Single Arm, Open Label Trial With Iptacopan Treatment for 24 Weeks, in Patients on Stable Regimen of Anti-C5 Who Switch to Iptacopan. (APPULSE)

A Multicenter, Single Arm, Open-label Trial to Evaluate Efficacy and Safety of Oral, Twice Daily Iptacopan in Adult PNH Patients Who Have Hb≥10 g/dL in Response to Anti-C5 Antibody and Switch to Iptacopan

The purpose of the study was to find out if iptacopan is effective and safe in adult patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) who switched from their current standard of care treatment (eculizumab or ravulizumab) to study treatment, iptacopan/LNP023.

Study Overview

• Status: Completed
• Conditions: Paroxysmal Nocturnal Hemoglobinuria
• Intervention / Treatment: Drug: Iptacopan

Detailed Description

This was a multicenter, single-arm, open label trial, with iptacopan treatment for 24 weeks in adult PNH patients.

This study was comprised of two periods:

• A Screening period lasting up to 8 weeks.
• A 24-week open-label, iptacopan Treatment period.

After completion of the treatment period, participants who continued to benefit from the iptacopan treatment based on the study doctor's evaluation were able to join the Roll-over extension study (CLNP023C12001B).

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Nantes, France, 44093
    • Novartis Investigative Site
  • Nice, France, 06202
    • Novartis Investigative Site
  • Paris, France, 75475
    • Novartis Investigative Site
• Germany
  • Aachen, Germany, 52074
    • Novartis Investigative Site
  • Essen, Germany, 45147
    • Novartis Investigative Site
  • Ulm, Germany, 89081
    • Novartis Investigative Site
  • Saxony
    • Dresden, Saxony, Germany, 01307
      • Novartis Investigative Site
• Italy
  • FI
    • Florence, FI, Italy, 50134
      • Novartis Investigative Site
  • VI
    • Bassano del Grappa, VI, Italy, 36061
      • Novartis Investigative Site
• South Korea
  • Seoul
    • Seoul, Seoul, South Korea, 06351
      • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08036
    • Novartis Investigative Site
• Turkey (Türkiye)
  • Fatih
    • Istanbul, Fatih, Turkey (Türkiye), 34093
      • Novartis Investigative Site
• United Kingdom
  • London, United Kingdom, SE5 9RS
    • Novartis Investigative Site
  • West Yorkshire
    • Leeds, West Yorkshire, United Kingdom, LS9 7TF
      • Novartis Investigative Site
• United States
  • California
    • Duarte, California, United States, 91010
      • City Of Hope National Med Center
    • Los Angeles, California, United States, 90033
      • USC Norris Cancer Center
  • Florida
    • Miami Lakes, Florida, United States, 33014
      • Lakes Research
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Mass Gen Hosp Cancer Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • New York
    • The Bronx, New York, United States, 10461
      • Montefiore Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • Prisma Health Upstate
  • Utah
    • Salt Lake City, Utah, United States, 84112 0550
      • Huntsman Cancer Institute Univ of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Signed informed consent must be obtained prior to participation in the study.
• Male and female participants ≥ 18 years of age, at the time of ICF signatures and with a diagnosis of PNH confirmed by treating physician.
• Stable regimen (dose and intervals) of anti-C5 antibody treatment (either eculizumab or ravulizumab) for at least 6 months prior to screening
• Mean hemoglobin level ≥10 g/dL
• Vaccination against Neisseria meningitidis and S. pneumoniae infection are required prior to the start of iptacopan treatment.
• If not received previously, vaccination against Haemophilus influenzae infections is recommended, if available and according to local regulations.
• Ability to communicate well with the investigator, to understand and comply with the requirements of the study
• Other protocol -defined inclusion criteria may apply at the end.

Exclusion Criteria:

• Participation in any other investigational drug trial or use of other investigational drugs at the time of enrollment
• Patients requiring red blood cell transfusion in the 6 months prior to screening or during screening
• History of stem cell transplantation or any solid organ transplantation
• Active systemic bacterial, viral (incl. COVID-19) or fungal infection within 14 days prior to study drug administration
• Presence of fever ≥ 38.0 °C (100.4 °F) within 7 days prior to study drug administration
• Human immunodeficiency virus (HIV) infection (known history of HIV or test positive for HIV antibody at Screening)
• A history of recurrent invasive infections caused by encapsulated organisms, e.g. meningococcus or pneumococcus
• Unstable medical condition including, but not limited to, myocardial ischemia, active gastrointestinal bleeding, coexisting chronic anemia unrelated to PNH, or unstable thrombotic event not amenable to active treatment as judged by the investigator at Screening.
• History of cancer of any part of the body within the past 5 years,
• Ongoing drug or alcohol abuse that could interfere with patient's participation in the trial.
• Any medical condition deemed likely to interfere with the patient's participation in the study
• Female patients who are pregnant or breastfeeding, or intending to conceive during the course of 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: LNP023 200mg b.i.d.; Iptacopan (LNP023) at a dose of 200 mg b.i.d. orally	Drug: Iptacopan; Treatment with iptacopan at a dose of 200 mg b.i.d. will start on the first day (Day 1) and continue for 24 weeks.; Other Names: LNP023

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Hb Levels as Mean of Visits Between Day 126 and Day 168 Compared to Baseline Tested for Non-inferiority	Change in hemoglobin (Hb) levels as mean of visits between Day 126 and Day 168 compared to baseline. Baseline is defined as as the mean of three Hb assessments conducted at the central laboratory: two during screening and the third on Day 1. The estimation of change from baseline in Hb levels was handled by the hypothetical strategy where participants were assumed as if they did not receive RBC transfusions while on treatment (RBC transfusions were expected to be rare). Assuming that participants had stable Hb levels at study entry, the mean change from baseline in Hb level between Day 126 and Day 168 was expected to be unchanged should participants have continued on anti-C5 treatment. Non-inferiority of iptacopan was therefore tested by the null hypothesis (H0) against the alternate hypothesis (H1) comparing the mean change from baseline in Hb level in iptacopan between Day 126 and Day 168 (μ) to -1 g/dL: H0: μ <= -1, H1: μ > -1.	Baseline, Day 126 to Day 168

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Hb Levels as Mean of Visits Between Day 126 and Day 168 Compared to Baseline Tested for Superiority	Change in hemoglobin (Hb) levels as mean of visits between Day 126 and Day 168 compared to baseline. Baseline is defined as as the mean of three Hb assessments conducted at the central laboratory: two during screening and the third on Day 1.	Baseline, Day 126 to Day 168
Proportion of Hematological Responders to Iptacopan Treatment	Response defined as Hb ≥12 g/dL assessed between visits Day 126 and Day 168 in the absence of RBC transfusions, on three out of four measurements taken at the visits occurring in last six weeks	Day 126 to Day 168
Proportion of Participants Who Remain Free From Transfusions	Number of participants with absence of administration of packed RBC transfusions between Day 1 and Day 168	Day 1 to Day 168
Change From Baseline in Absolute Reticulocytes Count (ARC) Levels	Change from baseline in ARC levels as mean of visits between Day 126 and Day 168	Baseline, Day 126 to Day 168
Percentage Change From Baseline in Lactate Dehydrogenase (LDH) Levels	Percentage change from baseline in LDH levels as mean of visits between Day 126 and Day 168	Baseline, Day 126 to Day 168
Change From Baseline in Treatment Satisfaction Score Using TSQM-9 Questionnaire	Difference in scores of the Treatment Satisfaction Questionnaire for Medication(TSQM-9) between baseline and Day 84 and Day 168 assessed after switching from SoC (anti-C5) to iptacopan. TSQM-9 is a patient reported outcomes measure that was designed to assess patients' satisfaction with medication across three domains of effectiveness, convenience and global satisfaction. The TSQM-9 contains 3 questions in each domain. Domain scores range from 0 - 100 with higher scores representing better outcomes for the domain.	Baseline, Day 84 and Day 168
Change From Baseline in Fatigue Score Using FACIT-F Questionnaire	Change from baseline in patient-reported scores for the functional assessment of chronic illness therapy - Fatigue (FACIT-F) collected at Day 84 and Day 168. The FACIT-F is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. All FACIT scales are scored so that a high score is better. As each of the 13 items of the FACIT-F scale ranges from 0-4, the range of possible scores is 0-52, with 0 being the worst possible score and 52 the best.	Baseline, Day 84 and Day 168
Percentage of Patients Who Had Breakthrough Hemolysis (BTH) Event	Wilson method is used to calculate the confidence interval for the proportion of patients who had events. The breakthrough is defined clinical if either there is a decrease in hemoglobin levels equal to or more than 2 g/dL (compared to the latest assessment) or if patients present signs or symptoms of gross hemoglobinuria, painful crisis, dysphagia or any other significant clinical PNH-related signs & symptoms, in presence of laboratory evidence of intravascular hemolysis.	Up to 168 Days
Percentage of Patients Who Had Major Adverse Vascular Events (MAVEs)	A MAVE is defined as: acute peripheral vascular occlusion, amputation (non-traumatic; nondiabetic), cerebral arterial occlusion/cerebrovascular accident, cerebral venous occlusion, dermal thrombosis, gangrene (non-traumatic; nondiabetic), hepatic/portal vein thrombosis (Budd-Chiari syndrome), mesenteric/visceral arterial thrombosis or infarction, mesenteric/visceral vein thrombosis or infarction, myocardial infarction, pulmonary embolus, renal arterial thrombosis, renal vein thrombosis, thrombophlebitis / deep vein thrombosis, transient ischemic attack, unstable angina or other.	Up to 168 Days

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available on www.novctrd.com

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2023
• Primary Completion (Actual): October 17, 2024
• Study Completion (Actual): October 17, 2024

Study Registration Dates

• First Submitted: November 18, 2022
• First Submitted That Met QC Criteria: November 18, 2022
• First Posted (Actual): November 29, 2022

Study Record Updates

• Last Update Posted (Estimated): January 13, 2026
• Last Update Submitted That Met QC Criteria: December 18, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: PNH; Paroxysmal Nocturnal Hemoglobinuria; LNP023; iptacopan; single arm open-label; Hb≥10 g/dL in response to anti-C5 antibody; switch to iptacopan
• Additional Relevant MeSH Terms: Hematologic Diseases; Bone Marrow Diseases; Anemia, Hemolytic; Anemia; Myelodysplastic Syndromes; Hemic and Lymphatic Diseases; Hemoglobinuria, Paroxysmal; iptacopan
• Other Study ID Numbers: CLNP023C12303; 2022-502148-10-00 (Other Identifier: EU CT)

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