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

NCT03339336 | Terminated Phase 2 DMC

• 2 other identifiers: 802NP2062017-000991-27
• Study Type: interventional
• Target: 265
• Locations: 14 countries
• Sites: 97

Brief Summary

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.

Conditions

Small Fiber Neuropathy; Diabetes Mellitus

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (11)

• Change from Baseline in Weekly Mean Worst Daily Pain (WDP) Score

  Baseline and Week 12 of the Double-Blind Period

• Change from Baseline in Weekly Mean Sleep Interference Numerical Rating Scale (S-NRS)

  Baseline and Week 12 of the Double-Blind Period

• Change from Baseline in Neuropathic Pain Symptom Inventory (NPSI) Total Score and Sum Score

  Baseline and Week 12 of Double-Blind Period

• Proportion of Participants with at least a 2-point Reduction from Baseline in Weekly Mean ADP

  Baseline and Week 12 of the Double-Blind Period

• Proportion of Participants with at least a 30% Reduction from Baseline in Weekly Mean ADP

  Baseline and Week 12 of Double-Blind Period

Study Arms (3)

BIIB074 350 mg

EXPERIMENTAL

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

BIIB074 200 mg

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

BIIB074 DRUG

Administered as specified in the treatment arm.

BIIB074 200 mg; BIIB074 350 mg

Placebo DRUG

Administered as specified in the treatment arm.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• Previous exposure to BIIB074 (formerly known as CNV1014802 or GSK1014802).
• Use of capsaicin patch within 3 months prior to Screening.
• Unable or unwilling to discontinue concomitant medications for SFN pain prior to Day 1.
• 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.
• 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.
• Unable or unwilling to discontinue medications that are P-glycoprotein substrates with a narrow therapeutic index, including but not limited to digoxin.
• History of hemophilia or Von Willebrand's disease, or use of anticoagulants that may result in bleeding risk during the skin biopsy.
• Any contraindication, as determined by the Investigator, to performing a skin biopsy for intraepidermal nerve fiber analysis.

Sponsors & Collaborators

• Biogen: lead

Study Sites (97)

Research Site

Byala, Bulgaria

Location

UMHAT 'Dr Georgi Stranski' EAD

Pleven, Bulgaria

Location

Research Site

Plovdiv, Bulgaria

Location

Research Site

Sofia, Bulgaria

Location

Vancouver General Hospital

Vancouver, British Columbia, Canada

Location

Toronto General Hospital

Toronto, Ontario, Canada

Location

Research Site

Greenfield Park, Quebec, Canada

Location

Research Site

Montreal, Quebec, Canada

Location

Recherche Médicale St-Jérôme Inc.

Saint-Jérôme, Quebec, Canada

Location

Research Site

Kingston, Canada

Location

Research Site

Winnipeg, Canada

Location

Fakultni Nemocnice Brno

Brno, Czechia

Location

Fakultni Nemocnice u sv. Anny v Brne

Brno, Czechia

Location

Research Site

Hradec Králové, Czechia

Location

Fakultni nemocnice Ostrava

Ostrava-Poruba, Czechia

Location

Nemocnice Pardubickeho kraje a.s. Pardubicka nemocnice

Pardubice, Czechia

Location

Fakultni nemocnice v Motole

Prague, Czechia

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Research Site

Aarhus, Denmark

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Research Site

Copenhagen, Denmark

Location

Research Site

Herlev, Denmark

Location

OUH

Odense, Denmark

Location

Research Site

Brest, Finistere, France

Location

Hopital Salengro - CHRU de Lille

Lille, Nord, France

Location

CHU Saint Etienne - Hôpital Nord

Saint Priest En Jarez, Pays de la Loire Region, France

Location

CHU Clermond Ferrand - Hopital Gabriel Montpied

Clermont-Ferrand, Puy De Dome, France

Location

Research Site

Vénissieux, Rhone, France

Location

Hôpital Ambroise Paré - Boulogne-Billancourt

Boulogne-Billancourt, France

Location

Research Site

Corbeil-Essonnes, France

Location

Hopital Henri Mondor

Créteil, France

Location

Research Site

Le Creusot, France

Location

Groupement Hospitalier Sud - Hôpital Bicêtre

Le Kremlin-Bicêtre, France

Location

CHU Nice - Hôpital de l'Archet 1

Nice, France

Location

Hopital Lariboisiere

Paris, France

Location

Clinical Research

Böblingen, Baden-Wurttemberg, Germany

Location

Research Site

Aschaffenburg, Bavaria, Germany

Location

Research Site

Künzing, Bavaria, Germany

Location

Clinical Research

Westerstede, Lower Saxony, Germany

Location

Clinical Research

Münster, Nord Rhein Westfalen, Germany

Location

Gemeinschaftspraxis Diabeteszentrum Dortmund Dr.med. Klaus Busch

Dortmund, North Rhine-Westphalia, Germany

Location

Hausarzt- und Diabetologische Schwerpunktpraxis

Lage, Saxony-Anhalt, Germany

Location

Zentrum fur Klinische Forschung

Bad Homburg, Germany

Location

Gemeinschaftspraxis für Neurologie

Berlin, Germany

Location

Research Site

Essen, Germany

Location

Diabetologische Schwerpunktpraxis Harburg

Hamburg, Germany

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Research Site

Mainz, Germany

Location

DKD Helios Klinik Wiesbaden

Wiesbaden, Germany

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Würzburg, Germany

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Athens, Greece

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Research Site

Heraklion, Greece

Location

Research Site

Pátrai, Greece

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AHEPA General Hospital of Thessaloniki

Thessaloniki, Greece

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Research Site

Baja, Hungary

Location

Bekes Megyei Kozponti Korhaz Dr. Rethy Pal Tagkorhaz

Békéscsaba, Hungary

Location

UNO Medical Trials Kft.

Budapest, Hungary

Location

Somogy Megyei Kaposi Mor Oktato Korhaz

Kaposvár, Hungary

Location

Research Site

Nyíregyháza, Hungary

Location

Research Site

Pécs, Hungary

Location

Research Site

Szeged, Hungary

Location

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)

Brescia, Italy

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Research Site

Genova, Italy

Location

Research Site

Milan, Italy

Location

Azienda Ospedaliero Univeraitaria Pisana

Pisa, Italy

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Università Campus Bio-Medico di Roma

Roma, Italy

Location

Research Site

Telese Terme, Italy

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Amsterdam UMC, Locatie AMC

Amsterdam, Netherlands

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Maastricht UMC+

Maastricht, Netherlands

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Research Site

Bydgoszcz, Poland

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Research Site

Chorzów, Poland

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PRATIA MCM Kraków

Krakow, Poland

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Research Site

Lublin, Poland

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Research Site

Oświęcim, Poland

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Praktyka Lekarska Ewa Krzyzagorska

Poznan, Poland

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Research Site

Warsaw, Poland

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Regionalna Poradnia Diabetologiczna Zytkiewicz-Jaruga,Stasinska

Wroclaw, Poland

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Research Site

A Coruña, Spain

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Hospital General Universitario de Alicante

Alicante, Spain

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Hospital Universitari de Bellvitge

Barcelona, Spain

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Research Site

Barcelona, Spain

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Hospital Universitario Reina Sofia

Córdoba, Spain

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Research Site

Madrid, Spain

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Hospital Universitario Puerta de Hierro Majadahonda

Majadahonda, Spain

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Hospital Universitari i Politecnic La Fe

Valencia, Spain

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CHUV - Centre Hospitalier Universitaire Vaudois

Lausanne, Switzerland

Location

Ospedale Regionale di Lugano

Lugano, Switzerland

Location

Kantonspital St. Gallen

Sankt Gallen, Switzerland

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Research Site

Zurich, Switzerland

Location

Royal Hallamshire Hospital

Sheffield, South Yorkshire, United Kingdom

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Clinical Reseach

Bath, United Kingdom

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Research Site

Ipswich, United Kingdom

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Research Site

Liverpool, United Kingdom

Location

Guy's Hospital

London, United Kingdom

Location

King's College Hospital

London, United Kingdom

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St Pancras Clinical Research

London, United Kingdom

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The Royal London Hospital

London, United Kingdom

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Research Site

Manchester, United Kingdom

Location

John Radcliffe Hospital

Oxford, United Kingdom

Location

Research Site

Swansea, United Kingdom

Location

Related Publications (1)

• Faber CG, Attal N, Lauria G, Dworkin RH, Freeman R, Dawson KT, Finnigan H, Hajihosseini A, Naik H, Serenko M, Morris CJ, Kotecha M. Efficacy and safety of vixotrigine in idiopathic or diabetes-associated painful small fibre neuropathy (CONVEY): a phase 2 placebo-controlled enriched-enrolment randomised withdrawal study. EClinicalMedicine. 2023 Apr 27;59:101971. doi: 10.1016/j.eclinm.2023.101971. eCollection 2023 May.

  PMID: 37152360 DERIVED

MeSH Terms

Conditions

Small Fiber Neuropathy; Diabetes Mellitus

Interventions

vixotrigine

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Medical Director

  Biogen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2017
• First Posted: November 13, 2017
• Study Start: May 31, 2018
• Primary Completion: April 12, 2021
• Study Completion: April 12, 2021
• Last Updated: May 5, 2021

Record last verified: 2021-04

Locations

CZ (6); IT (6); FR (12); CA (7); BU (4); HU (7); GR (4); NL (2); DK (4); DE (14); PL (8); ES (8); CH (4); GB (11)