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

Novartis

Status and phase: Enrolling; Phase 3

Conditions: Paroxysmal Nocturnal Hemoglobinuria (PNH)

Treatments: Drug: LNP023

Study type: Interventional

Funder types: Industry

Identifiers

NCT06934967

2024-515926-10 (EudraCT Number)

CLNP023I12201

Details and patient eligibility

About

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.

Full 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).

Enrollment: 12 estimated patients

Sex: All

Ages: 2 to 18 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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12 participants in 2 patient groups

LNP023-Cohort 1 (12 < 18 years old)

Experimental group

Description:

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).

Treatment:

Drug: LNP023

LNP023 -Cohort 2 (2 to < 12 years old)

Experimental group

Description:

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.

Treatment:

Drug: LNP023