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

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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Activated PI3Kdelta Syndrome (APDS); PASLI Disease
• Intervention / Treatment: Drug: CDZ173

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Belarus
  • Minsk, Belarus, 223053
    • Pharming Investigative Site
• Czechia
  • CZE
    • Prague 5, CZE, Czechia, 15006
      • Pharming Investigative Site
• Germany
  • Dresden, Germany, 01307
    • Pharming Investigative Site
• Italy
  • BS
    • Brescia, BS, Italy, 25123
      • Pharming Investigative Site
  • PA
    • Palermo, PA, Italy, 90127
      • Pharming Investigative Site
• Netherlands
  • Rotterdam, Netherlands, 3000 CA
    • Pharming Investigative Site
• Russian Federation
  • Moscow, Russian Federation, 117198
    • Pharming Investigative Site
• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Pharming Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CDZ173; 140mg/day	Drug: CDZ173; 140 mg/day

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pharming Technologies B.V.

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2016
• Primary Completion (Estimated): January 21, 2027
• Study Completion (Estimated): January 21, 2027

Study Registration Dates

• First Submitted: August 4, 2016
• First Submitted That Met QC Criteria: August 4, 2016
• First Posted (Estimated): August 9, 2016

Study Record Updates

• Last Update Posted (Actual): March 22, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: APDS; PASLI; PI3Kdelta; p110delta-activating mutation causing senescent T cells, lymphadenopathy and immunodeficiency; Activated PI3Kdelta Syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Lymphatic Diseases; Disease; Syndrome; Lymphadenopathy
• Other Study ID Numbers: CCDZ173X2201E1; 2016-000468-41 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No