Status:
RECRUITING
Leniolisib for Immune Dysregulation in PIDs
Lead Sponsor:
Pharming Technologies B.V.
Conditions:
Primary Immunodeficiency Disorders (PIDs)
Eligibility:
All Genders
12-75 years
Phase:
PHASE2
Brief Summary
This study is an exploratory, non-randomized, open-label, within-patient dose escalation study. The primary objective is to assess safety and tolerability of leniolisib. Secondary objectives include a...
Detailed Description
Patients ages 12-75 diagnosed with genetically defined PID disorders linked to PI3K signaling. This includes disorders caused by pathogenic variants in SOCS1, PTEN, CTLA4, NFKB1 (variants leading to N...
Eligibility Criteria
Inclusion
- Subjects 12 to 75 years of age.
- Diagnosed with a PID due to disease-causing pathogenic or likely pathogenic variant(s) in the following genes: SOCS1, PTEN, CTLA4, NFKB1 (only those variants leading to NFKB pathway activation), or FAS (germline or somatic), or diagnosed with RAS associated leukoproliferative disorder (and not juvenile myelomonocytic leukemia \[JMML\]) due to somatic variants in NRAS or KRAS.
- Subjects must have 1 or more of the following:
- One or more blood cytopenias related to the underlying PID defined as hemoglobin \<10 g/dL, platelet count \<100,000/µL, or neutrophil count \<1000/µL
- Splenomegaly evident by CT imaging with craniocaudal spleen measurement \>10 cm
- Lymphadenopathy evident by CT imaging with at least 1 measurable index lymph node (long axis \>1.5 cm) as per Cheson methodology
- GLILD or other PID-related ILD with quantifiable CT chest imaging findings evident on baseline CT scan
- At screening, vital signs.
- Systolic blood pressure 80-139 mm Hg
- Diastolic blood pressure 50-89 mm Hg
- Pulse rate 50-110 bpm
- Oxygen saturation 93-100%
- Subjects or their legal representatives (for subjects under the age of 18 years) must be able to provide written informed consent.
Exclusion
- Subject has had a successful hematopoietic stem-cell transplant (HSCT).
- Previous or concurrent use of immunosuppressive medication, such as:
- Use of an mTOR inhibitor or a PI3Kδ inhibitor within 3 weeks prior to first dosing .
- Rituximab or other B-cell depleting antibodies, belimumab, cyclophosphamide, or alemtuzumab within 6 months prior to first dosing.
- Cyclosporine A, mycophenolate mofetil, 6-mercaptopurine, azathioprine, methotrexate, tacrolimus, ruxolitinib, or other JAK inhibitors within 3 weeks prior to first dosing.
- Corticosteroids above 25 mg prednisone or equivalent per day within 2 weeks prior to first dosing.
- Other immunosuppressive agents expected to have a significant impact on immune cell number or function.
- Abatacept is allowed during study if the subject has been receiving a stable dosing regimen for more than 3 months prior to first dosing.
- Subject is receiving concurrent treatment with another investigational therapy or use of another investigational therapy less than 4 weeks or 5 half-lives (whichever is longer) prior to first dosing.
- History of hypersensitivity to the study drug or to drugs of similar chemical classes.
- Current use of medication known to be a strong inhibitor, or moderate or strong inducer, of isoenzyme P450 CYP3A.
- Current use of medications that act as BCRP, OATP1B1, and OATP1B3 substrates.
- Subject has a history or current electrocardiogram (ECG) abnormalities indicating a significant risk of safety for subjects participating in the study
- History of acquired immunodeficiency diseases, including a positive HIV test result at screening.
- Uncontrolled chronic or recurrent infectious disease (except those considered to be characteristic of a PID) or evidence of tuberculosis infection
- Any surgical or medical condition which may jeopardize the subject in case of participation in the study, or might significantly alter the absorption, distribution, metabolism, or excretion of drugs.
- A positive hepatitis B surface antigen, positive hepatitis B PCR, positive hepatitis C PCR, or positive hepatitis C antibody result at screening.
- Administration of live vaccines starting from 6 weeks before first dose of study medication.
- Subject has a previous diagnosis of lymphoma within 1 year of the first dose of study medication.
- Subject has a history of malignancy (except lymphoma) within 3 years before the first dose of study medication, except for adequately treated cancers of the skin (basal or squamous cell) or carcinoma in situ of the uterine cervix.
- Subject has uncontrolled post-transplant lymphoproliferative disease (PTLD)-like EBV related lymphoproliferative disease.
- Donation or loss of 400 mL or more of blood within 8 weeks before the first dose.
- Subject has had major surgery requiring hospitalization or radiotherapy within 4 weeks prior to the first dose or has a planned or expected major surgical procedure during the study period.
- Pregnant or nursing (lactating) individuals,.
- Individuals of child-bearing potential, unless they are using highly effective methods of contraception.
Key Trial Info
Start Date :
October 21 2024
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
October 1 2025
Estimated Enrollment :
12 Patients enrolled
Trial Details
Trial ID
NCT06549114
Start Date
October 21 2024
End Date
October 1 2025
Last Update
November 12 2024
Active Locations (1)
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1
National Institute of Health
Bethesda, Maryland, United States, 20892