A Study to Assess Safety and Tolerability, and Explore Efficacy of Leniolisib for Immune Dysregulation in Primary Immunodeficiency Disorders
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.
• Subjects 12 to 75 years of age.
• Diagnosed with a PID due to disease-causing pathogenic or likely pathogenic variant(s) in the following genes: SOCS1, PTEN, CTLA4, NFKB1 (only those variants leading to NFKB pathway activation), or FAS (germline or somatic), or diagnosed with RAS associated leukoproliferative disorder (and not juvenile myelomonocytic leukemia \[JMML\]) due to somatic variants in NRAS or KRAS.
• Subjects must have 1 or more of the following:
‣ One or more blood cytopenias related to the underlying PID defined as hemoglobin \<10 g/dL, platelet count \<100,000/µL, or neutrophil count \<1000/µL
⁃ Splenomegaly evident by CT imaging with craniocaudal spleen measurement \>10 cm
⁃ Lymphadenopathy evident by CT imaging with at least 1 measurable index lymph node (long axis \>1.5 cm) as per Cheson methodology
⁃ GLILD or other PID-related ILD with quantifiable CT chest imaging findings evident on baseline CT scan
• At screening, vital signs.
‣ Systolic blood pressure 80-139 mm Hg
⁃ Diastolic blood pressure 50-89 mm Hg
⁃ Pulse rate 50-110 bpm
⁃ Oxygen saturation 93-100%
• Subjects or their legal representatives (for subjects under the age of 18 years) must be able to provide written informed consent.