023) in idiopathic immune complex mediated membranoproliferative glomerulonephritis.
Eligibility
Sex
ALL
Min age
12 Years
Max age
60 Years
Healthy volunteers
No
Inclusion Criteria:
* Male and female patients including adults (aged at least 18 years to ≤ 60 years) and adolescents (12 -17 years in non-EU countries at screening and 16-17 years in EU countries at screening).
* Diagnosis of idiopathic IC-MPGN as confirmed by kidney biopsy within 12 months prior to screening in adults and within 3 years of screening in adolescents (a biopsy report, review and confirmation by the Investigator is required). If such a biopsy is not available in an adult participant, this must be obtained at screening (performed and assessed locally for adults only).
* Prior to randomization, all participants must have been on a maximally recommended or tolerated dose of renin angiotensin system inhibitors (RASi), e.g an ACEi or ARB for at least 90 days (or as according to local guidelines). The doses of other drugs administered to reduce proteinuria and control the disease including mycophenolic acids (MPAs - mycophenolate mofetil or mycophenolate sodium), corticosteroids, SGLT2 inhibitors and mineralocorticoid receptor antagonists should be stable for at least 90 days prior to randomization
* UPCR ≥ 1.0 g/g (≥ 113 mg/mmol) sampled from the first morning void urine sample at Day -75 and Day -15
* Estimated GFR (using the chronic kidney disease \[CKD\]-EPI formula for adult participants and modified Schwartz formula for adolescents aged 12 to 17 years) or measured GFR ≥ 30 ml/min/1.73m2 at screening and Day -15.
* Mandatory vaccination against Neisseria meningitidis and Streptococcus pneumoniae infection prior to the start of study treatment. If the participant has not been previously vaccinated, or if a booster is required, the vaccine should be given according to local regulations at least 2 weeks prior to the first administration of study treatment. If the study treatment has to start earlier than 2 weeks post vaccination, prophylactic antibiotic treatment should be initiated in accordance with local standard of care.
* If not previously vaccinated, or if a booster is required, vaccination against Haemophilus influenzae infections should be given, if available and according to local regulations, at least 2 weeks prior to the first study treatment administration.
Exclusion Criteria:
* Participants who have undergone cell or solid organ transplantation, including kidney transplantation.
* Participants diagnosed with secondary IC-MPGN including but not limited to any of the following conditions:
* Deposition of antigen-antibody immune complexes as a result of any chronic infections, including
* Hepatitis C virus (HCV) including HCV-associated mixed cryoglobulinemia, hepatitis B virus (HBV);
* Bacterial-endocarditis, infected ventriculo-atrial shunt, visceral abscesses, leprosy, meningococcal meningitis; chronic bacterial infections
* Protozoa/other infections- malaria, schistosomiasis, mycoplasma, leishmaniasis, filariasis, histroplasmosis
Renal deposition of immune complexes as a result of a systemic autoimmune disease:
* Systemic lupus erythematosus (SLE)
* Sjögren syndrome
* Rheumatoid arthritis
* Mixed connective tissue disease Deposition of monoclonal immunoglobulins because of a monoclonal gammopathy due to plasma cell or B cell disorders. Monoclonal gammopathy of undetermined significance (MGUS) confirmed by the measurement of serum free light chains or other investigation as per local standard of care.
Fibrillary glomerulonephritis
* Rapidly progressive crescentic glomerulonephritis defined as a 50% decline in the eGFR within 3 months with kidney biopsy findings of glomerular crescent formation seen in at least 50% of glomeruli on the most recent biopsy.
* Kidney biopsy showing interstitial fibrosis/tubular atrophy (IF/TA) of more than 50%.
* Participants with an active systemic bacterial, viral or fungal infection within 14 days prior to study treatment administration or the presence of fever ≥ 38°C (100.4°F) within 7 days prior to study treatment administration.
* A history of recurrent invasive infections caused by encapsulated organisms, e.g., Neisseria meningitidis and Streptococcus pneumoniae.
* The use of inhibitors of complement factors (e.g., Factor B, Factor D, complement 3 (C3) inhibitors, anti-Complement 5 (C5) antibodies, C5a receptor antagonists) within 3 months or 5 half-lives prior to the Screening visit.
* The use of immunosuppressants (except MPAs), cyclophosphamide or systemic corticosteroids at a dose \>7.5 mg/day (or equivalent for a similar corticosteroid medication) within 90 days of study drug administration.
* The use of MPAs is not permitted within 90 days prior to randomization in India, as per the local health authority requirement.
* Acute post-infectious glomerulonephritis at screening, based upon the opinion of the investigator.
* Body mass index (BMI) \>38 kg/m2 at screening and randomization. Body weight \<35 kg at screening and randomization
Primary outcome measure(s)
Log-transformed ratio to baseline in UPCR (sampled from a 24-hour urine collection) at 6 months. — 6 months (double-blind) To demonstrate the superiority of iptacopan compared to placebo in reducing proteinuria at 6 months.
Log-transformed ratio to baseline in UPCR at the 18-month visit (each study treatment arm) — 18 months To evaluate the effect of iptacopan on proteinuria at 18 months.
Log-transformed ratio to 12-month visit in UPCR at the 18-month visit in the placebo arm. — 18 months To evaluate the effect of iptacopan on proteinuria at 18 months.
Trial sites (131)
Facility
City
Region
Status
Ronald Reagan UCLA Medical Center
Los Angeles
California
Recruiting
Univ Cali Irvine ALS Neuromuscular
Orange
California
Recruiting
UCSF
San Francisco
California
Recruiting
Olive View UCLA Medical Center
Sylmar
California
Recruiting
Childrens Hospital Colorado
Aurora
Colorado
Recruiting
Nicklaus Childrens Hospital
Miami
Florida
Recruiting
Emory University School of Medicine-Winship Cancer Institute
Atlanta
Georgia
Recruiting
Massachusetts General Hospital
Boston
Massachusetts
Recruiting
Boston Univ School of Medicine
Boston
Massachusetts
Recruiting
University of Minnesota
Minneapolis
Minnesota
Recruiting
Washington University in St Louis
St Louis
Missouri
Recruiting
University of New Mexico
Albuquerque
New Mexico
Recruiting
Col Uni Med Center New York Presby
New York
New York
Recruiting
University Of Cincinnati
Cincinnati
Ohio
Recruiting
OHSU Dept of Nephrology
Portland
Oregon
Recruiting
Univ of Pennsylvania Medical Center
Philadelphia
Pennsylvania
Recruiting
MUSC Health Lancaster Med Ctr
Lancaster
South Carolina
Recruiting
UT Southwestern Medical Center
Dallas
Texas
Recruiting
Prolato Clinical Research Center
Houston
Texas
Recruiting
Baylor Scott and White Research
Temple
Texas
Recruiting
University of Utah
Salt Lake City
Utah
Recruiting
University of Wisconsin
Madison
Wisconsin
Recruiting
Novartis Investigative Site
CABA
Buenos Aires
Recruiting
Novartis Investigative Site
CABA
Buenos Aires
Recruiting
Novartis Investigative Site
Córdoba
Córdoba Province
Recruiting
Novartis Investigative Site
Buenos Aires
Argentina
Recruiting
Novartis Investigative Site
CABA
Argentina
Recruiting
Novartis Investigative Site
Santa Fe
Argentina
Recruiting
Novartis Investigative Site
Fortaleza
Ceará
Recruiting
Novartis Investigative Site
Brasília
Federal District
Withdrawn
Novartis Investigative Site
Belo Horizonte
Minas Gerais
Recruiting
Novartis Investigative Site
Recife
Pernambuco
Recruiting
Novartis Investigative Site
Niterói
Rio de Janeiro
Withdrawn
Novartis Investigative Site
Rio de Janeiro
Rio de Janeiro
Withdrawn
Novartis Investigative Site
Natal
Rio Grande do Norte
Recruiting
Novartis Investigative Site
Porto Alegre
Rio Grande do Sul
Recruiting
Novartis Investigative Site
Botucatu
São Paulo
Recruiting
Novartis Investigative Site
Santo André
São Paulo
Recruiting
Novartis Investigative Site
Sao Jose Rio Preto
São Paulo
Recruiting
Novartis Investigative Site
São Paulo
São Paulo
Recruiting
+ 91 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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