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CompletedNCT03304522Updated Nov 15, 2021Results posted

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

A Phase 2 interventional study of VX-150 and Placebo in Small Fiber Neuropathy, sponsored by Vertex Pharmaceuticals Incorporated. Completed at 34 sites in 4 countries. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2021-11-15.

Sponsored by Vertex Pharmaceuticals Incorporated · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
89
Allocation
Randomized
Ages
18 Years to 80 Years
Sex
All
01

Study summary

This is a Phase 2, randomized, double-blind, placebo-controlled, parallel-group, multicenter study evaluating the efficacy of VX-150 for the treatment of pain caused by small fiber neuropathy.

02

Conditions studied

  • Small Fiber Neuropathy

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03

Who can participate

Ages eligible
18 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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.

04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
89 participants (actual)

Study arms

  • Experimental
    VX-150

    Drug: VX-150

  • Placebo comparator
    Placebo

    Drug: Placebo

Interventions

  • DrugVX-150

    Participants received VX-150 1250 milligrams (mg) once daily (qd) orally for 6 weeks.

  • DrugPlacebo

    Participants received placebo matched to VX-150 for 6 weeks.

05

What researchers measure

Primary outcomes

  1. Change in Weekly Average of Daily Pain Intensity on the 11 Point NRS

    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.

    Time frame: From Baseline at Week 6

Secondary outcomes

  1. 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

    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.

    Time frame: From Baseline at Week 6

  2. Percentage of Participants With >=50% Reduction in the Weekly Average of Daily Pain Intensity on the 11-Point NRS

    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.

    Time frame: From Baseline at Week 6

  3. Change in the Daily Sleep Interference Scale (DSIS)

    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.

    Time frame: From Baseline at Week 6

  4. Percentage of Participants Categorized as Improved on the Patient Global Impression of Change (PGIC) Scale

    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.

    Time frame: At Week 6

  5. Change in Pain Intensity on the 11-Point NRS

    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.

    Time frame: From Baseline at Week 6

  6. Pre-dose Plasma Concentration (Ctrough) of VRT-1207355 and the Metabolite VRT-1268114

    Time frame: Pre-dose at Day 7

  7. Number of Participants With Clinically Meaningful Findings in Columbia Suicide Severity Rating Scale (C-SSRS) Responses

    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.

    Time frame: Day 1 up to Week 10

  8. Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Time frame: Day 1 up to Week 10

06

Results

Posted Nov 15, 2021

Participant flow

Participant flow — Overall Study
MilestoneVX-150Placebo
Started4643
Completed4535
Not completed18
Withdrew: Adverse event04
Withdrew: Withdrawal of consent (due to lack of efficacy)11
Withdrew: Withdrawal of consent (for other reason)02
Withdrew: Other01

Outcome measures

PrimaryChange in Weekly Average of Daily Pain Intensity on the 11 Point NRS

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.

Time frame:
From Baseline at Week 6
Reported as:
Least squares mean · units on a scale
Change in Weekly Average of Daily Pain Intensity on the 11 Point NRS
units on a scaleVX-150Placebo
Change in Weekly Average of Daily Pain Intensity on the 11 Point NRS-2.018 ± 0.274-0.933 ± 0.287
Statistical analysis
  • VX-150 vs Placebo · Mixed-effects Model for Repeated Measure · p = <0.0001 · Least squares (ls) mean difference: -1.085 · 95% CI -1.876 to -0.293
SecondaryPercentage of Participants With Greater Than or Equal to (>=) 30 Percent (%) Reduction in the Weekly Average of Daily Pain Intensity on the 11-Point NRS

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.

Time frame:
From Baseline at Week 6
Reported as:
Number · percentage of participants
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
percentage of participantsVX-150Placebo
Percentage of Participants With Greater Than or Equal to (>=) 30 Percent (%) Reduction in the Weekly Average of Daily Pain Intensity on the 11-Point NRS45.026.5
SecondaryPercentage of Participants With >=50% Reduction in the Weekly Average of Daily Pain Intensity on the 11-Point NRS

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.

Time frame:
From Baseline at Week 6
Reported as:
Number · percentage of participants
Percentage of Participants With >=50% Reduction in the Weekly Average of Daily Pain Intensity on the 11-Point NRS
percentage of participantsVX-150Placebo
Percentage of Participants With >=50% Reduction in the Weekly Average of Daily Pain Intensity on the 11-Point NRS32.517.6
SecondaryChange in the Daily Sleep Interference Scale (DSIS)

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.

Time frame:
From Baseline at Week 6
Reported as:
Least squares mean · units on a scale
Change in the Daily Sleep Interference Scale (DSIS)
units on a scaleVX-150Placebo
Change in the Daily Sleep Interference Scale (DSIS)-1.777 ± 0.276-0.665 ± 0.289
Statistical analysis
  • VX-150 vs Placebo · Mixed-effects Model for Repeated Measure · p = <0.0001 · Ls mean difference: -1.111 · 95% CI -1.911 to -0.312
SecondaryPercentage of Participants Categorized as Improved on the Patient Global Impression of Change (PGIC) Scale

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.

Time frame:
At Week 6
Reported as:
Number · percentage of participants
Percentage of Participants Categorized as Improved on the Patient Global Impression of Change (PGIC) Scale
percentage of participantsVX-150Placebo
Percentage of Participants Categorized as Improved on the Patient Global Impression of Change (PGIC) Scale39.513.5
SecondaryChange in Pain Intensity on the 11-Point NRS

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.

Time frame:
From Baseline at Week 6
Reported as:
Least squares mean · units on a scale
Change in Pain Intensity on the 11-Point NRS
units on a scaleVX-150Placebo
Change in Pain Intensity on the 11-Point NRS-1.7 ± 0.3-1.1 ± 0.3
Statistical analysis
  • VX-150 vs Placebo · Mixed-effects Model for Repeated Measure · p = <0.0001 · Ls mean difference: -0.6 · 95% CI -1.5 to 0.3
SecondaryPre-dose Plasma Concentration (Ctrough) of VRT-1207355 and the Metabolite VRT-1268114
Time frame:
Pre-dose at Day 7
Reported as:
Mean · microgram per milliliter (mcg/mL)
Pre-dose Plasma Concentration (Ctrough) of VRT-1207355 and the Metabolite VRT-1268114
microgram per milliliter (mcg/mL)VX-150
VRT-12073553.89 ± 2.73
VRT-12681141.35 ± 0.752
SecondaryNumber of Participants With Clinically Meaningful Findings in Columbia Suicide Severity Rating Scale (C-SSRS) Responses

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.

Time frame:
Day 1 up to Week 10
Reported as:
Number · participants
Number of Participants With Clinically Meaningful Findings in Columbia Suicide Severity Rating Scale (C-SSRS) Responses
participantsVX-150Placebo
Number of Participants With Clinically Meaningful Findings in Columbia Suicide Severity Rating Scale (C-SSRS) Responses00
SecondarySafety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame:
Day 1 up to Week 10
Reported as:
Number · participants
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
participantsVX-150Placebo
Participants with AEs2924
Participants with SAEs03

Adverse events

Collected over Day 1 up to Week 10. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
VX-1500/46 (0%)0/46 (0%)16/46 (34.8%)
Placebo0/43 (0%)3/43 (7%)7/43 (16.3%)
Most frequent serious events
Most frequent serious events
EventVX-150Placebo
Atrial fibrillationCardiac disorders0/461/43
DiverticulitisInfections and infestations0/461/43
Tendon ruptureInjury, poisoning and procedural complications0/461/43
Most frequent other events
Most frequent other events
EventVX-150Placebo
HeadacheNervous system disorders11/465/43
Dry mouthGastrointestinal disorders3/461/43
NauseaGastrointestinal disorders3/461/43
ArthralgiaMusculoskeletal and connective tissue disorders3/461/43
Muscle spasmsMusculoskeletal and connective tissue disorders3/460/43

Baseline characteristics

Age, Continuous
Age, Continuous(years)VX-150PlaceboTotal
Mean55.1 ± 12.3458.1 ± 11.8656.6 ± 12.14
Sex: Female, Male
Sex: Female, Male(Participants)VX-150PlaceboTotal
Female222143
Male242246
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)VX-150PlaceboTotal
Hispanic or Latino358
Not Hispanic or Latino433881
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)VX-150PlaceboTotal
American Indian or Alaska Native000
Asian011
Native Hawaiian or Other Pacific Islander000
Black or African American6410
White393473
More than one race123
Unknown or Not Reported022
Pain Intensity at Baseline on 11-point Numeric Rating Scale (NRS)
Pain Intensity at Baseline on 11-point Numeric Rating Scale (NRS)(units on a scale)VX-150PlaceboTotal
Mean6.433 ± 1.4405.990 ± 1.4136.219 ± 1.436
07

Study locations

34 sites
  • Xenoscience Inc. - 21st Century Neurology
    Phoenix, Arizona 85004, United States
  • Phoenix Neurological Associates, Ltd.
    Phoenix, Arizona 85251, United States
  • Sutter Health - Alta Bates Summit Medical Center - The Jordan Research & Education Institute
    Berkeley, California 94705, United States
  • Neuropain Medical Center
    Fresno, California 93710, United States
  • University of California San Diego
    La Jolla, California 92093, United States
  • SDS Clinical Trials, Inc.
    Orange, California 92868, United States
  • Stanford University School of Medicine
    Redwood City, California 94063, United States
  • Blue Sky Neurology
    Englewood, Colorado 80113, United States
  • Bioclinica Research - Orlando
    Orlando, Florida 32806, United States
  • Infinity Clinical Research
    Sunrise, Florida 33351, United States
  • Southern Illinois University (SIU) School of Medicine
    Springfield, Illinois 62702, United States
  • University of Iowa Hospitals and Clinics
    Iowa City, Iowa 52242, United States
  • University of Kansas Medical Center (KUMC)
    Kansas City, Kansas 66160, United States
  • International Clinical Research Institute (ICRI)
    Overland Park, Kansas 66210, United States
  • River Cities Clinical Research Center
    Shreveport, Louisiana 71105, United States
  • The Johns Hopkins Hospital
    Baltimore, Maryland 21287, United States
  • Washington University School of Medicine in St. Louis
    Saint Louis, Missouri 63110, United States
  • Dartmouth-Hitchcock Medical Center (DHMC)
    Lebanon, New Hampshire 03756, United States
  • Robert Wood Johnson Medical School
    New Brunswick, New Jersey 08901, United States
  • University of New Mexico Hospital
    Albuquerque, New Mexico 87131, United States
  • Albany Medical Center- Neurology Group
    Albany, New York 12208, United States
  • The Mount Sinai Hospital
    New York, New York 10029, United States
  • Columbia University Medical Center
    New York, New York 10032, United States
  • University of Rochester
    Rochester, New York 14618, United States
  • University of North Carolina School of Medicine
    Chapel Hill, North Carolina 27514, United States
  • Duke Neurological Disorders Clinic
    Durham, North Carolina 27710, United States
  • Carolinas Pain Institute
    Winston-Salem, North Carolina 27103, United States
  • Neurology Diagnostics, Inc
    Dayton, Ohio 45459, United States
  • The Richter Clinic for Neurology and Neuro-Psychiatry
    Tulsa, Oklahoma 74104, United States
  • Carilion Clinic Neurology
    Roanoke, Virginia 24013, United States
  • University of Washington
    Seattle, Washington 98105, United States
  • Universitätsklinikum Würzburg
    Würzburg, Germany
  • Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
    Milano, Italy
  • Maastricht UMC+
    Maastricht, Netherlands
08

References and documents

Study documents

  • Study protocol · May 25, 2018
  • Statistical analysis plan · Nov 6, 2018

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT03304522
Lead sponsor
Vertex Pharmaceuticals Incorporated
Responsible party
Sponsor
First posted
Oct 9, 2017
Start date
Sep 20, 2017
Primary completion
Oct 12, 2018
Completion
Nov 8, 2018
Results posted
Nov 15, 2021
Last update
Nov 15, 2021

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
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