Leniolisib OLE for Immune Dysregulation in PID

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pharming Technologies B.V.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

10 Feb 2026 → ongoing

Decision date (initial)

2026-01-23

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2025-522444-40-00

ClinicalTrials.gov

NCT06990529

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To assess the long-term safety and tolerability of leniolisib for immune dysregulation in PID

Secondary objectives 3

1. To assess the long-term impact of leniolisib on individual manifestations of immune dysregulation
2. To assess the long-term impact of leniolisib on B and T cell lymphocyte populations of interest
3. 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

Conditions and MedDRA coding

primary immunodeficiency

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. 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).
2. 2. Subject is deemed by the Investigator to benefit from continued leniolisib therapy.
3. 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 17

1. 1. Subject has had a successful allogeneic hematopoietic stem cell transplant.
2. 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.
3. 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.
4. 4. History of hypersensitivity to the study drug or to drugs of similar chemical classes.
5. 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.
6. 6. Current use of medications that to a larger extent are BCRP, OATP1B1, and/or OATP1B3 substrates.
7. 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.
8. 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.
9. 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.
10. 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.)
11. 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.
12. 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.
13. 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.
14. 14. Subject has uncontrolled post-transplant lymphoproliferative disease-like Epstein-Barr virus-related lymphoproliferative disease.
15. 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.
16. 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.
17. 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).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. AEs (via assessment of vital signs, safety labs, physical exams, and overall trial safety monitoring)

Secondary endpoints 14

1. Hemoglobin over time
2. Platelet count over time
3. ANC over time
4. CT evidence of granulomatous lymphocytic ILD or other PID-related ILD evaluated using Hartmann scoring methodology over time
5. Results of pulmonary function testing over time, including FEV1, FVC, TLC, RV, DLCO
6. Measurements of lymphoproliferation over time measured as the SPD in the index lesions selected at baseline of the preceding study per the Cheson methodology
7. 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
8. Spleen size over time measured by 3D volume and 2D size of spleen
9. CD4+ T cell count over time
10. CD8+ T cell count over time
11. B cell count over time
12. Percentages of naïve B cells and CD21low B cells over time
13. Levels of CXCL13 over time
14. Levels of soluble IL-2Rα over time

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pharming Technologies B.V.

Sponsor organisation

Pharming Technologies B.V.

Address

Darwinweg 24

City

Leiden

Postcode

2333 CR

Country

Netherlands

Scientific contact point

Organisation

Pharming Technologies B.V.

Contact name

Clinical Research Department

Public contact point

Organisation

Pharming Technologies B.V.

Contact name

Clinical Research Department

Third parties 5

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications