New Biomarker-based Strategy to Screen and Monitor for Activated Phosphoinositide 3-kinase δ Syndrome (BIO-APDS)

March 19, 2026 updated by: Assistance Publique - Hôpitaux de Paris

The study would like to compare patient samples at different time points using state-of the art-phenotyping tools.

Collection of blood samples of APDS patients undergoing PI3K inhibitor treatment will be collected when feasible according to the standard of care planning (a blood test is supposed to be performed for these patients at M0-M3-M6-M12 then each 6 months for a total period of 2 years from the beginning of the PI3K inhibitor treatment).

The whole blood will be processed in order to isolate the peripheral blood mononuclear cells (PBMC) and the plasma. Serum, RNA and DNA extraction will be performed on a separate sample.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Activated PI3K delta syndromes (PI3Kδ) (APDS type 1 and type 2) are combined immunodeficiencies with variable clinical manifestations caused by heterozygous gain-of-function mutations of the PIK3CD gene. APDS is a very young onset disease, most clinical manifestations appear in pediatric age. Patients may experience severe, disabling, and life-threatening clinical manifestations. Additionally, they may exhibit autoimmunity in addition to immune deficiency. APDS patients present a high risk of developing tumors especially B lymphomas. Hematopoietic stem cell transplantation (HSCT) is the only curative option and, given the risks, may be considered for patients with severe APDS (including those who have developed lymphoma). HSCT is curative, but carries a 10 to 20% mortality risk and cannot guarantee reversibility of organ damage. Positive data from the phase II/III study of the PI3Kδ selective inhibitor leniolisib met the co-primary criteria of reduced lymph node size and increased percentage of B naïve cells in patients with APDS. In addition, safety data from the study showed that leniolisib was well tolerated by participants. The drug is also under review by the European Medicines Agency and a marketing authorization for APDS patients older than 12 years old will be soon available. In the meantime the access to this drug is available by compassionate use for patients older than 12 years old.

In this context, it will be interesting to evaluate the clinical and biological profile of these patients before and after leniolisib treatment in order to identify useful biomarkers for the follow up of the disease. In addition, carful long-term monitoring of patients under PI3Kδ inhibitors is mandatory to detect adverse effects of iatrogenic overinhibition of the PI3K pathway.

Study Type

Observational

Enrollment (Estimated)

14

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients with genetic diagnosis of APDS type 1 or type 2 and planned to be treated by PI3Kδ selective inhibitor leniolisib and patients with genetic diagnosis of APDS type 1 or type 2 already treated by PI3Kδ selective inhibitor leniolisib in the last 2 years

Description

Inclusion Criteria:

Group 1:

  • Patients with genetic diagnosis of APDS type 1 or type 2 and planned to be treated by PI3Kδ selective inhibitor leniolisib
  • Primary immunodeficient patients with new disease-causing variants in the PIK3CD gene or PIK3R1 gene
  • Minimum age 12 years old
  • Patients or holders of parental authority do not oppose participation in this research.
  • Patients affiliated to a Health Insurance scheme or beneficiaries

Group 2 :

  • Patients with genetic diagnosis of APDS type 1 or type 2 already treated by PI3Kδ selective inhibitor leniolisib in the last 2 years
  • Patients whose pre-treatment samples are available/analyzable
  • Minimum age 12 years old
  • Patients or holders of parental authority do not oppose participation in this research.
  • patients affiliated to a Health Insurance scheme or beneficiaries

Exclusion Criteria:

  • Bone marrow transplantation
  • Refusal to participate to the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
1 - initiating treatment
10 patients with a genetic diagnosis of APDS type 1 or type 2 who are to be treated with a selective PI3Kδ inhibitor, Lenolisib.
Biological: Blood samples
A maximum of 27 ml of blood collected at each visit for metabolic markers analysis
Biological: Urine samples
One urine sample collected at each visit for enteric virus infection research
Biological: Stool samples
One stool sample collected at each visit for enteric virus infection research
2 - already on treatment
4 patients with a genetic diagnosis of APDS type 1 or type 2 already treated with a selective PI3Kδ inhibitor, Lenolisib.
Biological: Blood samples
A maximum of 27 ml of blood collected at each visit for metabolic markers analysis
Biological: Urine samples
One urine sample collected at each visit for enteric virus infection research
Biological: Stool samples
One stool sample collected at each visit for enteric virus infection research

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Biomarker
Time Frame: At 0 day, 3 months, 6 months, 12 months, 18 months and 24 months of treatment
Identify new biomarker marker for increased PI3K signaling to monitor the disease severity by mass cytometry, single cell RNA-sequencing, single cell ATAC-sequencing and screening for auto-antibodies
At 0 day, 3 months, 6 months, 12 months, 18 months and 24 months of treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
activation-induced cytidine deaminase (AID) off-target activity
Time Frame: At 0 day, 3 months, 6 months, 12 months, 18 months and 24 months of treatment
Investigate the possibility of activation-induced cytidine deaminase (AID) off-target activity in memory B cells due to PI3Kdelta inhibitor treatment by NGS panel sequencing
At 0 day, 3 months, 6 months, 12 months, 18 months and 24 months of treatment
Correlation between biological data with the clinical data
Time Frame: At 0 day, 3 months, 6 months, 12 months, 18 months and 24 months of treatment
the analyses results will be correlated with the clinical data collected for the patients enrolled in the trial and receiving PIK3CD inhibitor treatment (early access program) in order to explore a possible correlation between biological data and clinical characteristics.
At 0 day, 3 months, 6 months, 12 months, 18 months and 24 months of treatment
Enteric virus infection research
Time Frame: At 0 day, 3 months, 6 months, 12 months, 18 months and 24 months of treatment
Presence of Chronic enteric virus infection will be investigated by multiplex PCR and if negative by NGS in stools, plasma, urins
At 0 day, 3 months, 6 months, 12 months, 18 months and 24 months of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

URC-CIC Paris Descartes Necker Cochin

Investigators

  • Study Director: Sven Kracker, PHD, Institut National de la Santé Et de la Recherche Médicale, France

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 26, 2025

Primary Completion (Estimated)

June 27, 2029

Study Completion (Estimated)

December 27, 2029

Study Registration Dates

First Submitted

November 15, 2024

First Submitted That Met QC Criteria

November 15, 2024

First Posted (Actual)

November 19, 2024

Study Record Updates

Last Update Posted (Actual)

March 23, 2026

Last Update Submitted That Met QC Criteria

March 19, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • APHP240329
  • 2024-A01816-41 (Registry Identifier: ID-RCB)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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