An Open-label, Single Arm Study of the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of Leniolisib in Pediatric Patients (Aged 4 to 11 Years) with APDS (Activated Phosphoinositide 3-Kinase Delta Syndrome) Followed by an Open-label Long-term Extension

JRCT ID: jRCT2031220625

Registered date:09/02/2023

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: APDS (Activated Phosphoinositide 3-Kinase Delta Syndrome)
• Date of first enrollment: 10/07/2023
• Target sample size: 2
• Countries of recruitment: EU,Japan,UK,Japan,USA,Japan
• Study type: Interventional

Intervention(s)

Drug: Leniolisib
The doses selected range from 20 to 70 mg BID (resulting in total daily doses ranging from 40 to 140 mg per day) based on weight. The doses will be administered as (a combination of) 10 mg and 30 mg tablets

Outcome(s)

Primary Outcome

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 lymphadenopathy as measured by MRI or low-dose CT at end of 12 weeks of treatment
-Immunophenotype assessed by changes from baseline in the percentage of naive B cells to total 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)

Key inclusion & exclusion criteria

• Age minimum: >= 4age old
• Age maximum: <= 11age old
• Gender: Both

Include criteria

-Patient is male or female and between the age of 4 to 11 years old at time of the first study procedure. Females should be of nonchildbearing potential at screening.
-Patient weighs >=13 kg and <45 kg at baseline.
-Patient has confirmed PI3Kdelta 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 and/or organ dysfunction consistent with APDS).
-Patient has the ability to ingest unaltered study-related medications without difficulty.

Exclude criteria

-Patient has previous or concurrent use of immunosuppressive medication such as:
a. An mTOR inhibitor (eg, sirolimus, rapamycin, everolimus) or a PI3Kdelta 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. Systemic glucocorticoids above a dose equivalent to either >=2 mg/kg of body weight or >=20 mg/day of prednisone/prednisolone or equivalent.
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 (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]).

Related Information

• Primary Sponsor: Relan Anurag
• Secondary ID(s): NCT045438407