A Phase 2, Randomized, Double-blind, Placebo-controlled Pilot Study Assessing the Efficacy, Safety and Tolerability of Orally Administered BMS-986368, a FAAH/MAGL Inhibitor, for the Treatment of Spasticity in Participants With Post-stroke Spasticity
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Tardieu Scale
研究概览
简要总结
The goal of this clinical trial is to learn if the drug BMS-986368 works to treat post stroke spasticity in adults who have had a stroke. BMS-986368 is a designed to increase natural compounds in the body that may help calm nerves that cause muscles to be tight or spasm. The study will also learn about the safety of drug BMS-986368
详细描述
Post-stroke spasticity (PSS) is a common and disabling complication of stroke that can impair upper-limb function, limit activities of daily living, and negatively affect quality of life. Current treatment options, including oral antispasticity medications and botulinum toxin injections, may provide incomplete symptom control and are often associated with tolerability limitations. Therefore, there is a need for novel therapies that can improve both spasticity and functional recovery in individuals with PSS. Preclinical evidence and early clinical experience support evaluation of BMS-986368 as a treatment for post-stroke spasticity. The STIPS Study is a Phase 2, randomized, double-blind, placebo-controlled pilot trial designed to evaluate the efficacy, safety, and tolerability of BMS-986368 in adults with post-stroke spasticity. The study consists of:
- A screening period of up to 4 weeks
- An 8-week double-blind treatment period
- An optional 8-week double-blind active treatment extension (DBATE)
- A 4-week safety follow-up period The maximum study duration is approximately 24 weeks. During the double-blind treatment period, participants randomized to active treatment will receive oral BMS-986368 with dose escalation from 1 mg once daily, to 3 mg once daily and then 6 mg once daily. Participants randomized to placebo will receive matching placebo capsules. Participants who complete the double-blind treatment period may elect to enter the DBATE, during which all participants receive active treatment while maintaining study blinding. The study hypothesis is that BMS-986368 administered up to 6 mg once daily will result in greater improvement in spasticity and upper-extremity motor function compared with placebo, while demonstrating an acceptable safety and tolerability profile in participants with post-stroke spasticity
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ischemic or hemorrhagic stroke diagnosis 4 to 18 months prior to enrollment.
- •History of post stroke spasticity for at least 2 months prior to Screening Visit.
- •Modified Ashworth Scale (mAS) score ≥2 and <4 for affected elbow and wrist joints at Screen and Baseline Visits.
- •Fugl-Meyer Assessment for Upper Extremity (FMA-UE) greater than 22 at Screen and Baseline Visits
- •Willing to participate with no therapy additions during study duration.
- •Participant must be able to read, speak, and understand English usage
排除标准
- •Individuals who are pregnant or breastfeeding.
- •Participants must not have any concomitant disease or disorder that has symptoms of spasticity or that may influence the participant's level of spasticity.
- •Participants must not have a history of any substance abuse disorder as defined in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) Diagnostic Criteria for Drug and Alcohol Abuse.
- •Participants must not be currently taking a medication for spasticity that cannot be discontinued and washed out prior to randomization.
- •Participants must not have used FAAH/MAGL inhibitor medication or any cannabinoid-related products (including cannabis, cannabidiol (CBD), or tetrahydrocannabinol (THC)) within 30 days prior to randomization.
- •Other protocol-defined Inclusion/Exclusion criteria apply.
研究组 & 干预措施
Administration of BMS-986368
Drug: BMS-986368. Specified dose on specified days
干预措施: Administration of BMS-986368 (Drug)
Placebo
Drug: Placebo Specified dose on specified days
干预措施: Placebo (Drug)
结局指标
主要结局
Tardieu Scale
时间窗: At Week 8
Change from baseline in elbow and wrist Tardieu Scale. Clinical assessment with higher scores indicating greater spasticity.
Upper Limb Fugl-Meyer Assessment (FMA-UE) Scale
时间窗: At Week 8
Change from baseline, Clinical Assessment of upper-extremity motor function and sensorimotor recovery after stroke. Scores range from 0 to 66, with higher scores indicating better motor function.
次要结局
- AEs leading to death(Up to week 16])
- Tardieu Scale - DBATE(At week 16)
- Upper Limb Fugl-Meyer Assessment (FMA-UE) Scale- DBATE(At week 16)
- Total Numeric-transformed Modified Ashworth Scale (TNmAS)(At week 8 for all participants. Additionally at Week 16 for participants in the Optional Active Treatment Extension phase)
- Numeric Rating Scale - Spasticity (NRS-S)(At Week 8 for all participants. At Week 16 for participants in the Optional Active Treatment Extension Phase)
- Patient Health Questionnaire-9 (PHQ-9)(At Week 8 for all participants Additionally at Week 16 for participants in the Optional Active Treatment Extension Phase)
- Clinical Global Impression of Severity (CGI-S)(At Week 8 for all participants. Additionally at Week 16 for participants in the Optional Active Treatment Extension Phase)
- Treatment-Emergent Adverse Events (TEAEs)(Up to week 16])
- Serious adverse events (SAEs)(Up to week 16)
- Adverse events (AEs) leading to treatment discontinuation(Up to week 16])
- AEs leading to clinically significant lab abnormalities([Time Frame: Up to week 16])
- Suicidal Ideation and Behavior(Up to week 16])
- Cannabis Withdrawal Symptoms(Up to week 24)
- Plasma concentrations of BMS-986368(Up to Week 8)
研究者
Alberto Esquenazi
Chief Clinical Officer Jefferson Moss-Magee Rehabilitation
Thomas Jefferson University