Extension to the Study of Efficacy of CDZ173 in Patients With APDS/PASLI

Study Overview
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Brief Summary
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This study is designed to provide long-term CDZ173 treatment, a selective PI3Kδ inhibitor, to the patients with genetically activated PI3Kδ, i.e., patients with APDS/PASLI who participated in the CCDZ173X2201 study or who were treated previously with PI3Kδ inhibitors other than CDZ173. The study is open-label designed to establish the long-term safety, tolerability, efficay and pharmacokinetics of CDZ173 in the target population.

Official Title
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An Open-label, Non-randomized Extension Study to Evaluate the Long Term Safety, Tolerability, Efficacy and Pharmacokinetics of CDZ173 in Patients With APDS/PASLI (Activated Phosphoinositide 3-kinase Delta Syndrome/p110δ-activating Mutation Causing Senescent T Cells, Lymphadenopathy and Immunodeficiency)

Conditions
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Activated PI3Kdelta Syndrome (APDS); PASLI Disease

Intervention / Treatment
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* Drug: CDZ173


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent must be obtained before any assessment is performed. Paients must have participated in the study CCDZ173X2201 or were treated previously with PI3Kδ inhibitors other than CDZ173. Patients who are deemed by the Investigator to benefit from PI3Kδ inhibitor therapy. Patients or their legal representatives (for patients under the age of 18 years) must be able to communicate well with the Investigator, to understand and comply with the requirements of the study. Documented APDS/PASLI-associated genetic PI3K delta mutation. Exclusion Criteria: - Any medically significant disease or condition that is unrelated to APDS/PASLI Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CDZ173<br>140mg/day | Drug: CDZ173<br>* 140 mg/day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the long term safety and tolerability of CDZ173 in patients with APDS/PASLI | All safety parameters (including AEs, physical exam, vital signs, ECG, safety laboratory (hematology, blood chemistry, urinalysis)) | 6 years 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the long term efficacy of CDZ173 to modify health-related quality of life in patients with APDS/PASLI | SF-36 (Short Form 36) Survey and WPAI-CIQ (Work Productivity Activity Impairment plus Classroom Impairment Questionnaire), Visual analogue scales for Physician's Global Assessment (PGA) and Patient's Global Assessment (PtGA), patient narratives by Investigator | 6 years | 
| To evaluate the long term efficacy of CDZ173 by means of biomarkers reflecting the efficacy of CDZ173 to reduce systemic inflammatory components of the disease in patients with APDS/PASLI | High sensitivity C-reactive protein (CRP), lactate dehydrogenase (LDH), frequencies of infections and other disease complication | 8 months | 
| To characterize the pharmacokinetics (trough concentration) of CDZ173 in patients with APDS/PASLI | Steady-state trough concentration of CDZ173 | 9 months | 
| • To evaluate the pharmacokinetics and relative bioavailability of CDZ173 film-coated tablets compared to CDZ173 hard-gelatin capsules | PK parameters (including but not limited to AUC0-12,ss and Cmax,ss) | up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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APDS; PASLI; PI3Kdelta; p110delta-activating mutation causing senescent T cells, lymphadenopathy and immunodeficiency; Activated PI3Kdelta Syndrome;