Efficacy and Safety of Switching From Anti-C5 Antibody Treatment to Iptacopan Treatment in Study Participants With Atypical Hemolytic Uremic Syndrome (aHUS)

A Multicenter, Single Arm, Open-label Study to Evaluate Efficacy and Safety of Switching From Anti-C5 Antibody Treatment to Iptacopan Treatment in Study Participants With aHUS

The purpose of this Phase 3 study is to evaluate the efficacy and safety of iptacopan upon switching from anti-C5 antibody to iptacopan treatment in study participants with aHUS.

Study Overview

• Status: Recruiting
• Conditions: Atypical Hemolytic Uremic Syndrome
• Intervention / Treatment: Drug: Iptacopan

Detailed Description

The study is designed as a multicenter, single-arm, open label study to evaluate the efficacy and safety of iptacopan upon switching from anti-C5 antibody to iptacopan treatment in participants with aHUS. It consists of a screening period of up to 8 weeks followed by a 12-Month Core Treatment period and 12-Month Extension Treatment period.

The study will assess the effects of iptacopan on a range of efficacy assessments relevant to aHUS.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: 1-888-669-6682; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals; Phone Number: +41613241111

Study Locations

• Japan
  • Saitama
    • Iruma-gun, Saitama, Japan, 350-0495
      • Recruiting
      • Novartis Investigative Site
• Turkey
  • Ankara, Turkey, 06500
    • Recruiting
    • Novartis Investigative Site
  • Mersin, Turkey, 33079
    • Recruiting
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male and female adult participants ≥ 18 years of age with diagnosis of aHUS for whom etiologies of other types of TMA and non-aHUS kidney disease have been excluded.
• Currently on the recommended weight-based dosage regimen of anti-C5 antibody treatment for at least 3 months prior to the screening visit.

• Clinical evidence of response to anti-C5 antibody treatment (in absence of PE/PI) for at least 3 months prior to entering the screening period as defined by:

  1. Hematological normalization in platelet count ≥150 x 109/L and LDH below upper limit of normal [ULN], and
  2. Stable or improving kidney function as defined by ≤15% increase in serum creatinine.
• Vaccination against Neisseria meningitidis and Streptococcus pneumoniae infections is required prior to the start of treatment with iptacopan.
• If not received previously or if a booster is required, vaccination against Haemophilus influenzae infection, should be given, if available and according to local regulations.

Exclusion Criteria:

• History of aHUS disease relapse while on anti-C5 antibody treatment.
• eGFR < 30 ml/min/1.73m^2
• Active infection or history of recurrent invasive infections caused by encapsulated bacteria, i.e., meningococcus, pneumococcus (eg., N. meningitidis, S. pneumoniae) or H. influenzae.
• Participants with sepsis or active systemic bacterial, viral (including COVID-19) or fungal infection within 14 days prior to study treatment administration.
• Kidney, bone marrow transplant (BMT)/hematopoietic stem cell transplant (HSCT), heart, lung, small bowel, pancreas, liver transplantation or any other cell or solid organ transplantation
• Female patients who are pregnant or breastfeeding, or intending to conceive during the course of the study
• Any medical condition deemed likely to interfere with the patient's participation in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: iptacopan 200 mg b.i.d.; open label arm of iptacopan 200 mg b.i.d.	Drug: Iptacopan; Open Label; Other Names: LNP023

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants free of TMA manifestation	Absence of thrombotic microangiopathy (TMA) manifestation, without use of anti-C5 antibody, during the 12 months of iptacopan treatment following the switch of treatment from an anti-C5 antibody to iptacopan treatment.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants free of TMA manifestation in study participants with functionally significant mutations in complement genes or positive anti FH antibodies	Absence of thrombotic microangiopathy (TMA) manifestation in study participants with functionally significant mutations in complement genes or positive anti FH antibodies, without the use of anti-C5 antibody during iptacopan treatment following the switch of treatment from an anti-C5 antibody to iptacopan treatment.	12 months, 24 months
Percentage of participants free of TMA manifestation	Absence of thrombotic microangiopathy (TMA) manifestation, without use of anti-C5 antibody, during the 24 months of iptacopan treatment following the switch of treatment from an anti-C5 antibody to iptacopan treatment.	24 months
Time to TMA manifestation	Time to thrombotic microangiopathy (TMA) manifestation	12 months, 24 months
Change from baseline in platelets	Change from baseline in platelets at month 12 and month 24.	Baseline, month 12, month 24
Change from baseline in LDH	Change from baseline in lactate dehydrogenase (LDH) at month 12 and month 24.	Baseline, month 12, month 24
Change from baseline in hemoglobin	Change from baseline in hemoglobin at month 12 and month 24.	Baseline, month 12, month 24
Change from baseline in serum creatinine	Change from baseline in serum creatinine at month 12 and month 24.	Baseline, month 12, month 24
Change from baseline in UPCR	Change from baseline in urine protein to creatinine ratio (UPCR) at month 12 and month 24.	Baseline, month 12, month 24
Change from baseline in eGFR	Change from baseline in estimated glomerular filtration rate (eGFR) at month 12 and month 24.	Baseline, month 12, month 24
Change from baseline in CKD stage	Change from baseline in chronic kidney disease (CKD) stage at month 12 and month 24.	Baseline, month 12, month 24
Number of participants who require dialysis	Dialysis requirement status (Yes/ No)	month 12 and month 24
Percentage of participants with TMA related events.	Percentage of participants with thrombotic microangiopathy (TMA) related events.	month 12 and month 24

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2024
• Primary Completion (Estimated): January 25, 2029
• Study Completion (Estimated): July 21, 2029

Study Registration Dates

• First Submitted: June 29, 2023
• First Submitted That Met QC Criteria: June 29, 2023
• First Posted (Actual): July 7, 2023

Study Record Updates

• Last Update Posted (Estimated): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 12, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Atypical Hemolytic Uremic Syndrome; TMA; aHUS, thrombotic microangiopathy
• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease; Hematologic Diseases; Anemia; Thrombocytopenia; Blood Platelet Disorders; Anemia, Hemolytic; Thrombotic Microangiopathies; Uremia; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Cytopenia; Syndrome; Azotemia; Hemolysis; Hemolytic-Uremic Syndrome; Atypical Hemolytic Uremic Syndrome
• Other Study ID Numbers: CLNP023F12302

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No