Study of Efficacy of CDZ173 in Patients With APDS/PASLI
Condition: Common Variable Immunodeficiency (CVID), APDS / PASLI
MeSH terms: Immunologic Deficiency Syndromes; Common Variable Immunodeficiency
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      This study was designed to explore CDZ173, a selective PI3Kδ inhibitor, in patients with
      genetically activated PI3Kδ, i.e., patients with Activated phosphoinositide 3-kinase delta
      syndrome/ p110δ-activating mutation causing senescent T cells, lymphadenopathy and
      immunodeficiency (APDS/PASLI).

      The study consisted of two parts: Part I was the open label part designed to establish the
      safety and pharmacokinetics of CDZ173 in the target population, as well as to select the
      optimal dose to be tested in Part II. Part II was designed to assess efficacy and safety of
      CDZ173 in the target population.
    

Detailed description: 
      This was a 2-part (Part I and Part II), Phase 2/3, multi-center study in subjects with
      APDS/PASLI.

      Part I of the study was a non-randomized, open-label, within-patient up-titration
      dose-finding part in 6 participants with APDS/PASLI. The starting dose was 10 mg followed by
      30 mg and 70 mg b.i.d. for 4 weeks at each dose level respectively. Part I consisted of three
      distinct study periods:

      Screening / Baseline visit (Day -50 to Day-1): This period was used to confirm that the study
      inclusion and exclusion criteria were met. Participants who were deemed eligible for
      enrollment into the study attended the clinic on Day -1 for baseline assessments prior to
      randomization.

      Treatment period (Day 1 to Day 84): Participants started treatment on Day 1 receiving 10 mg
      of CDZ173 twice daily (b.i.d.) until Day 28. After a continuous safety review and a review of
      PK and PD data, participants assessed as satisfactory proceeded to the next dose levels: from
      Day 29 to Day 56 participants received 30 mg CDZ173 b.i.d. and from Day 57 to Day 84, if
      assessed as satisfactory, participants received 70 mg CDZ173 b.i.d.

      Follow-up (Day 85-114): After completion of the treatment period, participants were
      followed-up for safety for four weeks until Day 114.

      Part II was a randomized, subject, investigator and sponsor-blinded, placebo-controlled,
      fixed dose part investigating 31 participants with APDS/PASLI. The CDZ173 dose used in this
      Part was selected based on safety, tolerability, PK and PD data from Part I. Part II
      consisted of three distinct study periods:

      Screening / Baseline visit (Day -50 to Day-1): This period was used to confirm that the study
      inclusion and exclusion criteria were met. Participants who were deemed eligible for
      enrollment into the study attended the clinic on Day -1 for baseline assessments prior to
      randomization.

      Treatment period (Day 1 to Day 85): On Day 1, Participants were randomized to one of the two
      treatment groups in a 2:1 ratio to receive either 70 mg CDZ173 b.i.d. or matching placebo
      until Day 85.

      Follow-up (Day 86-115): On Day 86, a subset of participants rolled over to CCDZ173X2201E1
      extension study and were not followed up for safety after end of treatment in CCDZ173X2201.
      Participants, who did not directly roll over to the extension study, after last treatment
      dose were followed-up for safety for four weeks until Day 115.
    

Intervention name(s): CDZ173; Placebo
Intervention type(s): Drug; Other
Intervention description(s): CDZ173 10 and 70 mg capsules for oral administration.; Placebo capsules for oral administration
Other intervention name(s): Leniolisib
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Part I of the study was a non-randomized, open-label, within-patient up-titration dose-finding part in 6 participants with APDS/PASLI. Part II was a randomized, subject, investigator and sponsor-blinded, placebo-controlled, fixed dose part investigating 31 participants with APDS/PASLI.
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: APDS; PASLI; PI3Kdelta