An open-label, single-arm extension study to evaluate the long-term safety, tolerability, and efficacy of leniolisib for immune dysregulation in patients with primary immunodeficiency
- Trial ID
- 2025-522444-40-00
- Protocol
- LE 7X01
- Sponsor
- Pharming Technologies B.V.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to assess the long-term safety and tolerability of leniolisib for immune dysregulation in primary immunodeficiency. This evaluation is clinically relevant for establishing the extended safety profile of leniolisib in patients with primary immunodeficiency disorders characterized by immune dysregulation, providing essential data on the medication's long-term risk-benefit ratio in this patient population.
The secondary objectives include: • To assess the long-term impact of leniolisib on individual manifestations of immune dysregulation • To assess the long-term impact of leniolisib on B and T cell lymphocyte populations of interest • To examine the long-term impact of leniolisib on levels of chemokine (C-X-C motif) ligand (CXCL)13 and soluble interleukin-2 receptor (IL-2R)α
Participants
This clinical trial enrolled a total of **26 participants** diagnosed with **primary immunodeficiency** presenting with immune dysregulation. The study population included both **male and female subjects** across multiple age categories, encompassing **children**, **adolescents**, and **adults**. All participants had previously been enrolled in prior clinical studies (LE 7201 or LE 8201) and were selected based on the investigator's assessment that they would benefit from continued **leniolisib** therapy. The trial included a **vulnerable population**. Key inclusion criteria required prior participation in specified predecessor trials, anticipated clinical benefit from ongoing treatment as determined by the investigator, and the ability of subjects or their legal representatives to provide informed consent and comply with study requirements. The study focused on patients with ongoing therapeutic needs related to their underlying immunodeficiency condition.
Plans and Procedures
This is an open-label, single-arm extension study designed to evaluate the long-term safety, tolerability, and efficacy of leniolisib in patients with primary immunodeficiency presenting with immune dysregulation. The study is classified as a Phase 4 clinical trial. The investigational medicinal product consists of leniolisib phosphate administered as film-coated tablets via the oral route. Three different dose strengths are available, with maximum daily doses of 20 mg, 60 mg, and 140 mg. The maximum treatment period is 156 weeks, with corresponding maximum total doses of 21,840 mg, 65,520 mg, and 152,880 mg depending on the dose strength administered.
The primary objective of this trial is to assess the long-term safety and tolerability of leniolisib for immune dysregulation in primary immunodeficiency. The primary endpoint focuses on the evaluation of adverse events through assessment of vital signs, safety laboratory tests, physical examinations, and overall trial safety monitoring. Secondary endpoints include monitoring of hematological parameters over time such as hemoglobin, platelet count, and absolute neutrophil count. Additional secondary endpoints encompass evaluation of interstitial lung disease through computed tomography using Hartmann scoring methodology, pulmonary function testing including forced expiratory volume in one second, forced vital capacity, total lung capacity, residual volume, and diffusing capacity of the lungs for carbon monoxide. Measurements of lymphoproliferation are assessed using the sum of the products of diameters in both index and non-index lesions according to Cheson methodology. Spleen size is monitored through three-dimensional volume and two-dimensional measurements. Immunological parameters evaluated over time include CD4+ T cell count, CD8+ T cell count, B cell count, percentages of naïve B cells and CD21low B cells, as well as levels of CXCL13 and soluble IL-2Rα.
Eligible participants must have previously participated in studies LE 7201 or LE 8201 and be deemed by the investigator to benefit from continued leniolisib therapy. Subjects or their legal representatives must be able to communicate with the investigator, understand and comply with study requirements, and provide written informed consent before any study assessment is performed. The estimated recruitment start date is March 31, 2026, with an estimated study completion date of September 30, 2029. Participant involvement extends throughout the treatment period of up to 156 weeks, with study visits scheduled to monitor safety parameters, efficacy outcomes, and disease progression throughout the duration of the trial.
Treatment
The experimental medication utilized in this clinical trial is CDZ173/Leniolisib, a film-coated tablet formulation containing leniolisib phosphate as the active substance of chemical origin. The investigational product is administered via the oral route and is available in three different dosage strengths to accommodate individual patient dosing requirements. The dosing regimen includes a maximum daily dose of 20 mg, 60 mg, or 140 mg, depending on the specific dosage strength assigned to the participant. The maximum treatment period is established at 156 weeks, with corresponding maximum total dose amounts of 21,840 mg, 65,520 mg, or 152,880 mg for the respective daily dose levels. All formulations of the investigational medicinal product are manufactured by Pharming Technologies BV and are not specifically designated as paediatric formulations.
This is an open-label, single-arm extension study designed to evaluate the long-term safety, tolerability, and efficacy of leniolisib in patients with primary immunodeficiency presenting with immune dysregulation. The study design does not incorporate a placebo or active comparator treatment arm, as all enrolled participants receive the investigational medication. The primary objective focuses on assessing the long-term safety and tolerability profile of leniolisib in this patient population. Participant compliance monitoring and adherence to the prescribed dosing schedule are integral components of the study protocol to ensure accurate evaluation of the investigational product's safety and efficacy parameters throughout the extended treatment duration.
Efficacy
Efficacy will be assessed through multiple hematological, immunological, radiological, and pulmonary parameters. Hemoglobin, platelet count, and absolute neutrophil count (ANC) will be measured over time to evaluate hematological improvements. Lymphoproliferation will be assessed over time by measuring the sum of the products of diameters (SPD) in both index lesions and non-index lesions selected at baseline of the preceding study, using the Cheson methodology. Spleen size will be evaluated over time through three-dimensional volume measurements and two-dimensional size assessments. Pulmonary involvement will be monitored using computed tomography (CT) evidence of granulomatous lymphocytic interstitial lung disease (ILD) or other primary immunodeficiency-related ILD, evaluated over time using the Hartmann scoring methodology. Pulmonary function testing will be performed over time, including measurements of forced expiratory volume in one second (FEV1), forced vital capacity (FVC), total lung capacity (TLC), residual volume (RV), and diffusing capacity for carbon monoxide (DLCO). Immunological parameters will include CD4+ T cell count, CD8+ T cell count, B cell count, and percentages of naïve B cells and CD21low B cells, all measured over time. Biomarker levels will be assessed over time, including levels of CXCL13 and soluble IL-2Rα.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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).
- Subject is deemed by the Investigator to benefit from continued leniolisib therapy.
- 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
- Subject has had a successful allogeneic hematopoietic stem cell transplant.
- 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.
- 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.
- 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 CYP3A. Treatment can be discontinued or switched to a different medication prior to starting study treatment.
- Current use of medications that to a larger extent are BCRP, OATP1B1, and/or OATP1B3 substrates.
- 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.
- 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.
- 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.
- 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.)
- 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.
- 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.
- 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.
- Subject has uncontrolled post-transplant lymphoproliferative disease-like Epstein-Barr virus-related lymphoproliferative disease.
- 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.
- 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.
- 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).
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Spain | Recruiting | 31 Mar 2026 | 6 |
Sites & Investigators
Research sites
Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
CDZ173/Leniolisib | Test | FILM COATED TABLET | ORAL | 60 | 156 | PRD9615553 |
CDZ173/Leniolisib | Test | FILM COATED TABLET | ORAL | 140 | 156 | PRD10917159 |
CDZ173/Leniolisib | Test | FILM COATED TABLET | ORAL | 20 | 156 | PRD9615551 |
CDZ173/Leniolisib | Test | FILM COATED TABLET | ORAL | 140 | 156 | PRD9615550 |