Pediatric Patients Aged 4 to 11 Years With APDS

NCT05438407 | Active Not Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: LE 3301
• Study Type: interventional
• Target: 15
• Locations: 3 countries
• Sites: 7

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 4 to 11 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)

  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 chemistry, urinalysis)

  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 lymphoproliferation as measured by MRI or low-dose CT

  For the assessment of the impact of leniolisib on lymphoproliferation, 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

  The PDx effect of leniolisib will be assessed using ex vivo stimulated and unstimulated phosphorylation of Akt in B cells. Akt is a direct downstream target of activated PI3Kδ. Determination of the percentage (%) of CD20+ pAkt positive cells after ex vivo stimulation of whole blood is performed by flow cytometry analysis. Unstimulated cells will serve as controls.

  Part I: Baseline, Days 29, 57 and 85

Secondary Outcomes (10)

• Part I: To evaluate changes in Pharmacokinetic (PK) profile/parameters

  From baseline to end of 12 weeks of treatment]

• Part I: To evaluate changes in Pharmacodynamic (PD) profile/parameters

  From baseline to end of 12 weeks of treatment]

• 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

Study Arms (1)

Leniolisib

EXPERIMENTAL

Leniolisib - Film Coated Tablets Leniolisib tablets in 10 and 30 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 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

Leniolisib

Eligibility Criteria

• Age: 4 Years - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may not qualify if:

• Patients must satisfy all of the following criteria at the screening visit unless otherwise stated:
• Patient is male or female and between the age of 4 to 11 years old at the time of the first study procedure.
• Patient weighs ≥13 kg and \<45 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 magnetic resonance imaging/low-dose computed tomography 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 and/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 (systolic blood pressure \[BP\], diastolic BP, and pulse rate) 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.
• Diastolic BP: Less than the 95th percentile adjusted for sex, age, and height percentile.
• Heart rate (HR):
• i) Age 4 to \<10 years: 60 to 140 bpm ii) Age ≥10 years: 50 to 100 bpm
• Institutional review board-/independent ethics committee-approved written informed consent/assent and privacy language as per national and local regulations must be obtained from the patient and parent/legal guardian prior to any study-related procedures.
• Patient parent/legal guardian is willing and able to complete the informed consent/assent process and comply with study procedures and visit schedule.
• Patient parent/legal guardian agrees patient will not participate in any other interventional study while enrolled in this study.

Sponsors & Collaborators

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

Study Sites (7)

University of California Los Angeles

Los Angeles, California, 90095, United States

Location

Stanford University

Standford, California, 94305-5366, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

National Institutes of Health

Bethesda, Maryland, 20814, United States

Location

Necker Hospital Paris

Paris, 75015, France

Location

Kyoto University Hospital

Kyoto, 606-8507, Japan

Location

Institute of Science Tokyo Hospital

Tokyo, 113-8519, Japan

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: May 20, 2022
• First Posted: June 30, 2022
• Study Start: February 1, 2023
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

JP (2); US (4); FR (1)