E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pain Caused by Small Fiber Neuropathy |
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E.1.1.1 | Medical condition in easily understood language |
Severe pain attacks that typically begin in the feet or hands |
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E.1.1.2 | Therapeutic area | Body processes [G] - Bones and nerves physological processes [G11] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10033371 |
E.1.2 | Term | Pain |
E.1.2 | System Organ Class | 10018065 - General disorders and administration site conditions |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10073937 |
E.1.2 | Term | Small fiber neuropathy |
E.1.2 | System Organ Class | 100000004852 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of VX-150 for the treatment of pain caused by small fiber neuropathy |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the safety and tolerability of VX-150
• To evaluate the PK of VRT-1207355 and the metabolite VRT-1268114 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 to 38.0 kg/m2, inclusive, and a total body weight >50 kg
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 screening
7. Presence of sural nerve responses
8. Average NRS score between ≥4 and ≤9 reported in the daily diary on Days -7 through -1 |
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E.4 | Principal 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. History of 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, or exposure to neurotoxic drugs (i.e., chemotherapy) since diagnosis of small fiber neuropathy
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. A diagnosis of diabetes with HbA1C ≥8% at screening
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 relative of the subject, is the investigator or a subinvestigator, research assistant, pharmacist, study coordinator, or other staff directly involved with the conduct of the study at that site |
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E.5 End points |
E.5.1 | Primary end point(s) |
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 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• 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 AEs, changes from baseline in clinically significant laboratory test results, vital signs, and ECGs at each visit |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• At week 6
• Plasma PK parameters at day 7, week 3, week 6 and early termination visit
• Safety and tolerability at each visit |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Germany |
Italy |
Netherlands |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |