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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05630001

Collaborator

(none)

Enrollment

Arm

19.9

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Paroxysmal Nocturnal Hemoglobinuria	Drug: Iptacopan	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

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 iptacopanA 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

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Apr 28, 2023

Anticipated Primary Completion Date :

Dec 23, 2024

Anticipated Study Completion Date :

Dec 24, 2024

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Change from baseline in Hb levels to demonstrate non-inferiority of iptacopan [Up 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

Change in Hb levels to demonstrate superiority of iptacopan [Up to 168 days]
To assess efficacy of iptacopan after 24 weeks of treatment in PNH patients who switch to iptacopan from prior SoC
Percentage of hematological responders to iptacopan treatment [Up to 168 days]
Percentage of hematological responders to iptacopan treatment will be collected
Change from baseline in Absolute Reticulocytes count (ARC) levels [Up to 168 days]
To assess the effect of iptacopan on markers of Extravascular Hemolysis (EVH) and Intravascular Hemolysis (IVH).
Percentage change from baseline in lactate dehydrogenase (LDH) levels [Up to 168 days]
To assess the effect of iptacopan on markers of EVH and IVH.
Change in treatment satisfaction score using TSQM-9 questionnaire [Up 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.
Change in fatigue score using FACIT-F questionnaire [Up 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.
Rate of Breakthrough hemolysis (BTH) [24 weeks]
Occurrence of BTH reported from D1 to D168
Rate of Major Adverse Vascular Events (MAVEs) [24 weeks]
Occurrence of MAVEs reported from D1 to D168

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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