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

JRCT ID: jRCT2061230036

Registered date:04/07/2023

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: activated phosphoinositide 3-kinase delta syndrome (APDS)
• Date of first enrollment: 17/08/2023
• Target sample size: 3
• Study type: Interventional

Intervention(s)

Drug: Leniolisib
The doses selected range from 40 to 70 mg BID based on weight. The doses will be administered as a combination of 10- and 30-mg tablets or single 70-mg tablets.

Outcome(s)

Primary Outcome

Part 1
- Incidence of treatment-emergent adverse events (AEs), serious adverse events (SAEs), and AEs leading to discontinuation of study treatment
- Change from baseline in clinical laboratory test results (hematology, blood chemistry, urinalysis)
- Change from baseline in vital signs
- Change from baseline in physical examination findings
- Change from baseline in electrocardiograms (ECGs)
-Change from baseline in SPD of index lesions (selected as per the Cheson methodology from magnetic resonance imaging [MRI] or computed tomography [CT] imaging) at the end of treatment
- Change from baseline in the percentage of naive B cells out of total B cells at the end of treatment
Part 2
- Incidence of treatment-emergent AEs, SAEs, and AEs leading to discontinuation of study treatment
- Change from baseline in clinical laboratory test results (hematology, blood chemistry, urinalysis)
- Change from baseline in vital signs
- Change from baseline in physical examination findings
- Change from baseline in ECGs

Key inclusion & exclusion criteria

• Age minimum: >= 12age old
• Age maximum: <= 75age old
• Gender: Both

Include 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 PI3K delta 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

Exclude criteria

- Patient has previous or concurrent use of immunosuppressive medication such as the following:
a. A mammalian target of rapamycin inhibitor (e.g., sirolimus, rapamycin, or everolimus) or a PI3K delta inhibitor (selective or non-selective phosphoinositide 3-kinase inhibitors) within 6 weeks prior to first dose.
o 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.
b. B-cell depleters (e.g., rituximab) within 6 months prior to first dose of study treatment.
o If patient has received prior treatment with a B-cell depleter, absolute B lymphocyte counts in the blood must have regained normal values.
c. Belimumab or cyclophosphamide within 6 months prior to first dose of study treatment.
d. Cyclosporine A, mycophenolate, 6-mercaptopurine, azathioprine, or methotrexate within 3 months prior to first dose of study treatment.
e. Glucocorticoids above 25 mg prednisone or equivalent per day within 2 weeks prior to first dose of study treatment.
f. 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.

Related Information

• Primary Sponsor: Bradt Jason