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 Extensio

Phase 3

Recruiting

Conditions: Activated PI3K&delta
syndrome
10021429

Registration Number: NL-OMON53548

Lead Sponsor: Pharming Technologies b.v.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 5

Inclusion 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 PI3Kδ 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.

Exclusion Criteria

• Patient has previous or concurrent use of immunosuppressive medication such
as: a. An mTOR inhibitor (eg, sirolimus, rapamycin, everolimus) or a PI3Kδ
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]). e.
Patient is currently using medications known to be organic anion transporter
protein (OATP)1B1, OATP1B3, and breast cancer resistance protein (BCRP)
substrates