RECRUITING

An Open-label, Single-arm Extension Study to Evaluate the Long-term Safety, Tolerability, and Efficacy of Leniolisib for Immune Dysregulation in Primary Immunodeficiency Disorders

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is an open-label extension (OLE) study to extend treatment to patients with primary immunodeficiency (PID) disorders linked to phosphoinositide 3-kinase delta signaling who participated in a prior study of leniolisib, LE 7201. The primary objective is to assess long-term safety and tolerability of leniolisib. Secondary and exploratory objectives include various efficacy and immunophenotyping measures for leniolisib.

Official Title

An Open-label, Single-arm Extension Study to Evaluate the Long-term Safety, Tolerability, and Efficacy of Leniolisib for Immune Dysregulation in Primary Immunodeficiency Disorders

Quick Facts

Study Start:2025-04-29

Study Completion:2029-04-13

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06990529

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:12 Years to 75 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Subject must have participated in LE 7201. 2. Subject is deemed by the Investigator to benefit from continued leniolisib therapy. 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.	1. Subject has had a successful allogeneic hematopoietic stem cell transplant. 2. Previous or concurrent use of immunosuppressive medication, such as: 1. Use of an mTOR inhibitor or a PI3K delta inhibitor, besides leniolisib, within 3 weeks prior to first dosing of study medication. 2. Rituximab or other B-cell depleting antibodies, belimumab, cyclophosphamide, or alemtuzumab within 6 months prior to first dosing of study medication. 3. Cyclosporine A, mycophenolate mofetil, 6-mercaptopurine, azathioprine, methotrexate, tacrolimus, ruxolitinib or other Janus kinase (JAK) inhibitors within 3 weeks prior to first dosing of study medication. 4. Corticosteroids above 25 mg prednisone or equivalent per day within 2 weeks prior to first dosing of study medication. 5. Other immunosuppressive agents expected to have a significant impact on immune cell number or function. 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. History of hypersensitivity to the study drug or to drugs of similar chemical classes. 5. Current use of medication known to be a strong inhibitor or moderate or strong inducer, of isoenzyme cytochrome P450 (CYP)3A. 6. Current use of medications that to a larger extent are breast cancer resistant protein (BCRP), organic anion transporting polypeptide (OATP)1B1, and/or OATP1B3 substrates. 7. History of acquired immunodeficiency diseases, including a positive human immunodeficiency virus (HIV) test result at screening. 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. 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 (conditions due to underlying clinical PID phenotype may be permitted): 1. Uncontrolled hypertension 2. Congestive heart failure (New York Heart Association status of class III or IV) 3. Diagnosis of electrocardiogram (ECG) abnormalities indicating a significant risk of safety 4. Chronic obstructive pulmonary disease (Global Initiative for Chronic Obstructive Lung Disease \[GOLD\] stage 3-4) 5. Chronic need for supplemental oxygen or invasive or non-invasive respiratory support 6. Major GI tract surgery that may affect drug absorption (such as gastric bypass surgery, gastroenterostomy) 7. Acute pancreatitis 8. Liver failure or clinically significant liver disease or dysfunction as indicated by ALT or AST greater than 2.5 times the upper limit of normal, bilirubin greater than 2 times the upper limit of normal, INR greater than 1.5 in the absence of anticoagulation, or presence of diuretic refractory ascites 9. 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. 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. 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. 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. 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. Subject has uncontrolled post-transplant lymphoproliferative disease-like Epstein-Barr-virus-related lymphoproliferative disease. 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. Pregnant or nursing (lactating) women. 17. An individual of child-bearing potential who is physiologically capable of becoming pregnant, unless using highly effective methods of contraception.

Inclusion Criteria

Exclusion Criteria

1. Subject must have participated in LE 7201.
2. Subject is deemed by the Investigator to benefit from continued leniolisib therapy.
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.

1. Subject has had a successful allogeneic hematopoietic stem cell transplant.
2. Previous or concurrent use of immunosuppressive medication, such as:
1. Use of an mTOR inhibitor or a PI3K delta inhibitor, besides leniolisib, within 3 weeks prior to first dosing of study medication.
2. Rituximab or other B-cell depleting antibodies, belimumab, cyclophosphamide, or alemtuzumab within 6 months prior to first dosing of study medication.
3. Cyclosporine A, mycophenolate mofetil, 6-mercaptopurine, azathioprine, methotrexate, tacrolimus, ruxolitinib or other Janus kinase (JAK) inhibitors within 3 weeks prior to first dosing of study medication.
4. Corticosteroids above 25 mg prednisone or equivalent per day within 2 weeks prior to first dosing of study medication.
5. Other immunosuppressive agents expected to have a significant impact on immune cell number or function.
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. History of hypersensitivity to the study drug or to drugs of similar chemical classes.
5. Current use of medication known to be a strong inhibitor or moderate or strong inducer, of isoenzyme cytochrome P450 (CYP)3A.
6. Current use of medications that to a larger extent are breast cancer resistant protein (BCRP), organic anion transporting polypeptide (OATP)1B1, and/or OATP1B3 substrates.
7. History of acquired immunodeficiency diseases, including a positive human immunodeficiency virus (HIV) test result at screening.
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.
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 (conditions due to underlying clinical PID phenotype may be permitted):
1. Uncontrolled hypertension
2. Congestive heart failure (New York Heart Association status of class III or IV)
3. Diagnosis of electrocardiogram (ECG) abnormalities indicating a significant risk of safety
4. Chronic obstructive pulmonary disease (Global Initiative for Chronic Obstructive Lung Disease \[GOLD\] stage 3-4)
5. Chronic need for supplemental oxygen or invasive or non-invasive respiratory support
6. Major GI tract surgery that may affect drug absorption (such as gastric bypass surgery, gastroenterostomy)
7. Acute pancreatitis
8. Liver failure or clinically significant liver disease or dysfunction as indicated by ALT or AST greater than 2.5 times the upper limit of normal, bilirubin greater than 2 times the upper limit of normal, INR greater than 1.5 in the absence of anticoagulation, or presence of diuretic refractory ascites
9. 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.
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.
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. 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. 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. Subject has uncontrolled post-transplant lymphoproliferative disease-like Epstein-Barr-virus-related lymphoproliferative disease.
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. Pregnant or nursing (lactating) women.
17. An individual of child-bearing potential who is physiologically capable of becoming pregnant, unless using highly effective methods of contraception.

Contacts and Locations

Study Contact

Gulbu Uzel, MD

CONTACT

240-678-2572

guzel@niaid.nih.gov

Study Locations (Sites)

National Institute of Health

Bethesda, Maryland, 20892

United States

Collaborators and Investigators

Sponsor: Pharming Technologies B.V.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-04-29

Study Completion Date2029-04-13

Study Record Updates

Study Start Date2025-04-29

Study Completion Date2029-04-13

Terms related to this study

Additional Relevant MeSH Terms

PIDs Linked to PI3K