SFSN small nerve fiber neuropathy
Conditions
Interventions
Sponsors
Vertex Pharmaceuticals
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Subject will sign and date an informed consent form (ICF) 2. Willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures 3. Subjects (male and female) will be between the ages of 18 and 80 years, inclusive. 4. Body mass index (BMI) of >18.0 kg/m2 5. Diagnosis of small fiber neuropathy, as per European Federation Neurological Societies (EFNS)/American Academy of Neurology (AAN) guidelines, with pain for at least 3 months prior to screening 6. Reduction below the 5th percentile of sex and age-adjusted normal values in epidermal nerve fiber density on punch skin biopsy at the distal site of the leg performed at or within 6 months of screening 7. presence of sural response 8. Average NRS score between *4 and *9 reported in the daily diary on Days -7 through -1
Exclusion criteria
Exclusion criteria: 1. History in the past 10 years of malignancy except for squamous cell skin cancer, basal cell skin cancer, and Stage 0 cervical carcinoma in situ (all 3 with no recurrence for the last 5 years) 2. Exposure to neurtoxic drugs (i.e., chemotherapy) since diagnosis of small fiber neuropathy. Untreated or uncontrolled connective tissue disorders, sarcoidosis, Sjögren*s syndrome, amyloidosis, Fabry*s disease, celiac disease, Lyme disease, autoimmune disorders (i.e., as assessed by anti-nuclear antibodies, rheumatoid factor, sedimentation rate, and/or lupus anti-coagulant) including myasthenia gravis and Guillain-Barre syndrome, which in the opinion of the investigator makes the subject unsuitable for inclusion in this study. 3. A known or clinically suspected infection with human immunodeficiency virus or hepatitis B or C viruses 4. Current clinically significant liver or kidney dysfunction 5. Current uncontrolled thyroid dysfunction 6. Subjects with a diagnosis of diabetes who have any 1 of the following criteria: - HbA1C >11% at screening - are not stabilized on oral hypoglycemics and/or subcutaneous insulin or diet, in the opinion of the investigator -evidence of ulcers or severe nephropathy resulting from their diabetes -advanced retinopathy, defined as greater than State 3 (moderate non-proliferative diabetic retinopathy) - history of a clinical atherosclerotic event, such as myocardial infarction or stroke 7. History of cardiac dysrhythmias requiring anti-arrhythmia treatment(s); or history or evidence of abnormal ECGs that in the opinion of the investigator or medical monitor would preclude the subject's participation in the study 8. Standard 12-lead ECG demonstrating QTc >450 msec at screening. If QTc exceeds 450 msec, the ECG will be repeated 2 more times, and the average of the 3 QTc values will be used to determine the subject*s eligibility. 9. Concomitant severe pain conditions (i.e., low back pain, radiculopathy, severe bone and musculoskeletal disorders) which may impair self-assessment of pain due to small fiber neuropathy 10. Abnormal laboratory results indicative of any significant medical disease that, in the opinion of the investigator, would preclude the subject's participation in the study 11. Other serious, acute, or chronic medical or psychiatric illness that, in the judgment of the investigator, could compromise subject safety, limit the subject*s ability to complete the study and/or compromise the objectives of the study 12. Female subjects who are pregnant, nursing, or planning to become pregnant during the study or within 90 days after the last study drug dose 13. Male subjects with a female partner who is pregnant, nursing, or planning to become pregnant during the study or within 90 days after the last study drug dose 14. Use of restricted medication or food within the specified duration before the first dose of study drug 15. Alcohol, analgesic/opioid, and/or illicit drug abuse as defined by the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, in the last 12 months before screening, or a positive test for drugs of abuse at screening * A positive drug screen for a known concomitant medication that is not otherwise exclusionary (e.g., benzodiazepines) will not disqualify subjects; however, marijuana and marijuana derivatives will not be allowed 16. Subject, or close r
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline in the weekly average of daily pain intensity on the 11-point numeric rating scale (NRS), as reported in the daily diary, at Week 6 | — |
Secondary
| Measure | Time frame |
|---|---|
| * Proportion of subjects with *30% reduction in the weekly average of daily pain intensity on the 11-point NRS, as reported in the daily diary, at Week 6 * Proportion of subjects with *50% reduction in the weekly average of daily pain intensity on the 11-point NRS, as reported in the daily diary, at Week 6 * Change from baseline in the Daily Sleep Interference Scale (DSIS) at Week 6 * Proportion of subjects categorized as improved at Week 6 on the patient global impression of change (PGIC) assessment * Change from baseline in pain intensity on the 11-point NRS, as reported at study visits, at Week 6 * Plasma PK parameters of VRT-1207355 and the metabolite VRT-1268114 * Safety and tolerability based on the Columbia Suicide Severity Rating Scale (C- SSRS), incidence and type of adverse events (AEs), changes from baseline in clinically significant laboratory test results, vital signs, and ECGs at each visit | — |
Countries
Canada, Germany, Italy, Netherlands, United States of America
Outcome results
None listed