Clinical trial NCT05630001: Single Arm, Open Label Trial With Iptacopan Treatment for 24 Weeks, in Patients on Stable Regimen of Anti-C5 Who Switch to Iptacopan.
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Paroxysmal Nocturnal Hemoglobinuria
Keywords: Paroxysmal Nocturnal Hemoglobinuria
iptacopan
single arm open-label
Hb≥10 g/dL in response to anti-C5 antibody
switch to iptacopan
PNH
LNP023
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2022-11-29
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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 iptacopan
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline in Hb levels to demonstrate non-inferiority of iptacopan
timeFrame: Up to 168 days
Secondary outcomes:
measure: Change in Hb levels to demonstrate superiority of iptacopan
timeFrame: Up to 168 days
measure: Percentage of hematological responders to iptacopan treatment
timeFrame: Up to 168 days
measure: Change from baseline in Absolute Reticulocytes count (ARC) levels
timeFrame: Up to 168 days
measure: Percentage change from baseline in lactate dehydrogenase (LDH) levels
timeFrame: Up to 168 days
measure: Change in treatment satisfaction score using TSQM-9 questionnaire
timeFrame: Up to 168 days
measure: Change in fatigue score using FACIT-F questionnaire
timeFrame: Up to 168 days
measure: Rate of Breakthrough hemolysis (BTH)
timeFrame: 24 weeks
measure: Rate of Major Adverse Vascular Events (MAVEs)
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City Of Hope National Med Center
state: California
city: Los Angeles
country: United States
facility: USC Norris Cancer Center
state: California
city: Miami Lakes
country: United States
facility: Lakes Research
state: Florida
city: Boston
country: United States
facility: Mass Gen Hosp Cancer Center
state: Massachusetts
city: Minneapolis
country: United States
facility: University Of Minnesota
state: Minnesota
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Greenville
country: United States
facility: Prisma Health Upstate
state: South Carolina
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute Univ of Utah
state: Utah
city: Nantes Cedex 1
country: France
facility: Novartis Investigative Site
city: Nice
country: France
facility: Novartis Investigative Site
city: Paris 10
country: France
facility: Novartis Investigative Site
city: Aachen
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Ulm
country: Germany
facility: Novartis Investigative Site
city: Firenze
country: Italy
facility: Novartis Investigative Site
state: FI
city: Bassano Del Grappa
country: Italy
facility: Novartis Investigative Site
state: Vicenza
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Leeds
country: United Kingdom
facility: Novartis Investigative Site
state: West Yorkshire
city: London
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: