Assessing the safety and efficacy of leniolisib in Japanese patients with APDS

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

This study is testing a new medication called leniolisib to see if it can help Japanese patients with Activated Phosphoinositide 3-Kinase Delta Syndrome feel better and stay safe while using it.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 3 (estimated)
• Ages: 12 Years to 75 Years
• Sex: All
• Sponsor: Pharming Technologies B.V. (Industry-sponsored)
• Drugs / interventions: rituximab, Belimumab, methotrexate, cyclophosphamide, prednisone
• Locations: 2 sites (Tokyo, Bunkyo-ku and 1 other locations)
• Trial ID: NCT06249997 on ClinicalTrials.gov

What this trial studies

This is an open-label, non-randomized clinical trial designed to evaluate the safety and efficacy of leniolisib in Japanese patients diagnosed with Activated Phosphoinositide 3-Kinase Delta Syndrome (APDS). The study consists of two parts: a 12-week treatment period followed by a long-term extension where patients will receive leniolisib for up to one year. Participants will be monitored for safety, tolerability, and efficacy, particularly focusing on lymphoproliferation and immunophenotype normalization. A total of three patients aged 12 to 75 years will be enrolled, and their eligibility will be assessed during a 7-week screening period.

Who should consider this trial

Good fit: Ideal candidates are Japanese patients aged 12 to 75 years with a confirmed PI3Kδ genetic mutation and measurable lymphoproliferation.

Not a fit: Patients with previous or concurrent use of immunosuppressive medications may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve the management of APDS in affected patients.

How similar studies have performed: While this approach is focused on a specific genetic mutation, similar studies targeting PI3K pathways have shown promise in other conditions.

Eligibility criteria

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.

Where this trial is running

Tokyo, Bunkyo-ku and 1 other locations

• Tokyo Medical And Dental University Hospital — Tokyo, Bunkyo-ku, Japan (Recruiting)
• Hiroshima University Hospital — Hiroshima, Hiroshima City, Japan (Recruiting)

Study contacts

• Principal investigator: Hirokazu Kanegane, Prof. — Tokyo Medical And Dental University Hospital
• Study coordinator: Jason Bradt, MD

Conditions APDS Gene Mutation