Study of Leniolisib in Pediatric Patients (Aged 4 to 11 Years) with APDS (Activated Phosphoinositide 3-Kinase Delta Syndrome)
- Conditions
- Activated Phosphoinositide 3-Kinase Delta SyndromeMedDRA version: 20.0Level: PTClassification code 10078281Term: Activated PI3 kinase delta syndromeSystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2022-001624-14-NL
- Lead Sponsor
- Pharming Technologies B.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 15
1. Patient is male or female and between the age of 4 to 11 years old at the time of the first study procedure.
2. Patient weighs =13 kg and <45 kg at baseline.
3. Patient has a confirmed PI3Kd genetic mutation of either the PIK3CD (APDS1) or PIK3R1 (APDS2) gene.
4. Patient has at least 1 measurable nodal lesion on magnetic resonance imaging/low-dose computed tomography within 6 months of screening.
5. Patient has nodal or extranodal lymphoproliferation and clinical findings consistent with APDS (eg, a history of repeated oto-sino-pulmonary infections and/or organ dysfunction consistent with APDS).
6. Patient has the ability to ingest unaltered study-related medications without difficulty in the investigator's opinion.
7. At screening, vital signs (systolic blood pressure [BP], diastolic BP, and pulse rate) will be assessed in the sitting position after the patient has been at rest for at least 3 minutes. Patient’s sitting vital signs should be within the following ranges:
• Systolic BP: Less than the 95th percentile adjusted for sex, age, and height percentile.
• Diastolic BP: Less than the 95th percentile adjusted for sex, age, and height percentile.
• Heart rate (HR):
i) Age 4 to <10 years: 60 to 140 bpm
ii) Age =10 years: 50 to 100 bpm
8. Institutional review board-/independent ethics committee-approved written informed consent/assent and privacy language as per national and local regulations must be obtained from the patient and parent/legal guardian prior to any study-related procedures.
9. Patient parent/legal guardian is willing and able to complete the informed consent/assent process and comply with study procedures and visit schedule.
10. Patient parent/legal guardian agrees patient will not participate in any other interventional study while enrolled in this study.
11. Female patients should be of non-childbearing potential at screening (should not have reached menarche). Male patients with partners of childbearing potential should be willing to use a highly effective method of contraception for at least 30 days after the last study procedure if at risk of pregnancy.
12. Female patient and parent/legal guardian must agree to the following if menses develops after screening, up to 30 days after the last study procedure:
• True sexual abstinence defined as refraining from heterosexual activity during the entire period of the study through 6 months post-study or
• Using a highly effective method of contraception for at least 30 days after the last study procedure if at risk of pregnancy.
Are the trial subjects under 18? yes
Number of subjects for this age range: 15
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1. Patient has previous or concurrent use of immunosuppressive medication such as:
a. An mTOR inhibitor (eg, sirolimus, rapamycin, everolimus) or a PI3Kd inhibitor (selective or non-selective PI3K inhibitors) within 6 weeks prior to first dose.
b. B cell depleters (eg, rituximab) within 6 months prior to first dose of study medication.
c. Belimumab or cyclophosphamide within 6 months prior to first dose of study medication.
d. Cyclosporine A, mycophenolate, 6-mercaptopurine, azathioprine, or methotrexate within 3 months prior to first dose of study medication.
e. Systemic glucocorticoids above a dose equivalent to either =2 mg/kg of body weight or =20 mg/day of prednisone/prednisolone or equivalent.
f. Other immunosuppressive medication where effects are expected to persist at start of dosing of study medication.
2. Patient has a history or current diagnosis of electrocardiogram (ECG) abnormalities indicating significant risk of safety for patients participating in the study.
3. Patient is currently using a medication known to be a strong inhibitor or moderate or strong inducer of isoenzyme cytochrome P450 (CYP)3A, if treatment cannot be discontinued or switched to a different medication prior to starting study treatment.
4. Patient is currently using medications that are metabolized by isoenzyme CYP1A2 and have a narrow therapeutic index.
5.Patient is currently using medications known to be organic anion transporter protein (OATP)1B1, OATP1B3, and breast cancer resistance protein (BCRP) substrates
6. Patient had been administered live vaccines starting from 6 weeks before the anticipated first study drug administration, during the study, and up to 7 days after the last dose of leniolisib.
7. Patient has clinically significant abnormalities in hematology or clinical chemistry parameters as determined by the investigator or medical monitor.
8. Patient has liver disease or liver injury as indicated by clinically significant abnormal liver function tests (alanine aminotransferase and aspartate aminotransferase >2.5 times upper limit of normal), history of renal injury/renal disease (eg, renal trauma, glomerulonephritis, or one kidney only), or presence of impaired renal function as indicated by a serum creatinine level >1.5 mg/dL (133 µmol/L).
9. Patient has moderate or severe hepatic impairment (Child-Pugh Class B or C).
10. Patient is receiving concurrent treatment with another investigational therapy or use of another investigational therapy less than 4 weeks from the first study procedure.
11. Patient has active hepatitis B (eg, hepatitis B surface antigen reactive) or active hepatitis C (eg, hepatitis C virus RNA [qualitative] is detected) at screening.
12. Patient has human immunodeficiency virus (HIV) infection (HIV 1 or 2) at screening.
13. Patient has a positive coronavirus disease 19 result (polymerase chain reaction or antigen) within 1 week prior to first dose. The patient can be rescreened after a subsequent negative result.
14. Patient has a history of malignancy (except lymphoma) within 3 years before the first study procedure or has evidence of residual disease from a previously diagnosed malignancy.
15. Patient has a previous diagnosis of lymphoma that has been treated with chemotherapy, radiotherapy, or transplant within 1 year of the first study procedure or is anticipated to require lymphoma treatment within 6 months of the first study procedure.
16. Patient has a history of uncontrolled diabetes mellitus within 3 mo
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method