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An Open-label, Single Arm Study of the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of Leniolisib in Pediatric Patients (Aged 1 to 6 Years) with APDS (Activated Phosphoinositide 3-Kinase Delta Syndrome) Followed by an Open-label Long-term Extension

An Open-label, Single Arm Study of the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of Leniolisib in Pediatric Patients (Aged 1 to 6 Years) with APDS (Activated Phosphoinositide 3-Kinase Delta Syndrome) Followed by an Open-label Long-term Extension

Anurag Relan

Pharming Technologies BV

Darwinweg 24 2333 CR Leiden, The Netherlands

Medical-information@pharming.com

Kentaro Masumi

CMIC Co., Ltd.

1-1-1, Shibaura, Minato-ku, Tokyo

+81-3-6779-8000

ClinicalTrialInformation@cmic.co.jp

Recruiting

Nov. 01, 2023

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

- Patient is male or female and between the age of 1 to 6 years old at time of the first study procedure.
- Patient weighs >=8 and <=37 kg at baseline.
- Patient has a confirmed PI3Kd genetic mutation of either the PIK3CD (APDS1) or PIK3R1 (APDS2) gene.
- Patient has at least 1 measurable nodal lesion on magnetic resonance imaging (MRI)/low-dose computed tomography (CT).
- Patient has nodal or extranodal lymphoproliferation and clinical findings consistent with APDS (eg, a history of repeated oto-sino-pulmonary infections or organ dysfunction consistent with APDS).
- Patient has the ability to ingest unaltered study-related medications without difficulty in the investigator's opinion.

- Patient has previous or concurrent use of immunosuppressive medication such as:
a. An mTOR inhibitor (eg, sirolimus, rapamycin, everolimus) or a PI3Kd inhibitor (selective or non-selective PI3K inhibitors) within 6 weeks prior to first dose.
i. Short-term use for up to a total of 5 days is allowed but only up to 1 month prior to enrollment in the study.
b. B cell depleters (eg, rituximab) within 6 months prior to first dose of study medication.
i. If patient has received prior treatment with a B cell depleter, absolute B lymphocyte counts in the blood must have regained normal values.
c. Belimumab or cyclophosphamide within 6 months prior to first dose of study medication.
d. Cyclosporine A, mycophenolate, 6-mercaptopurine, azathioprine, or methotrexate within 3 months prior to first dose of study medication..
e. Glucocorticoids above a dose equivalent to either >=2 mg/kg of body weight for weights less than 10 kg or >=20 mg/day for weights >=10 kg of prednisone or prednisolone or equivalent within 2 weeks prior to first dose of study medication.
f. Other immunosuppressive medication where effects are expected to persist at start of dosing of study medication.
- Patient has a history or current diagnosis of electrocardiogram (ECG) abnormalities indicating significant risk of safety for patients participating in the study such as:
a. History of familial long QT syndrome or known family history of Torsades de Pointes.
b. Concomitant clinically significant cardiac arrhythmias, eg, sustained ventricular tachycardia, and clinically significant second or third degree atrioventricular block without a pacemaker.
c. Resting QTc (Fridericia preferred, but Bazett acceptable) >460 msec if the measurement is confirmed with an additional ECG repeated as soon as possible.
d. Concomitant use of agents known to prolong the QT interval unless it can be permanently discontinued for the duration of the study.
- Patient is currently using a medication known to be strong inhibitor or moderate or strong inducer of isoenzyme CYP3A (see Table 2), if treatment cannot be discontinued or switched to a different medication prior to starting study treatment.
- Patient is currently using medications that are metabolized by isoenzyme CYP1A2 and have a narrow therapeutic index (NTI) (drugs whose exposure response indicates that increases in their exposure levels by the concomitant use of potent inhibitors may lead to serious safety concerns [eg, Torsades de Pointes]).

Both

APDS (Activated Phosphoinositide 3-Kinase Delta Syndrome)

Drug: Leniolisib
The doses selected will range from 10 to 50 mg twice daily (BID) (resulting in total daily doses ranging from 20 to 100 mg per day).

Part I
- Incidence of treatment-emergent AEs (TEAEs), SAEs, and AEs leading to discontinuation of study drug
- Change from baseline in clinical laboratory test results (hematology, blood chemistry, urinalysis)
- Change from baseline in vital signs
- Change from baseline in physical examination findings
- Change from baseline in electrocardiograms (ECGs)
- Change from baseline in growth and physical development
- Reduction in lymphoproliferation as measured by MRI or low-dose CT at end of 12 weeks of treatment
- Immunophenotype normalization assessed by changes from baseline in the proportion of naive B cells among all B cells to end of 12 weeks of treatment.
Part II
- All safety parameters (including TEAEs, SAEs, AEs leading to discontinuation of study drug, physical exam, vital signs, ECGs, growth and physical development, and clinical laboratory results).

+81-3-5803-5612

Aug. 29, 2023

No

EU/UK/USA