Efficacy and Safety of Iptacopan (LNP023) in Adult Patients With Atypical Hemolytic Uremic Syndrome Naive to Complement Inhibitor Therapy

NCT04889430 | Completed Phase 3 DMC FDA Drug

• 2 other identifiers: CLNP023F123012020-005186-13
• Study Type: interventional
• Target: 34
• Locations: 8 countries
• Sites: 38

Brief Summary

The purpose of this Phase 3 study is to determine whether iptacopan (LNP023) is efficacious and safe for the treatment of aHUS in adult patients who are treatment naive to complement inhibitor therapy.

Conditions

Atypical Hemolytic Uremic Syndrome

Keywords

LNP023; iptacopan; aHUS; atypical hemolytic uremic syndrome; thrombotic microangiopathy

Outcome Measures

Primary Outcomes (2)

• Percentage of participants with complete TMA response without the use of PE/PI and anti-C5 antibody

  The number/percentage of participants treated with iptacopan achieving complete thrombotic microangiopathy (TMA) response during 26 weeks of study treatment. Complete TMA Response is defined as (1) hematological normalization in platelet count (platelet count ≥150 x 10\^9/L) and LDH (below ULN), and (2) improvement in kidney function (≥ 25% serum creatinine reduction from baseline), maintained for two measurements obtained at least four weeks apart, and any measurement in between

  26 weeks of study treatment

• Long term safety and efficacy evaluations

  Long term (one year) safety, tolerability and efficacy of iptacopan via 1) safety evaluations including adverse events/serious adverse events, safety laboratory parameters, vital signs etc. after 52 weeks of study treatment, and 2) efficacy evaluations including complete TMA response, hematological parameters (platelets, LDH, hemoglobin), eGFR, PROs after 52 weeks of study treatment

  52 weeks of study treatment

Secondary Outcomes (10)

• Time to achieve complete TMA response

  26 weeks of study treatment

• Percentage of participants with increase from baseline in hemoglobin levels ≥ 2 g/dL

  26 weeks of study treatment

• Change from baseline on hematologic parameters

  At week 26

• Percentage of participants on dialysis

  26 weeks of study treatment

• Change from baseline on estimated glomerular filtration rate

  At week 26

Study Arms (1)

Iptacopan 200 mg b.i.d

EXPERIMENTAL

Single arm open-label with 50 adult patients receiving 200mg oral twice daily doses of iptacopan

Drug: Iptacopan

Interventions

Iptacopan DRUG

Iptacopan 200mg twice daily oral

Also known as: LNP023

Iptacopan 200 mg b.i.d

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients with evidence of active thrombotic microangiopathy (TMA), including thrombocytopenia, evidence of hemolysis, and acute kidney injury
• Vaccinations against Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae infections are 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 or before vaccination is given, prophylactic antibiotic treatment must be administered at the start of study treatment and for at least 2 weeks after vaccination

You may not qualify if:

• Treatment with complement inhibitors, including anti-C5 antibody
• ADAMTS13 deficiency (\<10% activity or \<0.1U/ml), and/or Shiga toxin-related hemolytic uremic syndrome (STx-HUS), and/or Positive direct Coombs test
• Identified drug exposure-related HUS or HUS related to known genetic defects of cobalamin C metabolism or known diacylglycerol kinase ε (DGKE) mediated aHUS
• Receiving PE/PI, for 14 days or longer, prior to the start of screening for the current TMA
• Bone marrow transplantation (BMT)/hematopoietic stem cell transplantation (HSCT), heart, lung, small bowel, pancreas, or liver transplantation
• Patients with sepsis or active severe systemic bacterial, viral (including COVID-19) or fungal infection, systemic infection which confounds an accurate diagnosis of aHUS or impedes the ability to manage the aHUS disease, active infection (or history of recurrent invasive infections) caused by encapsulated bacteria
• Kidney disease suggestive of other disease than aHUS or of chronic kidney failure or family history of non-complement mediated genetic kidney disease
• Liver disease or liver injury at screening
• Systemic sclerosis (scleroderma), systemic lupus erythematosus (SLE), or antiphospholipid antibody positivity or syndrome
• Chronic hemo- or peritoneal dialysis

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (38)

USC Norris Cancer Center

Los Angeles, California, 90033, United States

Location

Univ of California at Los Angeles

Los Angeles, California, 90095, United States

Location

Univ Cali Irvine ALS Neuromuscular

Orange, California, 92868, United States

Location

Univ of California at Sacramento

Sacramento, California, 95817, United States

Location

Harbor-UCLA Medical Center .

Torrance, California, 90502, United States

Location

Georgetown University Lombardi Cancer Center

Washington D.C., District of Columbia, 20007-2197, United States

Location

University Of Miami

Miami, Florida, 33136, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Montefiore Medical Center .

The Bronx, New York, 10461, United States

Location

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267-0585, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Comprehensive Transplant Ctr at OSU

Columbus, Ohio, 43210, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Novartis Investigative Site

Fortaleza, Ceará, 60430 370, Brazil

Location

Novartis Investigative Site

Brasília, Federal District, 71635-580, Brazil

Location

Novartis Investigative Site

Belo Horizonte, Minas Gerais, 30150-221, Brazil

Location

Novartis Investigative Site

Recife, Pernambuco, 50740-900, Brazil

Location

Novartis Investigative Site

Porto Alegre, Rio Grande do Sul, 90035-074, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 01327 001, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 04038-002, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 05403 000, Brazil

Location

Novartis Investigative Site

Rio de Janeiro, 22270-060, Brazil

Location

Novartis Investigative Site

Salvador, 40323-010, Brazil

Location

Novartis Investigative Site

Beijing, 100034, China

Location

Novartis Investigative Site

Ostrava, Poruba, 708 52, Czechia

Location

Novartis Investigative Site

Nagpur, Maharashtra, 440015, India

Location

Novartis Investigative Site

Pune, Maharashtra, 411011, India

Location

Novartis Investigative Site

Chandigarh, Punjab, 160012, India

Location

Novartis Investigative Site

Vellore, Tamil Nadu, 632 004, India

Location

Novartis Investigative Site

Hyderabad, Telangana, 500012, India

Location

Novartis Investigative Site

Lucknow, Uttar Pradesh, 226014, India

Location

Novartis Investigative Site

Iruma-gun, Saitama, 3500495, Japan

Location

Novartis Investigative Site

Seoul, Seoul, 03080, South Korea

Location

Novartis Investigative Site

Taichung, 40447, Taiwan

Location

Novartis Investigative Site

Taoyuan, 33305, Taiwan

Location

MeSH Terms

Conditions

Atypical Hemolytic Uremic Syndrome; Thrombotic Microangiopathies

Interventions

iptacopan

Condition Hierarchy (Ancestors)

Hemolytic-Uremic Syndrome; Uremia; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombocytopenia; Blood Platelet Disorders; Cytopenia

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Masking Details: Open label single arm study
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2021
• First Posted: May 17, 2021
• Study Start: January 17, 2022
• Primary Completion: April 11, 2026
• Study Completion: April 11, 2026
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

CN (1); BR (10); IN (6); US (16); KR (1); TW (2); CZ (1); JP (1)