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

Phase 3

Recruiting

• Conditions: Atypical Hemolytic Uremic Syndrome
• Interventions: Drug: Iptacopan

• Registration Number: NCT04889430
• Lead Sponsor: Novartis Pharmaceuticals

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.

Detailed Description

The study is designed as a multicenter, single-arm, open label study to demonstrate the efficacy and safety of LNP023 (iptacopan) at a dose of 200 mg b.i.d. in adult patients with aHUS who are treatment naive to complement inhibitor therapy (including anti-C5 antibody). The study will enroll approximately 50 participants and assess the effects of iptacopan on a range of efficacy assessments relevant to aHUS including hematological and kidney parameters, dialysis requirement, changes in chronic kidney disease (CKD) stage, as well as patient reported outcomes (PRO) for fatigue and quality of life.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations
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Related News

Study Timeline

• Study First Submitted: 2021-05-07
• Study First Submitted QC: 2021-05-13
• Study First Posted: 2021-05-17
• Study Start: 2022-01-17
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-11
• Last Update Posted: 2024-12-12
• Primary Completion: 2025-12-23
• Study Completion: 2026-01-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

• 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

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Exclusion Criteria

• 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

Other protocol-defined inclusion/exclusion criteria may apply

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Iptacopan 200 mg b.i.d	Iptacopan	Single arm open-label with 50 adult patients receiving 200mg oral twice daily doses of iptacopan

Primary Outcome Measures

Name	Time	Method
Percentage of participants with complete TMA response without the use of PE/PI and anti-C5 antibody	26 weeks of study treatment	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
Long term safety and efficacy evaluations	52 weeks of study treatment	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

Secondary Outcome Measures

Name	Time	Method
Time to achieve complete TMA response	26 weeks of study treatment	Effect of study treatment iptacopan on time to complete TMA response during the first 26 weeks of study treatment
Percentage of participants with increase from baseline in hemoglobin levels ≥ 2 g/dL	26 weeks of study treatment	Response is defined as the percentage of participants with an increase in hemoglobin of ≥ 2 g/dL from baseline, observed at two measurements obtained at least 4 weeks apart and any measurement in between during 26 weeks of study treatment
Change from baseline on hematologic parameters	At week 26	Change from baseline in hematologic parameters (platelets, LDH, hemoglobin) at Week 26
Change from baseline on estimated glomerular filtration rate	At week 26	Change from baseline in eGFR after 26 weeks of study treatment.
Change from baseline in chronic kidney disease (CKD) stage	At week 26	Change from baseline in CKD stage (1-5) based on eGFR categories at Week 26
Change from baseline in patient-reported outcomes score as measured by the Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue Questionnaire	At week 26	Change from baseline in patient-reported outcomes scores for FACIT-Fatigue Questionnaire at Week 26
Change from baseline in patient-reported outcomes score as measured by the EuroQol 5-level EQ-5D version (EQ-5D-5L) Questionnaire	At Week 26	Change from baseline in patient-reported outcomes scores for the EuroQol 5-level EQ-5D version (EQ-5D-5L) Questionnaire at Week 26
Percentage of participants on dialysis	26 weeks of study treatment	For participants requiring dialysis within 5 days prior to iptacopan treatment initiation, the number of participants who no longer require dialysis through 26 weeks of study treatment will be evaluated by means of proportion and corresponding confidence interval
Change from baseline in patient-reported outcomes score as measured by the Patient Global Impression of Severity (PGIS) questionnaire	At Week 26	Change from baseline in patient-reported outcomes scores for Patient Global Impression of Severity (PGIS) at Week 26
Change from baseline in patient-reported outcomes score as measured by the Short-form 36 health survey questionnaire version 2 (SF-36 v2)	At Week 26	Change from baseline in patient-reported outcomes scores for Short-form 36 health survey questionnaire version 2 (SF-36 v2) at Week 26

Trial Locations

Locations (21)

Uni Of Alabama At Birmingham; 🇺🇸 Birmingham, Alabama, United States

Univ of California at Los Angeles; 🇺🇸 Los Angeles, California, United States

Univ Cali Irvine ALS Neuromuscular; 🇺🇸 Orange, California, United States

Brigham and Womens Hospital; 🇺🇸 Boston, Massachusetts, United States

WA Uni School Of Med; 🇺🇸 Saint Louis, Missouri, United States

Rut Univ for Translational Med Scie; 🇺🇸 New Brunswick, New Jersey, United States

University of New Mexico; 🇺🇸 Albuquerque, New Mexico, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

University of Cincinnati; 🇺🇸 Cincinnati, Ohio, United States

Cleveland Clinic Foundation; 🇺🇸 Cleveland, Ohio, United States

Comprehensive Transplant Ctr at OSU; 🇺🇸 Columbus, Ohio, United States

UT Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

Baylor Scott and White Research; 🇺🇸 Temple, Texas, United States

Virginia Commonwealth University; 🇺🇸 Richmond, Virginia, United States

USC Norris Cancer Center; 🇺🇸 Los Angeles, California, United States

Harbor-UCLA Medical Center .; 🇺🇸 Torrance, California, United States

Georgetown University Lombardi Cancer Center; 🇺🇸 Washington, District of Columbia, United States

University Of Miami; 🇺🇸 Miami, Florida, United States

University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States

Montefiore Medical Center .; 🇺🇸 Bronx, New York, United States

Novartis Investigative Site; 🇬🇧 Newcastle upon Tyne, United Kingdom