A Phase 3 interventional study of Leniolisib in APDS Gene Mutation, sponsored by Pharming Technologies B.V.. Recruiting at 2 sites in Japan. Open to participants aged 12 Years to 75 Years. Per ClinicalTrials.gov, last updated 2024-02-08.
Sponsored by Pharming Technologies B.V. (part of Pharming Group N.V.) · Phase 3, Interventional, and Treatment
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).
This is a 2-part, open-label, non-randomized study to assess the safety and efficacy of leniolisib in Japanese patients with APDS. At least3 patients, aged 12 to 75 years (inclusive), will be enrolled. Patient eligibility will be assessed during a 7-week Screening Period (Day -50 to Day -1). This will be followed by a 12-week Treatment Period (Part 1), in which patients will be administered leniolisib doses ranging from 40 to 70 mg twice daily (BID) based on body weight (see dose regimen table below). 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.
It is anticipated that a total of 3 patients will be enrolled into the study.
Objectives:
Part 1:
Primary:
Secondary:
Part 2:
Primary:
Secondary:
Pharming Technologies B.V. is the lead sponsor of 22 studies on the registry; 3 are open to participants now.
Of its 5 completed or terminated interventional studies of FDA-regulated products, 3 (60%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
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.
B-cell depleters (e.g., rituximab) within 6 months prior to first dose of study treatment.
Other immunosuppressive medications where effects are expected to persist at start of dosing of study treatment.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Live vaccines
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
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.
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
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: Between baseline until Day 85
Part I: Change from baseline in lymphoproliferation measured using MRI, CT imaging, or ultrasound
Parameters for change from baseline in lymphoproliferation as a secondary endpoint may include 3-dimensional (3D) volume of index and measurable non-index lesions (selected as per the Cheson methodology) and 3D volume and bi-dimensional sizes of spleen and liver, where appropriate.
Time frame: Between baseline until Day 85
Part II: Long-term change from baseline in lymphoproliferation measured using MRI, CT imaging, or ultrasound
Number of participants with change from in lymphoproliferation measured using MRI, CT imaging, or ultrasound (e.g., 3D volume of index and measurable non-index lesions \[selected as per the Cheson methodology\] and 3D volume and bi-dimensional sizes of spleen and liver, where appropriate) at the end of treatment.
Time frame: At Day 252, through study completion, an average of 1 year
Part I: To assess the PK of leniolisib in the Japanese population
Number of participants with change in PK parameters (including but not limited to area under the plasma concentration-time curve from time zero to 12 hours after dosing at steady state \[AUC0-12,ss\] and maximum plasma concentration following drug administration at steady state \[Cmax,ss\])
Time frame: Between baseline until Day 85
Part I: To assess the efficacy of leniolisib to modify health-related quality of life
Number of participants with change in Short Form-36 (SF-36) Survey and Work Productivity and Activity Impairment-Classroom Impairment Questionnaire (WPAI-CIQ) summary scores
Time frame: Between baseline until Day 85
Part II: To assess the long-term efficacy of leniolisib to modify health-related quality of life
Number of participants with long-term change in Short Form-36 (SF-36) Survey and Work Productivity and Activity Impairment-Classroom Impairment Questionnaire (WPAI-CIQ) summary scores
Time frame: At Day 252, through study completion, an average of 1 year
Part I: To assess the efficacy of leniolisib by the Patient's and Physician's Global Assessments
Number of participants with long-term change in visual analog scales (VAS) for Patient's and Physician's Global Assessments, measured by scale with no and maximal activity score
Time frame: Between baseline until Day 85
Part I: To assess the frequency of infections and assessment of impact on other disease-related outcomes (e.g., cytopenia, colitis, and lung function)
Number of participants with change in frequency of infections, use of antibiotics, Ig replacement therapy, and other disease complications
Time frame: Between baseline until Day 85
Part I: To assess biomarkers reflecting the efficacy of leniolisib to reduce systemic inflammatory components of the disease
Number of participants with change in High-sensitivity C-reactive protein (hsCRP), lactate dehydrogenase (LDH), beta2 microglobulin, ferritin, fibrinogen, and erythrocyte sedimentation rate
Time frame: Between baseline until Day 85
Part I: To assess the treatment benefit to individual patients
Number of patients that benefit from the treatment via narratives by the Investigator
Time frame: Between baseline until Day 85
Started Aug 2023 (actual). Primary completion is estimated for Jan 2025, 17 months after the start.
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Studies of the drug tested here: Leniolisib