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

Study Overview

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

Detailed Description

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

This study is 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 continue to benefit from the iptacopan treatment based on the study doctor's evaluation will be able to join the Roll-over extension study.

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

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

• France
  • Nantes Cedex 1, France, 44093
    • Recruiting
    • Novartis Investigative Site
  • Nice, France, 06202
    • Recruiting
    • Novartis Investigative Site
  • Paris 10, France, 75475
    • Recruiting
    • Novartis Investigative Site
• Germany
  • Aachen, Germany, 52074
    • Recruiting
    • Novartis Investigative Site
  • Dresden, Germany, 01307
    • Recruiting
    • Novartis Investigative Site
  • Ulm, Germany, 89081
    • Recruiting
    • Novartis Investigative Site
• Italy
  • AV
    • Avellino, AV, Italy, 83100
      • Recruiting
      • Novartis Investigative Site
  • FG
    • San Giovanni Rotondo, FG, Italy, 71013
      • Recruiting
      • Novartis Investigative Site
  • FI
    • Firenze, FI, Italy, 50134
      • Recruiting
      • Novartis Investigative Site
  • VI
    • Bassano Del Grappa, VI, Italy, 36061
      • Recruiting
      • Novartis Investigative Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 06351
    • Recruiting
    • Novartis Investigative Site
• Spain
  • Catalunya
    • Barcelona, Catalunya, Spain, 08036
      • Recruiting
      • Novartis Investigative Site
• Turkey
  • Aydin, Turkey, 09100
    • Recruiting
    • Novartis Investigative Site
  • Istanbul, Turkey, 34093
    • Recruiting
    • Novartis Investigative Site
• United Kingdom
  • Leeds, United Kingdom, LS9 7TF
    • Recruiting
    • Novartis Investigative Site
  • London, United Kingdom, SE5 9RS
    • Recruiting
    • Novartis Investigative Site
• United States
  • California
    • Cerritos, California, United States, 90703
      • Recruiting
      • Novartis Investigative Site
    • Duarte, California, United States, 91010
      • Recruiting
      • Novartis Investigative Site
    • Los Angeles, California, United States, 90033
      • Recruiting
      • Novartis Investigative Site
    • Torrance, California, United States, 90509-2910
      • Recruiting
      • Novartis Investigative Site
  • Florida
    • Miami Lakes, Florida, United States, 33014
      • Recruiting
      • Novartis Investigative Site
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Recruiting
      • Novartis Investigative Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Novartis Investigative Site
    • Worcester, Massachusetts, United States, 01665
      • Recruiting
      • Novartis Investigative Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • Novartis Investigative Site
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Novartis Investigative Site
  • New York
    • Bronx, New York, United States, 10461
      • Recruiting
      • Novartis Investigative Site
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Novartis Investigative Site
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Novartis Investigative Site
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • Recruiting
      • Novartis Investigative Site

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: Iptacopan treatment in adult PNH patients; Subjects will receive iptacopan 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in Hb levels to demonstrate non-inferiority of iptacopan	To assess the efficacy of iptacopan after 24 weeks of treatment in PNH patients who switch to iptacopan from prior SoC	Up to 168 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Hb levels to demonstrate superiority of iptacopan	To assess efficacy of iptacopan after 24 weeks of treatment in PNH patients who switch to iptacopan from prior SoC	Up to 168 days
Percentage of hematological responders to iptacopan treatment	Percentage of hematological responders to iptacopan treatment will be collected	Up to 168 days
Change from baseline in Absolute Reticulocytes count (ARC) levels	To assess the effect of iptacopan on markers of Extravascular Hemolysis (EVH) and Intravascular Hemolysis (IVH).	Up to 168 days
Percentage change from baseline in lactate dehydrogenase (LDH) levels	To assess the effect of iptacopan on markers of EVH and IVH.	Up to 168 days
Change in treatment satisfaction score using TSQM-9 questionnaire	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 representing better scores for the domain.	Up to 168 days
Change in fatigue score using FACIT-F questionnaire	The FACIT-Fatigue 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-Fatigue scale ranges from 0-4, the range of possible scores is 0-52, with 0 being the worst possible score and 52 the best.	Up to 168 days
Rate of Breakthrough hemolysis (BTH)	Occurrence of BTH reported from D1 to D168	24 weeks
Rate of Major Adverse Vascular Events (MAVEs)	Occurrence of MAVEs reported from D1 to D168	24 weeks

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2023
• Primary Completion (Estimated): January 8, 2025
• Study Completion (Estimated): January 9, 2025

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 15, 2024
• Last Update Submitted That Met QC Criteria: January 12, 2024
• Last Verified: January 1, 2024

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: Urologic Diseases; Urological Manifestations; Bone Marrow Diseases; Hematologic Diseases; Urination Disorders; Anemia; Proteinuria; Anemia, Hemolytic; Myelodysplastic Syndromes; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Hemoglobinuria; Hemoglobinuria, Paroxysmal
• 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