NCT05104476进行中（未招募）2 期
Interventional, Randomized, Double-blind, Parallel-group, Placebo-controlled, Multi-centre Study to Assess the Efficacy, Safety and Tolerability of Lu AF82422 in Patients With Multiple System Atrophy
适应症
干预措施
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 64
- 试验地点
- 22
- 主要终点
- Percentage Slowing of Clinical Progression Based on Change From Baseline in the UMSARS TS at the End of Treatment (EOT) DB Period (DBP)
研究概览
简要总结
To find out the effect of Lu AF82422 on disease progression in participants with multiple system atrophy.
详细描述
This study will consist of a double-blind period (DBP) and will include an optional open-label treatment extension (OLE) period. Participants in the DBP will be randomized to Lu AF82422 or placebo (2:1). All participants entering the OLE will receive Lu AF82422 during the OLE.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 40 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The participant is diagnosed with possible or probable MSA of the multiple system atrophy parkinsonian type (MSA-P) or multiple system atrophy cerebellar type (MSA-C) sub-type at the Screening Visit.
- •The participant had onset of motor and/or autonomic (orthostatic or urinary) MSA symptoms within 5 years prior to the Screening Visit in the judgement of the investigator.
- •The participant has an UMSARS Part I score ≤16 (omitting item 11 on sexual function) at the Screening Visit.
- •The participant has a cognitive performance evaluated by the Montreal Cognitive Assessment (MoCA) with a score ≥22 at the Screening Visit.
- •Open-label Extension Entry Criteria
- •The participant has completed the EoT Visit and did not withdraw in the DBP.
- •The participant has consented to participate in the OLE.
- •The participant has completed the DBP within the last 5 months and will be enrolled into the OLE no later than end of Q1
- •The participant is, in the Investigator's opinion, likely to comply with the protocol.
- •The participant has not received any other Investigational product since the EOoTDBP Visit.
排除标准
- •The participant has been treated with an anti-α-synuclein monoclonal antibody, mesenchymal stem cells or an inhibitor of α-synuclein aggregation within the last 12 months.
- •The participant has any past or current treatment with an active vaccine targeting α-synuclein.
- •The participant has 2 or more blood relatives with a history of MSA.
- •The participant has evidence (clinically or on MRI) and/or history of any clinically significant disease or condition other than MSA (for example, serious neurological disorder, other intracranial disease, or systemic disease).
- •The participant has a current diagnosis of movement disorders that could mimic MSA (for example, Parkinson' disease, dementia with Lewy bodies, essential tremor, progressive supranuclear palsy, spinocerebellar ataxia, spastic paraparesis, corticobasal degeneration, or vascular, pharmacological, or post-encephalitic parkinsonism), per investigator discretion.
- •Other inclusion and exclusion criteria may apply.
研究组 & 干预措施
Lu AF82422
Experimental
Participants in the DBP will receive Lu AF82422 intravenous (IV) infusion every 4 weeks (Q4W) from Baseline for a minimum 48 weeks up to a maximum 72 weeks. In the optional OLE, all participants will receive Lu AF82422 IV infusion starting on Day 1 of the OLE up to week 188.
干预措施: Lu AF82422 (Drug)
Placebo
Experimental
Participants in the DBP will receive Lu AF82422 matching placebo IV infusion Q4W from Baseline for a minimum 48 weeks up to a maximum 72 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage Slowing of Clinical Progression Based on Change From Baseline in the UMSARS TS at the End of Treatment (EOT) DB Period (DBP)
时间窗: Baseline up to Week 72
The primary endpoint assessed disease progression by a Bayesian repeated measures model on UMSARS TS. Reported here is the estimated slowing (%) of clinical progression in participants receiving Lu AF82422 relative to those receiving placebo. UMSARS is a combined clinician and patient-reported outcome assessment developed to provide a surrogate measure of disease progression in multiple system atrophy (MSA). UMSARS TS was obtained by the sum of the items from Part I and Part II. Part I assesses historical information on symptoms and activities of daily living over the past 2 weeks and Part II consists of a clinical examination of key MSA motor signs and symptoms. UMSARS TS score was the sum of all items and ranged from 0 (no impairment) to 104 (severe impairment). A higher score indicated greater impairment.
次要结局
- Change From Baseline in the UMSARS TS at the End of Treatment (EOT) DBP(Baseline, Weeks 48 and 72)
- Change From Baseline in the Modified UMSARS Part I (mUMSARS) Score at the EOT DBP(Baseline, Weeks 48 and 72)
- Change From Baseline in the UMSARS Part I Scores at the EOT DBP(Baseline, Weeks 48 and 72)
- Change From Baseline in the UMSARS Part II Scores at the EOT DBP(Baseline, Weeks 48 and 72)
- Change From Baseline in Schwab and England Activities of Daily Living (SE-ADL) Score at Week 48 in the DBP(Baseline, Week 48)
- Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score at Week 48 in the DBP(Baseline, Week 48)
- Change From Baseline in Patient Global Impression - Severity of Illness (PGI-S) Score at Week 48 in the DBP(Baseline, Week 48)
- Change From Baseline in Observer-Reported Global Impression - Severity of Illness (OGI-S) Score at Week 48 in the DBP(Baseline, Week 48)
- Composite Autonomic Symptom Score Select Change (COMPASS Select Change) Total Score at Week 48 in the DBP(Week 48)
- Change From Baseline in UMSARS Part IV Score at Week 48 in the DBP(Baseline, Week 48)
- Change From Baseline in Speech, Swallowing, Falls, and Walking, as Assessed by the UMSARS Part I Item Scores at Week 48 in the DBP(Baseline, Week 48)
- Change From Baseline in Number of Falls, as Assessed by the Fall Diary Periods (Weeks 44 to 48) in the DBP(Baseline, Weeks 44 to 48)
- Change From Baseline in EuroQol 5-Dimension, 5-Level (EQ-5D-5L) Score at Week 48 in the DBP(Baseline, Week 48)
- Percent Change From Baseline in Brain Volume With Ventricles, as Measured by Volumetric MRI (vMRI) at Week 48 in the DBP(Baseline, Week 48)
- Percent Change From Baseline in P-Neurofilament Light Chain (NfL) Protein Concentration at Week 48 in the DBP(Baseline, Week 48)
- Lu AF82422 Plasma Concentration in the DBP(Weeks 0, 4, 6, 8, 12, 24, 36, 48, 60, 72, 88)
- Lu AF82422 Cerebrospinal Fluid (CSF) Concentrations in the DBP(Weeks 0 and 48)
- Lu AF82422 CSF/Plasma Concentration Ratio in the DBP(Weeks 0 and 48)
研究者
研究点 (22)
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相关资讯
Lundbeck Presents Phase II Data for Amlenetug in Multiple System Atrophy at International Congress- Lundbeck presented results from the AMULET phase II trial investigating amlenetug, a monoclonal antibody targeting α-synuclein, as a potential treatment for multiple system atrophy (MSA).
- The company shared new insights from the TALISMAN natural history study, providing critical data on early disease progression in MSA patients to support phase III development.
- Patient perspectives from the AMULET trial informed the design of the upcoming phase III MASCOT trial, demonstrating Lundbeck's commitment to patient-centered drug development.
- MSA remains a rare, rapidly progressing neurodegenerative disease with no approved therapies and significant unmet medical need.last yearAmlenetug Receives FDA Fast Track Designation for Multiple System Atrophy- The FDA has granted Fast Track Designation to Lundbeck's amlenetug for the potential treatment of Multiple System Atrophy (MSA).
- The designation is supported by Phase II AMULET trial outcomes and will expedite the drug development process through rolling reviews and intensive guidance.
- Amlenetug, a human monoclonal antibody, targets extracellular α-synuclein to prevent uptake and aggregation, potentially slowing MSA progression.
- Lundbeck has initiated the Phase III MASCOT trial to evaluate the efficacy, safety, and tolerability of amlenetug in MSA patients across North America, Europe, and Asia.last yearLu AF82422 Shows Potential in Slowing MSA Progression in Phase 2 Trial- Lu AF82422, an anti-alpha-synuclein antibody, showed promise in slowing disease progression in patients with multiple system atrophy (MSA) in the Phase 2 AMULET trial.
- Although the primary endpoint was not met, a more pronounced efficacy signal was observed in a less impaired subgroup of MSA patients.
- The investigational agent was generally safe and well-tolerated, with a significant number of patients opting to continue treatment in an open-label extension.
- These findings support further investigation of Lu AF82422 in a Phase 3 trial for MSA, targeting the underlying pathophysiology of the disease.last yearLundbeck Presents Promising Data on Amlenetug for Multiple System Atrophy at MDS Congress- Lundbeck presented data from the TALISMAN natural history study, enhancing the understanding of Multiple System Atrophy (MSA) progression in early-stage patients.
- The AMULET trial of amlenetug (Lu AF82422) in MSA showed a consistent slowing of clinical progression, with a post-hoc analysis revealing a 42% slowing in a less impaired subgroup.
- Based on the AMULET trial's encouraging results, Lundbeck is set to initiate a Phase III trial of amlenetug at the beginning of 2025, marking a significant step in MSA treatment.
- Amlenetug (Lu AF82422), a human monoclonal antibody, targets extracellular α-synuclein, potentially preventing uptake and inhibiting aggregation in MSA patients.last year