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

ConditionParoxysmal Nocturnal Hemoglobinuria (PNH)

Trial statusRecruiting

Trial phasePhase 3

Trial typeInterventional

Biological sexAll

Age2-18

SponsorNovartis Pharmaceuticals

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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).

Trial design

Design model

Sequential

Treatments tested in this trial

LNP023
Drug
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.

Treatment groups

12 Participants

are divided into 2 treatment groups

Group A: LNP023-Cohort 1 (12 < 18 years old)Experimental treatment 1 intervention

Group B: LNP023 -Cohort 2 (2 to < 12 years old)Experimental treatment 1 intervention

Trial outcomes

Primary outcomes

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.

Time frame

26 weeks

PK parameter (Cmax)

Cmax is defined as the maximum (peak) observed concentration following a dose.

Time frame

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).

Time frame

Week 2

PK parameter (AUCtau)

AUCtau describes the area under the curve limited to the end of a dosing interval.

Time frame

Week 2

Secondary outcomes

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).

Time frame

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).

Time frame

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).

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

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.

Time frame

Week 26 and Week 52