Leniolisib for Primary Immunodeficiency

Overseen By Gulbu Uzel, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Pharming Technologies B.V.

Must be taking: Leniolisib

Must not be taking: Immunosuppressants, Corticosteroids, CYP3A inhibitors, others

Disqualifiers: HIV, Uncontrolled infections, Hepatitis, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: Approximately 3 years

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the long-term safety and effects of leniolisib, a medication for individuals with certain primary immunodeficiency disorders. These disorders relate to a specific part of the immune system known as phosphoinositide 3-kinase delta signaling. The trial targets patients who participated in a previous leniolisib study and could benefit from continued treatment. Ideal candidates are those who took part in the earlier study and are expected to benefit from ongoing leniolisib therapy. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important research.

Will I have to stop taking my current medications?

You may need to stop taking certain medications before joining the trial. Specifically, you should not use certain immunosuppressive drugs, strong inhibitors or inducers of CYP3A, or medications that affect specific proteins like BCRP and OATP1B1/1B3. Check with the study team to see if your current medications are affected.

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

Research has shown that leniolisib is generally safe for people with primary immunodeficiency. In earlier studies, side effects were mild or moderate, with no serious side effects linked to the drug. One study found that leniolisib was well-tolerated over 12 weeks and achieved important treatment goals. Additionally, safety data from eight months of use support its safety. These findings suggest leniolisib is relatively safe for humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Leniolisib is unique because it targets a specific enzyme called phosphoinositide 3-kinase delta (PI3Kδ), which plays a crucial role in immune cell function. Unlike other treatments for primary immunodeficiency that might broadly suppress the immune system, leniolisib offers a more targeted approach, potentially reducing side effects. Researchers are excited about leniolisib because it promises to improve immune function by fine-tuning the immune response, rather than dampening it across the board. This precision could lead to better management of the condition with fewer complications.

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

Research shows that leniolisib may help treat certain immune system disorders related to a specific cell signaling pathway. Studies have found that leniolisib significantly lowers infection rates in patients, regardless of their past infection history. It also reduces swollen lymph nodes and increases the number of a type of immune cell important for a healthy immune response. Overall, leniolisib has demonstrated better results than placebo treatments in these areas. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for patients with primary immunodeficiency disorders related to PI3K delta signaling who were previously in the leniolisib study LE 7201. It aims to continue treatment and further evaluate safety and effectiveness.

Inclusion Criteria

Subject is deemed by the Investigator to benefit from continued leniolisib therapy

Subject must have participated in LE 7201

I can communicate with the study team and follow the study requirements.

Exclusion Criteria

History of acquired immunodeficiency diseases, including a positive human immunodeficiency virus (HIV) test result at screening

A positive hepatitis B surface antigen (HBsAg), positive hepatitis B polymerase chain reaction (PCR), positive hepatitis C PCR, or positive hepatitis C antibody result at screening

I haven't had major surgery or radiotherapy in the last 4 weeks and don't plan to during the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive leniolisib film-coated tablets to assess long-term safety, tolerability, and efficacy

Approximately 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants continue to receive leniolisib to evaluate long-term safety and efficacy

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Leniolisib

Trial Overview The trial tests the long-term safety, tolerability, and efficacy of a drug called Leniolisib for individuals with immune dysregulation due to primary immunodeficiency disorders.

How Is the Trial Designed?

Group I: Treatment Arm Experimental Treatment 1 Intervention

All subjects will receive leniolisib film-coated tablets (FCTs)

Who Is Running the Clinical Trial?

Pharming Technologies B.V.

Lead Sponsor

Trials

23

Recruited

1,400+

Aixial Group

Industry Sponsor

Trials

4

Recruited

90+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11230794/

Leniolisib: a drug providing a promising avenue for the ... In the placebo group (n=5), 20% achieved complete response, while the remaining 80% experienced worsening disease. The Leniolisib group also showed improvement ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S108112062500626X

r205 effectiveness of leniolisib in reducing infections ... Treatment with leniolisib consistently demonstrated significant reductions in infection rates, regardless of patients' infection history. These results align ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06990529

Long-term Safety and Efficacy of Leniolisib in PIDs With ... This is an open-label extension (OLE) study to extend treatment to patients with primary immunodeficiency (PID) disorders linked to phosphoinositide ...

4. rheumatologyadvisor.com rheumatologyadvisor.com/news/leniolisib-gets-priority-review-for-young-children-with-apds/

Leniolisib Gets Priority Review for Young Children With ... Findings showed all 21 patients completed the full treatment period. Leniolisib reduced lymphadenopathy and increased naïve B cells across all 4 ...

5. ashpublications.org ashpublications.org/blood/article/141/9/971/493284/A-randomized-placebo-controlled-phase-3-trial-of

A randomized, placebo-controlled phase 3 trial of the PI3Kδ ... Overall, leniolisib was well tolerated and significant improvement over placebo was notable in the coprimary endpoints, reducing lymphadenopathy ...

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

Interim Analysis: Open-Label Extension Study of Leniolisib for ... The OLE's primary endpoints are all safety parameters, including reported AEs and data collected via routine physical examinations, vital ...

7. healio.com healio.com/news/allergy-asthma/20251019/fda-accepts-supplemental-new-drug-application-for-leniolisib-for-children-with-apds

Supplemental NDA for leniolisib accepted for children with ... Also, the application included safety data from 8 months of treatment. ... “APDS is an underdiagnosed and progressive primary immunodeficiency ...

8. 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.