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

Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03339336
• Other study ID #: 802NP206
• Secondary ID: 2017-000991-27
• Status: Terminated
• Phase: Phase 2
• Start date: May 31, 2018
• Est. completion date: April 12, 2021

Study information

• Verified date: April 2021
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 265
• Est. completion date: April 12, 2021
• Est. primary completion date: April 12, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Small Fiber Neuropathy

Intervention

Drug:
• BIIB074
Administered as specified in the treatment arm.
• Placebo
Administered as specified in the treatment arm.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Countries where clinical trial is conducted

Bulgaria,  Canada,  Czechia,  Denmark,  France,  Germany,  Greece,  Hungary,  Italy,  Netherlands,  Poland,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)