Pediatric Patients Aged 1 to 6 Years With APDS

Running, not enrolling · Phase 3

Conditions studied: APDS

In brief

This is a 2-part, prospective, open-label, single arm, multicenter study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PDx), and efficacy of leniolisib in at least 15 pediatric patients (aged 1 to 6 years) with activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS)

Key facts

Study ID

NCT05693129

Run by

Pharming Technologies B.V.

People needed

16

Starts

2023-08-30

Expected to finish

2028-10-28

Last updated by the study team

2026-06-15

Who can join

Age: 1 and older, up to 6. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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 PI3Kδ genetic mutation of either the PIK3CD (APDS1) or PIK3R1 (APDS2) gene.
• Patient has at least 1 measurable nodal lesion on MRI or low-dose CT within 6 months of screening.
• 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.
• At screening, vital signs (body temperature, systolic BP, diastolic BP, and pulse rate [PR]) will be assessed in the sitting position after the patient has been at rest for at least 3 minutes. Patient's sitting vital signs should be within the following ranges:
• Systolic BP: Less than the 95th percentile adjusted for sex, age, and height percentile. See Section 10.5, Appendix 5 to determine BP percentiles adjusted for sex, age, and height percentile. (National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents, 2004). See Section 10.5, Appendix 5 to determine height percentiles.
• Diastolic BP: Less than the 95th percentile adjusted for sex, age, and height percentile. See Section 10.5, Appendix 5 to determine BP percentiles adjusted for sex, age, and height percentile. See Section 10.6, Appendix 6 to determine height percentiles.
• Pulse rate (Fleming 2011):
• i. Age <2 years: 100 to 190 bpm ii. Age 2 to 6 years: 60 to 140 bpm
• Institutional review board- or IEC-approved written informed consent or assent and privacy language as per national and local regulations must be obtained from the patient and/or parent or legal guardian prior to any study-related procedures.
• Patient parent or legal guardian is willing and able to complete the informed consent or assent process and comply with study procedures and visit schedule.
• Patient parent or legal guardian agrees patient will not participate in any other interventional study while enrolled in this study.

You may not qualify if…

• Patient has previous or concurrent use of immunosuppressive medication such as:
• an mTOR inhibitor (eg, sirolimus, rapamycin, everolimus) or a PI3Kδ inhibitor (selective or non-selective PI3K inhibitors) within 6 weeks prior to first dose.
• o 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 cell depleters (eg, rituximab) within 6 months prior to first dose of study medication.
• o If patient has received prior treatment with a B cell depleter, absolute B lymphocyte counts in the blood must have regained normal values.
• Belimumab or cyclophosphamide within 6 months prior to first dose of study medication.
• Cyclosporine A, mycophenolate, 6-mercaptopurine, azathioprine, or methotrexate within 3 months prior to first dose of study medication.
• 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.
• Other immunosuppressive medication where effects are expected to persist at start of dosing of study medication.
• Patient has a history or current diagnosis of ECG abnormalities indicating significant risk of safety for patients participating in the study such as:
• History of familial long QT syndrome or known family history of Torsades de Pointes.
• Concomitant clinically significant cardiac arrhythmias, eg, sustained ventricular tachycardia, and clinically significant second or third degree atrioventricular block without a pacemaker.
• Resting QTc (Fridericia preferred, but Bazett acceptable) >460 msec if the measurement is confirmed with an additional ECG repeated as soon as possible.
• 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]).
• Patient had been administered live vaccines (this includes any attenuated live vaccines) starting from 6 weeks before the anticipated first study drug administration, during the study, and up to 7 days after the last dose of leniolisib.
• Patient has clinically significant abnormalities in hematology or clinical chemistry (blood chemistry or urinalysis) parameters as determined by the investigator or medical monitor.
• Patient has liver disease or liver injury as indicated by clinically significant abnormal liver function tests (LFTs) (alanine aminotransferase and aspartate aminotransferase >2.5 times upper limit of normal), history of renal injury or renal disease (eg, renal trauma, glomerulonephritis, or one kidney only), or presence of impaired renal function as indicated by a serum creatinine level >1.5 mg/dL (133 μmol/L).
• Patient has moderate or severe hepatic impairment (Child-Pugh Class B or C).
• Patient is receiving concurrent treatment with another investigational therapy or use of another investigational therapy less than 4 weeks from the first study procedure.
• Patient has active hepatitis B (eg, hepatitis B surface antigen reactive) or active hepatitis C (eg, hepatitis C virus RNA [qualitative] is detected) at screening.
• Patient has human immunodeficiency virus (HIV) infection (HIV 1 or 2) at screening.
• Patient has a positive COVID-19 result (polymerase chain reaction or antigen) within 1 week prior to first dose. The patient can be rescreened after a subsequent negative result.
• Patient has a history of malignancy (except lymphoma) within 3 years before the first study procedure or has evidence of residual disease from a previously diagnosed malignancy.

Where it is running

• University of California Los Angeles — Los Angeles, California, United States
• National Institutes of Health — Bethesda, Maryland, United States
• Rainbow Childrens Hospital — Shaker Heights, Ohio, United States
• Texas Children's Hospital — Houston, Texas, United States
• Kyoto University Hospital — Kyoto, Japan
• Institute of Science Tokyo Hospital — Tokyo, Japan
• Hospital Pediátrico de Coimbra da ULS Coimbra UNIDADE LOCAL DE SAÚDE DE COIMBRA — Coimbra, Portugal
• Hospital Universitario Virgen del Rocío — Seville, Spain
• Great Ormond Street Hospital — London, United Kingdom

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.