Chronic Neuropathic Pain
Conditions
Keywords
Small Fiber Neuropathy
Brief summary
This research is being done to study a possible treatment for refractory pain due to small fiber neuropathy (SFN). 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 (SFN).
Detailed description
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 it 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.
Interventions
GENETICST-503
Genomic Medicine
PROCEDURESham (No Treatment)
Sham Procedure
Sponsors
Sangamo Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
double-blind, randomized, sham-controlled dose escalation study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of treatment emergent adverse events (TEAEs) | 12 weeks | To assess safety and tolerability of ST-503 over a 12-week post-dosing observation period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of subjects with pain intensity reduction from baseline at Week 12 | 12 weeks | * 30% in the weekly average of daily pain intensity measurements performed using the PI-NRS * 50% in the weekly average of daily pain intensity measurements performed using the PI-NRS * Dose of rescue medication use * Frequency of rescue medication use |
| Percentage of subjects at Week 12 | 12 weeks | * Categorized as improved on the patient global impression of change (PGIC) assessment * With a ≥ 1-point improvement in suicidal ideation in Columbia Suicide Severity Rating Scale (C-SSRS) responses |
| Columbia Suicide Severity Rating Scale (CSSRS) Rating | 12 weeks | With a ≥ 1-point decline in suicidal ideation in Columbia Suicide Severity Rating Scale (CSSRS) responses |
| Overall Pain Intensity Numerical Rating Scale (PI-NRS) score | 12 Weeks | Participants will rate their pain intensity using an 11-point Numerical Rating Scale (0=no pain and 10=worst possible pain) and record their score in an electronic diary. |
| Short Form McGill Pain Questionnaire-2 (SF-MQ-2) | 12 Weeks | This pain scale was developed to evaluate chronic neuropathic and non-neuropathic pain in adults. It consists of 22 descriptors of pain in 4 parts (continuous, intermittent, neuropathic, and affective pain types) to be rated from 0-10 with 0 indicating no pain and 10 the worst pain ever during the past week. |
| Daily Sleep Interference Score (DSIS) | 12 Weeks | DSIS is assessed on an 11-point NRS, which ranges from 0 (none) to 10 (severe). |
| Hospital Anxiety and Depression Scale (HADS) | 12 Weeks | HADS is a screening tool for anxiety and depression in non-psychiatric clinical populations consisting of 14 items (seven each for anxiety and depression). Higher scores correlate with worse symptoms. |
| Rasch-Transformed 13-item SFN Symptoms Inventory Questionnaire | 12 Weeks | The 13-item SFN-SIQ evaluates changes in physiological functions such as sweating patterns and incontinence using a four-point Likert scale (0 = never present, 1 = sometimes, 2 = often, and 3 = always present) to get a sum of the grading scores attributed to each of the 13 items with a 0 to 39 range. Higher scores correlate with worse symptoms. |
| SFN-specific Rasch-built Overall Disability Scale (SFN-RODS) | 12 Weeks | The 32-item SFN-RODS is a disease-specific interval measure suitable to detect activity limitations and participation restrictions in patients with SFN. The scale ranges from 0 to 64 with higher numbers indicating worse disability. |
| 36-Item Short Form Health Survey (SF-36) domains and summary scores | 12 Weeks | This measures quality of life measures such as physical functioning, emotional well-being, energy levels, and social functioning. The range is from 0-100 with higher scores being associated with a better perceived quality of life. |
| Pain Catastrophizing Questionnaire (PCS) | 12 Weeks | PCS has 13 questions related to rumination, magnification and helplessness with values ranging 0 to 4 for a total possible score of 52. The higher the score the more pain catastrophizing is present. |
Countries
United States
Contacts
CONTACTPatient Advocacy
STUDY_DIRECTORMedical Monitor
Sangamo Therapeutics Inc.
Outcome results
None listed