2023-505893-14-00招募中3 期
A Phase 2b/3 Study of Safety and Efficacy of AMX0035 in Progressive Supranuclear Palsy (ORION)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 269
- 试验地点
- 35
- 主要终点
- Change from Baseline at Week 52 in the total PSPRS Score * *A primary endpoint—which meets evidentiary requirements of the United States of America (USA) and outside of the USA, respectively—was selected as follows: change from baseline in the 10-item PSPRS at Week 52 (for the USA) and change from baseline in the 28-item PSPRS at Week 52 (for outside of the USA). For each region, only the endpoint which meets evidentiary requirements of that region is considered the primary endpoint; ...
研究概览
简要总结
To assess the impact of AMX0035 compared to placebo on disease progression rate as measured by the total Progressive Supranuclear Palsy (PSP) Rating Scale (PSPRS).
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Provides a signed informed consent form (ICF) and has the mental capability to understand the ICF. If participant is unable to sign the ICF, the ICF must be signed by a representative in accordance with local regulatory requirements.
- •Score of ≥24 on the Mini Mental State Examination (MMSE).
- •Dosing of anti-Parkinsonian drugs (coenzyme Q10, levodopa/carbidopa, levodopa/benserazide, fava bean extract, a dopamine agonist, catechol-O-methyltransferase inhibitor, amantadine, or other Parkinson’s disease medications) should be stable for 60 days before enrollment and anticipated to remain stable for the double-blind phase of the Phase 2b or Phase 3 study portion, as applicable to the participant, at the discretion of the Investigator.
- •All female participants must have a negative serum pregnancy test at Screening.
- •Female participants of childbearing potential (women of childbearing potential [WOCBP]) who engage in heterosexual intercourse must have a negative urine pregnancy test on Day 1 prior to the first dose of study drug.
- •WOCBP must agree to abstain from heterosexual intercourse or use a highly effective birth control method for the duration of the study and for 6 months after the last dose of study drug. Female participants who are two years postmenopausal or surgically sterile are not considered be of childbearing potential.
- •Female participants must not be planning to become pregnant for the duration of the study and for 6 months after the last dose of study drug.
- •Female participants must not be planning to breastfeed or be breastfeeding for the duration of the study and for 6 months after the last dose of study drug.
- •Male participants must agree to abstain from heterosexual intercourse or use a highly effective birth control method for the duration of the study and for 6 months after the last dose of study drug.
- •Male participants must not be planning to father a child or provide sperm for donation for the duration of the study and for 6 months after the last dose of study drug.
- •Is willing and able to comply with the scheduled visits, treatment schedule, laboratory tests, and other requirements of the study, including MRI scans.
- •Participant’s study partner is willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the study. The participant’s study partner is defined as a caregiver, family member, social worker, or friend who has frequent contact with the participant (approximately 10 hours per week), will accompany the participant to study visits to provide information as to the participant’s functional abilities, and will speak the local language fluently to ensure comprehension of informed consent and informant-based assessments of the participant.
- •Is male or female 40 to 80 years of age, inclusive.
- •Participant must reside outside a skilled nursing facility or dementia care facility at the time of Screening and admission to such a facility must not be planned. Residence in an assisted living facility is allowed.
- •Meets the following criteria for possible or probable PSP (Steele-Richardson-Olszewski Syndrome) according to MDS 2017 criteria (Höglinger 2017): a. Gradually progressive disorder, with age at disease onset ≥ 40 years. b. Either or both of the following two criteria are met: i. Vertical supranuclear gaze palsy OR slow velocity of vertical saccades AND postural instability with repeated unprovoked falls within 3 years, OR tendency to fall on the pull-test within 3 years. ii. Slow velocity of vertical saccades AND postural instability with more than two steps backward on the pull-test within 3 years.
- •Presence of PSP symptoms for <5 years (as determined by the best judgement of the Investigator). For the purpose of this inclusion criterion, a PSP symptom is defined as any neurological, cognitive, or behavioral symptom consistent with known symptoms of PSP, occurring newly and subsequently progressing during the clinical course in the absence of another identifiable cause.
- •Score of <40 on the total (28-item) PSPRS Score.
- •Is Able to walk independently or with minimal assistance, defined as the ability to walk 5 steps with minimal assistance (stabilization of one arm).
排除标准
- •Has exposure to AMX0035 or has a known hypersensitivity to AMX0035, either of its components, any of its excipients, or bile salts. Note that under this exclusion criterion, participants in the Phase 2b study portion are not eligible to take part in the Phase 3 portion.
- •Clinically significant infection, inflammation, or medical condition other than PSP that would pose a risk to the participant if they were to participate or impair their ability to participate in the study, in the judgment of the Investigator, including any of the following: a. Acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea) at time of Screening or on Day 1 prior to study drug dosing. b. Presence of pathologies that can alter the enterohepatic circulation of bile acids (e.g., ileal resection and stoma, regional ileitis). c. Severe salt restriction, where added salt intake due to treatment with study drug would put the participant at risk in the judgment of the Investigator.
- •Evidence of any clinically significant neurological disorder other than PSP, including significant cerebrovascular abnormalities, vascular dementia, motor neuron disease or ALS, Huntington’s disease, normal pressure hydrocephalus, brain tumor, seizure disorder, multiple sclerosis, or known structural brain abnormalities. Evidence of disease may be provided by MRI.
- •Prior or current diagnosis of 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
- •Presence of unstable psychiatric disease, cognitive impairment (e.g., major cognitive dysfunction), dementia, major depression, or substance abuse that would impair ability of the participant to provide informed consent and follow instructions, in the judgment of the Investigator.
- •Significant suicidal ideation within 1 year prior to Screening as evidenced by answering “yes” to questions 4 or 5 on the suicidal ideation portion of the Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening or history of suicidal attempts within the last 2 years.
- •Participation in any other clinical investigation using an experimental drug within 5 half-lives or within 6 weeks (small molecules) or 6 months (monoclonal antibodies, antisense oligonucleotides, or other biologics), whichever is longer, prior to Day
- •Exposure to gene or cell therapy prior to Screening or during study.
- •Exposure to any prohibited therapy within 30 days prior to Screening.
- •Any factor which, in the opinion of the Investigator, precludes the participant’s full compliance with or completion of this study.
- •Requires use of a feeding tube.
- •Evidence of any neurological disorder that could explain signs of PSP, including any of the following: a. Signs of idiopathic Parkinson's disease (e.g., severe asymmetric Parkinsonian signs, clinically significant tremor at rest, or prominent and sustained response to levodopa therapy or other medications that are used to treat Parkinson’s disease). b. Signs of multiple system atrophy (MSA) (e.g., prominent early cerebellar limb ataxia or unexplained symptomatic autonomic dysfunction). c. Signs of Lewy body disease (e.g., hallucinations or delusions unrelated to dopaminergic therapy or other illness). d. Probable Alzheimer’s (AD) disease according to National Institute of Aging – Alzheimer’s Association (NIA-AA) core clinical criteria for mild cognitive impairment due to AD or AD dementia. e. History of repeated strokes with stepwise progression of Parkinsonian features. f. History of major stroke. g. History of severe or repeated head injury. h. History of encephalitis. i. History of neuroleptic use within the past 6 months. Clozapine or quetiapine may be permitted if at a stable dose for 60 days prior to Screening. j. History of oculogyric crises. k. History of street-drug–related Parkinsonism.
- •Any contraindication to MRI or abnormal findings evidenced by MRI including any of the following: a. Severe leukoencephalopathy. b. Relevant structural abnormalities (normal pressure or obstructive hydrocephalus) including basal ganglia, diencephalic, mesencephalic, pontine, or medullary infarctions, hemorrhages, hypoxic-ischemic lesions, tumors, or malformations. c. Arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). d. Severe cerebral amyloid angiopathy.
- •History of autosomal dominant PSP due to a Microtubule Associated Protein Tau (MAPT) mutation.
- •History of an autosomal dominant mutation associated with Frontotemporal Lobar Degeneration (FTLD) (e.g., an autosomal dominant mutation in C9ORF72 or GRN)
- •Abnormal clinical laboratory results including any of the following findings (at Screening only): a. Abnormal liver function defined as aspartate transaminase (AST) and/or alanine transaminase (ALT) > 3× the upper limit of normal (ULN). b. Renal insufficiency as defined by estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m
- •c. Ongoing anemia with hemoglobin concentration < 10.0 g/dL.
- •Current biliary disease which may lead to biliary obstruction or impaired biliary flow, including active cholecystitis, primary biliary cirrhosis, sclerosing cholangitis, gallbladder cancer, gallbladder polyps, gangrene of the gallbladder, or abscess of the gallbladder.
- •History of Class III/IV heart failure per New York Heart Association (NYHA) criteria.
结局指标
主要结局
Change from Baseline at Week 52 in the total PSPRS Score * *A primary endpoint—which meets evidentiary requirements of the United States of America (USA) and outside of the USA, respectively—was selected as follows: change from baseline in the 10-item PSPRS at Week 52 (for the USA) and change from baseline in the 28-item PSPRS at Week 52 (for outside of the USA). For each region, only the endpoint which meets evidentiary requirements of that region is considered the primary endpoint; ...
Change from Baseline at Week 52 in the total PSPRS Score * *A primary endpoint—which meets evidentiary requirements of the United States of America (USA) and outside of the USA, respectively—was selected as follows: change from baseline in the 10-item PSPRS at Week 52 (for the USA) and change from baseline in the 28-item PSPRS at Week 52 (for outside of the USA). For each region, only the endpoint which meets evidentiary requirements of that region is considered the primary endpoint; ...
次要结局
- Change from Baseline at Week 52 in the PSPRS Score * * Same as above
- Change from Baseline at Week 52 in the MDS-UPDRS Part II Score.
- Frequency of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
研究者
Medical Information
Scientific
Amylyx Pharmaceuticals Inc.
研究点 (35)
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