Pediatric Patients Aged 4 to 11 Years with APDS
- Registration Number
- NCT05438407
- Lead Sponsor
- Pharming Technologies B.V.
- 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).
- Detailed Description
Part I will consist of a 12-week period to assess the safety and efficacy of treatment with leniolisib. Part II will consist of a 1-year, long-term, safety follow-up extension with a possible interim analysis.
The leniolisib doses to be used in study were selected based on safety, tolerability, PK, and PDx data from the adult Phase 2/3 study, as well as PK modeling data. In both parts of the study, leniolisib will be administered orally based on weight.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 15
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Leniolisib Leniolisib 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.
- Primary Outcome Measures
Name Time Method Part I & II: Change from baseline in physical examination findings From baseline to end of 12 weeks, & From baseline to through study completion, an average of 1 year Number of Participants with change in physical examination findings
Part I & II: Change from baseline in electrocardiograms (ECGs) From baseline to end of 12 weeks, & From baseline to through study completion, an average of 1 year, plus 30 Days Number of Participants with change in electrocardiograms (ECGs)
Part I & II: Change from baseline in clinical laboratory test results From baseline to end of 12 weeks, & From baseline to through study completion, an average of 1 year Number of Participants with change in clinical laboratory test results (hematology, blood chemistry, urinalysis)
Part I & II: Change from baseline in vital signs From baseline to end of 12 weeks, & From baseline to through study completion, an average of 1 year Number of Participants with change in vital signs
Part I & II: Change from baseline in growth and physical development From baseline to end of 12 weeks, & From baseline to through study completion, an average of 1 year Number of Participants with change in growth and physical development
Part I: A Percentage of Inhibition of Unstimulated and Stimulated pAkt Levels in B Cells Part I: Baseline, Days 29, 57 and 85 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 & II: Number of Participants with Treatment-emergent adverse events (TEAEs), Serious Adverse Events (SAEs) , and Adverse Events (AEs) From baseline to end of 12 weeks, & From baseline to through study completion, an average of 1 year, plus 30 days Number of Participants with TEAEs, SAEs, and AEs leading to discontinuation of study drug
Part I & II: Reduction in lymphoproliferation as measured by MRI or low-dose CT Part I: Baseline and Day 85 Part II: at Day 252, through study completion, an average of 1 year 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.
- Secondary Outcome Measures
Name Time Method Part I: To evaluate changes in Pharmacokinetic (PK) profile/parameters From baseline to end of 12 weeks of treatment] To evaluate changes in Cmax, Tmax AUC, T1/2
Part I: To evaluate changes in Pharmacodynamic (PD) profile/parameters From baseline to end of 12 weeks of treatment] To evaluate changes in pAkt and Serum Immunoglobulin Profile
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 Population pharmacokinetics (popPK) model that describes the appropriate covariates (eg, body weight and age) that influence leniolisib PK in pediatric patients.
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 Population pharmacokinetics (popPK) model that describes the appropriate covariates (eg, body weight and age) that influence leniolisib PK in pediatric patients.
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 Population pharmacokinetics (popPK) model that describes the appropriate covariates (eg, body weight and age) that influence leniolisib PK in pediatric patients.
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 Parameters for reduction in 3D volume and bi-dimensional or 3D sizes of liver, where appropriate. Summary statistics will be provided by visit. Arithmetic mean with SD of absolute values and change from baseline values may be plotted across time.
Part I and II: Key secondary efficacy outcomes for Part I include incidence of infections and use of antibiotics. Part I: Baseline to Day 85 Part II: through study completion, an average of 1 year The number and percentage of patients with infections, and the total number of infections will be summarized. The number and percentage of antibiotics taken will be presented along with number of patients for Part I. Use of immunoglobulin replacement therapy over time will be summarized.
Part I and II: Pediatric Quality of Life Inventory (PedsQLTM) Parent Report for Children Questionnaire 4.0 Generic Core Scales Part I: Baseline, Day 29, 57, & 85 Part II: through study completion, an average of 1 year To assess the ability of leniolisib to modify health related quality of life in pediatric patients with APDS. The unabbreviated scale title is SCALING AND SCORING OF THE PedsQL. The minimum and maximum values; are reversed scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. Higher scores indicate better HRQOL.
Trial Locations
- Locations (7)
Institute of Science Tokyo Hospital
🇯🇵Tokyo, Japan
Kyoto University Hospital
🇯🇵Kyoto, Japan
University of California Los Angeles
🇺🇸Los Angeles, California, United States
Stanford University
🇺🇸Standford, California, United States
Children's Healthcare of Atlanta
🇺🇸Atlanta, Georgia, United States
National Institutes of Health
🇺🇸Bethesda, Maryland, United States
Necker Hospital Paris
🇫🇷Paris, France