Leniolisib for Activated PI3K Delta Syndrome

Not currently recruiting at 11 trial locations

Overseen By Leisa Waynick, BSBA

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Pharming Technologies B.V.

Must not be taking: Immunosuppressants, QT prolongers, CYP3A inhibitors

Disqualifiers: ECG abnormalities, Liver disease, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 281

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of leniolisib in children with activated PI3K delta syndrome (APDS), a condition that can cause frequent infections and immune system issues. Researchers seek to determine how well leniolisib treats these symptoms. Eligible children must have APDS confirmed by a genetic test and a history of frequent infections. As a Phase 3 trial, this study is the final step before FDA approval, offering participants the opportunity to contribute to the potential availability of a new treatment.

Will I have to stop taking my current medications?

The trial requires stopping certain medications before participating. If you're taking immunosuppressive drugs, some need to be stopped weeks or months before starting the study. Check with the trial team to see if your specific medications are affected.

Is there any evidence suggesting that leniolisib is likely to be safe for humans?

Research shows that leniolisib is generally easy for people to take. Studies have found that leniolisib, a pill, does not have the serious safety issues seen with other similar treatments. In a 12-week study, both adults and children over 12 with activated PI3K delta syndrome (APDS) took leniolisib and tolerated it well.

Although this study focuses on younger children, the treatment is already approved for older ones, suggesting it might be safe for them too. Trials reported no major side effects, making it a promising option for managing APDS. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Leniolisib is unique because it specifically targets the PI3K delta pathway, which is overactive in Activated PI3K Delta Syndrome (APDS). Unlike standard treatments that might not directly address this pathway, Leniolisib acts directly to inhibit PI3K delta, potentially reducing symptoms more effectively. Researchers are excited about Leniolisib because it offers a targeted approach that could improve the quality of life for patients with APDS by directly addressing the underlying cause of the condition.

What evidence suggests that leniolisib might be an effective treatment for activated PI3K delta syndrome?

Research has shown that leniolisib, the investigational treatment in this trial, is effective and well-tolerated for treating Activated PI3K Delta Syndrome (APDS). In earlier studies, leniolisib achieved important goals by reducing symptoms compared to a placebo. The results demonstrated improved immune cell function and a decrease in the uncontrolled growth of white blood cells. These findings suggest that leniolisib could be a promising treatment option for people with APDS. ^{4 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for pediatric patients aged 4 to 11 with Activated PI3K Delta Syndrome (APDS). They must weigh between 13 kg and <45 kg, have a measurable nodal lesion, and a confirmed genetic mutation in the PIK3CD or PIK3R1 gene. Participants should not be on other trials or certain immunosuppressants, and girls who reach menarche must use contraception.

Inclusion Criteria

Your heart rate is within a normal range.

- Heart rate (HR):

I am 10 years or older and my heart rate is between 50 to 100 bpm.

Exclusion Criteria

I haven't taken B cell depleters like rituximab in the last 6 months.

I do not have serious heart rhythm problems.

My family has a history of long QT syndrome or Torsades de Pointes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive leniolisib orally based on weight for 12 weeks to assess safety and efficacy

12 weeks

Baseline, Days 29, 57, and 85

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label long-term extension

Participants continue to receive leniolisib for 1 year to assess long-term safety and efficacy

1 year

Day 252, through study completion

What Are the Treatments Tested in This Trial?

Interventions

• Leniolisib

Trial Overview The study tests Leniolisib's safety, tolerability, how it's processed by the body (pharmacokinetics), its effects on the disease (pharmacodynamics), and effectiveness in at least 15 children with APDS. It's an open-label trial where everyone gets Leniolisib; there are no comparison groups.

How Is the Trial Designed?

Group I: Leniolisib Experimental Treatment 1 Intervention

Leniolisib - Film Coated Tablets Leniolisib tablets in 10 and 30 mg strengths administered orally BID by body weight for 12 weeks for Part I and for 1 year for Part II.

Leniolisib is already approved in United States for the following indications:

Approved in United States as Joenja for:

• Activated phosphoinositide 3-kinase delta syndrome (APDS)

Who Is Running the Clinical Trial?

Pharming Technologies B.V.

Lead Sponsor

Trials

23

Recruited

1,400+

University of California, Los Angeles

Collaborator

Trials

1,594

Recruited

10,430,000+

Fortrea

Industry Sponsor

Trials

22

Recruited

5,800+

Aixial Group

Industry Sponsor

Trials

4

Recruited

90+

CMIC Co, Ltd. Japan

Industry Sponsor

Trials

11

Recruited

3,800+

Labcorp Central Laboratory

Collaborator

Trials

2

Recruited

30+

Fortrea

Collaborator

Trials

8

Recruited

2,500+

Aixial Group

Collaborator

Trials

4

Recruited

90+

Labcorp Drug Development, Inc.

Industry Sponsor

Trials

11

Recruited

540+

Labcorp Drug Development Inc

Industry Sponsor

Trials

17

Recruited

2,100+

Published Research Related to This Trial

Leniolisib (JOENJA®) is an oral medication that selectively inhibits the PI3Kδ enzyme and has been approved for treating activated PI3Kδ syndrome (APDS) in patients aged 12 and older, marking a significant advancement in immunodeficiency treatment.

The drug is currently under review in the European Union for the same indication, although its development for Sjögren's syndrome has been discontinued.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Leniolisib: First Approval. Duggan, S., Al-Salama, ZT.[2023]

In a clinical trial involving 6 patients with activated PI3Kδ syndrome (APDS), the selective PI3Kδ inhibitor leniolisib demonstrated a dose-dependent reduction in immune dysregulation and normalization of B cell populations after 12 weeks of treatment.

Leniolisib was well tolerated and led to significant reductions in lymph node and spleen sizes (39% and 40% respectively), indicating its potential as a targeted therapy for APDS and similar conditions characterized by PI3Kδ pathway overactivation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effective "activated PI3Kδ syndrome"-targeted therapy with the PI3Kδ inhibitor leniolisib. Rao, VK., Webster, S., Dalm, VASH., et al.[2021]

Leniolisib is the only PI3Kδ inhibitor that has demonstrated both efficacy and tolerability for treating activated phosphoinositide 3-kinase δ syndrome (APDS), a genetic condition affecting immune function.

Unlike other PI3Kδ inhibitors that can cause severe side effects like colitis and neutropenia, leniolisib selectively targets the δ isoform without affecting the δ or γ isoforms, making it a safer option for patients with APDS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PI3Kδ Pathway Dysregulation and Unique Features of Its Inhibition by Leniolisib in Activated PI3Kδ Syndrome and Beyond. Cant, AJ., Chandra, A., Munro, E., et al.[2023]

In a phase 3 trial involving 31 patients with Activated Phosphoinositide 3-Kinase Delta Syndrome (APDS), the oral drug leniolisib significantly reduced lymph node size and increased the percentage of naïve B cells, indicating improved immune function.

Leniolisib was well tolerated, with fewer treatment-related adverse events reported compared to placebo, suggesting it is a safe and effective option for managing immune dysregulation in APDS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, placebo-controlled phase 3 trial of the PI3Kδ inhibitor leniolisib for activated PI3Kδ syndrome. Rao, VK., Webster, S., Šedivá, A., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39673396

Comparative efficacy of leniolisib (CDZ173) versus ... Leniolisib, an oral, targeted phosphoinositide 3-kinase delta (PI3Kδ) inhibitor, was well-tolerated and efficacious versus placebo in treating individuals ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11754865/

Comparative efficacy of leniolisib (CDZ173) versus ... Leniolisib, an oral, targeted phosphoinositide 3-kinase delta (PI3Kδ) inhibitor, was well-tolerated and efficacious versus placebo in treating individuals ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1521661624005096

A randomised, placebo-controlled, phase III trial of ... In a 12-week phase III randomised placebo-controlled trial, leniolisib, a selective PI3Kδ inhibitor, was well-tolerated and met both co-primary endpoints.

4. ashpublications.org ashpublications.org/blood/article/130/21/2307/36662/Effective-activated-PI3K-syndrome-targeted-therapy

targeted therapy with the PI3Kδ inhibitor leniolisib | Blood Data are shown as mean values of the indicated number of patients with SD. (B) Individual observed leniolisib blood exposure and pAKT inhibition ...

5. jacionline.org jacionline.org/article/S0091-6749(23)01244-7/fulltext

Interim analysis: Open-label extension study of leniolisib ... Leniolisib, a selective PI3Kδ inhibitor, demonstrated favorable impact on immune cell subsets and lymphoproliferation over placebo in patients ...

6. joenja-hcp.com joenja-hcp.com/additional-safety/

Additional Safety - - Joenja® (leniolisib) Interim safety and efficacy analysis of an ongoing long-term open-label extension study of leniolisib for patients with activated PI3K delta syndrome (APDS).

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2023/217759s000lbl.pdf

JOENJA® (leniolisib) tablets - accessdata.fda.gov The safety of JOENJA reflects exposure based on 38 adult and pediatric patients 12 years of age and older with activated phosphoinositide 3-kinase delta (PI3Kδ) ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10841669/

Interim Analysis: Open-Label Extension Study of Leniolisib for ... Other PI3Kδ inhibitors used to treat malignancy have demonstrated significant safety concerns, which were not observed with leniolisib.

9. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2025/217759s005lbl.pdf

JOENJA® (leniolisib) tablets, for oral use - accessdata.fda.gov The safety of JOENJA reflects exposure based on 38 adult and pediatric patients 12 years of age and older with activated phosphoinositide 3-kinase delta (PI3Kδ) ...