Pediatric Patients Aged 1 to 6 Years With APDS

NCT05693129 | Active Not Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: LE 3302
• Study Type: interventional
• Target: 16
• Locations: 5 countries
• Sites: 9

Brief Summary

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)

Conditions

APDS

Outcome Measures

Primary Outcomes (8)

• Part I & II: Number of Participants with Treatment-emergent adverse events (TEAEs), Serious Adverse Events (SAEs) , and Adverse Events (AEs)

  To assess number of Participants with TEAEs, SAEs, and AEs leading to discontinuation of study drug

  From baseline to end of 12 weeks, & From baseline to through study completion, an average of 1 year, plus 30 days

• Part I & II: Change from baseline in clinical laboratory test results

  Number of Participants with change in clinical laboratory test results (hematology, blood

  From baseline to end of 12 weeks, & From baseline to through study completion, an average of 1 year

• Part I & II: Change from baseline in vital signs

  Number of Participants with change in vital signs

  From baseline to end of 12 weeks, & From baseline to through study completion, an average of 1 year

• Part I & II: Change from baseline in physical examination findings

  Number of Participants with change in physical examination findings

  From baseline to end of 12 weeks, & From baseline to through study completion, an average of 1 year

• Part I & II: Change from baseline in electrocardiograms (ECGs)

  Number of Participants with change in electrocardiograms (ECGs)

  From baseline to end of 12 weeks, & From baseline to through study completion, an average of 1 year, plus 30 days

• Part I & II: Change from baseline in growth and physical development

  Number of Participants with change in growth and physical development

  From baseline to end of 12 weeks, & From baseline to through study completion, an average of 1 year

• Part I & II: Reduction in lymphadenopathy as measured by MRI or low-dose CT

  To assess the impact of leniolisib on lymphadenopathy, patients will be scanned in an MRI or a CT scanner as based on clinical practice and local regulation. Index lesions will be selected from measurable nodal and extra nodal lesions as per the Cheson methodology. The same imaging modality will be used throughout the study for the same patient. Patients will be assessed by MRI, or in sites where local practice and local authorities/IECs/IRBs approve CT scans for research purposes using a low-dose CT scan.

  Part I: Baseline and Day 85 Part II: at Day 252, through study completion, an average of 1 year

• Part I: A Percentage of Inhibition of Unstimulated and Stimulated pAkt Levels in B Cells

  To assess change in the PDx effect of leniolisib will be assessed using ex vivo stimulated and unstimulated

  Part I: Baseline, Days 29, 57 and 85

Secondary Outcomes (8)

• Part I: To assess the total drug exposure (AUC) of leniolisib in pediatric patients (aged 4 to 11 years) with APDS

  From baseline to end of 12 weeks of treatment

• Part I: To assess the maximum concentration (Cmax) of leniolisib in pediatric patients (aged 4 to 11 years) with APDS

  From baseline to end of 12 weeks of treatment

• Part I: To assess the time to maximum concentration (Tmax) of leniolisib in pediatric patients (aged 4 to 11 years) with APDS

  From baseline to end of 12 weeks of treatment

• Part II: Changes from baseline for Reduction in lymphadenopathy as measured by MRI or low-dose CT

  Day 85 to through study completion, an average of 1 year

• Part II: Changes from baseline for Reduction in lymphadenopathy as measured by MRI or low-dose CT

  Day 85 to through study completion, an average of 1 year

Study Arms (1)

Leniolisib

EXPERIMENTAL

Leniolisib film-coated granules in 10, 15 and 20 mg strengths administered orally BID by body weight for 12 weeks for Part I and for 1 year for Part II.

Drug: Leniolisib

Interventions

Leniolisib DRUG

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).

Leniolisib

Eligibility Criteria

• Age: 1 Year - 6 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

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.

Sponsors & Collaborators

• Pharming Technologies B.V.: lead
• CMIC Co, Ltd. Japan: collaborator
• Labcorp Central Laboratory: collaborator
• Fortrea: collaborator
• Aixial Group: collaborator

Study Sites (9)

University of California Los Angeles

Los Angeles, California, 90095, United States

Location

National Institutes of Health

Bethesda, Maryland, 20814, United States

Location

Rainbow Childrens Hospital

Shaker Heights, Ohio, 44122, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Kyoto University Hospital

Kyoto, 606-8507, Japan

Location

Institute of Science Tokyo Hospital

Tokyo, 113-8519, Japan

Location

Hospital Pediátrico de Coimbra da ULS Coimbra UNIDADE LOCAL DE SAÚDE DE COIMBRA

Coimbra, 3000-075, Portugal

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Great Ormond Street Hospital

London, WC1N3JH, United Kingdom

Location

MeSH Terms

Interventions

leniolisib

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 17, 2022
• First Posted: January 20, 2023
• Study Start: August 30, 2023
• Primary Completion (Estimated): July 9, 2026
• Study Completion (Estimated): October 28, 2026
• Last Updated: October 28, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

PT (1); JP (2); ES (1); US (4); GB (1)