biogen/studies/attachments/NCT03339336-LLS.pdf

NCT03339336-LLS

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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.

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

Small Fiber Neuropathy

Neurological Disorders

Diabetes Mellitus

Diabetes

Metabolic Diseases

Placebo

BIIB074

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

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.

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.

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.

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.

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.

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.

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.

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.

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."

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.

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.

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.

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.

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.

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.

Research Site

UMHAT 'Dr Georgi Stranski' EAD

Vancouver General Hospital

Toronto General Hospital

Recherche Médicale St-Jérôme Inc.

Fakultni Nemocnice Brno

Fakultni Nemocnice u sv. Anny v Brne

Fakultni nemocnice Ostrava

Nemocnice Pardubickeho kraje a.s. Pardubicka nemocnice

Fakultni nemocnice v Motole

CHU Saint Etienne - Hôpital Nord

Hopital Salengro - CHRU de Lille

CHU Clermond Ferrand - Hopital Gabriel Montpied

Hôpital Ambroise Paré - Boulogne-Billancourt

Hopital Henri Mondor

Groupement Hospitalier Sud - Hôpital Bicêtre

CHU Nice - Hôpital de l'Archet 1

Hopital Lariboisiere

Clinical Research

Gemeinschaftspraxis Diabeteszentrum Dortmund Dr.med. Klaus Busch

Hausarzt- und Diabetologische Schwerpunktpraxis

Zentrum fur Klinische Forschung

Gemeinschaftspraxis für Neurologie

Diabetologische Schwerpunktpraxis Harburg

DKD Helios Klinik Wiesbaden

AHEPA General Hospital of Thessaloniki

Bekes Megyei Kozponti Korhaz Dr. Rethy Pal Tagkorhaz

UNO Medical Trials Kft.

Somogy Megyei Kaposi Mor Oktato Korhaz

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

Azienda Ospedaliero Univeraitaria Pisana

Università Campus Bio-Medico di Roma

Amsterdam UMC, Locatie AMC

Maastricht UMC+

PRATIA MCM Kraków

Praktyka Lekarska Ewa Krzyzagorska

Regionalna Poradnia Diabetologiczna Zytkiewicz-Jaruga,Stasinska

Hospital General Universitario de Alicante

Hospital Universitari de Bellvitge

Hospital Universitario Reina Sofia

Hospital Universitario Puerta de Hierro Majadahonda

Hospital Universitari i Politecnic La Fe

CHUV - Centre Hospitalier Universitaire Vaudois

Ospedale Regionale di Lugano

Kantonspital St. Gallen

Royal Hallamshire Hospital

Clinical Reseach

Guy's Hospital

King's College Hospital

St Pancras Clinical Research

The Royal London Hospital

John Radcliffe Hospital

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.

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.

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.

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.

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.

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.

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.

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.

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."

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.

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.

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.

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.

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.