Leniolisib for APDS

Not currently recruiting at 16 trial locations

Overseen By Jason Bradt, MD

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Pharming Technologies B.V.

Must not be taking: Immunosuppressants, CYP3A inhibitors, others

Disqualifiers: ECG abnormalities, Liver disease, 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: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores leniolisib (also known as Joenja or CDZ173) for young children with activated phosphoinositide 3-kinase delta syndrome (APDS), a condition causing immune system problems and frequent infections. Researchers aim to assess the safety and effectiveness of leniolisib in treating APDS in children. They seek participants aged 1 to 6 years with specific genetic mutations related to APDS and a history of repeated infections. Participants will take leniolisib orally over a period to observe its effects on their condition. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires stopping certain medications before starting, such as immunosuppressive drugs and some heart medications. If you're taking any of these, you may need to stop them for a specific time before joining the study.

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

Research has shown that leniolisib maintains a good safety record from previous studies. In one study involving 38 patients aged 12 and older with activated phosphoinositide 3-kinase delta syndrome (APDS), the treatment was generally well-tolerated. Most side effects were mild to moderate: 78.4% were mild, 48.6% were moderate, and 27% were more severe, but none were extremely severe. Only one serious side effect occurred.

Leniolisib was also tested against a placebo (a harmless pill with no active drug) and proved to be well-tolerated and effective in meeting its goals. These results suggest that leniolisib is relatively safe for patients with APDS. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Leniolisib is unique because it targets a specific pathway in the immune system related to APDS (Activated Phosphoinositide 3-Kinase Delta Syndrome). Unlike standard treatments that often involve general immune suppression, Leniolisib specifically inhibits the PI3K delta pathway, which is overactive in APDS. This targeted approach can potentially offer more effective management of symptoms with fewer side effects. Researchers are excited because this precision can improve patients' quality of life by directly addressing the root cause of the condition.

What evidence suggests that leniolisib might be an effective treatment for APDS?

Research has shown that leniolisib effectively treats activated phosphoinositide 3-kinase delta syndrome (APDS). One study demonstrated that leniolisib, which targets a specific enzyme, was well-tolerated and met key effectiveness goals compared to a placebo. Experts recommend it for treating APDS because it enhances the immune system in affected individuals. Leniolisib has shown promising results in reducing symptoms and improving patient outcomes, offering hope for those with this rare immune disorder. ^{4 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for children aged 1 to 6 with Activated PI3K Delta Syndrome (APDS), who can take oral medication and have a confirmed genetic mutation related to APDS. They should weigh between 8 and 37 kg, have normal blood pressure and heart rate, and not be on certain immunosuppressants or medications that affect the immune system.

Inclusion Criteria

Institutional review board- or IEC-approved written informed consent or assent and privacy language as per national and local regulations must be obtained from the patient and/or parent or legal guardian prior to any study-related procedures

I can take pills without any trouble.

I have a measurable cancerous node identified by MRI or CT scan in the last 6 months.

Exclusion Criteria

I have had cancer before.

My diabetes is not well-managed currently.

I, or my guardian, have not refused to sign the consent form.

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

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants continue to receive leniolisib for long-term safety follow-up

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Leniolisib

Trial Overview The study tests Leniolisib's safety, tolerability, how it affects the body (pharmacokinetics/pharmacodynamics), and effectiveness in at least 15 pediatric patients with APDS. It's an open-label trial where everyone gets the same treatment without any comparison group.

How Is the Trial Designed?

Group I: Leniolisib Experimental Treatment 1 Intervention

Leniolisib film-coated granules in 10, 15 and 20 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+

Labcorp Drug Development Inc

Industry Sponsor

Trials

17

Recruited

2,100+

University of California, Los Angeles

Collaborator

Trials

1,594

Recruited

10,430,000+

CMIC Co, Ltd. Japan

Industry Sponsor

Trials

11

Recruited

3,800+

Aixial Group

Collaborator

Trials

4

Recruited

90+

Labcorp Central Laboratory

Collaborator

Trials

2

Recruited

30+

Fortrea

Collaborator

Trials

8

Recruited

2,500+

Cmed

Collaborator

Trials

2

Recruited

30+

Labcorp Corporation of America Holdings, Inc

Industry Sponsor

Trials

22

Recruited

3,600+

Fortrea

Industry Sponsor

Trials

22

Recruited

5,800+

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. 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.

3. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK615808

Leniolisib for treating activated phosphoinositide 3-kinase ... Leniolisib is recommended, within its marketing authorisation, for treating activated phosphoinositide 3-kinase delta syndrome (APDS) in people ...

4. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0333341

An e-Delphi panel study and responder threshold application Activated phosphoinositide 3-kinase delta syndrome (APDS) is an ultra-rare, underrecognized inborn error of immunity. This study aimed to identify outcomes ...

5. academic.oup.com academic.oup.com/cei/article/219/1/uxae107/7914686

Comparative efficacy of leniolisib (CDZ173) versus standard ... Longer-term data comparing the efficacy of leniolisib, an oral, targeted phosphoinositide 3-kinase delta (PI3Kδ) inhibitor, versus standard ...

6. 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) ...

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

Additional Safety - - Joenja® (leniolisib) Thirty-two of 37 patients had ≥1 AE (333 AEs reported) · 78.4% were grade 1, 48.6% were grade 2, and 27% were grade 3 · No grade 4 AEs reported · One grade 5 ( ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10894968/

Leniolisib: a novel treatment for activated phosphoinositide ... Leniolisib has demonstrated a good safety profile due to its significant chemical and structural differences from the previous PI3K inhibitors.

9. eocco.com eocco.com/-/media/EOCCO/PDFs/Formulary/EOCCO-leniolisib-Joenja-Policy.pdf

leniolisib (Joenja™) The safety and efficacy of leniolisib (Joenja) were evaluated in a Phase 3, blinded, randomized, placebo controlled clinical trial (Study 2201-02). Patients (N= ...