Leniolisib phosphate for Primary immunodeficiency

Inclusion criteria

• {"criterion_text":"- 1. Subject must have participated in LE 7201 or LE 8201. a. Specifically at sites located in the United Kingdom subjects must be 18 to 75 years of age (inclusive)."}
• {"criterion_text":"- 2. Subject is deemed by the Investigator to benefit from continued leniolisib therapy."}
• {"criterion_text":"- 3. Subject or their legal representatives (for a patient under the age of 18 years) must be able to communicate with the Investigator and understand and comply with the requirements of the study, including an ability to provide written informed consent before any assessment is performed (through an interpreter if non-English speaking)."}

Exclusion criteria

• {"criterion_text":"- 1. Subject has had a successful allogeneic hematopoietic stem cell transplant."}
• {"criterion_text":"- 10. A positive hepatitis B surface antigen (HBsAg), positive hepatitis B polymerase chain reaction (PCR), positive hepatitis C PCR, or positive hepatitis C antibody result at screening. − Testing only needs to be performed with enrollment into the OLE study if more than 4 weeks have elapsed between completion of the preceding study and enrollment into the OLE. − Subjects who are positive for hepatitis B core antibody (HBcAb) but negative for HBsAg and negative for hepatitis B PCR should receive tenofovir or other appropriate therapy while on study if the testing is judged by the Investigator to reflect past infection. It is recommended to have monthly HBsAg and hepatitis B PCR monitoring. (Anti-HBcAb positivity may also be observed following IRT and represent passive transfer in which case therapy is not indicated, but laboratory monitoring may be considered per the discretion of the Investigator. Patients should end study if HBsAg or hepatitis B PCR become positive.)"}
• {"criterion_text":"- 11. Administration of live vaccines (this includes any attenuated live vaccines) starting from 6 weeks prior to first dosing of study medication, during the study, and up to 7 days after the last dose of leniolisib."}
• {"criterion_text":"- 12. Subject has a previous diagnosis of lymphoma that has been treated with chemotherapy, radiotherapy, or transplant within 1 year prior to first dosing of study medication or is anticipated to require lymphoma treatment within 6 months of the first dose of study medication."}
• {"criterion_text":"- 13. Subject has a history of malignancy (except lymphoma) within 3 years prior to first dosing of study medication or has evidence of residual disease from a previously diagnosed malignancy, except for adequately treated cancers of the skin (basal or squamous cell) or carcinoma in situ of the uterine cervix."}
• {"criterion_text":"- 14. Subject has uncontrolled post-transplant lymphoproliferative disease-like Epstein-Barr virus-related lymphoproliferative disease."}
• {"criterion_text":"- 15. Subject has had major surgery requiring hospitalization or radiotherapy within 4 weeks prior to first dosing of study medication or has a planned or expected major surgical procedure during the study period."}
• {"criterion_text":"- 16. Pregnant or nursing (lactating) women, 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 (hCG) serum laboratory test."}
• {"criterion_text":"- 17. An individual of child-bearing potential who is physiologically capable of becoming pregnant, unless using highly effective methods of contraception starting at least 7 days prior to first dose of study medication, during dosing of study medication, and for 7 days after stopping study treatment (as described in Section 5.6.1)."}
• {"criterion_text":"- 2. Previous or concurrent use of immunosuppressive medication, such as: a. Use of an mTOR inhibitor (e.g., sirolimus, everolimus) or a PI3Kδ inhibitor besides leniolisib (selective or non-selective PI3K inhibitors) within 3 weeks prior to first dosing of study medication. b. Rituximab or other B-cell depleting antibodies, belimumab, cyclophosphamide, or alemtuzumab within 6 months prior to first dosing of study medication. c. Cyclosporine A, mycophenolate mofetil, 6-mercaptopurine, azathioprine, methotrexate, tacrolimus, ruxolitinib or other Janus kinase (JAK) inhibitors (Section 5.6.2.1) within 3 weeks prior to first dosing of study medication. d. Corticosteroids above 25 mg prednisone or equivalent per day within 2 weeks prior to first dosing of study medication. e. Other immunosuppressive agents expected to have a significant impact on immune cell number or function. Note: - Abatacept is allowed during study if the subject has been receiving a stable dosing regimen for more than 3 months prior to first dosing of study medication. - Enteral budesonide is allowed during study if the subject has been receiving a stable dosing regimen for more than 3 months prior to first dosing of study medication."}
• {"criterion_text":"- 3. 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 of study medication."}
• {"criterion_text":"- 4. History of hypersensitivity to the study drug or to drugs of similar chemical classes."}
• {"criterion_text":"- 5. Current use of medication known to be a strong inhibitor, or moderate or strong inducer, of isoenzyme CYP3A. Treatment can be discontinued or switched to a different medication prior to starting study treatment."}
• {"criterion_text":"- 6. Current use of medications that to a larger extent are BCRP, OATP1B1, and/or OATP1B3 substrates."}
• {"criterion_text":"- 7. History of acquired immunodeficiency diseases, including a positive human immunodeficiency virus (HIV) test result at screening. − Testing only needs to be performed with enrollment into the OLE study if more than 4 weeks have elapsed between completion of the preceding study and enrollment into the OLE."}
• {"criterion_text":"- 8. Uncontrolled chronic or recurrent infectious disease (except those considered to be characteristic of PID), or evidence of tuberculosis (TB) infection as defined by a positive QuantiFERON® TB-Gold test at Screening. − Testing only needs to be performed with enrollment into the OLE study if more than 4 weeks have elapsed between completion of the preceding study and enrollment into the OLE. − If the QuantiFERON® TB-Gold test is not readily available, an alternative TB test is acceptable. − If the presence of latent TB is established, treatment should be completed following current guidelines and based on best clinical care practice. Exception can be made for patients with a positive test due to a history of having TB that was adequately treated or due to previously treated infection with cross-reactive non-tuberculous mycobacteria."}
• {"criterion_text":"- 9. 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. The Investigator should make this determination in consideration of the patients’ medical history and/or clinical or laboratory evidence of any of the following (conditions due to underlying clinical PID phenotype may be permitted): a. Uncontrolled hypertension b. Congestive heart failure (New York Heart Association status of class III or IV) c. Diagnosis of ECG abnormalities indicating a significant risk of safety d. Chronic obstructive pulmonary disease (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 3-4) e. Chronic need for supplemental oxygen or invasive or non-invasive respiratory support f. Major GI tract surgery that may affect drug absorption (such as gastric bypass surgery, gastroenterostomy) g. Acute pancreatitis h. Liver failure or clinically significant liver disease or dysfunction as indicated by alanine transaminase (ALT) or aspartate transaminase (AST) greater than 2.5 times the upper limit of normal, bilirubin greater than 1.5 times the upper limit of normal, INR greater than 1.5 in the absence of anticoagulation, or presence of diuretic refractory ascites • Elevation of ALT or AST up to 6 times the upper limit of normal is allowed if elevation is determined to be a consequence of immune dysregulation by the site Principal Investigator and if the elevation has been stable for 3 months prior to enrollment i. History of significant renal injury/renal disease severely affecting renal function or presence of impaired renal function as indicated by estimated glomerular filtration rate (eGFR) of less than 30 mL/min/1.73 m2. − eGFR testing only needs to be performed with enrollment into the OLE study if more than 4 weeks have elapsed between completion of the preceding study and enrollment into the OLE."}

Primary endpoints

• {"endpoint_text":"- AEs (via assessment of vital signs, safety labs, physical exams, and overall trial safety monitoring)","definition_or_measurement_approach":"Assessment of adverse events via vital signs, safety laboratory tests, physical examinations, and overall trial safety monitoring."}

Secondary endpoints

• {"endpoint_text":"- Hemoglobin over time","definition_or_measurement_approach":"Measurement of hemoglobin values longitudinally over time."}
• {"endpoint_text":"- Platelet count over time","definition_or_measurement_approach":"Measurement of platelet counts longitudinally over time."}
• {"endpoint_text":"- ANC over time","definition_or_measurement_approach":"Measurement of absolute neutrophil count (ANC) longitudinally over time."}
• {"endpoint_text":"- CT evidence of granulomatous lymphocytic ILD or other PID-related ILD evaluated using Hartmann scoring methodology over time","definition_or_measurement_approach":"CT imaging evaluated using the Hartmann scoring methodology to assess granulomatous lymphocytic interstitial lung disease (ILD) or other PID-related ILD over time."}
• {"endpoint_text":"- Results of pulmonary function testing over time, including FEV1, FVC, TLC, RV, DLCO","definition_or_measurement_approach":"Pulmonary function tests measured longitudinally, including FEV1, FVC, TLC, RV, and DLCO."}
• {"endpoint_text":"- Measurements of lymphoproliferation over time measured as the SPD in the index lesions selected at baseline of the preceding study per the Cheson methodology","definition_or_measurement_approach":"Lymphoproliferation measured as the sum of the product of the diameters (SPD) in index lesions selected at baseline of the preceding study using Cheson methodology, assessed over time."}
• {"endpoint_text":"- Measurements of lymphoproliferation over time measured as the SPD in the non-index lesions selected at baseline of the preceding study per the Cheson methodology","definition_or_measurement_approach":"Lymphoproliferation measured as SPD in non-index lesions selected at baseline of the preceding study per Cheson methodology, assessed over time."}
• {"endpoint_text":"- Spleen size over time measured by 3D volume and 2D size of spleen","definition_or_measurement_approach":"Spleen size measured longitudinally by 3D volume and 2D size measurements."}
• {"endpoint_text":"- CD4+ T cell count over time","definition_or_measurement_approach":"Measurement of CD4+ T cell counts longitudinally over time."}
• {"endpoint_text":"- CD8+ T cell count over time","definition_or_measurement_approach":"Measurement of CD8+ T cell counts longitudinally over time."}
• {"endpoint_text":"- B cell count over time","definition_or_measurement_approach":"Measurement of B cell counts longitudinally over time."}
• {"endpoint_text":"- Percentages of naïve B cells and CD21low B cells over time","definition_or_measurement_approach":"Measurement of percentages of naïve B cells and CD21low B cells longitudinally over time."}
• {"endpoint_text":"- Levels of CXCL13 over time","definition_or_measurement_approach":"Measurement of CXCL13 levels longitudinally over time."}
• {"endpoint_text":"- Levels of soluble IL-2Rα over time","definition_or_measurement_approach":"Measurement of soluble IL-2Rα levels longitudinally over time."}

Spain

Earliest CTIS Part Ii Submission Date

11-12-2025

Latest Decision Or Authorization Date

24-03-2026

Processing Time Days

103

Number Of Sites

1

Number Of Participants

6

Primary sponsor

Full Name

Pharming Technologies B.V.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Netherlands

Contract research organisations

Name

Icon Clinical Research LLC

Responsibilities

[{"id":917990,"code":"4"}]

Name

Almac Clinical Service Limited

Responsibilities

[{"id":917988,"code":"14"}]

Third parties

• {"country":"United States","full_name":"Icon Clinical Research LLC","duties_or_roles":"[{\"id\":917990,\"code\":\"4\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Aixial UK Limited","duties_or_roles":"[{\"id\":917991,\"code\":\"1\"},{\"id\":917992,\"code\":\"11\"},{\"id\":917993,\"code\":\"12\"},{\"id\":917994,\"code\":\"5\"},{\"id\":917995,\"code\":\"6\"}]","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"Almac Clinical Service Limited","duties_or_roles":"[{\"id\":917988,\"code\":\"14\"}]","organisation_type":"Industry"}
• {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"[{\"id\":917996,\"code\":\"15\",\"value\":\"Patient reimbursement\"}]","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"[{\"id\":917989,\"code\":\"4\"}]","organisation_type":"Pharmaceutical company"}