Activated PI3K Delta SyndromeBIO-APDSNCT06694363
New Biomarker-based Strategy to Screen and Monitor for Activated Phosphoinositide 3-kinase δ Syndrome
An observational study of Activated PI3K Delta Syndrome, run by Assistance Publique - Hôpitaux de Paris at 7 sites in France.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Activated PI3K Delta Syndrome
- What is being tested?
- Blood samples, Urine samples and Stool samples
- How many people
- 14 participants
- Where
- 7 sitesFrance
- Study dates
- 26 Jun 2025to 27 Dec 2029
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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
Who may be able to join
- 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
Show all 12Show fewer
- 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
Who cannot join
- Bone marrow transplantation
- Refusal to participate to the study.
Trial locations and contacts
7 sites in 1 country. Contact the study team or a site near you to ask about taking part.
7 sites in 1 country
France7 sites, 7 recruiting
- Not yet recruiting
Hôpital Haut Levêque - BORDEAUX
Bordeaux, 33000
Jean François VIALLARD, MD, PhD, jean-françois.viallard@chu-bordeaux.fr
- Not yet recruiting
Hôpital Pellerin Enfants - BORDEAUX
Bordeaux, 33000
Nathalie ALADJIDI, MD, nathalie.aladjidi@chu-bordeaux.fr
- Recruiting
Hôpital Jeanne de Flandres - LILLE
Lille, 59000
Wadih ABOU-CHALA, MD, wadih.abouchala@chu-lille.fr
- Not yet recruiting
Hôpital La Timone adulte - MARSEILLE
Marseille, 13000
Nicolas SCHLEINITZ, MD, PhD, nicolas.schleinitz@ap-hm.fr
- Recruiting
Hôpital Necker Enfants Malades - PARIS
Paris, 75015
Michaela SEMERARO, MD, PhD, michaela.semeraro@aphp.fr
- Not yet recruiting
CHU IUCT Oncopole - TOULOUSE
Toulouse
Pierre COUGOUL, MD, cougoul.pierre@iuct-oncopole.fr
- Not yet recruiting
Hôpital des enfants - TOULOUSE
Toulouse
Marlène PASQUET, MD, pasquet.m@chu-toulouse.fr
About this study
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.
Read the 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.
- Conditions
- Activated PI3K Delta Syndrome
- Being tested
- Blood samples, Urine samples, Stool samples
- Keywords
- Activated PI3K delta syndromes, APDS, Leniolisib
- Medical subject headings
- Activated PI3K-delta Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood samplesBiological
A maximum of 27 ml of blood collected at each visit for metabolic markers analysis
Urine samplesBiological
One urine sample collected at each visit for enteric virus infection research
Stool samplesBiological
One stool sample collected at each visit for enteric virus infection research
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: Blood samples; Biological: Urine samples; Biological: Stool samples | |
| 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. Receives: Biological: Blood samples; Biological: Urine samples; Biological: Stool samples |
What is being measured
The primary outcome is the main question the study is designed to answer.
Biomarker
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
Measured: At 0 day, 3 months, 6 months, 12 months, 18 months and 24 months of treatment
Secondary outcomes (3)
activation-induced cytidine deaminase (AID) off-target activity
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
Measured: At 0 day, 3 months, 6 months, 12 months, 18 months and 24 months of treatment
Correlation between biological data with the clinical data
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.
Measured: At 0 day, 3 months, 6 months, 12 months, 18 months and 24 months of treatment
Enteric virus infection research
Presence of Chronic enteric virus infection will be investigated by multiplex PCR and if negative by NGS in stools, plasma, urins
Measured: At 0 day, 3 months, 6 months, 12 months, 18 months and 24 months of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2024
- Study start26 Jun 2025
- Primary completion27 Jun 2029 (estimated)
- Study completion27 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Activated PI3K Delta SyndromeStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 14 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Responsible party
- Sponsor
- Investigators
- Sven Kracker, PHD, Study director, Institut National de la Santé Et de la Recherche Médicale, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06694363
- Sponsor's protocol ID
- APHP240329
- Other IDs
- 2024-A01816-41
- Acronym
- BIO-APDS
- Status last verified
- Mar 2026
- First submitted
- 15 Nov 2024
- Last updated
- 23 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- New Biomarker-based Strategy to Screen and Monitor for Activated Phosphoinositide 3-kinase δ Syndrome
- ClinicalTrials.gov ID
- NCT06694363
- Acronym / sponsor ID
- BIO-APDS / APHP240329
- Conditions
- Activated PI3K Delta Syndrome
- Keywords
- Activated PI3K delta syndromes, APDS, Leniolisib
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 14 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Study start
- 26 Jun 2025 (actual)
- Primary completion
- 27 Jun 2029 (estimated)
- Study completion
- 27 Dec 2029 (estimated)
- First posted
- 19 Nov 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 - initiating treatment | – | Biological: Blood samples, Biological: Urine samples, Biological: Stool samples10 patients with a genetic diagnosis of APDS type 1 or type 2 who are to be treated with a selective PI3Kδ inhibitor, Lenolisib. |
| 2 - already on treatment | – | Biological: Blood samples, Biological: Urine samples, Biological: Stool samples4 patients with a genetic diagnosis of APDS type 1 or type 2 already treated with a selective PI3Kδ inhibitor, Lenolisib. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- 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
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (2 listed)
- Bone marrow transplantation
- Refusal to participate to the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood samplesA maximum of 27 ml of blood collected at each visit for metabolic markers analysis | Biological | 1 - initiating treatment, 2 - already on treatment |
| Urine samplesOne urine sample collected at each visit for enteric virus infection research | Biological | 1 - initiating treatment, 2 - already on treatment |
| Stool samplesOne stool sample collected at each visit for enteric virus infection research | Biological | 1 - initiating treatment, 2 - already on treatment |
Primary outcome
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
3 secondary outcomes
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
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
Enteric virus infection research
Time frame: At 0 day, 3 months, 6 months, 12 months, 18 months and 24 months of treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2026.
- Individual participant dataSharing planned: No
Related trials for Activated PI3K Delta Syndrome
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
Active, not recruitingPhase 3
Pediatric Patients Aged 1 to 6 Years With APDS
APDS
Active, not recruitingPhase 3
Pediatric Patients Aged 4 to 11 Years With APDS
APDS
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Sven Kracker, PHD study director
Institut National de la Santé Et de la Recherche Médicale, France
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Activated PI3K Delta Syndrome, run by Assistance Publique - Hôpitaux de Paris at 7 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 23 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Michaela SEMERARO, MD, PhD (01 42 19 27 16 ext. +33, michaela.semeraro@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Biomarker (time frame: At 0 day, 3 months, 6 months, 12 months, 18 months and 24 months of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Mar 2026.