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

Official title

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

Overview

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.

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).

Interventions

• 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.

Primary outcome measures

• Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time frame: 26 weeks]
• PK parameter (Cmax) [Time frame: Week 2]
• PK parameter (AUClast) [Time frame: Week 2]
• PK parameter (AUCtau) [Time frame: Week 2]
• PK parameter (Ctrough) [Time frame: Weeks 2, 4, 12 and 26]

Secondary outcome measures (6)

• Change in hemoglobin (Hb) from baseline ≥1 g/dL (in the absence of RBC transfusions from Day 14). [Time frame: Baseline, Week 26, Week 52]
• Change in Hb from baseline ≥2 g/dL (in the absence of RBC transfusions from Day 14). [Time frame: Baseline, Week 26, Week 52]
• Normal Hb in the absence of red blood cell (RBC) transfusions from Day 14. [Time frame: Week 26 and Week 52]
• Absence of packed-RBC transfusions and not meeting transfusion criteria from Day 14 at Week 26 and Week 52 [Time frame: Week 26 and Week 52]
• Change from baseline in hemoglobin [Time frame: Baseline, Week 26, Week 52]
• Change from baseline in lactate dehydrogenase (LDH) [Time frame: Baseline, Week 26, Week 52]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Brazil · 6 centers

• Novartis Investigative Site — Brasília
• Novartis Investigative Site — Natal
• Novartis Investigative Site — Porto Alegre
• Novartis Investigative Site — Santo André
• Novartis Investigative Site — São Paulo
• Novartis Investigative Site — São Paulo

United States · 4 centers

• Childrens Healthcare of Atlanta — Atlanta
• Cancer Institute of New Jersey — New Brunswick
• Childrens Hospital of Philadelphia — Philadelphia
• St Jude Childrens Research Hospital — Memphis

Germany · 2 centers

• Novartis Investigative Site — Cologne
• Novartis Investigative Site — Berlin

Colombia · 1 center

• Novartis Investigative Site — Cali

Italy · 1 center

• Novartis Investigative Site — Genova

Netherlands · 1 center

• Novartis Investigative Site — Utrecht

Identifiers

NCT: NCT06934967 · CLNP023I12201 · 2024-515926-10

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗