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

Phase 3
Completed
Conditions
Paroxysmal Nocturnal Hemoglobinuria
Interventions
Registration Number
NCT05630001
Lead Sponsor
Novartis Pharmaceuticals
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
52
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Iptacopan treatment in adult PNH patientsIptacopanSubjects will receive iptacopan at a dose of 200 mg b.i.d. orally
Primary Outcome Measures
NameTimeMethod
Change from baseline in Hb levels to demonstrate non-inferiority of iptacopanUp to 168 days

To assess the efficacy of iptacopan after 24 weeks of treatment in PNH patients who switch to iptacopan from prior SoC

Secondary Outcome Measures
NameTimeMethod
Rate of Breakthrough hemolysis (BTH)24 weeks

Occurrence of BTH reported from D1 to D168

Percentage of hematological responders to iptacopan treatmentUp to 168 days

Percentage of hematological responders to iptacopan treatment will be collected

Change in Hb levels to demonstrate superiority of iptacopanUp to 168 days

To assess efficacy of iptacopan after 24 weeks of treatment in PNH patients who switch to iptacopan from prior SoC

Change from baseline in Absolute Reticulocytes count (ARC) levelsUp to 168 days

To assess the effect of iptacopan on markers of Extravascular Hemolysis (EVH) and Intravascular Hemolysis (IVH).

Change in fatigue score using FACIT-F questionnaireUp to 168 days

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.

Change in treatment satisfaction score using TSQM-9 questionnaireUp to 168 days

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.

Percentage change from baseline in lactate dehydrogenase (LDH) levelsUp to 168 days

To assess the effect of iptacopan on markers of EVH and IVH.

Rate of Major Adverse Vascular Events (MAVEs)24 weeks

Occurrence of MAVEs reported from D1 to D168

Trial Locations

Locations (10)

City Of Hope National Med Center

🇺🇸

Duarte, California, United States

Lakes Research

🇺🇸

Miami Lakes, Florida, United States

Huntsman Cancer Institute Univ of Utah

🇺🇸

Salt Lake City, Utah, United States

USC Norris Cancer Center

🇺🇸

Los Angeles, California, United States

Mass Gen Hosp Cancer Center

🇺🇸

Boston, Massachusetts, United States

University Of Minnesota

🇺🇸

Minneapolis, Minnesota, United States

Cleveland Clinic Foundation

🇺🇸

Cleveland, Ohio, United States

Prisma Health Upstate

🇺🇸

Greenville, South Carolina, United States

Novartis Investigative Site

🇬🇧

London, United Kingdom

Montefiore Medical Center

🇺🇸

Bronx, New York, United States

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