Efficacy and Safety Study of BIIB074 in Participants With Small Fiber Neuropathy

A Phase 2 Placebo-Controlled, Double-Blind, Enriched Enrollment Randomized Withdrawal Study to Evaluate the Efficacy and Safety of BIIB074 (Vixotrigine) in Treating Pain Experienced by Subjects With Confirmed Small Fiber Neuropathy That is Idiopathic or Associated With Diabetes Mellitus

The primary objective of this study is to evaluate the efficacy of BIIB074 in treating pain experienced by participants with confirmed small fiber neuropathy (SFN) that is idiopathic or associated with diabetes mellitus. A secondary endpoint that relates to the primary objective is the change from Randomization to Week 12 of the double-blind period in mean average daily pain score.

The secondary objectives of this study are to evaluate the effect on worst pain, neuropathic pain quality, sleep interference due to pain, patient global impression, use of rescue medication, and SFN symptoms in participants treated with BIIB074; to investigate the safety and tolerability of BIIB074 in participants with SFN; and to characterize the pharmacokinetics (PK) of BIIB074 in participants with SFN.

Study Overview

• Status: Terminated
• Conditions: Diabetes Mellitus; Small Fiber Neuropathy
• Intervention / Treatment: Drug: Placebo; Drug: BIIB074

• Study Type: Interventional
• Enrollment (Actual): 265
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Byala, Bulgaria
    • Research Site
  • Pleven, Bulgaria
    • UMHAT 'Dr Georgi Stranski' EAD
  • Plovdiv, Bulgaria
    • Research Site
  • Sofia, Bulgaria
    • Research Site
• Canada
  • Kingston, Canada
    • Research Site
  • Winnipeg, Canada
    • Research Site
  • British Columbia
    • Vancouver, British Columbia, Canada
      • Vancouver General Hospital
  • Ontario
    • Toronto, Ontario, Canada
      • Toronto General Hospital
  • Quebec
    • Greenfield Park, Quebec, Canada
      • Research Site
    • Montreal, Quebec, Canada
      • Research Site
    • St-Jerome, Quebec, Canada
      • Recherche Médicale St-Jérôme Inc.
• Czechia
  • Brno, Czechia
    • Fakultni Nemocnice Brno
  • Brno, Czechia
    • Fakultni nemocnice u sv. Anny v Brne
  • Hradec Kralove, Czechia
    • Research Site
  • Ostrava-Poruba, Czechia
    • Fakultni nemocnice Ostrava
  • Pardubice, Czechia
    • Nemocnice Pardubickeho kraje a.s. Pardubicka nemocnice
  • Prague, Czechia
    • Fakultni nemocnice v Motole
• Denmark
  • Aarhus, Denmark
    • Research Site
  • Copenhagen, Denmark
    • Research Site
  • Herlev, Denmark
    • Research Site
  • Odense, Denmark
    • OUH
• France
  • Boulogne-Billancourt, France
    • Hôpital Ambroise Paré - Boulogne-Billancourt
  • Corbeil-Essonnes, France
    • Research Site
  • Creteil, France
    • Hôpital Henri Mondor
  • Le Creusot, France
    • Research Site
  • Le Kremlin Bicêtre, France
    • Groupement Hospitalier Sud - Hôpital Bicêtre
  • Nice, France
    • CHU Nice - Hôpital de l'Archet 1
  • Paris, France
    • Hôpital Lariboisière
  • Finistere
    • Brest, Finistere, France
      • Research Site
  • Loire
    • Saint Priest En Jarez, Loire, France
      • CHU Saint Etienne - Hôpital Nord
  • Nord
    • Lille, Nord, France
      • Hopital Salengro - CHRU de Lille
  • Puy De Dome
    • Clermont Ferrand, Puy De Dome, France
      • CHU Clermond Ferrand - Hopital Gabriel Montpied
  • Rhone
    • Venissieux, Rhone, France
      • Research Site
• Germany
  • Bad Homburg, Germany
    • Zentrum für klinische Forschung
  • Berlin, Germany
    • Gemeinschaftspraxis für Neurologie
  • Essen, Germany
    • Research Site
  • Hamburg, Germany
    • Diabetologische Schwerpunktpraxis Harburg
  • Mainz, Germany
    • Research Site
  • Wiesbaden, Germany
    • DKD Helios Klinik Wiesbaden
  • Wurzburg, Germany
    • Research Site
  • Baden-Württemberg
    • Böblingen, Baden-Württemberg, Germany
      • Clinical research
  • Bayern
    • Aschaffenburg, Bayern, Germany
      • Research Site
    • Kuenzing, Bayern, Germany
      • Research Site
  • Niedersachsen
    • Westerstede, Niedersachsen, Germany
      • Clinical research
  • Nord Rhein Westfalen
    • Muenster, Nord Rhein Westfalen, Germany
      • Clinical research
  • Nordrhein Westfalen
    • Dortmund, Nordrhein Westfalen, Germany
      • Gemeinschaftspraxis Diabeteszentrum Dortmund Dr.med. Klaus Busch
  • Sachsen Anhalt
    • Lage, Sachsen Anhalt, Germany
      • Hausarzt- und Diabetologische Schwerpunktpraxis
• Greece
  • Athens, Greece
    • Research Site
  • Heraklion, Greece
    • Research Site
  • Patras, Greece
    • Research Site
  • Thessaloniki, Greece
    • AHEPA General Hospital of Thessaloniki
• Hungary
  • Baja, Hungary
    • Research Site
  • Bekescsaba, Hungary
    • Békés Megyei Központi Kórház Dr. Réthy Pál Tagkórház
  • Budapest, Hungary
    • UNO Medical Trials Kft.
  • Kaposvar, Hungary
    • Somogy Megyei Kaposi Mor Oktato Korhaz
  • Nyiregyhaza, Hungary
    • Research Site
  • Pecs, Hungary
    • Research Site
  • Szeged, Hungary
    • Research Site
• Italy
  • Brescia, Italy
    • Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)
  • Genova, Italy
    • Research Site
  • Milan, Italy
    • Research Site
  • Pisa, Italy
    • Azienda Ospedaliero Univeraitaria Pisana
  • Roma, Italy
    • Università Campus Bio-Medico di Roma
  • Telese Terme, Italy
    • Research Site
• Netherlands
  • Amsterdam, Netherlands
    • Amsterdam UMC, locatie AMC
  • Maastricht, Netherlands
    • Maastricht UMC+
• Poland
  • Bydgoszcz, Poland
    • Research Site
  • Chorzow, Poland
    • Research Site
  • Kraków, Poland
    • Pratia McM Krakow
  • Lublin, Poland
    • Research Site
  • Oswiecim, Poland
    • Research Site
  • Poznan, Poland
    • Praktyka Lekarska Ewa Krzyzagorska
  • Warszawa, Poland
    • Research Site
  • Wroclaw, Poland
    • Regionalna Poradnia Diabetologiczna Zytkiewicz-Jaruga,Stasinska
• Spain
  • Alicante, Spain
    • Hospital General Universitario de Alicante
  • Barcelona, Spain
    • Research Site
  • Barcelona, Spain
    • Hospital Universitari de Bellvitge
  • Cordoba, Spain
    • Hospital Universitario Reina Sofía
  • La Coruna, Spain
    • Research Site
  • Madrid, Spain
    • Research Site
  • Majadahonda, Spain
    • Hospital Universitario Puerta de Hierro Majadahonda
  • Valencia, Spain
    • Hospital Universitari i Politecnic La Fe
• Switzerland
  • Lausanne, Switzerland
    • CHUV - Centre Hospitalier Universitaire Vaudois
  • Lugano, Switzerland
    • Ospedale Regionale di Lugano
  • St. Gallen, Switzerland
    • Kantonspital St. Gallen
  • Zurich, Switzerland
    • Research Site
• United Kingdom
  • Bath, United Kingdom
    • Clinical Reseach
  • Ipswich, United Kingdom
    • Research Site
  • Liverpool, United Kingdom
    • Research Site
  • London, United Kingdom
    • The Royal London Hospital
  • London, United Kingdom
    • King's College Hospital
  • London, United Kingdom
    • Guy's Hospital
  • London, United Kingdom
    • St Pancras Clinical Research
  • Manchester, United Kingdom
    • Research Site
  • Oxford, United Kingdom
    • John Radcliffe Hospital
  • Swansea, United Kingdom
    • Research Site
  • South Yorkshire
    • Sheffield, South Yorkshire, United Kingdom
      • Royal Hallamshire Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

1. This study will be conducted in subjects who have had a diagnosis of at least probable SFN, length-dependent distribution, for 6 months and ≤10 years prior to screening, defined as a history of the symptoms and clinical signs based on discussions at the ACTTION CONCEPPT meeting on diagnosis of SFN, Washington, DC March 2018, and confirmed by intraepidermal nerve fiber density (IENFD) values, and weekly mean average daily pain (ADP) score of ≥5 and ≤9 on an 11-point Pain Intensity Numeric Rating Scale (PI-NRS) over the last 7 days of prior to the Screening visit.
2. In addition to these criteria, subjects with diabetes will be required to have HbA1c ≤11%, treated with oral hypoglycemics and/or subcutaneous insulin or diet, no evidence of ulcers, advanced retinopathy (defined as greater than State 3 [moderate non-proliferative diabetic retinopathy]) (DCCT/EDIC Research Group 2017), severe nephropathy, or clinically significant obstructive atherosclerotic disease or current class IV heart failure to be eligible for the study.

Key Exclusion Criteria:

1. Previous exposure to BIIB074 (formerly known as CNV1014802 or GSK1014802).
2. Use of capsaicin patch within 3 months prior to Screening.
3. Unable or unwilling to discontinue concomitant medications for SFN pain prior to Day 1.
4. Unable or unwilling to comply with the prohibited concomitant medication restrictions, including but not limited to UDP-glucuronosyltransferase (UGT) inducers and inhibitors, monoamine oxidase inhibitors (MAOIs), and Nav blockers.
5. Use of over-the-counter medications, vitamin and mineral supplements, herbal remedies (including St. John's wort), dietary supplements, or foods (including grapefruit juice) that affect and UGTs.
6. Unable or unwilling to discontinue medications that are P-glycoprotein substrates with a narrow therapeutic index, including but not limited to digoxin.
7. History of hemophilia or Von Willebrand's disease, or use of anticoagulants that may result in bleeding risk during the skin biopsy.
8. Any contraindication, as determined by the Investigator, to performing a skin biopsy for intraepidermal nerve fiber analysis.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BIIB074 350 mg; Taper Period (if applicable) from neuropathic pain medication, followed by a washout period, then BIIB074 350 mg tablets orally twice daily (BID) Open-Label Run-In Period, then BIIB074 350 mg tablets orally BID Double-Blind Treatment Period.	Drug: BIIB074; Administered as specified in the treatment arm.
Experimental: BIIB074 200 mg; Taper Period (if applicable) from neuropathic pain medication, followed by a washout period, then BIIB074 350 mg tablets orally twice daily (BID) Open-Label Run-In Period, then BIIB074 200 mg tablets orally BID Double-Blind Treatment Period.	Drug: BIIB074; Administered as specified in the treatment arm.
Placebo Comparator: Placebo; Taper Period (if applicable) from neuropathic pain medication, followed by a washout period, then BIIB074 350 mg tablets orally twice daily (BID) Open-Label Run-In Period, then BIIB074 placebo-matching tablets orally BID Double-Blind Treatment Period.	Drug: Placebo; Administered as specified in the treatment arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Weekly Mean Average Daily Pain (ADP) Score	Participants will rate their ADP using an 11-point Numerical Rating Scale (NRS) (0=no pain and 10=worst possible pain) and record their score in an electronic diary (eDiary). Weekly mean ADP scores for Baseline (the 5 days prior to the first dose of study treatment in the open-label run-in period) and Week 12 (the 7 days prior to the visit at the end of Week 12) will be derived from the ADP scores and calculated as the mean of the daily scores over the last 7 days.	Baseline and Week 12 of the Double-Blind Period
Change from Randomization in Weekly Mean ADP Score	Participants will rate their ADP using an 11-point NRS (0=no pain and 10=worst possible pain) and record their score in an eDiary. Weekly mean ADP scores for Randomization (the 7 days prior to the first dose of study treatment in the double-blind period) and Week 12 (the 7 days prior to the visit at the end of Week 12) will be derived from the ADP scores and calculated as the mean of the daily scores over the last 7 days.	Randomization and Week 12 of the Double-Blind Period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Weekly Mean Worst Daily Pain (WDP) Score	Participants will rate their WDP using an 11-point NRS (0=no pain and 10=worst possible pain) and record their score in an eDiary. Weekly mean WDP scores for Baseline (the 5 days prior to the first dose of study treatment in the open-label run-in period) and Week 12 (the 7 days prior to the visit at the end of Week 12) will be derived from the WDP scores and calculated as the mean of the daily scores over the last 7 days.	Baseline and Week 12 of the Double-Blind Period
Change from Baseline in Weekly Mean Sleep Interference Numerical Rating Scale (S-NRS)	Participants will rate their S-NRS using an 11-point NRS (0=pain does not interfere with sleep and 10= pain completely interferes with sleep) and record their score in an eDiary. Weekly mean S-NRS scores for Baseline (the 5 days prior to the first dose of study treatment in the open-label run-in period) and Week 12 (the 7 days prior to the visit at the end of Week 12) will be derived from the daily S-NRS scores and calculated as the mean of the daily scores over the last 7 days.	Baseline and Week 12 of the Double-Blind Period
Change from Baseline in Neuropathic Pain Symptom Inventory (NPSI) Total Score and Sum Score	Participant will use the NPSI questionnaire to rate different symptoms of neuropathic pain. The NPSI includes ten items related to different pain descriptors (e.g. burning and pressure) that are rated on an 11-point NRS (0=no symptoms to 10=worst symptoms imaginable). A score in each dimension and also a total score (from 0-100) is generated using data from the questionnaire.	Baseline and Week 12 of Double-Blind Period
Proportion of Participants with at least a 2-point Reduction from Baseline in Weekly Mean ADP	Participants will rate their ADP using an 11-point NRS (0=no pain and 10=worst possible pain) and record their score in an electronic diary (eDiary). Weekly mean ADP scores for Baseline (the 5 days prior to the first dose of study treatment in the open-label run-in period) and Week 12 (the 7 days prior to the visit at the end of Week 12) will be derived from the ADP scores and calculated as the mean of the daily scores over the last 7 days.	Baseline and Week 12 of the Double-Blind Period
Proportion of Participants with at least a 30% Reduction from Baseline in Weekly Mean ADP	Participants will rate their ADP using an 11-point NRS) (0=no pain and 10=worst possible pain) and record their score in an electronic diary (eDiary). Weekly mean ADP scores for Baseline (the 5 days prior to the first dose of study treatment in the open-label run-in period) and Week 12 (the 7 days prior to the visit at the end of Week 12) will be derived from the ADP scores and calculated as the mean of the daily scores over the last 7 days.	Baseline and Week 12 of Double-Blind Period
Mean Weekly Amount of Rescue Medication	Use of rescue medication (paracetamol/acetaminophen) will be monitored and dosage will be recorded on a daily basis by the participant using an electronic Diary (eDiary). Mean weekly amount of rescue medication used for neuropathic pain during the double-blind period.	Weekly from Baseline to Week 12 of the Double-Blind Period
Patient Global Impression of Change (PGIC)	PGIC is a 7-point self-administered scale that depicts changes in a participant's overall status. Participants will rate their change as "1=very much improved," "2=much improved," "3=minimally improved," "4=no change," "5=minimally worse," "6=much worse," or "7=very much worse."	Week 12 of the Double-Blind Period
Change from Baseline in Brief Pain Inventory-Short Form (BPI-SF) Interference Score	The BPI-SF is a 7-item self-administered questionnaire that measures how much pain has interfered with daily functioning. Participants will rate the level of pain interference on daily functioning on an 11-point NRS where 0=does not interfere and 10=completely interferes.	Baseline and Week 12 of the Double-Blind Period
Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) During Double-Blind Period	AEs: any sign, symptom, or diagnosis/disease that is unfavorable or unintended, that is new, or if pre-existing, worsens in participants administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. SAEs: an event that results in death; an event that, in the view of the investigator, places the participant at immediate risk of death (a life-threatening event); an outcome that results in a congenital anomaly/birth defect diagnosed in a child of a participant; an event that requires or prolongs inpatient hospitalization; an event that results in persistent or significant disability/incapacity. Any other medically important event that, in the opinion of the investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed in the definition above.	Week 5 to Week 17
Area Under the Concentration-time Curve at Steady State		Week 1, 3, 5, 9, 13 and 17 prior to dosing and 1 to 2 hours after dosing, and at Day 123 (Follow-up clinic visit)
Maximum Observed Concentration (Cmax) at Steady State		Week 1, 3, 5, 9, 13 and 17 prior to dosing and 1 to 2 hours after dosing, and at Day 123 (Follow-up clinic visit)

Collaborators and Investigators

• Sponsor: Biogen

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2018
• Primary Completion (Actual): April 12, 2021
• Study Completion (Actual): April 12, 2021

Study Registration Dates

• First Submitted: November 8, 2017
• First Submitted That Met QC Criteria: November 8, 2017
• First Posted (Actual): November 13, 2017

Study Record Updates

• Last Update Posted (Actual): May 5, 2021
• Last Update Submitted That Met QC Criteria: April 30, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Nervous System Diseases; Endocrine System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Diabetes Mellitus; Small Fiber Neuropathy
• Other Study ID Numbers: 802NP206; 2017-000991-27 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No