A Randomized, Double-Blind, Placebo-Controlled Multiple Dose Study to Assess Efficacy, Safety, Tolerability, and Pharmacokinetics of ABBV-8E12 in Progressive Supranuclear Palsy
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 378
- 试验地点
- 66
- 主要终点
- Change From Baseline to Week 52 in Progressive Supranuclear Palsy Rating Scale (PSPRS) Total Score
研究概览
简要总结
The purpose of this study was to assess efficacy, safety, tolerability, and pharmacokinetics of ABBV-8E12 in participants with progressive supranuclear palsy (PSP).
详细描述
This was a Phase 2, randomized, double-blind, placebo-controlled, multiple dose, multicenter study consisting of a screening period of up to 8 weeks (56 days), a 52-week double-blind treatment period, and a post-treatment follow-up period of approximately 20 weeks following last study drug administration (for those participants who prematurely discontinued from treatment, declined to participate in or did not qualify for participation in a long term extension [LTE] study). At the end of the treatment period, extended treatment was available for eligible participants who completed the 52-week treatment period and entered the separate long-term extension study (NCT03391765; Study M15-563). There were 3 cohorts in the study (Cohort 1, Cohort J1, and Cohort 2). Cohort 1 had augmented safety and pharmacokinetic (PK) assessments in the first 30 participants enrolled into the global study from countries other than Japan. Cohort J1 had augmented safety and PK assessments in the first 9 participants enrolled into the study from Japan. Cohort 2 consisted of all other participants enrolled in the global study not participating in Cohort 1 or Cohort J1.
This study was prematurely discontinued because the program for progressive supranuclear palsy was discontinued due to lack of efficacy of study drug.
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
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female participant with age 40 years or greater at the time of signed consent
- •Meets the criteria for possible or probable progressive supranuclear palsy (PSP; Steele-Richardson-Olszewski Syndrome)
- •Presence of PSP symptoms for less than 5 years
- •Participant is able to walk 5 steps with minimal assistance (stabilization of one arm or use of cane/walker)
- •Participant has an identified, reliable, study partner (e.g., caregiver, family member, social worker, or friend)
排除标准
- •Participants who weigh less than 44 kg (97 lbs) at screening
- •Mini-Mental State Examination (MMSE) score less than 15 at screening
- •Any contraindication or inability to tolerate brain magnetic resonance imaging (MRI)
- •Participant resides at a skilled nursing or dementia care facility, or admission to such a facility is planned during the study period
- •Evidence of any clinically significant neurological disorder other than PSP
- •The participant has a history of or currently has schizophrenia, schizoaffective disorder or bipolar disorder according to Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V) or International Classification of Diseases (ICD-10) criteria
- •Participant has had a significant illness or infection requiring medical intervention in the past 30 days
研究组 & 干预措施
Placebo
0.9% Sodium Chloride Injection/Solution for Infusion; intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks
干预措施: Placebo (Drug)
ABBV-8E12 2000 mg
Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)
干预措施: ABBV-8E12 (Drug)
ABBV-8E12 4000 mg
Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)
干预措施: ABBV-8E12 (Drug)
结局指标
主要结局
Change From Baseline to Week 52 in Progressive Supranuclear Palsy Rating Scale (PSPRS) Total Score
时间窗: Baseline, Week 52
The PSPRS consists of 28 items grouped in six domains: daily activities (by history); behavior; bulbar; ocular motor; limb motor; and gait/midline. Items are scored on a 0 to 4 scale, except for six items that are scored on a 0 to 2 scale, with the total score ranging from 0 to 100. Higher scores indicate more severe disability or movement abnormality. Positive changes in score indicate worsening from baseline.
Number of Participants With Adverse Events
时间窗: From the first dose of study drug until 20 weeks following discontinuation of study drug administration have elapsed (approximately 5 half-lives), up to 80 weeks
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either reasonable possibility or no reasonable possibility. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the subject and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent events (TEAEs) are defined as any event that began or worsened in severity from first dose of study drug until 20 weeks after the last dose. For more details on AEs please see the Adverse Event section.
次要结局
- Mean Change From Baseline to Week 52 in Midbrain Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI)(Baseline, Week 52)
- Maximum Observed Serum Concentration (Cmax) for ABBV-8E12(First Dosing Interval, 2 weeks, Day 1-14; Fifth Dosing Interval, 4 weeks, Day 85-113)
- Mean Change From Baseline to Week 52 in Progressive Supranuclear Palsy Staging System Score (PSP-SS) Score(Baseline, Week 52)
- Mean Change From Baseline to Week 52 in Superior Cerebellar Peduncle Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI)(Baseline, Week 52)
- Mean Change From Baseline to Week 52 in Brainstem Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI)(Baseline, Week 52)
- Mean Change From Baseline to Week 52 in Whole Brain Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI)(Baseline, Week 52)
- Mean Change From Baseline to Week 52 in Frontal Lobe Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI)(Baseline, Week 52)
- Mean Change From Baseline to Week 52 in Clinical Global Impression of Severity (CGI-S) Score(Baseline, Week 52)
- Mean Change From Baseline to Week 52 in Unified Parkinson's Disease Rating Scale (UPDRS) Part II (Activities of Daily Living)(Baseline, Week 52)
- Mean Change From Baseline to Week 52 in Schwab and England Activities of Daily Living Scale (SEADL)(Baseline, Week 52)
- Area Under the Concentration Time Curve (AUC) for ABBV-8E12(First Dosing Interval, 2 weeks, Day 1-14; Fifth Dosing Interval, 4 weeks, Day 85-113)
- Mean Change From Baseline to Week 52 in Progressive Supranuclear Palsy Health Related Quality of Life Scale (PSP-QoL) Total Score(Baseline, Week 52)
- Clinical Global Impression of Change (CGI-C) Score at Week 52(Week 52)
- Time to Maximum Observed Serum Concentration (Tmax) for ABBV-8E12(First Dosing Interval, 2 weeks, Day 1-14; Fifth Dosing Interval, 4 weeks, Day 85-113)
- Mean Change From Baseline to Week 52 in Third Ventricle Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI)(Baseline, Week 52)
- Serum Concentration of ABBV-8E12 Prior to Infusion of a Day of Dosing (Ctrough)(First day of the Fifth Dosing Interval, Day 85)
- Time to Loss of Ability to Walk Independently as Measured by Progressive Supranuclear Palsy Rating Scale (PSPRS) Item 26(From Baseline to Week 52)