ST-503 gene therapy for refractory small fiber neuropathy pain

A Multicenter Phase 1 / 2 Double-blind, Randomized, Sham-controlled Dose Escalation Study to Determine Safety and Tolerability of Single Dose Intrathecal ST-503 Gene Therapy for Refractory Pain Due to Peripheral Neuropathy (Small Fiber Predominant, SFN)

This trial will test whether a single dose of ST-503 gene therapy can reduce long-standing nerve pain in people with small fiber neuropathy.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 27 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sangamo Therapeutics (Industry-sponsored)
• Locations: 11 sites (Scottsdale, Arizona and 10 other locations)
• Trial ID: NCT06980948 on ClinicalTrials.gov

What this trial studies

This first-in-human, phase 1/2 interventional study gives an AAV9-delivered gene (ST-503) designed to repress Nav1.7-related pain signals to people with small fiber neuropathy and refractory neuropathic pain. The primary aim is to measure safety and tolerability, with a secondary aim of seeing if pain levels decrease compared with a sham (no treatment) group. Participants must meet ACTTION diagnostic criteria for SFN, have pain refractory to at least two of three first-line medication classes for ≥6 months, and be negative for anti-AAV9 antibodies. The study is conducted at three US centers and includes follow-up visits to monitor adverse events and pain outcomes.

Who should consider this trial

Good fit: Adults with a clinical diagnosis of small fiber neuropathy who have had refractory neuropathic pain for at least six months despite trials of two of three first-line therapies and who are negative for anti-AAV9 antibodies.

Not a fit: Patients who have non-small-fiber or non-neuropathic pain, are positive for anti-AAV9 antibodies, have recent substance abuse or unstable opioid use, or do not meet the refractory-treatment criteria are unlikely to benefit from this study.

Why it matters

Potential benefit: If successful, ST-503 could provide sustained reduction in neuropathic pain by silencing Nav1.7 signals, potentially giving relief to patients who have not responded to standard medications.

How similar studies have performed: This is a novel, first-in-human AAV9 gene therapy approach targeting Nav1.7; Nav1.7 blockade has shown promise in preclinical and early-phase research, but AAV-mediated gene repression in humans is untested.

Eligibility criteria

Inclusion Criteria

1. Diagnostic characterization of Small Fiber Neuropathy (SFN) according to the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities and Networks (ACTTION) criteria.
2. Medical record documentation that pain is refractory to 2 of 3 categories of first line medical therapy for at ≥ 6 months prior to screening.
3. Serum sample negative for pre-existing anti-AAV9 antibodies determined by assay detection limit

Exclusion Criteria

1. Drug- and alcohol-related:

   1. Persons using opioid analgesics for under 3 months or persons who are not on a stable dose of opioids; if on a stable dose, the dose may decrease over the course of the study but should not be increased.
   2. History of known alcohol abuse, opioid analgesic abuse, or illicit drug abuse within 2 years of Screening.
   3. Positive urine test for drugs of abuse (including opiates, benzodiazepines, amphetamines, cocaine, barbiturates, and phencyclidine) without prescription and investigator approval, at Screening and Day -1.
   4. Use of cannabinoids is not permitted.
2. Persons with Fabry's disease, with erythromelalgia, with peripheral neuropathies due to alcohol or drug toxicity, or with diagnosed channelopathies
3. Procedure-related:

   1. Contraindications to LP, general anesthesia or sedation
   2. Any medical disorders that, in the opinion of the Investigator, could interfere with LP including but not limited to evidence for a pressure gradient between supratentorial and infratentorial compartments, Arnold-Chiari malformation, bleeding diathesis, clinically significant coagulopathy, thrombocytopenia, increased intracranial pressure, or spine disease or past surgical procedures involving the spine
4. Infectious disease-related:

   1. Active viral infection or bacterial
   2. A severe infection (e.g., pneumonia, septicemia, central nervous system infections \[e.g., meningitis, encephalitis\]) within 12 weeks prior to Screening
5. Hepatic disease- and hepatotoxic medication-related:

   1. Presence of clinically relevant liver disease
   2. Hepatic dysfunction as indicated by one or more of the following: i. Albumin ≤ 3.5 g/dL ii. Total bilirubin \> 1.5 x ULN and direct bilirubin ≥0.5 mg/dL iii. Alkaline phosphatase (ALP) \> 2 x ULN iv. Alanine transaminase (ALT) or aspartate transaminase (AST) \> 1.5 x ULN
   3. Hepatotoxic medications should be avoided during the study period including acetaminophen exceeding 4 gm/day unless essential to patient's treatment, approved by investigator, and hepatic dysfunction is not identified
   4. Hepatotoxic supplement use during the study period
6. Cancer-related:

   a. History of cancer, including B-cell cancers, within 5 years of Screening

   i. Exceptions to this exclusion are fully excised non-melanoma skin cancers, non-metastatic prostate cancer, and fully treated ductal carcinoma in situ of the breast, provided subject has been stable for at least 6 months

   b. Previous autologous or allogeneic bone marrow transplant, peripheral stem cell transplant or solid organ transplantation
7. Previously received gene or cellular therapy

Where this trial is running

Scottsdale, Arizona and 10 other locations

• HonorHealth — Scottsdale, Arizona, United States (Recruiting)
• University of Arkansas for Medical Sciences — Little Rock, Arkansas, United States (Recruiting)
• The University of California, San Diego — La Jolla, California, United States (Not_yet_recruiting)
• Johns Hopkins University — Baltimore, Maryland, United States (Not_yet_recruiting)
• Massachusetts General Hospital — Boston, Massachusetts, United States (Recruiting)
• Dartmouth Hitchcock Medical Center — Lebanon, New Hampshire, United States (Not_yet_recruiting)
• Columbia University Irving Medical Center (CUIMC) and New York-Presbyterian Hospital (NYPH) — New York, New York, United States (Recruiting)
• University of North Carolina Medical Center — Chapel Hill, North Carolina, United States (Not_yet_recruiting)
• Vanderbilt University — Nashville, Tennessee, United States (Not_yet_recruiting)
• University of Utah — Salt Lake City, Utah, United States (Not_yet_recruiting)
• Virginia Commonwealth University — Richmond, Virginia, United States (Recruiting)

Study contacts

• Study coordinator: Patient Advocacy

Conditions Chronic Neuropathic Pain; Small Fiber Neuropathy