Leniolisib for Immune Dysregulation in PIDs
NCT Number: NCT06549114
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Primary Immunodeficiency Disorders (PIDs)
Interventions: DRUG: Leniolisib
Sponsor: Pharming Technologies B.V.
Collaborators: Aixial Group
Sex: ALL
Age: CHILD, ADULT, OLDER_ADULT
Enrollment: 12
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-08
Completion Date: 2025-11

Summary:
This study is an exploratory, non-randomized, open-label, within-patient dose escalation study. The primary objective is to assess safety and tolerability of leniolisib. Secondary objectives include assessments of PK/PD, and to explore clinical efficacy measures with administration of three different dose levels of leniolisib.

Primary Outcome Measures: Number of Participants with Treatment-emergent adverse events (TEAEs), Serious Adverse Events (SAEs) , and Adverse Events (AEs), • To assess the number of participants with Adverse events (AEs), Serious Adverse Events (SAEs) to discontinuation of study drug, From Baseline to the end of 20 weeks of Treatment|Change from baseline in clinical laboratory test results, • Number of Participants with change in clinical laboratory test results, From Baseline to the end of 20 weeks of Treatment|Change from baseline in clinical vital signs, • Number of participants with change in vital signs, From Baseline to the end of 20 weeks of Treatment|Change from baseline in clinical physical examinations, • Number of Participants with change in physical examination findings, From Baseline to the end of 20 weeks of Treatment
Secondary Outcome Measures: To assess the PK of leniolisib in PID disorders linked to PI3K, • PK parameters for leniolisib defined by Cmax, AUC (0-inf), Tmax, t1/2, and AUC (0-t), From Baseline to the end of 20 weeks of Treatment|To characterize PI3K pathway activity in PID disorders linked to PI3K, • Baseline percentage and median channel fluorescence of pAKT and/or pS6 in B cells and/or T cells, under resting and/or stimulated conditions, as feasible, From Baseline to the end of 20 weeks of Treatment|To assess the impact of leniolisib on lymphocyte PI3K/AKT/mTOR pathway activity in PID disorders linked to PI3K, including the dose-PD and PK/PD relationship for percent change in pAKT and/or pS6 in B & T cells, • Percent change in pAKT and/or pS6 in B cells and/or T cells, under resting and stimulated conditions, at different dose levels of leniolisib relative to baseline pAKT/pS6 levels, as feasible, From Baseline to the end of 20 weeks of Treatment|To assess the impact of leniolisib on lymphocyte PI3K/AKT/mTOR pathway activity in PID disorders linked to PI3K, including the dose-PD and PK/PD relationship for stimulated and unstimulated conditions, * Percent change in pAKT and/or pS6 in B cells and/or T cells, under resting and stimulated conditions, at different dose levels of leniolisib relative to baseline pAKT/pS6 levels, as feasible
* Effect of leniolisib on B cell and/or T cell pAKT and/or pS6 in unstimulated and stimulated conditions over time, as feasible, From Baseline to the end of 20 weeks of Treatment|To assess the impact of leniolisib on hemoglobin counts in PID disorders linked to PI3K, • Hemoglobin over time, From Baseline to the end of 20 weeks of Treatment|To assess the impact of leniolisib on platelet counts in PID disorders linked to PI3K, • Platelet count over time, From Baseline to the end of 20 weeks of Treatment|To assess the impact of leniolisib on absolute neutrophil counts in PID disorders linked to PI3K, • Absolute neutrophil count over time, From Baseline to the end of 20 weeks of Treatment|To assess the clinical efficacy of leniolisib on individual disease manifestations and change in CT in PID disorders linked to PI3K, • Change in CT evidence of GLILD or other PID-related ILD evaluated using Hartmann scoring methodology, From Baseline to the end of 20 weeks of Treatment|To assess the clinical efficacy of leniolisib on individual disease manifestations and PFTs in PID disorders linked to PI3K for FEV1, • Change in pulmonary function testing by including forced expiratory volume 1 (FEV1), From Baseline to the end of 20 weeks of Treatment|To assess the clinical efficacy of leniolisib on individual disease manifestations and PFTs in PID disorders linked to PI3K for forced vital capacity, • Change in pulmonary function testing by forced vital capacity (FVC), From Baseline to the end of 20 weeks of Treatment|To assess the clinical efficacy of leniolisib on individual disease manifestations and PFTs in PID disorders linked to PI3K for total lung capacity, • Change in pulmonary function testing by total lung capacity (TLC), From Baseline to the end of 20 weeks of Treatment|To assess the clinical efficacy of leniolisib on individual disease manifestations and PFTs in PID disorders linked to PI3K for diffusing capacity, • Change in pulmonary function testing by diffusing capacity (DLCO), From Baseline to the end of 20 weeks of Treatment|To assess the percent change and clinical efficacy of leniolisib on individual lymphadenopathy in PID disorders linked to PI3K, * Percent change from baseline in lymphadenopathy measured as SPD of measurable non-index lymph node lesions selected as per the Cheson methodology
* Percent change from baseline in lymphadenopathy measured as the sum of product of diameters (SPD) in the index lymph node lesions selected per the Cheson methodology, From Baseline to the end of 20 weeks of Treatment|To assess the percent change and clinical efficacy of leniolisib on individual splenomegaly in PID disorders linked to PI3K, • Percent change from baseline in splenomegaly measured by three-dimensional (3D) volume and bi-dimensional (2D) size of spleen, From Baseline to the end of 20 weeks of Treatment|To assess the impact of leniolisib on white blood cell counts and lymphocyte numbers in PID disorders linked to PI3K, • White blood cell count over time, From Baseline to the end of 20 weeks of Treatment|To assess the impact of leniolisib on absolute monocyte counts and lymphocyte numbers in PID disorders linked to PI3K, • Absolute monocyte count over time, From Baseline to the end of 20 weeks of Treatment|To assess the impact of leniolisib on absolute lymphocyte counts and lymphocyte numbers in PID disorders linked to PI3K, • Absolute lymphocyte count over time, From Baseline to the end of 20 weeks of Treatment|To assess the impact of leniolisib on eosinophil counts and lymphocyte numbers in PID disorders linked to PI3K, • Absolute eosinophil count over time, From Baseline to the end of 20 weeks of Treatment|To assess the impact of leniolisib on absolute basophil counts and lymphocyte numbers in PID disorders linked to PI3K, • Absolute basophil count over time, From Baseline to the end of 20 weeks of Treatment|To assess the impact of leniolisib on CD4+ T cell counts and lymphocyte numbers in PID disorders linked to PI3K, • CD4+ T cell count over time, From Baseline to the end of 20 weeks of Treatment|To assess the impact of leniolisib on CD8+ T cell counts and lymphocyte numbers in PID disorders linked to PI3K, • CD8+ T cell count over time, From Baseline to the end of 20 weeks of Treatment|To assess the impact of leniolisib on natural killer cell count and lymphocyte numbers in PID disorders linked to PI3K, • Natural killer (NK) cell count over time, From Baseline to the end of 20 weeks of Treatment|To assess the impact of leniolisib on B cell counts and lymphocyte numbers in PID disorders linked to PI3K, • B cell count over time, From Baseline to the end of 20 weeks of Treatment|To assess the impact of leniolisib on B cell phenotypic populations of interest in PID disorders linked to PI3K, • Percentages of naïve B cells and CD21lo B cells over time, From Baseline to the end of 20 weeks of Treatment|To assess the impact of leniolisib on T cell phenotypic populations of interest in PID disorders linked to PI3K, • Percentage of T regulatory cells over time, From Baseline to the end of 20 weeks of Treatment|To examine levels of CXCL13 and assess the impact of leniolisib in PID disorders linked to PI3K, * Levels of CXCL13 over time
* Levels of soluble IL-2Rα over time, From Baseline to the end of 20 weeks of Treatment|To examine levels of soluble IL-2Rα and assess the impact of leniolisib in PID disorders linked to PI3K, • Levels of soluble IL-2Rα over time, From Baseline to the end of 20 weeks of Treatment