Overview

An Open-Label, Non-Randomized Study to Assess the Safety and Efficacy of Leniolisib in Japanese Patients With Activated Phosphoinositide 3-Kinase Delta Syndrome (APDS) Followed By an Open-Label Long-Term Extension.

For the treatment of activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS).

Eligibility

Inclusion Criteria:

• Patient is Japanese.
• Patient is male or female and 12 to 75 years of age (inclusive) at the time of the first study procedure.
• Patient weighs ≥35 kg at baseline.
• Patient has a PI3Kδ genetic mutation of either the PIK3CD (APDS1) or PIK3R1 (APDS2) gene.
• Patient has at least 1 measurable nodal lesion on computed tomography (CT) or magnetic resonance imaging (MRI) scan within 6 months of Screening.
• Patient has nodal and/or extranodal lymphoproliferation and clinical findings and manifestations consistent with APDS (e.g., a history of repeated oto-sino-pulmonary infections and/or organ dysfunction consistent with APDS).
• At Screening, patient has sitting vital signs (with patient rested for at least 3 minutes) within the following ranges:
• Systolic blood pressure, 90-160 mm Hg
• Diastolic blood pressure, 50-95 mm Hg
• Pulse rate, 40-100 bpm; up to 110 bpm in adolescents

Exclusion Criteria:

• Patient has previous or concurrent use of immunosuppressive medication such as the

  following

  1. A mammalian target of rapamycin inhibitor (e.g., sirolimus, rapamycin, or everolimus) or a PI3Kδ inhibitor (selective or non-selective phosphoinositide 3-kinase inhibitors) within 6 weeks prior to first dose.
     • 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.
  2. B-cell depleters (e.g., rituximab) within 6 months prior to first dose of study

     treatment.

     • If patient has received prior treatment with a B-cell depleter, absolute B lymphocyte counts in the blood must have regained normal values.
  3. Belimumab or cyclophosphamide within 6 months prior to first dose of study treatment.
  4. Cyclosporine A, mycophenolate, 6-mercaptopurine, azathioprine, or methotrexate within 3 months prior to first dose of study treatment.
  5. Glucocorticoids above 25 mg prednisone or equivalent per day within 2 weeks prior to first dose of study treatment.
  6. Other immunosuppressive medications where effects are expected to persist at start of dosing of study treatment.
     • Patient has had a hematopoietic stem-cell transplant, hematopoietic cell transplant, or bone marrow transplant.
     • Patient is currently using a medication known to be a strong inhibitor or moderate or strong inducer of isoenzyme cytochrome P450 (CYP)3A if treatment cannot be discontinued or switched to a different medication prior to starting study treatment.
     • Patient is currently using medications that are metabolized by isoenzyme CYP1A2 and have a narrow therapeutic index (drugs whose exposure response indicates that increases in their exposure levels by the concomitant use of potent inhibitors may lead to serious safety concerns [e.g., Torsades de Pointes]).
     • Patient had been administered a live vaccine (this includes any attenuated live vaccines) starting from 6 weeks before the anticipated first dose of study treatment, during the treatment period, and up to 7 days after the last dose of leniolisib.
     • Patient is a pregnant or nursing (lactating) woman, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin laboratory test.
     • Patient is a woman of child-bearing potential, defined as a woman physiologically capable of becoming pregnant, unless she is using highly effective methods of contraception during dosing of study treatment and for 30 days after the last study procedure.