Study to assess long-term safety and efficacy of CDZ173 in patients with APDS/PASLI

• Register: EUCTR
• Last refreshed on: 2 August 2021
• Main ID: EUCTR2016-000468-41-IE
• Date of registration: 27/02/2018
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: Study to assess long-term safety and efficacy of CDZ173 in patients with APDS/PASLI
• Scientific title: An open-label, non-randomized extension study to evaluate the long term safety, tolerability, efficacy and pharmacokinetics of CDZ173 (leniolisib) in patients with APDS/PASLI (Activated phosphoinositide 3-kinase delta syndrome/p110d- activating mutation causing senescent T cells, lymphadenopathy and immunodeficiency) - Extension to the study of safety and efficacy of CDZ173 in patients with APDS/PASLI
• Date of first enrolment: 25/10/2018
• Target sample size: 42
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-000468-41
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belarus, Czech Republic, Czechia, France, Germany, Ireland, Italy, Netherlands, Russian Federation, United Kingdom, United States

Contacts

• Name: Medical Information Department
• Affiliation: Novartis Ireland Limited

• Name: Medical Information Department
• Affiliation: Novartis Ireland Limited

Key inclusion & exclusion criteria

Inclusion criteria:
• Patients must have participated in study CCDZ173X2201 or were treated previously with PI3Kd inhibitors other than CDZ173
• Patients who are deemed by the Investigator to benefit from PI3K 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.
Patients with mutations in either PIK3CD or PIK3R1 can be included.
Other protocol-defined inclusion criteria may apply
Are the trial subjects under 18? yes
Number of subjects for this age range: 15
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 26
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1

Exclusion criteria:
• Patients who withdrew consent from the study CCDZ173X2201.
• Use of other investigational drugs, except CDZ173, within 5 half -lives of enrollment, or within 30 days, whichever is longer.
•Previous or concurrent use of immunosuppressive medication
• Administration of any live vaccines (including 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 should be excluded.
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation.
• 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 and for 2 days after last dose of study medication.
• Uncontrolled chronic or recurrent infectious disease (with the exception of those that are considered to be characteristic of APDS/PASLI).
For patients who did not participate in study CCDZ173X2201 but were treated previously with PI3Kd inhibitors other than CDZ173, the following additional exclusion criteria apply:
• 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.
• Patient must have a minimum body weight of 45 kg
• Evidence of tuberculosis infection as defined by a positive QuantiFERON TB test (or comparable test) at screening. If presence of latent tuberculosis is established then treatment according to local country guidelines must have been completed before patients can be considered for enrollment.
• Intentionally blank; exclusion criterion removed in this protocol amendment.
• History of acquired immunodeficiency diseases, or a positive HIV (ELISA and Western blot) test result at screening.
• A positive Hepatitis B surface antigen or Hepatitis C test (by PCR) result at screening.
Other protocol-defined exclusion criteria may apply


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

APDS/PASLI (Activated phosphoinositide 3-kinase delta syndrome/p110d-activating mutation causing senescent T cells, lymphadenopathy and immunodeficiency)
MedDRA version: 20.0 Level: PT Classification code 10064859 Term: Primary immunodeficiency syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Product Name: Leniolisib
Product Code: CDZ173
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: leniolisib
Current Sponsor code: CDZ173
Other descriptive name: CDZ173
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 70-

Product Name: Leniolisib
Product Code: CDZ173
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: leniolisib
Current Sponsor code: CDZ173
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 70-

Primary Outcome(s)

Main Objective: To evaluate the long term safety and tolerability of CDZ173 in patients with APDS/PASLI.

Secondary Objective: • To evaluate the long term efficacy of CDZ173 to modify health -related
quality of life in patients with APDS/PASLI.
• 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.
• To characterize the pharmacokinetics (trough concentrations) of
CDZ173 in patients with APDS/PASLI
• To evaluate the pharmacokinetics and relative bioavailability of
CDZ173 film-coated tablets compared to CDZ173 hard-gelatin capsules

Timepoint(s) of evaluation of this end point: 5 years and 3 months

Primary end point(s): • All safety parameters (including AEs, physical exam, vital signs, ECG, safety laboratory (hematology, blood chemistry, urinalysis)).

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 5 years and 3 months

Secondary end point(s): • 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
• High sensitivity C-reactive protein (CRP), lactate dehydrogenase (LDH), frequencies of infections and other disease complications.
• Steady-state trough concentration of CDZ173.
• PK parameters (including but not limited to AUC0-12,ss and Cmax,ss)

Secondary ID(s)

CCDZ173X2201E1

2016-000468-41-CZ

Source(s) of Monetary Support

Novartis Pharma Services AG

Ethics review

Status: Approved
Approval date: 25/10/2018
Contact: