Using soquelitinib to treat autoimmune lymphoproliferative syndrome

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

This study is testing if a new drug called soquelitinib can help people with autoimmune lymphoproliferative syndrome feel better and manage their symptoms.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 16 Years to 120 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Drugs / interventions: prednisone, soquelitinib
• Locations: 3 sites (Bethesda, Maryland and 2 other locations)
• Trial ID: NCT06730126 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and effectiveness of soquelitinib, an interleukin-2 inducible T-cell kinase inhibitor, in patients with autoimmune lymphoproliferative syndrome (ALPS) caused by FAS gene mutations. Participants aged 16 and older will take the drug twice daily for up to 360 days, with regular clinic and remote visits to monitor their health and response to treatment. The study is designed in two stages, with an interim analysis to determine if the trial should proceed based on participant responses and safety data.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 16 years and older with a documented diagnosis of ALPS-FAS and evidence of active disease.

Not a fit: Patients with stable disease not requiring treatment or those unable to comply with study requirements may not benefit from this trial.

Why it matters

Potential benefit: If successful, this treatment could significantly improve symptoms and quality of life for patients with ALPS.

How similar studies have performed: While this approach is novel for ALPS, similar studies targeting immune system disorders have shown promising results.

Eligibility criteria

* INCLUSION CRITERIA:

To be eligible to participate in this study, an individual must meet all the following criteria:

1. Aged \>= 16 years.
2. Able to provide informed consent (for ages \>= 18 years) or has a parent(s) or guardian(s) who can provide permission to participate on their behalf (for ages \<18 years).
3. Has a documented diagnosis of ALPS-FAS.
4. Has clinical evidence of active disease, defined as at least one enlarged lymph node and/or enlarged spleen.
5. If currently on corticosteroid therapy, then dose is less than 20 mg/day (prednisone equivalent) and has been stable for at least 4 weeks.
6. For participants to be seen at the NIH CC, co-enrolled on NIH protocol 93-I-0063.
7. Participants who can become pregnant or who can impregnate their partner must agree to either remain sexually abstinent or use two highly effective methods of contraception when engaging in sexual activities that can result in pregnancy, beginning 28 days before baseline until 3 months after the last dose. One method must be a barrier (eg, internal or external condom, cervical cap, or diaphragm). The second method may be any of the following:

7a. Oral contraceptive pill or hormonal patch or ring.

7b. Parenteral hormonal contraceptive implant.

7c. Intrauterine device.

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Profound grade 3 or 4 cytopenias that cannot be improved with immunomodulatory treatments prior to enrolling in the clinical trial and starting the study drug. Per investigator discretion, individuals on a single agent may be included if the dose is stable for 12 weeks at screening and is not expected to confer additive toxicity.
2. Renal impairment, defined as serum creatinine \>1.5 mg/dL (or 133 micromol/L) or estimated glomerular filtration rate \<60 mL/min/1.73 m\^2.
3. Liver impairment, defined as bilirubin, alanine aminotransferase, or aspartate aminotransferase greater than 2.5 times the upper limit of normal.
4. History of EBV-associated lymphoma.
5. Active EBV infection with EBV load \>300 copies/mL.
6. Tuberculosis infection (active or latent) or undergoing tuberculosis treatment.
7. Infection with HIV or hepatitis B or C.
8. Current other invasive or systemic fungal, bacterial, or viral infection requiring therapy.
9. History of opportunistic infection within the previous 180 days.
10. History of invasive malignancy that required systemic therapy within the last 3 years.
11. Current use of moderate or strong cytochrome P450 isozyme (CYP)3A inhibitors or inducers that cannot be stopped before day 0.
12. Current use of P-glycoprotein (P-gp) inhibitors that cannot be stopped before day 0.
13. Known hypersensitivity or contraindication to CT contrast agent.
14. Pregnant or breastfeeding.
15. Any condition that, in the opinion of the study team contraindicates participation in this study.

Where this trial is running

Bethesda, Maryland and 2 other locations

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)
• The Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States (Recruiting)
• Texas Children's Hospital — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: V. Koneti Rao, M.D. — National Institute of Allergy and Infectious Diseases (NIAID)
• Study coordinator: Alanvin D Orpia, R.N.

Conditions Autoimmune Lymphoproliferative Syndrome; Fas; Hypersplenism; Lymphoproliferation; Interleukin-2 Inducible T-cell Kinase; Soquelitinib; Targeted Treatment