Clinical trial NCT03339336: Efficacy and Safety Study of BIIB074 in Participants With Small Fiber Neuropathy
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Small Fiber Neuropathy
Diabetes Mellitus
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2017-11-13
Enrollment: 265
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change from Baseline in Weekly Mean Average Daily Pain (ADP) Score
timeFrame: Baseline and Week 12 of the Double-Blind Period
measure: Change from Randomization in Weekly Mean ADP Score
timeFrame: Randomization and Week 12 of the Double-Blind Period
Secondary outcomes:
measure: Change from Baseline in Weekly Mean Worst Daily Pain (WDP) Score
timeFrame: Baseline and Week 12 of the Double-Blind Period
measure: Change from Baseline in Weekly Mean Sleep Interference Numerical Rating Scale (S-NRS)
timeFrame: Baseline and Week 12 of the Double-Blind Period
measure: Change from Baseline in Neuropathic Pain Symptom Inventory (NPSI) Total Score and Sum Score
timeFrame: Baseline and Week 12 of Double-Blind Period
measure: Proportion of Participants with at least a 2-point Reduction from Baseline in Weekly Mean ADP
timeFrame: Baseline and Week 12 of the Double-Blind Period
measure: Proportion of Participants with at least a 30% Reduction from Baseline in Weekly Mean ADP
timeFrame: Baseline and Week 12 of Double-Blind Period
measure: Mean Weekly Amount of Rescue Medication
timeFrame: Weekly from Baseline to Week 12 of the Double-Blind Period
measure: Patient Global Impression of Change (PGIC)
timeFrame: Week 12 of the Double-Blind Period
measure: Change from Baseline in Brief Pain Inventory-Short Form (BPI-SF) Interference Score
timeFrame: Baseline and Week 12 of the Double-Blind Period
measure: Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) During Double-Blind Period
timeFrame: Week 5 to Week 17
measure: Area Under the Concentration-time Curve at Steady State
timeFrame: 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)
measure: Maximum Observed Concentration (Cmax) at Steady State
timeFrame: 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)
Other outcomes:
Locations:
city: Byala
country: Bulgaria
facility: Research Site
city: Pleven
country: Bulgaria
facility: UMHAT 'Dr Georgi Stranski' EAD
city: Plovdiv
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Greenfield Park
country: Canada
facility: Research Site
state: Quebec
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: St-Jerome
country: Canada
facility: Recherche Médicale St-Jérôme Inc.
state: Quebec
city: Kingston
country: Canada
facility: Research Site
city: Winnipeg
country: Canada
facility: Research Site
city: Brno
country: Czechia
facility: Fakultni Nemocnice Brno
city: Brno
country: Czechia
facility: Fakultni Nemocnice u sv. Anny v Brne
city: Hradec Kralove
country: Czechia
facility: Research Site
city: Ostrava-Poruba
country: Czechia
facility: Fakultni nemocnice Ostrava
city: Pardubice
country: Czechia
facility: Nemocnice Pardubickeho kraje a.s. Pardubicka nemocnice
city: Prague
country: Czechia
facility: Fakultni nemocnice v Motole
city: Aarhus
country: Denmark
facility: Research Site
city: Copenhagen
country: Denmark
facility: Research Site
city: Herlev
country: Denmark
facility: Research Site
city: Odense
country: Denmark
facility: OUH
city: Brest
country: France
facility: Research Site
state: Finistere
city: Saint Priest En Jarez
country: France
facility: CHU Saint Etienne - Hôpital Nord
state: Loire
city: Lille
country: France
facility: Hopital Salengro - CHRU de Lille
state: Nord
city: Clermont Ferrand
country: France
facility: CHU Clermond Ferrand - Hopital Gabriel Montpied
state: Puy De Dome
city: Venissieux
country: France
facility: Research Site
state: Rhone
city: Boulogne-Billancourt
country: France
facility: Hôpital Ambroise Paré - Boulogne-Billancourt
city: Corbeil-Essonnes
country: France
facility: Research Site
city: Creteil
country: France
facility: Hopital Henri Mondor
city: Le Creusot
country: France
facility: Research Site
city: Le Kremlin Bicêtre
country: France
facility: Groupement Hospitalier Sud - Hôpital Bicêtre
city: Nice
country: France
facility: CHU Nice - Hôpital de l'Archet 1
city: Paris
country: France
facility: Hopital Lariboisiere
city: Böblingen
country: Germany
facility: Clinical Research
state: Baden-Württemberg
city: Aschaffenburg
country: Germany
facility: Research Site
state: Bayern
city: Kuenzing
country: Germany
facility: Research Site
state: Bayern
city: Westerstede
country: Germany
facility: Clinical Research
state: Niedersachsen
city: Muenster
country: Germany
facility: Clinical Research
state: Nord Rhein Westfalen
city: Dortmund
country: Germany
facility: Gemeinschaftspraxis Diabeteszentrum Dortmund Dr.med. Klaus Busch
state: Nordrhein Westfalen
city: Lage
country: Germany
facility: Hausarzt- und Diabetologische Schwerpunktpraxis
state: Sachsen Anhalt
city: Bad Homburg
country: Germany
facility: Zentrum fur Klinische Forschung
city: Berlin
country: Germany
facility: Gemeinschaftspraxis für Neurologie
city: Essen
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Diabetologische Schwerpunktpraxis Harburg
city: Mainz
country: Germany
facility: Research Site
city: Wiesbaden
country: Germany
facility: DKD Helios Klinik Wiesbaden
city: Wurzburg
country: Germany
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Heraklion
country: Greece
facility: Research Site
city: Patras
country: Greece
facility: Research Site
city: Thessaloniki
country: Greece
facility: AHEPA General Hospital of Thessaloniki
city: Baja
country: Hungary
facility: Research Site
city: Bekescsaba
country: Hungary
facility: Bekes Megyei Kozponti Korhaz Dr. Rethy Pal Tagkorhaz
city: Budapest
country: Hungary
facility: UNO Medical Trials Kft.
city: Kaposvar
country: Hungary
facility: Somogy Megyei Kaposi Mor Oktato Korhaz
city: Nyiregyhaza
country: Hungary
facility: Research Site
city: Pecs
country: Hungary
facility: Research Site
city: Szeged
country: Hungary
facility: Research Site
city: Brescia
country: Italy
facility: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)
city: Genova
country: Italy
facility: Research Site
city: Milan
country: Italy
facility: Research Site
city: Pisa
country: Italy
facility: Azienda Ospedaliero Univeraitaria Pisana
city: Roma
country: Italy
facility: Università Campus Bio-Medico di Roma
city: Telese Terme
country: Italy
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, Locatie AMC
city: Maastricht
country: Netherlands
facility: Maastricht UMC+
city: Bydgoszcz
country: Poland
facility: Research Site
city: Chorzow
country: Poland
facility: Research Site
city: Kraków
country: Poland
facility: PRATIA MCM Kraków
city: Lublin
country: Poland
facility: Research Site
city: Oswiecim
country: Poland
facility: Research Site
city: Poznan
country: Poland
facility: Praktyka Lekarska Ewa Krzyzagorska
city: Warszawa
country: Poland
facility: Research Site
city: Wroclaw
country: Poland
facility: Regionalna Poradnia Diabetologiczna Zytkiewicz-Jaruga,Stasinska
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Barcelona
country: Spain
facility: Hospital Universitari de Bellvitge
city: Barcelona
country: Spain
facility: Research Site
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: La Coruna
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: Lausanne
country: Switzerland
facility: CHUV - Centre Hospitalier Universitaire Vaudois
city: Lugano
country: Switzerland
facility: Ospedale Regionale di Lugano
city: St. Gallen
country: Switzerland
facility: Kantonspital St. Gallen
city: Zurich
country: Switzerland
facility: Research Site
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital
state: South Yorkshire
city: Bath
country: United Kingdom
facility: Clinical Reseach
city: Ipswich
country: United Kingdom
facility: Research Site
city: Liverpool
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Guy's Hospital
city: London
country: United Kingdom
facility: King's College Hospital
city: London
country: United Kingdom
facility: St Pancras Clinical Research
city: London
country: United Kingdom
facility: The Royal London Hospital
city: Manchester
country: United Kingdom
facility: Research Site
city: Oxford
country: United Kingdom
facility: John Radcliffe Hospital
city: Swansea
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References: