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 research is being done to study a possible treatment for refractory pain due to small fiber neuropathy (SFN).

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.

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 SFN disease. The gene will be delivered into your cells using a special delivery tool called a vector.

Sex: ALL
Minimum Age: 18 Years
Healthy Volunteers: No
Age Groups: ADULT, OLDER_ADULT

Inclusion Criteria

1. Signed and dated informed consent document indicating that the subject (or a legal representative) has been informed of all pertinent aspects of the study.
2. ≥ 18 years of age.
3. Diagnostic characterization of peripheral neuropathy (small fiber predominant) according to the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities and Networks (ACTTION) criteria.

a. Minimal large fiber polyneuropathy by clinical examination and by nerve conduction studies (NCS) during screening. NCS results may be based on unilateral assessment. However, bilateral SNAP responses must be within normal range for age and gender in the ulnar, radial, and sural nerves to enhance sensitivity of monitoring for DRG ganglionopathy post ST-503 dosing or sham procedure treatment. Only persons with normal SNAP responses may be enrolled.
4. An IENFD punch skin biopsy demonstrating reduction below the 5th percentile of sex and age-adjusted normal values must be performed and sent for IENFD evaluation at the Cutaneous Nerve Lab at University of Utah.
5. Medical record documentation that pain is refractory to 2 of 3 categories of first line medical therapy for at ≥ 6 months prior to screening.

a. “Refractory to first line medical therapy” is defined as failure to have an average weekly pain score 450 msec

i. If QTcF exceeds 450 msec, the ECG should be repeated two more times and the average of the three QTcF values should be used to determine the subject’s eligibility. The ECG can be repeated after the subject is supine for 10 minutes. A third ECG can be obtained after an additional 10 minutes while remaining supine.

d. Presence of uncontrolled hypertension
10. 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. ALP > 2 x ULN iv. ALT or 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
11. Hematologic-related:

1. Personal or family history of coagulopathy
2. Presence of condition or treatment associated with increased bleeding risk associated with LP
3. Hematocrit < 35% (assigned male at birth) or < 32% (assigned female at birth)
4. Absolute neutrophil count < 2000 cells/µL
5. International normalized rate (INR) above normal range for lab at study site
6. Platelet count below laboratory lower limits of normal (LLN)
12. Renal-related:

a. History of chronic renal disease or creatinine ≥ 1.5 mg/dL
13. 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
14. Allergy- and immunology-related:

1. History of severe allergic or anaphylactic reactions
2. History of hypersensitivity to any inactive ingredient of the IP or to corticosteroids
3. Chronic autoimmune disease that is being treated with immunosuppressants, including but not limited to corticosteroids
4. Previous autologous or allogeneic bone marrow transplant, peripheral stem cell transplant or solid organ transplantation
15. Previously received gene or cellular therapy
16. Participation in other interventional studies during the period of current study participation
17. Planned surgery within three months prior to consent or during the study
18. Any active legal action related to pain disorder
19. Any other reason that, in the opinion of the Site Investigator or the Study Medical Monitor, would render the subject unsuitable for participation in the study. A suicide risk of imminent risk of self-harm according to the C-SSRS is an exclusion criterion for the clinical study.