NCT06730126

Study of the ITK Inhibitor Soquelitinib to Reduce Lymphoproliferation and Improve Cytopenias in Autoimmune Lymphoproliferative Syndrome (ALPS)-FAS Patients

A Phase 2a Study of the ITK Inhibitor Soquelitinib to Reduce Lymphoproliferation and Improve Cytopenias in Autoimmune Lymphoproliferative Syndrome (ALPS)-FAS Patients

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 15 (estimated)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 16 Years – 120 Years
• Healthy volunteers: Not accepted

Summary

Background: Autoimmune lymphoproliferative syndrome (ALPS) is a rare disorder of the immune system caused by a mutation in the FAS gene. In ALPS, the body stores too many germ-fighting cells called lymphocytes. This can lead to an enlarged spleen and lymph nodes. Current treatments for ALPS can have many adverse effects. Better treatments for ALPS are needed. Objective: To test a study drug (soquelitinib) in people with ALPS. Eligibility: People aged 16 years and older with ALPS. Design: Participants will have 8 clinic visits and 6 remote visits within 1 year. Participants will be screened. They will have a physical exam with blood and urine tests. Some may have tests of their lung function. Soquelitinib is a tablet taken by mouth twice a day. Participants will record their doses and any symptoms on a paper or online form. Blood tests and other procedures will be repeated during study visits. Three visits will include imaging scans. Participants will lie on a table that slides through a doughnut-shaped machine while X-rays capture pictures of the inside of their body. Some participants may be able to remain in the study for a second year.

Detailed description

Study Description: This is a multisite open-label phase 2a study to evaluate the safety, tolerability, and preliminary efficacy of the interleukin (IL)-2 inducible Tcell kinase (ITK) inhibitor soquelitinib for treating ALPS-FAS. This study will be conducted in two stages, though the first stage may be repeated. In the first stage, 8 participants will be enrolled to receive 200 mg of soquelitinib twice daily for up to 360 days, with approximately monthly study visits (in person or remote). A safety and futility interim analysis will be conducted after all 8 participants have had a computed tomography (CT) or positron emission tomography (PET)/CT scan at day 90 and have completed at least 80% of their study drug regimen. If at least one participant has a positive response to the study drug and there are no safety concerns among the 8 participants, then the study will proceed to stage 2, in which 6 new participants will be enrolled and receive the same dosage as stage 1 (200 mg twice daily for 360 days). If no stage 1 participant demonstrates a positive response to study drug but there are no safety concerns, then stage 1 will be repeated at a dosage of 400 mg twice daily for up to 360 days. New participants may be enrolled and/or the previous stage 1 participants may continue following a 90-day study drug washout. The safety and futility interim analysis will be repeated after all 8 participants have had a CT or PET/CT scan at day 90 and have completed at least 80% of their study drug regimen. Again, if there is at least 1 positive response and no safety concerns among these 8 participants, then the study will proceed to stage 2, in which 6 new participants will be enrolled and receive soquelitinib at 400 mg twice daily for up to 360 days. The primary endpoints will be assessed after all 6 participants of stage 2 have had a CT or PET/CT scan at day 90 and have completed at least 80% of their study drug regimen. The trial will automatically be determined a failure if safety concerns or lack of positive response prevent procession to stage 2. Primary Objectives: To determine the efficacy of soquelitinib in reducing spleen volume or target lymph node volume in people with ALPS-FAS. Secondary Objective: 1. To determine the efficacy of soquelitinib in improvement of lymphoproliferation and autoimmune disease, including cytopenias, in people with ALPS-FAS. 2. To determine the safety and tolerability of soquelitinib in people with ALPS-FAS. Primary Endpoints: Reduction of spleen volume or target lymph node volume by 25% from baseline to day 90, assessed by CT or PET/CT scan. Secondary Endpoints: 1. Shrinkage in spleen volume from baseline to day 90. 2. Shrinkage in target lymph node volume from baseline to day 90. 3. Reduction of cytopenias by one severity level from baseline to day 90. 4. Reduction in prednisone dosage. 5. Grade 3 or 4 systemic infections within 360 days. 6. Clinically significant worsening of viral, mycobacterial, or fungal infection requiring new treatment or change of treatment by day 360. 7. Any drug-related grade 3 or 4 adverse event (AE) that triggers a pause.

Conditions

• Autoimmune Lymphoproliferative Syndrome

Interventions

Type	Name	Description
DRUG	Soquelitinib	Soquelitinib is an ITK inhibitor in clinical development for treating relapsed/refractory T-cell lymphoma.

Timeline

• Start date: 2025-03-10
• Primary completion: 2026-12-01
• Completion: 2026-12-01
• First posted: 2024-12-12
• Last updated: 2026-04-16

Locations

3 sites across 1 country: United States

Regulatory

• FDA-regulated drug study