Clinical trial NCT06980948: Safety and Tolerability Study of ST-503 for Small Fiber Neuropathy-associated Refractory Pain
Official title: A Multicenter Phase 1 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 Idiopathic Small Fiber Neuropathy (iSFN)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Chronic Neuropathic Pain
Keywords: Small Fiber Neuropathy
Lead sponsor: Sangamo Therapeutics
Sponsor class: INDUSTRY
First posted: 2025-05-20
Enrollment: 27
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: double-blind, randomized, sham-controlled dose escalation study
Primary purpose: TREATMENT

Brief summary: This research is being done to study a possible treatment for refractory pain due to small fiber neuropathy (iSFN).

ST-503 is intended to deliver a modified copy of the gene which will ideally repress Nav1.7 tissue-related pain signals reaching the brain, which should reduce the refractory pain due to small fiber neuropathy (iSFN).

Detailed description: This research is being done to study a possible treatment for refractory pain due to small fiber neuropathy (iSFN).

Small fiber neuropathy happens when something damages small nerve fibers in your skin, causing symptoms like painful tingling or burning sensations in your hands and feet. Pain originating in the nerves outside of the brain and spinal cord is defined by doctors as neuropathic pain. Scientists have discovered that certain proteins in our bodies called sodium channels are important for communicating pain signals in nerves, specifically, Nav1.7, Nav1.8 and Nav1.9. About half of small fiber neuropathy cases happen for no known reason. Doctors may call these cases "idiopathic small fiber neuropathy" or "iSFN".

This first-in-human study will test the use of a type of experimental treatment called "gene therapy." The primary goal is to determine if is safe and well tolerated. The second goal is to determine if it reduces the level of refractory pain due to iSFN disease. The gene will be delivered into your cells using a special delivery tool called a vector.

Eligibility criteria: Inclusion Criteria:

* Diagnostic characterization of idiopathic Small Fiber Neuropathy (iSFN) without impaired or abnormal glucose metabolism performed according to the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities and Networks (ACTTION) criteria.
* Medical record documentation that pain is refractory to 2 of 3 categories of first line medical therapy for at ≥ 6 months prior to screening.
* 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 Lumbar Puncture (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:

   a. Presence of clinically relevant liver disease b. 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 c. 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 d. 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
8. Planned surgery within three months prior to consent or during the study
9. Any active legal action related to pain disorder

Primary outcomes:
measure: Incidence and severity of treatment emergent adverse events (TEAEs)
timeFrame: 52 weeks
Secondary outcomes:
measure: Percentage of subjects with pain intensity reduction from baseline at Weeks 24 and 52
timeFrame: 52 weeks
measure: Percentage of subjects at Weeks 12, 24, and 52
timeFrame: 52 weeks
measure: Columbia Suicide Severity Rating Scale (CSSRS) Rating
timeFrame: 52 weeks
measure: Overall Pain Intensity Numerical Rating Scale (PI-NRS) score
timeFrame: Week 12, Week 24, Week 52
measure: Short Form McGill Pain Questionnaire-2 (SF-MQ-2)
timeFrame: Week 12, Week 24, Week 52
measure: Daily Sleep Interference Score (DSIS)
timeFrame: Week 12, Week 24, Week 52
measure: Hospital Anxiety and Depression Scale (HADS)
timeFrame: Week 12, Week 24, Week 52
measure: Rasch-Transformed 13-item SFN Symptoms Inventory Questionnaire
timeFrame: Week 12, Week 24, Week 52
measure: SFN-specific Rasch-built Overall Disability Scale (SFN-RODS)
timeFrame: Week 12, Week 24, Week 52
measure: 36-Item Short Form Health Survey (SF-36) domains and summary scores
timeFrame: Week 12, Week 24, Week 52
measure: Pain Catastrophizing Questionnaire (PCS)
timeFrame: Week 12, Week 24, Week 52
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: New York City
country: United States
facility: Columbia University
state: New York
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: Sangamo Therapeutics Inc.
name: Medical Monitor
role: STUDY_DIRECTOR
References: