A Study to Evaluate the Efficacy and Safety of VX-150 in Treating Subjects With Pain Caused by Small Fiber Neuropathy

• VX-150 (Drug): Participants received VX-150 1250 milligrams (mg) once daily (qd) orally for 6 weeks.
• Placebo (Drug): Participants received placebo matched to VX-150 for 6 weeks.

Primary outcomes

• Change in Weekly Average of Daily Pain Intensity on the 11 Point NRS [From Baseline at Week 6]: Pain intensity was evaluated using the 11-point NRS (where 0 signified no pain and 10 signified worst imaginable pain) during the last 24 hours on the NRS each evening. Higher score indicates greater level of pain.

Secondary outcomes

• Percentage of Participants With Greater Than or Equal to (>=) 30 Percent (%) Reduction in the Weekly Average of Daily Pain Intensity on the 11-Point NRS [From Baseline at Week 6]: Pain intensity was evaluated using the 11-point NRS (where 0 signified no pain and 10 signified worst imaginable pain) during the last 24 hours on the NRS each evening. Higher score indicates greater level of pain. Percentage of participants >= 30% reduction in the weekly average of daily pain intensity on the 11-Point NRS were reported.
• Percentage of Participants With >=50% Reduction in the Weekly Average of Daily Pain Intensity on the 11-Point NRS [From Baseline at Week 6]: Pain intensity was evaluated using the 11-point NRS (where 0 signified no pain and 10 signified worst imaginable pain) during the last 24 hours on the NRS each evening. Higher score indicates greater level of pain. Percentage of participants >= 50% reduction in the weekly average of daily pain intensity on the 11-Point NRS were reported.
• Change in the Daily Sleep Interference Scale (DSIS) [From Baseline at Week 6]: Pain-associated sleep interference was assessed using DSIS, based on an 11-point scale (where 0 signified none: pain does not interfere with sleep and 10 signified severe: pain completely interferes with sleep, unable to sleep). Higher score indicates greater pain associated sleep interference.
• Percentage of Participants Categorized as Improved on the Patient Global Impression of Change (PGIC) Scale [At Week 6]: PGIC scale evaluated the change in activity limitations, symptoms, emotions, and overall quality of life (QoL) related to the participants painful condition on 7-point scale from 1 (improved) to 7 (worse). Participants were categorized as following: scale from 1 - 2 were categorized as "improved", scale from 3 - 4 as "no change" and scale from 5 - 7 were categorized as "worse". Percentage of participants categorized as improved on PGIC scale at week 6 were reported for this outcome measure.
• Change in Pain Intensity on the 11-Point NRS [From Baseline at Week 6]: Pain intensity was evaluated using the 11-point NRS (where 0 signified no pain and 10 signified worst imaginable pain) during the last 24 hours on the NRS each evening. Higher score indicates greater level of pain. Higher score indicates greater level of pain.
• Pre-dose Plasma Concentration (Ctrough) of VRT-1207355 and the Metabolite VRT-1268114 [Pre-dose at Day 7]
• Number of Participants With Clinically Meaningful Findings in Columbia Suicide Severity Rating Scale (C-SSRS) Responses [Day 1 up to Week 10]: The C-SSRS is an interview-based rating scale was evaluated through a series of questions about suicidal thoughts and behaviors with the possible answers yes or no. Yes represents a worse outcome. Clinically Meaningfulness of C-SSRS responses were judged by investigator based on answers received from participants.
• Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [Day 1 up to Week 10]

Sex: All, ages: 18 Years to 80 Years

Inclusion Criteria:

* Body mass index (BMI) of 18.0 to 31.0 kg/m2, inclusive, and a total body weight >50 kg
* 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
* 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
* Normal nerve conduction studies (NCS), including presence of sural response.
* Average NRS score between ≥4 and ≤9 reported in the daily diary on Days -7 through -1

Exclusion Criteria:

* 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
* History of connective tissue disorders, sarcoidosis, Sjögren's syndrome, amyloidosis, Fabry's disease, celiac disease, lyme disease, autoimmune disorders
* A known or clinically suspected infection with human immunodeficiency virus or hepatitis B or C viruses
* Current clinically significant liver or kidney dysfunction
* Current uncontrolled thyroid dysfunction
* A diagnosis of diabetes, HbA1C ≥8% at screening
* History of cardiac dysrhythmias requiring anti-arrhythmia treatment(s)
* Concomitant severe pain conditions which may impair self-assessment of pain due to small fiber neuropathy

Other protocol defined Inclusion/Exclusion criteria may apply.

Participant flow

Outcome results

• Change in Weekly Average of Daily Pain Intensity on the 11 Point NRS (Primary), Least squares mean, units on a scale: VX-150 -2.018 +/- 0.274; Placebo -0.933 +/- 0.287 (p <0.0001)
• Percentage of Participants With Greater Than or Equal to (>=) 30 Percent (%) Reduction in the Weekly Average of Daily Pain Intensity on the 11-Point NRS (Secondary), Number, percentage of participants: VX-150 45.0; Placebo 26.5
• Percentage of Participants With >=50% Reduction in the Weekly Average of Daily Pain Intensity on the 11-Point NRS (Secondary), Number, percentage of participants: VX-150 32.5; Placebo 17.6
• Change in the Daily Sleep Interference Scale (DSIS) (Secondary), Least squares mean, units on a scale: VX-150 -1.777 +/- 0.276; Placebo -0.665 +/- 0.289 (p <0.0001)
• Percentage of Participants Categorized as Improved on the Patient Global Impression of Change (PGIC) Scale (Secondary), Number, percentage of participants: VX-150 39.5; Placebo 13.5
• Change in Pain Intensity on the 11-Point NRS (Secondary), Least squares mean, units on a scale: VX-150 -1.7 +/- 0.3; Placebo -1.1 +/- 0.3 (p <0.0001)
• Pre-dose Plasma Concentration (Ctrough) of VRT-1207355 and the Metabolite VRT-1268114 (Secondary), Mean, microgram per milliliter (mcg/mL): VX-150 3.89 +/- 2.73
• Number of Participants With Clinically Meaningful Findings in Columbia Suicide Severity Rating Scale (C-SSRS) Responses (Secondary), Number, participants: VX-150 0; Placebo 0
• Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) (Secondary), Number, participants: VX-150 29; Placebo 24

Adverse events

Time frame: Day 1 up to Week 10

Serious adverse events by term

Other adverse events by term

• Study Protocol (PDF, 2018-05-25)
• Statistical Analysis Plan (PDF, 2018-11-06)

NIH grants: 2017