Leniolisib for Immune Dysregulation in CVID

NCT06897358 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: LE 8201
• Study Type: interventional
• Target: 20
• Locations: 3 countries
• Sites: 7

Brief Summary

In this study, common variable immunodeficiency (CVID) patients will all receive the study drug, leniolisib, for a treatment period of 6 months. Participants will start on a lower dose of leniolisib, followed by a mid and then a higher dose level. The primary goal is to assess the safety and tolerability of leniolisib, and secondary goal is to assess the potential for leniolisib to provide benefits for patients.

Conditions

Common Variable Immunodeficiency (CVID)

Outcome Measures

Primary Outcomes (1)

• Safety & Tolerability

  To assess the number of AEs/SAEs and number of participants with AEs/SAEs

  From baseline to the end of 24 weeks of treatment

Secondary Outcomes (17)

• Impact of leniolisib on lymphoproliferation measured as index lesions

  From baseline to the end of 24 weeks of treatment

• Impact of leniolisib on lymphoproliferation measured as non-index lesions

  From baseline to the end of 24 weeks of treatment

• Impact of leniolisib on spleen size

  From baseline to the end of 24 weeks of treatment

• Impact of leniolisib on hemoglobin

  From baseline to the end of 24 weeks of treatment

• Impact of leniolisib on platelets

  From baseline to the end of 24 weeks of treatment

Study Arms (1)

Leniolisib

EXPERIMENTAL

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.

Drug: Leniolisib

Interventions

Leniolisib DRUG

Planned dose will range from 10 mg twice daily to 70 mg twice daily

Also known as: Joenja

Leniolisib

Eligibility Criteria

• Age: 12 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is 12 to 75 years of age (inclusive).
• a. Specifically at sites located in the United Kingdom subjects must be 18 to 75 years of age (inclusive)
• Subject must have a minimum body weight of 45 kg
• Subject has a clinical diagnosis of CVID supported by all of the following (a thru c):
• A low IgG level compared to age-adjusted reference range \[OR if this cannot be documented, subject must have one of the following: i) absent isohemagglutinins and/or poor response to vaccines; or ii) Low class-switched memory B cells less than 2%\]
• Low IgA and/or IgM compared to age-adjusted reference range
• No identified secondary causes of hypogammaglobulinemia
• Inborn Errors of Immunity/ PID Panel testing:
• Lacks an identified pathogenic/likely pathogenic genetic driver for their CVID primary immunodeficiency OR
• Subject has an identified pathogenic/likely pathogenic genetic driver(s) for their CVID limited to the following genes: TNFRSF13B (TACI), TNFRSF13C (BAFFR), CD19, CD20, CD81, CR2 (CD21), LRBA, CTLA4, NFKB1, NFKB2, IKZF1 (excluding variants associated with combined immune deficiency), CARD11 (gain of function), SH3KBP1, SEC61A1 IRF2BP2, CTNNBL1, TWEAK or PTEN.
• Subject has lymphoproliferation, as evidenced by CT imaging: splenomegaly with craniocaudal spleen measurement \>10 cm and/or lymphadenopathy with at least 1 measurable index lymph node (long axis \>1.5 cm) as per Cheson methodology.
• Subject has at least ONE of the following CVID clinical manifestations of immune dysregulation:
• Clinical symptoms related to splenomegaly or lymphadenopathy which interfere with activities of daily living or are associated with chronic pain, dyspnea, functional impairment, or limitations in usual activities
• One or more blood cytopenias related to CVID (and not due to other medical conditions such as iron-deficiency or lead exposure) defined as hemoglobin \<10 g/dL, platelet count \<100,000/µL, and/or neutrophil count \<1,000/µL
• Previous pathologic confirmation of ILD and attributed to CVID by the Investigator with quantifiable CT chest imaging findings evident on baseline CT scan

You may not qualify if:

• Laboratory evidence of significant T cell deficiency including CD4+ T cells \<200/uL.
• Laboratory evidence of significant NK cell deficiency including NK cells \<1% of peripheral blood lymphocytes or less than 50/mcL.
• Clinical history of infections suggestive of clinically significant T cell or NK cell deficiency such as Pneumocystis jirovecii, atypical mycobacteria, severe warts, or unusually severe (as determined by the PI) infections with herpesviruses.
• Presence of uncontrolled chronic/recurrent infectious disease (except those considered to be characteristic of antibody deficiency).
• Positive blood polymerase chain reaction (PCR) for cytomegalovirus.
• Evidence of tuberculosis infection
• Positive blood cryptococcal antigen
• Previous or concurrent use of immunosuppressive medication, such as:
• Use of an mTOR inhibitor or a PI3K inhibitor within 3 weeks.
• Rituximab or other B cell depleting antibodies, belimumab, cyclophosphamide, or alemtuzumab within 6 months.
• Cyclosporine A, mycophenolate mofetil, 6-mercaptopurine, azathioprine, methotrexate, tacrolimus, ruxolitinib, or other Janus kinase (JAK) inhibitors within 3 weeks.
• Glucocorticoids above 25 mg prednisone or equivalent per day within 2 weeks
• Immunosuppressive monoclonal or polyclonal antibody therapeutics such as directed against TNF-alpha, α₄β₇ integrin, IL-6, IL-12/IL-23 and others within 5 half-lives
• Other immunosuppressive agents expected to have a significant impact on immune cell number or function.
• Abatacept is allowed during study if the subject has been receiving a stable dosing regimen for more than 3 months .

Sponsors & Collaborators

• Pharming Technologies B.V.: lead
• Lahey Hospital & Medical Center: collaborator

Study Sites (7)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

National Institute of Health

Bethesda, Maryland, 20892, United States

Location

Lahey Hospital & Medical Center

Burlington, Massachusetts, 01805, United States

Location

Mount Sinai Hospital

New York, New York, 10029, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

IIS La Fe

Valencia, Spain

Location

Leeds Teaching Hospital NHS Trust

Leeds, United Kingdom

Location

MeSH Terms

Conditions

Common Variable Immunodeficiency

Interventions

leniolisib

Condition Hierarchy (Ancestors)

Immunologic Deficiency Syndromes; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2025
• First Posted: March 26, 2025
• Study Start: February 12, 2025
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: February 12, 2026

Record last verified: 2026-02

Locations

ES (1); GB (1); US (5)