Safety and Tolerability Study of ST-503 for Small Fiber Neuropathy-associated Refractory Pain

Sangamo Therapeutics

Status and phase: Begins enrollment in 1 month; Phase 1

Conditions: Chronic Neuropathic Pain

Treatments: Genetic: ST-503; Procedure: Sham (No Treatment)

Study type: Interventional

Funder types: Industry

Identifiers

NCT06980948

ST-503-101

Details and patient eligibility

About

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).

Full 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.

Enrollment: 27 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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27 participants in 2 patient groups

Sham Controlled Study

Sham Comparator group

Treatment:

Procedure: Sham (No Treatment)

Investigational Agent

Experimental group

Treatment:

Genetic: ST-503