Leniolisib for Common Variable Immunodeficiency

Recruiting at 5 trial locations

Overseen By Derrick Carter

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Pharming Technologies B.V.

Must not be taking: Immunosuppressants, mTOR inhibitors

Disqualifiers: T cell deficiency, NK cell deficiency, 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: 24 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests leniolisib, a potential treatment for common variable immunodeficiency (CVID), a condition where the immune system malfunctions, causing frequent infections. The study aims to determine if leniolisib is safe and well-tolerated by participants and whether it can improve their symptoms. Participants will take increasing doses of leniolisib over six months. Ideal candidates are those diagnosed with CVID who experience symptoms like an enlarged spleen or lymph nodes that interfere with daily activities. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires stopping certain medications before participating. You must not have used immunosuppressive medications like mTOR or PI3K inhibitors within 3 weeks, or B cell depleting antibodies like rituximab within 6 months. Some medications like abatacept and enteral budesonide are allowed if you've been on a stable dose for over 3 months.

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

Research has shown that leniolisib is generally safe for use. In earlier studies, patients who took leniolisib experienced manageable side effects, with no major safety issues reported. Long-term use has also proven safe, with regular monitoring for side effects and overall health. Leniolisib has been tested for other conditions, providing extensive safety information. While some side effects were noted, they were usually mild and temporary. Overall, leniolisib appears safe based on current research. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for CVID?

Unlike the standard treatments for Common Variable Immunodeficiency (CVID), which primarily involve immunoglobulin replacement therapy, leniolisib offers a novel approach by targeting the PI3Kδ pathway. This pathway is crucial for immune cell function, and by modulating it, leniolisib aims to correct the underlying immune dysfunction in CVID. Researchers are excited about leniolisib because it could potentially enhance immune system performance directly, providing a more targeted and effective treatment option compared to current therapies.

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

Research shows that leniolisib, the treatment under study in this trial, may help treat common variable immunodeficiency (CVID). Studies have found that leniolisib can greatly reduce the number of respiratory infections, which frequently occur in people with CVID. It also helps balance immune cell levels over time, which is important for improving overall immune health. In other trials, leniolisib was well tolerated and led to noticeable improvements in reducing symptoms like swollen lymph nodes. These findings suggest that leniolisib could offer real benefits for people with CVID. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for people aged 12-75 with common variable immunodeficiency (CVID). They should have low immune protein levels, no secondary causes of the condition, specific genetic markers if present, and signs of lymphoproliferation. Participants must also experience symptoms like chronic pain or blood cell count issues related to CVID.

Inclusion Criteria

I have been diagnosed with CVID due to low IgG levels.

At screening, vital signs ranges must meet specified criteria

I am between 12 and 75 years old.

Exclusion Criteria

I am taking medication that affects the CYP3A enzyme.

Positive blood PCR for cytomegalovirus or adenovirus

I have a history of infections indicating a significant immune deficiency.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive leniolisib with dose escalation: 10 mg BID for 4 weeks, 30 mg BID for 4 weeks, and 70 mg BID for 16 weeks

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Leniolisib

Trial Overview

The study tests leniolisib in CVID patients over a 6-month period. It starts with a lower dose that increases to mid and higher levels. The main aim is to check how safe it is and how well participants tolerate it; the second aim is to see if it helps improve their health.

How Is the Trial Designed?

Group I: Leniolisib Experimental Treatment 1 Intervention

All subjects participating will receive leniolisib film-coated tablets (FCTs) with a planned dose regimen consisting of a starting dose of 10 mg twice daily (BID) for 4 weeks, followed by a dose escalation to 30 mg BID for 4 weeks, and then 70 mg BID for an additional 16 weeks.

Who Is Running the Clinical Trial?

Pharming Technologies B.V.

Lead Sponsor

Trials

23

Recruited

1,400+

Lahey Hospital & Medical Center

Collaborator

Trials

4

Recruited

3,100+

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 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 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]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06897358

NCT06897358 | Leniolisib for Immune Dysregulation in CVID

In this study, common variable immunodeficiency (CVID) patients will all receive the study drug, leniolisib, for a treatment period of 6 months.

2.

pmc.ncbi.nlm.nih.gov

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

Comparative efficacy of leniolisib (CDZ173) versus ...

Significant reductions in the annual rate of respiratory tract infections and serum IgM levels were observed in leniolisib-treated individuals versus standard ...

3.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S1081120624012109

m253 redefining cvid: the role of genetic insights in ...

Clinical trials (PMID: 36399712) have shown that Leniolisib therapy often normalizes immune cell subsets over time. We anticipate similar improvements in our ...

4.

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 ...

5.

clinicaltrialvanguard.com

clinicaltrialvanguard.com/news/pharming-group-announces-first-patient-dosed-in-phase-ii-trial-for-cvid/

Pharming Group Announces First Patient Dosed in Phase II ...

Pharming Group NV has initiated a Phase II clinical trial for leniolisib, targeting common variable immunodeficiency (CVID) patients with immune dysregulation.

6.

sciencedirect.com

sciencedirect.com/science/article/pii/S2473952924002271

Long-term treatment with selective PI3Kδ inhibitor leniolisib ...

The OLE's primary end point is safety, including adverse events (AEs), laboratory parameters, and physical examinations. Safety measurements ...

7.

firstwordpharma.com

firstwordpharma.com/story/5943437

Pharming Group announces first patient dosed in Phase II ...

... leniolisib for common variable immunodeficiency (CVID) with immune dysregulation ... data has supported the safety and tolerability of long ...

8.

withpower.com

withpower.com/trial/leniolisib-for-common-variable-immunodeficiency-606e1

Leniolisib for Common Variable Immunodeficiency

Prior Safety DataThis treatment has passed at least one previous human trial ... The primary goal is to assess the safety and tolerability of leniolisib ...