Clinical trial NCT06934967: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Paroxysmal Nocturnal Hemoglobinuria (PNH)
Keywords: Iptacopan,
PNH,
hemoglobin,
anemia
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2025-04-18
Enrollment: 12
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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).

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.

Primary outcomes:
measure: Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: 26 weeks
measure: PK parameter (Cmax)
timeFrame: Week 2
measure: PK parameter (AUClast)
timeFrame: Week 2
measure: PK parameter (AUCtau)
timeFrame: Week 2
measure: PK parameter (Ctrough)
timeFrame: Weeks 2, 4, 12 and 26
Secondary outcomes:
measure: Change in hemoglobin (Hb) from baseline ≥1 g/dL (in the absence of RBC transfusions from Day 14).
timeFrame: Baseline, Week 26, Week 52
measure: Change in Hb from baseline ≥2 g/dL (in the absence of RBC transfusions from Day 14).
timeFrame: Baseline, Week 26, Week 52
measure: Normal Hb in the absence of red blood cell (RBC) transfusions from Day 14.
timeFrame: Week 26 and Week 52
measure: Absence of packed-RBC transfusions and not meeting transfusion criteria from Day 14 at Week 26 and Week 52
timeFrame: Week 26 and Week 52
measure: Change from baseline in hemoglobin
timeFrame: Baseline, Week 26, Week 52
measure: Change from baseline in lactate dehydrogenase (LDH)
timeFrame: Baseline, Week 26, Week 52
Other outcomes:
Locations:
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: