Leniolisib for Immune Dysregulation in PIDs

NCT06549114 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: LE 7201
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This study is an exploratory, non-randomized, open-label, within-patient dose escalation study. The primary objective is to assess safety and tolerability of leniolisib. Secondary objectives include assessments of PK/PD, and to explore clinical efficacy measures with administration of three different dose levels of leniolisib.

Conditions

Primary Immunodeficiency Disorders (PIDs)

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Treatment-emergent adverse events (TEAEs), Serious Adverse Events (SAEs) , and Adverse Events (AEs)

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

  From Baseline to the end of 20 weeks of Treatment

Secondary Outcomes (26)

• To assess the PK of leniolisib in PID disorders linked to PI3K

  From Baseline to the end of 20 weeks of Treatment

• To assess the PK of leniolisib in PID disorders linked to PI3K

  From Baseline to the end of 20 weeks of Treatment

• To assess the PK of leniolisib in PID disorders linked to PI3K

  From Baseline to the end of 20 weeks of Treatment

• To assess the PK of leniolisib in PID disorders linked to PI3K

  From Baseline to the end of 20 weeks of Treatment

• To assess the impact of leniolisib on lymphocyte PI3K/AKT/mTOR pathway activity in PID disorders linked to PI3K

  From Baseline to the end of 20 weeks of Treatment

Study Arms (1)

Leniolisib

EXPERIMENTAL

All subjects participating will receive Leniolisib film-coated tablets (FCTs) at a starting dose of 10 mg BID for 4 weeks, followed by 30 mg BID for 4 weeks, and then 70 mg BID for 12 weeks.

Drug: Leniolisib

Interventions

Leniolisib DRUG

The doses selected will range from 10 to 70 mg twice daily (BID) (resulting in total daily doses ranging from 20 to 140 mg per day).

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:

• Subjects 12 to 75 years of age.
• Diagnosed with a PID due to disease-causing pathogenic or likely pathogenic variant(s) in the following genes: SOCS1, PTEN, CTLA4, NFKB1 (only those variants leading to NFKB pathway activation), or FAS (germline or somatic), or diagnosed with RAS associated leukoproliferative disorder (and not juvenile myelomonocytic leukemia \[JMML\]) due to somatic variants in NRAS or KRAS.
• Subjects must have 1 or more of the following:
• One or more blood cytopenias related to the underlying PID defined as hemoglobin \<10 g/dL, platelet count \<100,000/µL, or neutrophil count \<1000/µL
• Splenomegaly evident by CT imaging with craniocaudal spleen measurement \>10 cm
• Lymphadenopathy evident by CT imaging with at least 1 measurable index lymph node (long axis \>1.5 cm) as per Cheson methodology
• GLILD or other PID-related ILD with quantifiable CT chest imaging findings evident on baseline CT scan
• At screening, vital signs.
• Systolic blood pressure 80-139 mm Hg
• Diastolic blood pressure 50-89 mm Hg
• Pulse rate 50-110 bpm
• Oxygen saturation 93-100%
• Subjects or their legal representatives (for subjects under the age of 18 years) must be able to provide written informed consent.

You may not qualify if:

• Subject has had a successful hematopoietic stem-cell transplant (HSCT).
• Previous or concurrent use of immunosuppressive medication, such as:
• Use of an mTOR inhibitor or a PI3Kδ inhibitor within 3 weeks prior to first dosing .
• Rituximab or other B-cell depleting antibodies, belimumab, cyclophosphamide, or alemtuzumab within 6 months prior to first dosing.
• Cyclosporine A, mycophenolate mofetil, 6-mercaptopurine, azathioprine, methotrexate, tacrolimus, ruxolitinib, or other JAK inhibitors within 3 weeks prior to first dosing.
• Corticosteroids above 25 mg prednisone or equivalent per day within 2 weeks prior to first dosing.
• 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 prior to first dosing.
• 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) prior to first dosing.
• 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 P450 CYP3A.
• Current use of medications that act as BCRP, OATP1B1, and OATP1B3 substrates.
• Subject has a history or current electrocardiogram (ECG) abnormalities indicating a significant risk of safety for subjects participating in the study
• History of acquired immunodeficiency diseases, including a positive HIV test result at screening.
• Uncontrolled chronic or recurrent infectious disease (except those considered to be characteristic of a PID) or evidence of tuberculosis infection

Sponsors & Collaborators

• Pharming Technologies B.V.: lead

Study Sites (1)

National Institute of Health

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• Hassan C, Ponstein Y, Hanssen R, Thorneloe KS, Marsh RA, Rao VK. Leniolisib reduced lymphoproliferative disease in murine autoimmune lymphoproliferative syndrome. J Hum Immun. 2025 Nov 17;2(1):e20250125. doi: 10.70962/jhi.20250125. eCollection 2026 Jan 5.

  PMID: 41608120 DERIVED

MeSH Terms

Conditions

Primary Immunodeficiency Diseases

Interventions

leniolisib

Condition Hierarchy (Ancestors)

Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Gulbu Uzel, M.D.

  National Institutes of Health (NIH)

  PRINCIPAL INVESTIGATOR

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: July 17, 2024
• First Posted: August 12, 2024
• Study Start: October 21, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: February 13, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)