This study is currently recruiting participants.
Primary immunodeficiencies (PID) are rare disorders that develop when the immune system does not develop or function properly. Issues with immune function can affect many organs and lead to serious health problems. In a previous study (protocol LE 7201), some participants were helped by a drug called leniolisib. This drug was approved by the FDA to treat 1 specific PID disorder (APDS). Researchers want to follow-up on these participants to find out if leniolisib is safe for long-term use.
To study long-term effects of leniolisib in people with PID.
People aged 12 years and older who participated in protocol LE 7201.
Participants will have 9 study visits in 3 years.
Participants will be screened. They will have a physical exam with blood tests. They may also need imaging scans. They may have tests of their heart and lung function. They will complete surveys about their health and how their PID affects their life. All these tests may take up to 28 days.
Leniolisib is a tablet taken by mouth twice a day. Participants will start with the same dose they had been taken during the previous study. This dose may be adjusted over time as needed.
Participants will have clinic visits every 4 months during the first year and then every 6 months for the next 2 years.
Participants may opt to participate in a phone interview during the study. The interview will take about 1 hour.
They will have a follow-up visit 4 weeks after their last treatment.
INCLUSION CRITERIA
To be included in this study, each individual must satisfy all the following 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 (through an interpreter if non-English speaking).
EXCLUSION CRITERIA
If an individual meets any of the following criteria, he or she is ineligible for this study:
1. Subject has had a successful allogeneic hematopoietic stem cell transplant.
2. Previous or concurrent use of immunosuppressive medication, such as:
2a. Use of an mTOR inhibitor (e.g., sirolimus, everolimus) or a PI3Kdelta inhibitor besides leniolisib (selective or non-selective PI3K inhibitors) within 3 weeks prior to first dosing of study medication.
2b. Rituximab or other B-cell depleting antibodies, belimumab, cyclophosphamide, or lemtuzumab within 6 months prior to first dosing of study medication.
2c. 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.
2d. Corticosteroids above 25 mg prednisone or equivalent per day within 2 weeks prior to first dosing of study medication.
2e. 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. 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 CYP3A. Treatment can be discontinued or switched to a different medication prior to starting study treatment.
6. Current use of medications that to a larger extent are BCRP, OATP1B1, and/or OATP1B3 substrates.
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. 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(R) 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(R) 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. 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):
9a. Uncontrolled hypertension
9b. Congestive heart failure (New York Heart Association status of class III or IV)
9c. Diagnosis of ECG abnormalities indicating a significant risk of safety
9d. Chronic obstructive pulmonary disease (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 3-4)
9e. Chronic need for supplemental oxygen or invasive or non-invasive respiratory support
9f. Major GI tract surgery that may affect drug absorption (such as gastric bypass surgery, gastroenterostomy)
9g. Acute pancreatitis
9h. 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 2 times the upper limit of normal, INR greater than 1.5 in the absence of anticoagulation, or presence of diuretic refractory ascites
9i. 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 m^2.
-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. 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. 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, 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. 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.