Leniolisib for Activated PI3K Delta Syndrome

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

15 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing leniolisib, an oral medicine, in children aged 4 to 11 with a genetic condition called APDS. The medicine aims to calm an overactive part of their immune system to improve their health. Leniolisib has shown benefits in patients with APDS in previous clinical trials.

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.

What data supports the effectiveness of the drug leniolisib for treating activated PI3K Delta Syndrome?

Research shows that leniolisib effectively reduces lymph node size and increases the percentage of naïve B cells in patients with activated PI3K Delta Syndrome, indicating improved immune function. It was well tolerated in clinical trials, with fewer side effects compared to placebo. ^{1 2 3 4 5}

Is leniolisib safe for humans?

Leniolisib has been shown to be generally safe and well-tolerated in humans, with fewer treatment-related side effects compared to other similar drugs. In clinical trials, most side effects were mild, and leniolisib was effective in improving immune function in patients with activated PI3K delta syndrome. ^{1 2 3 4 6}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

PI3Kδ Pathway Dysregulation and Unique Features of Its Inhibition by Leniolisib in Activated PI3Kδ Syndrome and Beyond. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

A randomized, placebo-controlled phase 3 trial of the PI3Kδ inhibitor leniolisib for activated PI3Kδ syndrome. [2023]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Leniolisib: First Approval. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Effective "activated PI3Kδ syndrome"-targeted therapy with the PI3Kδ inhibitor leniolisib. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

PI3Kδ inhibition by idelalisib in patients with relapsed indolent lymphoma. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

The Oral PI3Kδ Inhibitor Linperlisib for the Treatment of Relapsed and/or Refractory Follicular Lymphoma: A Phase II, Single-Arm, Open-Label Clinical Trial. [2023]