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
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Biogen
- 入组人数
- 265
- 试验地点
- 53
- 主要终点
- Change from Randomization in Weekly Mean ADP Score
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
- •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.
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
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.
干预措施: BIIB074 (Drug)
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.
干预措施: BIIB074 (Drug)
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.
干预措施: Placebo (Drug)
结局指标
主要结局
Change from Randomization in Weekly Mean ADP Score
时间窗: Randomization and Week 12 of the Double-Blind Period
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.
Change from Baseline in Weekly Mean Average Daily Pain (ADP) Score
时间窗: Baseline and Week 12 of the Double-Blind Period
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.
次要结局
- Change from Baseline in Weekly Mean Sleep Interference Numerical Rating Scale (S-NRS)(Baseline and Week 12 of the 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)
- Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) During Double-Blind Period(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))
- Change from Baseline in Weekly Mean Worst Daily Pain (WDP) Score(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)
- Patient Global Impression of Change (PGIC)(Week 12 of the Double-Blind Period)
- Change from Baseline in Brief Pain Inventory-Short Form (BPI-SF) Interference Score(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)
- Mean Weekly Amount of Rescue Medication(Weekly from Baseline to Week 12 of the Double-Blind Period)