Study of Efficacy of CDZ173 in Patients With APDS/PASLI

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.

Timeline

Start

2015-08-24

Primary completion

2021-08-16

Completion

2021-08-16

Outcome

Met primary endpoint

registry analysis (superiority test); Part II: CDZ173 vs Part II: Placebo; p = 0.0012; Adjusted means difference -0.24 (95% CI -0.37 to -0.11); ANCOVA NCT02435173 ↗

registry analysis (superiority test); Part II: CDZ173 vs Part II: Placebo; p <0.0001; Adjusted means difference 40.13 (95% CI 28.51 to 51.75); ANCOVA NCT02435173 ↗

paper Both primary outcomes were met: PMID 36399712 ↗

release “Leniolisib met both of its primary end points in a registration enabling Phase 2/3 study in the United States and Europe.” pharming.com ↗

release “the global, randomized, placebo-controlled study in patients aged 12 years and older, in which leniolisib met its co-primary endpoints” pharming.com ↗

Publications

• Upton JEM, Williams KW, Cant A, Santos A, Bana E Costa J, Bradt J, Harrington A, Gwaltney C. Key outcomes in treatment of activated phosphoinositide 3-kinase delta syndrome: An e-Delphi panel study and responder threshold application. PLoS One. 2025 Oct 15;20(10):e0333341. doi: 10.1371/journal.pone.0333341. eCollection 2025.
• Rao VK, Webster S, Sediva A, Plebani A, Schuetz C, Shcherbina A, Conlon N, Coulter T, Dalm VA, Trizzino A, Zharankova Y, Kulm E, Korholz J, Lougaris V, Rodina Y, Radford K, Bradt J, Kucher K, Relan A, Holland SM, Lenardo MJ, Uzel G. A randomized, placebo-controlled phase 3 trial of the PI3Kdelta inhibitor leniolisib for activated PI3Kdelta syndrome. Blood. 2023 Mar 2;141(9):971-983. doi: 10.1182/blood.2022018546.
• Rao VK, Webster S, Dalm VASH, Sediva A, van Hagen PM, Holland S, Rosenzweig SD, Christ AD, Sloth B, Cabanski M, Joshi AD, de Buck S, Doucet J, Guerini D, Kalis C, Pylvaenaeinen I, Soldermann N, Kashyap A, Uzel G, Lenardo MJ, Patel DD, Lucas CL, Burkhart C. Effective "activated PI3Kdelta syndrome"-targeted therapy with the PI3Kdelta inhibitor leniolisib. Blood. 2017 Nov 23;130(21):2307-2316. doi: 10.1182/blood-2017-08-801191. Epub 2017 Sep 29.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Leniolisib	Small molecule	70 mg	Oral

Indications