An Open-Label Study to Assess the Safety & Efficacy of Leniolisib in Japanese Patients With APDS

NCT06249997 | Unknown Phase 3 DMC

• 1 other identifier: LE 4301
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 2

Brief Summary

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).

Conditions

APDS Gene Mutation

Outcome Measures

Primary Outcomes (12)

• Part I: Incidence of treatment-emergent adverse events ((AEs), serious adverse events (SAEs), and AEs

  Incidence of treatment-emergent adverse events (AEs), serious adverse events (SAEs), and AEs leading to discontinuation of study treatment

  Between baseline until Day 85

• Part II: Long-term Incidence of treatment-emergent adverse events ((AEs), serious adverse events (SAEs), and AEs

  Long-term Incidence of treatment-emergent adverse events ((AEs), serious adverse events (SAEs), and AEs leading to discontinuation of study treatment

  At Day 252, through study completion, an average of 1 year

• Part I: Change from baseline in clinical laboratory test results

  Number of participants with change in clinical laboratory test results (hematology, blood chemistry, urinalysis). Absolute values and change from baseline values of vital signs (including body weight) and ECG results at each visit will be listed for each patient and may be summarized using descriptive statistics. Tanner staging will be listed for each patient at each visit. Plots may also be used to display the patient data over time.

  Between baseline until Day 85

• Part II: Long-term change from baseline in clinical laboratory test results

  Number of participants with long-term change in clinical laboratory test results (hematology, blood chemistry, urinalysis). Absolute values and change from baseline values of vital signs (including body weight) and ECG results at each visit will be listed for each patient and may be summarized using descriptive statistics. Tanner staging will be listed for each patient at each visit. Plots may also be used to display the patient data over time.

  At Day 252, through study completion, an average of 1 year

• Part I: Change from baseline in vital signs

  Number of Participants with change in vital signs

  Between baseline until Day 85

• Part II: Long-term change from baseline in vital signs

  Number of Participants with long-term change in vital signs

  At Day 252, through study completion, an average of 1 year

• Part I: Change from baseline in physical examination findings

  Number of participants with change in physical examination findings

  Between baseline until Day 85

• Part II: Long-term change from baseline in physical examination findings

  Number of participants with long-term change in physical examination findings

  At Day 252, through study completion, an average of 1 year

• Part I: Change from baseline in electrocardiograms (ECGs)

  Number of participants with change in electrocardiograms (ECGs)

  Between baseline until Day 85

• Part II: Long-term change from baseline in electrocardiograms (ECGs)

  Number of participants with long-term change in electrocardiograms (ECGs)

  At Day 252, through study completion, an average of 1 year

• Part I: To assess the efficacy of leniolisib on lymphoproliferation (SPD of index lymph node lesions) and immunophenotype normalization (percentage of naïve B cells out of total B cells)

  Number of patients with change 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

  Between baseline until Day 85

• Part I: Change from baseline in the percentage of naïve B cells out of total B cells at the end of treatment

  Number of participants with change in percentage of naïve B cells out of total B cells at the end of treatment

  Between baseline until Day 85

Secondary Outcomes (9)

• Part I: Change from baseline in lymphoproliferation measured using MRI, CT imaging, or ultrasound

  Between baseline until Day 85

• Part II: Long-term change from baseline in lymphoproliferation measured using MRI, CT imaging, or ultrasound

  At Day 252, through study completion, an average of 1 year

• Part I: To assess the PK of leniolisib in the Japanese population

  Between baseline until Day 85

• Part I: To assess the efficacy of leniolisib to modify health-related quality of life

  Between baseline until Day 85

• Part II: To assess the long-term efficacy of leniolisib to modify health-related quality of life

  At Day 252, through study completion, an average of 1 year

Study Arms (1)

Leniolisib

EXPERIMENTAL

Leniolisib - Film coated tablets Leniolisib tablets in doses ranging from 40 to 70 mg twice daily (BID) based on body weight. A Part 1 clinical study report will be generated once the last patient completes the Day 85 Visit for Part 1. Patients who complete the Day 85 Visit will enter the Extension Period of the study (Part 2), in which patients will be administered leniolisib doses ranging from 40 to 70 mg BID (based on body weight) for 1 year or until marketing approval in Japan, whichever is longer. A 4-week Follow-up Period will occur after the last dose of study treatment is received.

Drug: Leniolisib

Interventions

Leniolisib DRUG

The doses selected range from 40 to 70 mg BID (based on body weight, resulting in total daily doses ranging from 80 to 140 mg a day for 12 weeks in Part I and 1 year in Part II, or until marketing approval in Japan, whichever is longer.

Leniolisib

Eligibility Criteria

• Age: 12 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• \- Patient has previous or concurrent use of immunosuppressive medication such as the following:
• 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.
• 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.
• Belimumab or cyclophosphamide within 6 months prior to first dose of study treatment.
• Cyclosporine A, mycophenolate, 6-mercaptopurine, azathioprine, or methotrexate within 3 months prior to first dose of study treatment.
• Glucocorticoids above 25 mg prednisone or equivalent per day within 2 weeks prior to first dose of study treatment.
• 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.

Sponsors & Collaborators

• Pharming Technologies B.V.: lead
• Laboratory Corporation of America: collaborator
• Axial Biotech, Inc: collaborator
• CMIC Co, Ltd. Japan: collaborator

Study Sites (2)

Tokyo Medical And Dental University Hospital

Tokyo, Bunkyo-ku, 113-8510, Japan

RECRUITING

Hiroshima University Hospital

Hiroshima, Hiroshima City, 734-8551, Japan

RECRUITING

MeSH Terms

Interventions

leniolisib

Study Officials

• Hirokazu Kanegane, Prof.

  Tokyo Medical And Dental University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jason Bradt, MD

CONTACT

+31715247400; J.Bradt@pharming.com

Elaine Cueto, MD

CONTACT

+1 201 320 2142; E.Cueto@pharming.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2023
• First Posted: February 8, 2024
• Study Start: August 3, 2023
• Primary Completion: January 31, 2025
• Study Completion: March 31, 2025
• Last Updated: February 8, 2024

Record last verified: 2024-01

Locations

JP (2)