Leniolisib for Immune Dysregulation in CVID

Running, not enrolling · Phase 2

Conditions studied: Common Variable Immunodeficiency (CVID)

In brief

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.

Key facts

Study ID

NCT06897358

Run by

Pharming Technologies B.V.

People needed

20

Starts

2025-02-12

Expected to finish

2026-10-01

Last updated by the study team

2026-02-12

Who can join

Age: 12 and older, up to 75. Sex: any. Healthy volunteers: not accepted.

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
• Clinical diagnosis of CVID enteropathy or other GI tract diagnosis attributable to CVID by the Investigator which involves the small intestine and meets the following enteropathy criteria:
• i. Clinical symptoms of GI disease including at least 1 of: abdominal pain or diarrhea at least 3 days of the week for at least 4 weeks or longer, or dependence on supplemental enteral or parenteral nutrition ii. Lacks a clinical diagnosis of Celiac Disease, and negative human leukocyte antigen (HLA)-DQ2 and -DQ8 testing at screening iii. Presence of small bowel villous shortening/atrophy/blunting with or without intraepithelial lymphocytosis noted in a pathology report pertaining to a small bowel biopsy performed within 5 years of enrollment iv. Negative stool PCR Gastrointestinal Profile at screening
• At screening, vital signs. Ranges:
• Systolic blood pressure 80-159 mm Hg Diastolic blood pressure 50-109 mm Hg Pulse rate 50-110 beats per minute (bpm) Oxygen saturation 93-100%
• Subjects or their legal representatives (for subjects under the age of 18 years) must be able to communicate with the Investigator and understand and comply with the requirements of the study, including an ability to provide written informed consent.

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 .
• Enteral budesonide is allowed during study if the subject has been receiving a stable dosing regimen for more than 3 months.
• Subject is receiving concurrent treatment with another investigational therapy or use of another investigational therapy less than 4 weeks or 5 half-lives (whichever is longer).
• HIstory of hypersensitivity to the study drug or to drugs of similar chemical classes.
• Current use of medication known to be a strong inhibitor, or moderate or strong inducer, of isoenzyme cytochrome P450 CYP3A.
• Current use of medications that, to a larger extent, are BCRP, OATP1B1, and/or OATP1B3 substrates.
• History of HIV or positive test result at screening.
• Any surgical or medical condition which may jeopardize the subject in case of participation in the study.
• Chronic need for supplemental oxygen or invasive or non-invasive respiratory support.
• Liver failure or clinically significant liver disease or dysfunction as indicated by alanine transaminase (ALT) or aspartate transaminase (AST) greater than 2.5 times the upper limit of normal, bilirubin greater than 1.5 times the upper limit of normal, international normalized ratio (INR) greater than 1.5 in the absence of anticoagulation, or presence of diuretic refractory ascites.
• Elevation of ALT or AST up to 6 times the upper limit of normal is allowed if elevation is determined to be a consequence of immune dysregulation by the site Principal Investigator and if the elevation has been stable for 3 months prior to enrollment.

Where it is running

• Children's Hospital Colorado — Aurora, Colorado, United States
• National Institute of Health — Bethesda, Maryland, United States
• Lahey Hospital & Medical Center — Burlington, Massachusetts, United States
• Mount Sinai Hospital — New York, New York, United States
• Texas Children's Hospital — Houston, Texas, United States
• IIS La Fe — Valencia, Spain
• Leeds Teaching Hospital NHS Trust — Leeds, United Kingdom

Full record on ClinicalTrials.gov

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