Study to assess the safety and efficacy of CDZ173 in patients with APDS/PASLI
- Conditions
- APDS/PASLI (Activated phosphoinositide 3-kinase delta syndrome/ p110d-activating mutation causing senescent T cells, lymphadenopathy and immunodeficiency)Therapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2014-003876-22-IE
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 36
• Male and female patients 12 to 75 years of age (inclusive), who have a documented APDS/PASLI-associated genetic PI3K delta mutation
Patients with mutations in either PIK3CD or PIK3R1 can be included.
• In Part I and Part II, patients must have nodal and/or extranodal lymphoproliferation, and clinical findings and manifestations compatible with APDS/PASLI such as a history of repeated oto-sino-pulmonary infections and/or organ dysfunction (e.g., lung, liver). Additionally, in part II, patients must have at least one measurable nodal lesion on a CT or MRI scan.
• At screening, vital signs (systolic and diastolic blood pressure and pulse rate) will be assessed in the sitting position after the patient has rested for at least three minutes. Sitting vital signs should be within the following ranges:
• Systolic blood pressure, 90-139 mm Hg
• Diastolic blood pressure, 50-89 mm Hg
• Pulse rate, 50 - 100 bpm; up to 110 bpm in adolescents
Are the trial subjects under 18? yes
Number of subjects for this age range: 11
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 24
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1
• Use of unstable i.v. Ig / s.c. Ig in the last 6 months before screening. Stable maintenance immunoglobulin regimen, as per local practice, such as regular injections with a consistent dosing interval (e.g., monthly) injections is acceptable
• Previous or concurrent use of immunosuppressive medication such as:
?• use of an mTOR inhibitor (e.g., sirolimus, rapamycin, everolimus) or a PI3Kd inhibitor (selective or non-selective PI3K inhibitors) within 6 weeks prior to first dosing, however short-term use for up to a total of 5 days is allowed but only up to 1 month prior to enrollment in the study.
?• B cell depleters (e.g., rituximab) within 6 months prior to first dosing of study medication; if patients have received prior treatment with a B cell depleter, absolute B lymphocyte counts in the blood must have regained normal values.
?• Belimumab or cyclophosphamide within 6 months prior to first dosing of study medication.
? Cyclosporine A, mycophenolate, 6-mercaptopurine, azathioprine or methotrexate within 3 months prior to first dosing of study medication.
?• Glucocorticoids above 25 mg prednisone or equivalent per day within 2 weeks prior to first dosing of study medication.
?• Other immunosuppressive medication where effects are expected to persist at start of dosing of study medication.
• Current use of medication known to be strong inhibitor or moderate or strong inducers of isoenzyme CYP3A, if treatment cannot be discontinued or switched to a different medication prior to starting study treatment.
• Current use of medications that are metabolized by isoenzyme CYP1A2 and have a narrow therapeutic index (drugs whose exposure-response indicates that increases in their exposure levels by the concomitant use of potent inhibitors may lead to serious safety concerns (e.g., Torsades
de Pointes)).
• Administration of live vaccines (this includes any attenuated live vaccines) starting from 6 weeks before study entry, during the study and up to 7 days after the last dose of CDZ173
• 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 hCG laboratory test.
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing of study medication and for 2 days after stopping study treatment.
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