Study to Assess the Pharmacokinetics, Safety, and Tolerability of Iptacopan in Pediatric PNH Patients

An Open-label, Single-arm, Multicenter, Phase 3 Study to Assess Pharmacokinetics, Safety and Tolerability of Iptacopan in Pediatric PNH Patients 2 to <18 Years of Age

The purpose of this open-label, single arm, multicenter, phase 3 study is to assess the pharmacokinetics of iptacopan in pediatric patients and to assess whether iptacopan is safe and well tolerated when used for the treatment of pediatric paroxysmal nocturnal hemoglobinuria (PNH) patients 2 to < 18 years of age.

Study Overview

• Status: Recruiting
• Conditions: Paroxysmal Nocturnal Hemoglobinuria (PNH)
• Intervention / Treatment: Drug: LNP023

Detailed Description

This is a multicenter, open-label, single arm study comprised of an up to a 8-week Screening Period, and a 26-week Treatment Period followed by a 26-week Extension Treatment Period.

This study will enroll a minimum of 12 pediatric patients 2 to < 18 years of age in a staggered manner into 3 cohorts: Cohort 1 (adolescents 12 to < 18 years of age, approximately 6 patients), Cohort 2a (6 to < 12 years of age, approximately 4 patients), and Cohort 2b (2 to < 6 years of age, approximately 2 patients).

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: 1-888-669-6682; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals; Phone Number: +41613241111

Study Locations

• Brazil
  • Federal District
    • Brasília, Federal District, Brazil, 70684-831
      • Recruiting
      • Novartis Investigative Site
  • Rio Grande do Norte
    • Natal, Rio Grande do Norte, Brazil, 59012 300
      • Recruiting
      • Novartis Investigative Site
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-003
      • Recruiting
      • Novartis Investigative Site
  • São Paulo
    • Santo André, São Paulo, Brazil, 09090-401
      • Recruiting
      • Novartis Investigative Site
    • São Paulo, São Paulo, Brazil, 04038-002
      • Recruiting
      • Novartis Investigative Site
    • São Paulo, São Paulo, Brazil, 01323001
      • Recruiting
      • Novartis Investigative Site
• Colombia
  • Valle del Cauca Department
    • Cali, Valle del Cauca Department, Colombia, 760012
      • Recruiting
      • Novartis Investigative Site
• Germany
  • Berlin, Germany, 13353
    • Recruiting
    • Novartis Investigative Site
• Italy
  • GE
    • Genova, GE, Italy, 16147
      • Recruiting
      • Novartis Investigative Site
• Netherlands
  • Utrecht, Netherlands, 3584 CX
    • Recruiting
    • Novartis Investigative Site
• United States
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Recruiting
      • Cancer Institute Of New Jersey
      • Principal Investigator: Richard DRACHTMAN
      • Contact: Serban Morojanu; Phone Number: +1 732-235-7577; Email: moroiasa@cinj.rutgers.edu
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104 4399
      • Recruiting
      • Childrens Hospital of Philadelphia
      • Principal Investigator: Timothy Olson
      • Contact: Ariel Rivera; Phone Number: +1 267 425 2136; Email: riveraa12@chop.edu
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • Recruiting
      • St Jude Childrens Research Hospital
      • Contact: Kelsey Ray; Email: kelsey.ray@stjude.org
      • Principal Investigator: Marcin Wlodarski

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male and female participants 2 to < 18 years of age with a diagnosis of PNH confirmed by high-sensitivity flow cytometry with red blood cells (RBCs) and with white blood cells granulocytes/monocytes clone size ≥ 10%. The minimum body weight for patients in Cohort 1 is 35 kg.
• Patients being treated with anti-C5 therapy and who have been on a stable regimen (dose and interval) for at least 6 months prior to enrollment, may be screened and enrolled in the study and switched to iptacopan irrespective of their anemia and hemolysis status, at the discretion of the Principal Investigator.
• Patients who are anti-C5 treatment naive: mean hemoglobin level < 10 g/dL confirmed by central laboratory assessment during screening.
• Patients who are anti-C5 treatment naive: lactate dehydrogenase (LDH) > 1.5 × upper limit of normal (ULN) documented by at least 2 laboratory measurements 2 to 6 weeks apart during the screening period, one of which is to be done by the central lab.
• Vaccination against Neisseria meningitidis and Streptococcus pneumoniae infection is required prior to the start of study treatment. If the participant has not been previously vaccinated, or if a booster is required, vaccine should be given according to local guidelines at least 2 weeks prior to first study drug administration. If study treatment has to start earlier than 2 weeks post-vaccination, prophylactic antibiotic treatment should be initiated.
• Vaccination against Haemophilus influenzae is recommended, according to local guidelines, at least 2 weeks before iptacopan.

Exclusion Criteria:

• History of hypersensitivity to the study drug or its excipients or to drugs of similar chemical classes.
• Known or suspected hereditary complement deficiency at screening.
• History of hematopoietic stem cell transplantation (HSCT) or scheduled for HSCT within 52 weeks from enrollment into the study (Day 1).
• Patients with laboratory evidence of bone marrow failure (reticulocytes < 100 x 10 to the ninth/L; platelets < 30 × 10 to the ninth/L; neutrophils < 0.5 × 10 to the ninth/L).
• Active systemic bacterial, viral (including COVID-19), or fungal infection within 14 days prior to study drug administration.
• Presence of fever ≥ 38 °C (100.4 °F) within 7 days prior to study drug administration.

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LNP023-Cohort 1 (12 < 18 years old); Participants (12 to < 18 years old) will take iptacopan at the dose of 200 mg twice per day (in the morning and in the evening).	Drug: LNP023; Cohort 1-administered orally a dosing scheme of 200 mg twice-daily (two 100 mg capsules). Cohort 2- administered orally a dosing scheme based on weight at the Day 1, Week 12, 26 and 38.; Other Names: Iptacopan
Experimental: LNP023 -Cohort 2 (2 to < 12 years old); Participants (2 to < 12 years old) will be dosed based on weight at the Day 1 visit, initially. The study medication dose will be reassessed and re-adjusted as needed based on their weight at Week 12, 26, and 38.	Drug: LNP023; Cohort 1-administered orally a dosing scheme of 200 mg twice-daily (two 100 mg capsules). Cohort 2- administered orally a dosing scheme based on weight at the Day 1, Week 12, 26 and 38.; Other Names: Iptacopan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)	Incidence and severity of AEs and SAEs by treatment group, including changes in vital signs, electrocardiograms (ECGs) and laboratory results qualifying and reported as AEs.	26 weeks
PK parameter (Cmax)	Cmax is defined as the maximum (peak) observed concentration following a dose.	Week 2
PK parameter (AUClast)	AUClast is the area under the plasma concentration-time curve from time zero to the time of last quantifiable concentration (tlast).	Week 2
PK parameter (AUCtau)	AUCtau describes the area under the curve limited to the end of a dosing interval.	Week 2
PK parameter (Ctrough)	Ctrough is the observed plasma concentration that is just prior to the beginning of, or at the end of a dosing interval.	Weeks 2, 4, 12 and 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in hemoglobin (Hb) from baseline ≥1 g/dL (in the absence of RBC transfusions from Day 14).	To evaluate the proportion of patients who achieve an increase in hemoglobin levels from baseline of ≥ 1 g/dL at 26 weeks and at 52 weeks (in the absence of RBC transfusions from Day 14 until the end of the 26-week and 52-week treatment periods).	Baseline, Week 26, Week 52
Change in Hb from baseline ≥2 g/dL (in the absence of RBC transfusions from Day 14).	To evaluate the proportion of patients who achieve an increase in hemoglobin levels from baseline of ≥ 2 g/dL at 26 weeks and at 52 weeks (in the absence of RBC transfusions from Day 14 until the end of the 26-week and 52-week treatment periods).	Baseline, Week 26, Week 52
Normal Hb in the absence of red blood cell (RBC) transfusions from Day 14.	To evaluate the proportion of participants achieving hemoglobin normalization at 26 weeks and at 52 weeks (in the absence of RBC transfusions from Day 14 until the end of the 26-week and 52-week treatment periods).	Week 26 and Week 52
Absence of packed-RBC transfusions and not meeting transfusion criteria from Day 14 at Week 26 and Week 52	To evaluate transfusion avoidance as the proportion of participants who remain free from transfusions and do not meet transfusion criteria from Day 14 until the end of the 26-week treatment period and until the end of the 52-week treatment period.	Week 26 and Week 52
Change from baseline in hemoglobin	To evaluate mean changes from baseline in hemoglobin at 26 weeks and at 52 weeks (evaluation of naive patients and prior anti-C5 treated patients, separately).	Baseline, Week 26, Week 52
Change from baseline in lactate dehydrogenase (LDH)	To evaluate mean changes from baseline in LDH at 26 weeks and at 52 weeks (evaluation of naive patients and prior anti-C5 treated patients, separately).	Baseline, Week 26, Week 52

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2025
• Primary Completion (Estimated): November 19, 2031
• Study Completion (Estimated): December 19, 2031

Study Registration Dates

• First Submitted: March 31, 2025
• First Submitted That Met QC Criteria: April 10, 2025
• First Posted (Actual): April 18, 2025

Study Record Updates

• Last Update Posted (Actual): April 16, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: anemia; Iptacopan,; PNH,; hemoglobin,
• 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: CLNP023I12201; 2024-515926-10 (EudraCT 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