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

Paroxysmal Nocturnal Hemoglobinuria Clinical Trial

— APPULSE  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05630001
• Other study ID #: CLNP023C12303
• Secondary ID: 2022-502148-10-0
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: April 24, 2023
• Est. completion date: October 18, 2024

Study information

• Verified date: June 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 52
• Est. completion date: October 18, 2024
• Est. primary completion date: October 18, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hemoglobinuria
• Hemoglobinuria, Paroxysmal
• Paroxysmal Nocturnal Hemoglobinuria

Intervention

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.

Locations

Country	Name	City	State
France	Novartis Investigative Site	Nantes Cedex 1
France	Novartis Investigative Site	Nice
France	Novartis Investigative Site	Paris 10
Germany	Novartis Investigative Site	Aachen
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Ulm
Italy	Novartis Investigative Site	Bassano Del Grappa	VI
Italy	Novartis Investigative Site	Firenze	FI
Korea, Republic of	Novartis Investigative Site	Seoul
Spain	Novartis Investigative Site	Barcelona	Catalunya
Turkey	Novartis Investigative Site	Istanbul
United Kingdom	Novartis Investigative Site	Leeds
United Kingdom	Novartis Investigative Site	London
United States	Mass Gen Hosp Cancer Center	Boston	Massachusetts
United States	Montefiore Medical Center .	Bronx	New York
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	City Of Hope National Med Center City of Hope Medical Center	Duarte	California
United States	Prisma Health Upstate	Greenville	South Carolina
United States	USC Norris Cancer Center	Los Angeles	California
United States	Novartis Investigative Site	Miami Lakes	Florida
United States	University Of Minnesota	Minneapolis	Minnesota
United States	Huntsman Cancer Institute Univ of Utah .	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  France,  Germany,  Italy,  Korea, Republic of,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Percentage of hematological responders to iptacopan treatment	Percentage of hematological responders to iptacopan treatment will be collected	Up to 168 days
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Rate of Breakthrough hemolysis (BTH)	Occurrence of BTH reported from D1 to D168	24 weeks
Secondary	Rate of Major Adverse Vascular Events (MAVEs)	Occurrence of MAVEs reported from D1 to D168	24 weeks