NCT06643481进行中（未招募）2 期
A Phase 2, Randomized, Double-blind, Placebo-controlled Parallel Group Study of VHB937 in Amyotrophic Lateral Sclerosis (ALS) Over 40 Weeks Followed by an Open Label Extension (ASTRALS)
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
- 251
- 试验地点
- 87
- 主要终点
- The composite of PAV-free survival and change in ALSFRS-R. Analysis method: Combined Assessment of Function and Survival (CAFS)
研究概览
简要总结
This is a multicenter, randomized, double-blind, placebo-controlled, parallel group Phase II study to evaluate the efficacy and safety of VHB937 in participants with early-stage ALS (within 2 years of ALS symptoms onset). The study comprises a core double-blind (DB) 40-week treatment period followed by an open label extension (OLE).
详细描述
The main questions this trial aims to answer in comparing VHB937 to placebo are:
- How long will participants live without needing permanent help from a machine to breathe after starting the trial treatment?
- What is the change in the participant's ability to perform daily activities? This will be measured using a questionnaire called the amyotrophic lateral sclerosis functional rating scale-revised (ALSFRS-R).
- What adverse events are reported during this trial? An adverse event is any sign or symptom that participants have during a trial. Adverse events may or may not be caused by treatments in the trial. The trial doctors will check participants' ALS and general health throughout the trial.
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, Investigator, Outcomes Assessor)
盲法说明
Blinded placebo for infusion
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •are 18 years of age or older
- •male or female, if of childbearing potential, strict contraception required
- •have ALS confirmed by the trial doctors using different tests.
- •have mild symptoms of ALS as measured by the ALSFRS-R questionnaire (total score >=30).
- •have had symptoms of ALS (weakness) within 24 months of taking part in this trial.
- •have not received treatment for ALS or are currently on a stable dose of an approved treatment for ALS.
- •have the ability to slowly exhale a volume of air at least 60% of what is expected for the participant's sex, height and age.
排除标准
- •Use of other investigational drugs within 5 half-lives of screening, or within 30 days (e.g., small molecules) / or until the expected pharmacodynamic effect has returned to baseline (e.g., biologics), whichever is longer; or longer if required by local regulations.
- •Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception while taking study treatment and for 24 weeks after stopping study medication.
- •History or current diagnosis of cardiac conditions or ECG abnormalities indicating significant risk of safety for participants in the study.
- •Clinical evidence of liver or renal disease/injury.
- •Laboratory evidence of hematological abnormalities
- •Presence of unstable psychiatric disease, cognitive impairment, neurological disease other than ALS, dementia or substance abuse that would impair ability of the participant to provide informed consent, in the investigator's opinion.
- •Participants that reported 'yes' on any suicidal ideation section except for the "Non-Suicidal Self-Injurious Behavior" in the past 2 years as per C-SSRS.
- •Presence of cancer, HIV, Hep B, Hep C, tuberculosis, uncontrolled diabetes
- •History of active severe respiratory disease, including Chronic Obstructive Pulmonary Disease, interstitial lung disease or pulmonary fibrosis.
- •Taking any prohibited medications
研究组 & 干预措施
Arm 1
Experimental
I.V. infusions
干预措施: VHB937 (Biological)
Arm 2
Placebo Comparator
I.V. infusions
干预措施: Placebo (Other)
结局指标
主要结局
The composite of PAV-free survival and change in ALSFRS-R. Analysis method: Combined Assessment of Function and Survival (CAFS)
时间窗: Baseline to DB Week 40
To compare the efficacy of VHB937 vs. placebo on a composite of permanent assisted ventilation (PAV) free survival and function in DB epoch
次要结局
- ALS Functional Rating Scale Revised (ALSFRS-R) total score(Baseline to DB Week 40 or until death or PAV (whichever occurs first) and Baseline to OLE Week 100 or until death or PAV (whichever occurs first)
- Slow Vital Capacity (SVC) (% of predicted normal value)(Baseline to DB Week 40 or until death or PAV (whichever occurs first) and Baseline to OLE Week 100 or until death or PAV (whichever occurs first))
- Ratio to baseline in Neurofilament Light (NfL) concentration in serum(DB up to Week 40; DB and OLE up to Week 100])
- Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)(Baseline to end of study)
- Time to death and Time to event (death or PAV, whichever comes first).(Baseline to DB Week 40)
- Time to death and Time to event (death or PAV, whichever comes first) - endpoints referring to treatment policy estimand(Baseline to OLE Week 100, and Baseline to end of study)
- Patient Global Impression of change in functional ability and ALS symptom severity (PGI-C)(DB up to Week 40; DB and OLE up to Week 100)
- Change in QoL from baseline as measured with Amyotrophic Lateral Sclerosis Assessment Questionnaire -5 (ALSAQ-5)(DB up to Week 40; DB and OLE up to Week 100)
- Change in Clinician Global Impression of change in functional ability and ALS symptom severity (CGI-C)(DB up to Week 40; DB and OLE up to Week 100)
- Change in QoL from baseline as measured with EuroQoL 5 Dimension 5 Level (EQ-5D-5L)(DB up to Week 40; DB and OLE up to Week 100)
- Change in QoL from baseline as measured with 12-item Short form health survey (SF-12)(DB up to Week 40; DB and OLE up to Week 100)
- Pharmacokinetics (PK) of VHB937-CMAX(Day 1 to end of study)
- Pharmacokinetics (PK) of VHB937-TMAX(Day 1 to end of study)
- Pharmacokinetics (PK) of VHB937-CTROUGH(Day 1 to end of study)
- To assess immunogenicity (IG) of VHB937(Day 1 up to end of study)
- Cerebralspinal Spinal Fluid Pharmacokinetics (PK) of VHB937-CMAX(Screening to Week 12)
- Cerebralspinal Spinal Fluid Pharmacokinetics (PK) of VHB937-TMAX(Screening to Week 12)
- Cerebralspinal Spinal Fluid Pharmacokinetics (PK) of VHB937-CTROUGH(Screening to Week 12)
研究者
研究点 (87)
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