What is the mechanism of action of this treatment?

Selective PI3Kδ inhibitors, such as CDZ173, work by specifically targeting and inhibiting the delta isoform of the phosphoinositide 3-kinase (PI3K) enzyme. This inhibition is crucial for patients with Activated PI3Kdelta Syndrome (APDS) or PASLI Disease because the condition is characterized by hyperactivation of the PI3Kδ pathway due to genetic mutations. By blocking this pathway, PI3Kδ inhibitors help to reduce abnormal immune cell proliferation and function, thereby alleviating symptoms and preventing disease progression. This targeted approach is essential for managing APDS/PASLI effectively, as it directly addresses the underlying molecular dysfunction.

What side effects are associated with this type of intervention?

The most common treatments for Activated PI3Kdelta Syndrome (APDS) or PASLI Disease, particularly selective PI3Kδ inhibitors like CDZ173, are associated with several side effects. These include increased glucose levels, increased creatinine, diarrhea, rash, and decreased lymphocyte count. These side effects are consistent with those observed in similar treatments for other conditions involving PI3K inhibitors.

What prior FDA approvals exist?

There is no specific mention of prior FDA approvals for the treatment of Activated PI3Kdelta Syndrome (APDS) or PASLI Disease in the provided context. However, leniolisib, another selective PI3Kδ inhibitor, has shown promise in clinical trials for improving laboratory and clinical parameters in APDS, suggesting that selective inhibition of PI3Kδ is a promising therapeutic approach for this condition.

What other types of research exist?

As of 2024, promising alternatives to CDZ173 for APDS/PASLI patients may include other selective PI3Kδ inhibitors currently in clinical trials or recently approved. Additionally, therapies targeting related pathways, such as mTOR inhibitors or other immunomodulatory agents, could be considered. Consulting with a healthcare provider for the latest clinical trial data and emerging treatments is recommended.

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PI3Kδ inhibitor

CDZ173 for Activated PI3Kdelta Syndrome

Phase 2 & 3

Waitlist Available

Research Sponsored by Novartis Pharmaceuticals

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients must have participated in the study CCDZ173X2201 or were treated previously with PI3Kδ inhibitors other than CDZ173

Documented APDS/PASLI-associated genetic PI3K delta mutation

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 6 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests CDZ173, a drug that blocks a protein to calm the immune system, in patients with a genetic condition causing an overactive immune system (APDS/PASLI).

Who is the study for?

This trial is for patients with APDS/PASLI, a genetic condition causing enlarged lymph nodes and immune system issues. Participants must have been in the CCDZ173X2201 study or treated with other PI3Kδ inhibitors, understand the study requirements, and provide informed consent.

What is being tested?

The trial tests long-term use of CDZ173, a drug targeting a specific part of cells (PI3Kδ) that's overactive in APDS/PASLI. It's an open-label study to assess safety, tolerability, effectiveness, and how the body processes the drug over time.

What are the potential side effects?

As CDZ173 targets immune cell function, potential side effects may include increased risk of infections, possible allergic reactions to the medication itself or its components. Specific side effect details are not provided but will be monitored throughout the trial.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I have been part of the CCDZ173X2201 study or treated with PI3Kδ inhibitors.

Select...

My condition is linked to a specific genetic mutation in PI3K delta.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 6 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~6 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 6 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

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

Secondary study objectives

To characterize the pharmacokinetics (trough concentration) of CDZ173 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 evaluate the long term efficacy of CDZ173 to modify health-related quality of life in patients with APDS/PASLI

+1 more

Side effects data

From 2021 Phase 2 & 3 trial • 37 Patients • NCT02435173

17%

Blood creatine phosphokinase increased

17%

Cough

17%

Amylase increased

17%

Lipase increased

100%

80%

60%

40%

20%

Study treatment Arm

Part I: CDZ173 10 mg

Part I: CDZ173 30 mg

Part I: CDZ173 70 mg

Part II: Placebo

Part II: CDZ173 70 mg

Part I: Total

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: CDZ173Experimental Treatment1 Intervention

140mg/day

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

CDZ173

2015

Completed Phase 3

~70

0 / 2Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Selective PI3Kδ inhibitors, such as CDZ173, work by specifically targeting and inhibiting the delta isoform of the phosphoinositide 3-kinase (PI3K) enzyme. This inhibition is crucial for patients with Activated PI3Kdelta Syndrome (APDS) or PASLI Disease because the condition is characterized by hyperactivation of the PI3Kδ pathway due to genetic mutations. By blocking this pathway, PI3Kδ inhibitors help to reduce abnormal immune cell proliferation and function, thereby alleviating symptoms and preventing disease progression. This targeted approach is essential for managing APDS/PASLI effectively, as it directly addresses the underlying molecular dysfunction.

Dual Targeting by Inhibition of Phosphoinositide-3-Kinase and Mammalian Target of Rapamycin Attenuates the Neuroinflammatory Responses in Murine Hippocampal Cells and Seizures in C57BL/6 Mice.A systematic review of the safety and efficacy of currently used treatment modalities in the treatment of patients with PIK3CA-related overgrowth spectrum.SHORT syndrome due to a novel de novo mutation in PRKCE (Protein Kinase Cɛ) impairing TORC2-dependent AKT activation.