Study to Evaluate the Impact of Iptacopan on Top of SOC on Biopsy Changes in Kidneys of Adult Patients With IgAN

NCT06797518 | Recruiting Phase 2 FDA Drug

• 1 other identifier: CLNP023A2201
• Study Type: interventional
• Target: 20
• Locations: 5 countries
• Sites: 18

Brief Summary

A study to investigate the impact of iptacopan treatment on the underlying immunopathology in patients with IgAN by assessing changes in key clinical and molecular markers from baseline to 9 months. The study aims to provide insights into the treatment's systemic and kidney-specific aspects by quantifying the change in mesangial C3c containing fragments deposition, as an indicator of complement activation, and evaluating a variety of biomarkers related to kidney function, damage, and disease progression, including but not limited to Oxford MEST-C score.

Conditions

Glomerulonephritis, IGA; Immunoglobulin A Nephropathy

Keywords

IgAN, Renal Biopsy, Iptacopan

Outcome Measures

Primary Outcomes (1)

• Proportion of participants achieving a reduction of minimum one order of magnitude in complement C3c mesangial deposition.

  Mesangial C3c deposition is assessed by intensity of immunofluorescence (IF) staining using the following grading system: 0 (absent) 1 (+) 2 (++) 3 (+++)

  BSL, Month 9

Secondary Outcomes (2)

• Change from baseline at 9 months in CD68 cells

  BSL, Month 9

• Change from baseline at 9 months in staining of Immunoglobulins (IgA and IgG)

  BSL, Month 9

Study Arms (1)

Iptacopan

EXPERIMENTAL

All the study participants will receive iptacopan 200 mg oral capsule b.i.d, while remaining on the maximally tolerated or locally approved maximal daily doses of ACEi/ARB throughout the treatment period.

Drug: Iptacopan

Interventions

Iptacopan DRUG

LNP023 oral capsule 200 mg b.i.d

Also known as: LNP023

Iptacopan

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent must be obtained prior to participation in the study; participants should be able to communicate well with the investigator, understand and comply with the requirements of the study.
• Male and female participants ≥18 years of age with biopsy-confirmed IgA nephropathy and an eGFR ≥ 30 mL/min/1.73m2. eGFR will be calculated using the CKD-EPI 2009 formula.
• Proteinuria as assessed at screening by UPCR ≥ 0.8g/g or 1g/d sampled from FMV.
• Biopsy at baseline should confirm IgAN with \< 50% tubulointerstitial fibrosis.
• Participants must be on ACEi or ARB treatment at either the locally approved maximal daily dose or the maximally tolerated dose (per investigators' judgment) for approximately 90 days prior to baseline visit and continue on a stable dose throughout the study. Participants with allergies or intolerance to ACEi and ARB are eligible for the study, but the investigator should clearly document the reasons for not being on maximal ACEi/ARB dose in the source documents. In addition, if participants are taking diuretics, other antihypertensive medication or Sodium-Glucose Co-Transporter 2 inhibitors (SGLT2i), the doses should be stabilized for at least 90 days prior to baseline.
• Vaccination against Neisseria meningitidis and Streptococcus pneumoniae infections required to be completed at least 2 weeks prior to the start of study treatment. If the participants have 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 must start earlier than 2 weeks post-vaccination, prophylactic antibiotic treatment should be initiated.
• Vaccination against Haemophilus influenzae infection should be given, if available and according to local regulations, at least 2 weeks prior to first study drug administration.

You may not qualify if:

• Any secondary IgAN (at historic or baseline biopsies) as defined by the investigator and IgA vasculitis Henoch-Scholein Purpura (HSP). 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.
• Any secondary diagnosis at baseline biopsy (other than IgA nephropathy).
• Evidence of significant urinary obstruction or difficulty in voiding; any urinary tract disorder other than IgAN at screening and before first study drug administration.
• Current or planned usage of any homeopathic and/or herbal medications for IgAN disease progression, such as but not limited to Lei Gong Teng.
• Current acute kidney injury (AKI) defined by Acute Kidney Injury Network (AKIN) criteria within 4 weeks of screening.
• Presence of rapidly progressive glomerulonephritis (RPGN) as defined by 50% decline in eGFR within 3 months prior to screening, or presence of nephrotic syndrome.
• Sitting office SBP \>140 mmHg or DBP \>90 mmHg at the screening visit.
• Participants treated with immunosuppressive or other immunomodulatory agents such as but not limited to cyclophosphamide, rituximab, infliximab, eculizumab, canakinumab, mycophenolate mofetil (MMF) or mycophenolate sodium (MPS), cyclosporine, tacrolimus, sirolimus, everolimus, systemic corticosteroids exposure (\>7.5 mg/d prednisone/prednisolone equivalent) or targeted release formulation (TRF) of budesonide within 90 days (or 180 days for rituximab) prior to first study drug administration. Participants using other medication such us hydroxychloroquine or Endothelin receptor antagonists (ERAs).
• Use of other investigational drugs within 5 half-lives or within 30 days of enrollment, whichever is longer.
• Prior use of iptacopan or prior enrollment in any other iptacopan clinical trial where study drug was taken, including matching placebo.
• All transplanted participants (any solid organ transplantation, including bone marrow transplantation).
• History of recurrent invasive infections caused by encapsulated organisms, such as meningococcus and pneumococcus.
• Major concurrent comorbidities including but not limited to advanced cardiac disease (e.g., New York Heart Association (NYHA) class IV), severe pulmonary disease (e.g., severe pulmonary hypertension (World Health Organization (WHO) class IV)), or hepatic disease (e.g., active hepatitis) that in the opinion of the investigator precludes participant's participation in the study.
• Any medical condition deemed likely to interfere with the participant's participation in the study or that will require the use of prohibited medications.
• Active systemic bacterial, viral (including COVID-19) or fungal infection within 14 days prior to study drug administration.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (18)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

RECRUITING

UCLA Medical Center

Los Angeles, California, 90095, United States

RECRUITING

Central Florida Kidney Specialists

Orlando, Florida, 32806, United States

RECRUITING

Georgia Nephrology Research Inst

Lawrenceville, Georgia, 30046, United States

RECRUITING

CaRe Research

Chubbuck, Idaho, 83202, United States

RECRUITING

DaVita Clinical Research

Las Vegas, Nevada, 89146, United States

RECRUITING

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

RECRUITING

OSU Wexner Medical Center

Columbus, Ohio, 43210, United States

RECRUITING

Prolato Clinical Research Center

Houston, Texas, 77054, United States

RECRUITING

Novartis Investigative Site

CABA, Buenos Aires, 1280, Argentina

RECRUITING

Novartis Investigative Site

CABA, Buenos Aires, 1425, Argentina

RECRUITING

Novartis Investigative Site

Córdoba, Córdoba Province, 5000, Argentina

RECRUITING

Novartis Investigative Site

Ashdod, 7747629, Israel

RECRUITING

Novartis Investigative Site

Hadera, 3820302, Israel

RECRUITING

Novartis Investigative Site

Haifa, 3109601, Israel

RECRUITING

Novartis Investigative Site

Nahariya, 2210001, Israel

RECRUITING

Novartis Investigative Site

Kuala Lumpur, Selangor, 43000, Malaysia

RECRUITING

Novartis Investigative Site

Riyadh, 11211, Saudi Arabia

RECRUITING

MeSH Terms

Conditions

Glomerulonephritis, IGA

Interventions

iptacopan

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

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Novartis Pharmaceuticals

CONTACT

1-888-669-6682; novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

+41613241111

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2025
• First Posted: January 28, 2025
• Study Start: February 21, 2025
• Primary Completion (Estimated): November 27, 2027
• Study Completion (Estimated): November 27, 2027
• Last Updated: April 27, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

SA (1); US (9); AR (3); IL (4); MY (1)