Long-term Safety and Tolerability of Iptacopan in Patients With Paroxysmal Nocturnal Hemoglobinuria

An Open Label, Multicenter Roll-over Extension Program (REP) to Characterize the Long-term Safety and Tolerability of Iptacopan (LNP023) in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Who Have Completed PNH Phase 2 and Phase3 Studies With Iptacopan

This study is an open-label, single arm, multicenter, roll-over extension study to characterize long-term safety, tolerability and efficacy of iptacopan and to provide access to iptacopan to patients with PNH who have completed Novartis-sponsored Phase 2 or 3 studies with iptacopan

Study Overview

• Status: Active, not recruiting
• Conditions: Paroxysmal Nocturnal Hemoglobinuria
• Intervention / Treatment: Drug: Iptacopan

Detailed Description

The purpose of this phase 3 open-label, single arm, multicenter study is to evaluate the long-term safety, tolerability and efficacy of iptacopan in patients with PNH and to provide access to patients who have completed (without tapering down) Phase 2 and Phase 3 trials and derived benefit from iptacopan treatment.

• Study Type: Interventional
• Enrollment (Actual): 208
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • São Paulo
    • Santo André, São Paulo, Brazil, 09090-790
      • Novartis Investigative Site
    • São Paulo, São Paulo, Brazil, 01323-900
      • Novartis Investigative Site
• China
  • Beijing, China, 100730
    • Novartis Investigative Site
  • Tianjin, China, 300052
    • Novartis Investigative Site
  • Tianjin, China, 300020
    • Novartis Investigative Site
• Czechia
  • Brno, Czechia, 625 00
    • Novartis Investigative Site
  • Poruba
    • Ostrava, Poruba, Czechia, 708 52
      • Novartis Investigative Site
• France
  • Lille, France, 59037
    • Novartis Investigative Site
  • Nantes, France, 44093
    • Novartis Investigative Site
  • Nice, France, 06202
    • Novartis Investigative Site
  • Paris, France, 75475
    • Novartis Investigative Site
  • Toulouse, France, 31059
    • Novartis Investigative Site
• Germany
  • Aachen, Germany, 52074
    • Novartis Investigative Site
  • Essen, Germany, 45147
    • Novartis Investigative Site
  • Hamburg, Germany, 20246
    • Novartis Investigative Site
  • Riesa, Germany, 01589
    • Novartis Investigative Site
  • Ulm, Germany, 89081
    • Novartis Investigative Site
  • Saxony
    • Dresden, Saxony, Germany, 01307
      • Novartis Investigative Site
• Italy
  • AP
    • Ascoli Piceno, AP, Italy, 63100
      • Novartis Investigative Site
  • AV
    • Avellino, AV, Italy, 83100
      • Novartis Investigative Site
  • FI
    • Florence, FI, Italy, 50134
      • Novartis Investigative Site
  • MI
    • Milan, MI, Italy, 20122
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00161
      • Novartis Investigative Site
  • TO
    • Torino, TO, Italy, 10126
      • Novartis Investigative Site
  • VI
    • Bassano del Grappa, VI, Italy, 36061
      • Novartis Investigative Site
• Japan
  • Fukushima, Japan, 9601295
    • Novartis Investigative Site
  • Ishikawa, Japan, 9208641
    • Novartis Investigative Site
  • Kyoto, Japan, 6068507
    • Novartis Investigative Site
  • Niigata, Japan, 9518520
    • Novartis Investigative Site
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 453-8511
      • Novartis Investigative Site
  • Kanagawa
    • Isehara, Kanagawa, Japan, 259-1193
      • Novartis Investigative Site
  • Nagano
    • Suwa, Nagano, Japan, 392-8510
      • Novartis Investigative Site
  • Osaka
    • Suita, Osaka, Japan, 565-0871
      • Novartis Investigative Site
  • Tokyo
    • Shinjuku Ku, Tokyo, Japan, 160-0023
      • Novartis Investigative Site
• Lithuania
  • Vilnius, Lithuania, LT-08406
    • Novartis Investigative Site
• Malaysia
  • Sabah
    • Kota Kinabalu, Sabah, Malaysia, 88586
      • Novartis Investigative Site
  • Sarawak
    • Kuching, Sarawak, Malaysia, 93586
      • Novartis Investigative Site
• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6500HB
      • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 119074
    • Novartis Investigative Site
• South Korea
  • Seoul
    • Seoul, Seoul, South Korea, 06351
      • Novartis Investigative Site
    • Seoul, Seoul, South Korea, 03080
      • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08036
    • Novartis Investigative Site
  • A Coruna
    • Santiago Compostela, A Coruna, Spain, 15706
      • Novartis Investigative Site
  • Gipuzkoa
    • Donostia / San Sebastian, Gipuzkoa, Spain, 20014
      • Novartis Investigative Site
• Taiwan
  • Hualien City, Taiwan, 970
    • Novartis Investigative Site
  • Taipei, Taiwan, 10002
    • Novartis Investigative Site
• Turkey (Türkiye)
  • Fatih
    • Istanbul, Fatih, Turkey (Türkiye), 34093
      • Novartis Investigative Site
• United Kingdom
  • London, United Kingdom, SE5 9RS
    • Novartis Investigative Site
  • West Yorkshire
    • Leeds, West Yorkshire, United Kingdom, LS9 7TF
      • Novartis Investigative Site
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • Duarte, California, United States, 91010
      • City Of Hope National Med Center
    • Los Angeles, California, United States, 90033
      • USC Norris Cancer Center
    • Orange, California, United States, 92868
      • Univ Cali Irvine ALS Neuromuscular
    • Orange, California, United States, 92868
      • Univ of California Irvine (Chao Family Comprehensive Cancer Center)
  • Florida
    • Miami Lakes, Florida, United States, 33014
      • Lakes Research
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Augusta University
    • Augusta, Georgia, United States, 30912
      • Augusta University Georgia
  • New York
    • The Bronx, New York, United States, 10461
      • Montefiore Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • Prisma Health Upstate

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• Male and female participants ≥ 18 years of age with a diagnosis of PNH who have completed the treatment extension period (without tapering down) of Phase II iptacopan studies (CLNP023X2204, CLNP023X2201), Period 4 of LFG316X2201 or Phase III (CLNP023C12302 and CLNP023C12301) clinical studies at the time point of enrollment visit in this roll over extension.
• Prior vaccinations against Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae infections
• Per investigator's clinical judgement benefit from continued treatment with iptacopan and has been clinically stable on iptacopan monotherapy for at least 3 months

Exclusion Criteria:

• Any comorbidity or medical condition (including but not limited to any active systemic bacterial, viral or fungal infection or malignancy) that, in the opinion of the investigator, could put the subject at increased risk or potentially confound study data.
• History of recurrent invasive infections caused by encapsulated organisms, such as Neisseria meningitidis, Streptococcus pneumoniae or Haemophilus influenzae
• History of hematopoietic stem cell transplantation

Other protocol-defined inclusion/exclusion criteria may apply.

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; Participants will be receiving open label oral iptacopan 200 mg b.i.d monotherapy	Drug: Iptacopan; Taken orally b.i.d. Dosage supplied: 200 mg Dosage form: hard gelatin capsule Route of administration: oral; Other Names: LNP023

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with adverse events	Safety evaluations including but not limited to adverse events/serious adverse events, safety laboratory parameters, vital signs, etc. through End of Study visit	60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants achieving sustained hemoglobin levels ≥ 12 g/dL in the absence of red blood cell transfusions	Proportion of participants achieving sustained hemoglobin levels ≥ 12 g/dL in the absence of red blood cell transfusions evaluated over yearly intervals	60 months
Proportion of participants who remain free from transfusions	Proportion of participants who remain free from transfusions evaluated over yearly intervals	60 months
Rate of breakthrough hemolysis (BTH)	Rate of breakthrough hemolysis (BTH)	60 months
Proportion of participants with Major Adverse Vascular Events MAVEs	MAVEs (incl. thrombosis) evaluated over yearly intervals	60 months

Collaborators and Investigators

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

Publications and helpful links

General Publications

• DeCastro C, Sheinberg P, Han B, Vallow S, Bermann G, Dhalke M, Kumar R, Dickie G, Galipeau N, Lamoureux R, Rupinski K, Lowe C, Nieves A, de Fontbrune FS, de Latour RP. Patient-Reported Meaningful Change in Symptoms and Impacts of Paroxysmal Nocturnal Hemoglobinuria (PNH) in Three Phase III Clinical Trials of Iptacopan. Patient. 2025 Nov;18(6):699-712. doi: 10.1007/s40271-025-00755-5. Epub 2025 Jul 22.

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2021
• Primary Completion (Estimated): October 18, 2027
• Study Completion (Estimated): October 18, 2027

Study Registration Dates

• First Submitted: February 5, 2021
• First Submitted That Met QC Criteria: February 9, 2021
• First Posted (Actual): February 10, 2021

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Anemia; Hemoglobin; Paroxysmal Nocturnal Hemoglobinuria (PNH); Iptacopan; LNP023
• Additional Relevant MeSH Terms: Hematologic Diseases; Bone Marrow Diseases; Anemia, Hemolytic; Myelodysplastic Syndromes; Hemic and Lymphatic Diseases; Anemia; Hemoglobinuria, Paroxysmal; iptacopan
• Other Study ID Numbers: CLNP023C12001B; 2023-509843-28-00 (Other Identifier: EU CT Number)

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