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)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 27
- 试验地点
- 21
- 主要终点
- Incidence and severity of treatment emergent adverse events (TEAEs)
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnostic characterization of Small Fiber Neuropathy (SFN) 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
排除标准
- •Drug- and alcohol-related:
- •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.
- •History of known alcohol abuse, opioid analgesic abuse, or illicit drug abuse within 2 years of Screening.
- •Positive urine test for drugs of abuse (including opiates, benzodiazepines, amphetamines, cocaine, barbiturates, and phencyclidine) without prescription and investigator approval, at Screening and Day -
- •Use of cannabinoids is not permitted.
- •Persons with Fabry's disease, with erythromelalgia, with peripheral neuropathies due to alcohol or drug toxicity, or with diagnosed channelopathies
- •Procedure-related:
- •Contraindications to LP, general anesthesia or sedation
- •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
- •Infectious disease-related:
- •Active viral infection or bacterial
- •A severe infection (e.g., pneumonia, septicemia, central nervous system infections [e.g., meningitis, encephalitis]) within 12 weeks prior to Screening
- •Hepatic disease- and hepatotoxic medication-related:
- •Presence of clinically relevant liver disease
- •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
- •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
- •Hepatotoxic supplement use during the study period
- •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
- •Previously received gene or cellular therapy
研究组 & 干预措施
Sham Controlled Study
干预措施: Sham (No Treatment) (Procedure)
Investigational Agent
干预措施: ST-503 (Genetic)
结局指标
主要结局
Incidence and severity of treatment emergent adverse events (TEAEs)
时间窗: 12 weeks
To assess safety and tolerability of ST-503 over a 12-week post-dosing observation period.
次要结局
- Pain Catastrophizing Questionnaire (PCS)(12 Weeks)
- Percentage of subjects with pain intensity reduction from baseline at Week 12(12 weeks)
- Percentage of subjects at Week 12(12 weeks)
- Columbia Suicide Severity Rating Scale (CSSRS) Rating(12 weeks)
- Overall Pain Intensity Numerical Rating Scale (PI-NRS) score(12 Weeks)
- Short Form McGill Pain Questionnaire-2 (SF-MQ-2)(12 Weeks)
- Daily Sleep Interference Score (DSIS)(12 Weeks)
- Hospital Anxiety and Depression Scale (HADS)(12 Weeks)
- Rasch-Transformed 13-item SFN Symptoms Inventory Questionnaire(12 Weeks)
- SFN-specific Rasch-built Overall Disability Scale (SFN-RODS)(12 Weeks)
- 36-Item Short Form Health Survey (SF-36) domains and summary scores(12 Weeks)