NCT07724132招募中3 期
Alzheimer's Disease- Systematic Multi-Arm Adaptive Randomised Trial
适应症
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 1,200
- 试验地点
- 2
- 主要终点
- Change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) score
研究概览
简要总结
A multicentre, interventional, multi-arm, multi-stage Phase 3 trial including randomisation, double blinding, placebo control evaluation of treatments for sustained clinical response (18 months) in symptomatic Alzheimer's Disease in a population representative of people with Alzheimer's disease in the UK.
详细描述
AD-SMART is a platform trial using a multi-arm multi-stage (MAMS) adaptive design.
Participants are randomised (1:1:1) to standard of care plus placebo, atomoxetine, or metformin. Interim analyses are conducted in stages (Stage 1, Stage 2, and Stage 3) to determine whether treatment arms should continue or stop early for lack of activity.
The primary objective is to assess therapeutic benefit by measuring change in cognitive function and activities of daily living over 18 months. Secondary outcomes include neuropsychiatric symptoms, quality of life, caregiver burden, safety, and health economic outcomes.
Exploratory analyses include blood biomarkers and MRI imaging to investigate disease progression and treatment response.
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)
盲法说明
Double (Participant, Investigator)
入排标准
- 年龄范围
- 55 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient meets all inclusion criteria:
- •1. Adults aged ≥55 years on the day of screening, no upper age limit
- •Confirmed clinical diagnosis of Alzheimer's Disease (AD)
- •Confirmed clinical diagnosis of Mixed Dementia consisting of Alzheimer's Disease and Vascular Dementia
- •Mini Mental State Examination score of ≥17
- •Confirmatory blood biomarker testing (pTau-217) (positive or intermediate via validated assays) ≤ 365 days prior to screening or between screening and randomisation or a positive amyloid PET scan (if available) or a positive amyloid CSF test (if available)
- •Randomisation should ideally take place within 4 weeks of the screening visit but no later than 8 weeks after the screening visit
- •Must be able and willing to comply with the treatment and assessment schedule and requirements including being able to start trial treatment ≤ 2 weeks after randomisation
- •Willing and able to have MRI scans in accordance with the assessment schedule unless participant is clinically contraindicated due to:
- •Pacemakers or defibrillators (unless MRI-conditional models)
- •Aneurysm clips, stents or metal implants (unless MRI safe)
- •Cochlear implants (unless MRI-conditional models)
- •Metal fragments in the body
- •Severe claustrophobia
- •Negative pregnancy test ≤4 weeks prior to randomisation for women of child-bearing potential
- •Normal liver function at screening consisting of all the following:
- •Total serum bilirubin <1.5 x ULN (except for participants with Gilbert's disease, for whom the upper limit of total serum bilirubin is 51.3 μmol/l or 3mg/dl)
- •Alanine aminotransferase (ALT) <3 x ULN;
- •Alkaline phosphatase <3 x ULN
- •Documented participant and study partner informed consent
- •If a participant is being re-randomised into the trial, additional timing of entry requirements must also be met:
- •For participants being re-randomised after completing 18 months' follow-up and the arm was not closed due to lack of activity, a 12-week washout period from last dose of IMP must be completed before their screening visit. If the efficacy analysis indicates that the IMP was ineffective then this washout period can be reduced to 6 weeks.
- •For participants being re-randomised following treatment arm termination due to lack of activity, a 6-week washout period from their last dose of IMP must be completed prior to screening assessment
- •Study Partner inclusion criteria:
- •Participant that meets the AD-SMART eligibility criteria has consented to participation in the trial
- •Has at least twice-weekly contact with participant
- •Be 18 years or older at the time of providing consent
- •Willing to complete study partner questionnaires as outlined in visit schedule
- •Willing to attend remote and in-person study visits with participant
- •Documented informed consent
排除标准
- •Patient meets none of the exclusion criteria:
- •Fazekas Score =3 reported from an MRI taken at any time prior to randomisation, if an MRI is not clinically contraindicated (reasons specified in Inclusion Criteria 7) A. MRI does not need to be repeated if Fazekas score = 0, 1 or 2 reported from an MRI performed ≤365 days to screening visit (if Fazekas score has not been reported, refer to Section 7.4) b. MRI should be conducted if participant is not clinically contraindicated to MRIs and previous MRI where Fazekas score = 0, 1 or 2 was >365 days or previous MRI scan is not available for Fazekas score reporting or participant has never had an MRI
- •Clinical diagnosis of Dementia with Lewy bodies
- •Clinical diagnosis of Parkinson's disease
- •Clinical diagnosis of Frontotemporal Dementia
- •Cardiac failure (American Heart Association Stage C or D)
- •Significant respiratory comorbidity (hospitalisation within the previous ≤6 months due to respiratory comorbidity)
- •Renal failure (CKD IV or eGFR ≤45 mL/min/1.73m²) at any time point prior to randomisation
- •Malignancy (except if in complete remission) e.g. solid organ or haematological or melanoma
- •Score of ≥1 on C-SSRS at screening visit
- •Individuals without an identified study partner (refer to Section 4 for further details on study partners)
- •Individuals who have an Alzheimer's Disease or Central Nervous System medication (e.g. antidepressant) change or dose change ≤28 days prior to screening
- •Use of an Investigational Medicinal Product (IMP) or Investigational Medical Device (IMD) ≤26 weeks prior to randomisation (except for AD-SMART participants that are being re-randomised. See Section 5.4 for further information).
- •Receiving antibody-based amyloid clearing treatment for Alzheimer's Disease within 26 weeks prior to randomisation
- •Unable or unwilling to comply with study procedures
- •Unable to swallow whole capsules
- •Individuals who are living in the same household as an AD-SMART participant who is actively taking trial medication
- •Female participants that are pregnant or breastfeeding
- •Women of child-bearing potential (WOCBP) who are unwilling or unable to use an acceptable method of contraception (see acceptable methods of contraception) whilst on trial treatment and up to 12 weeks after the last dose of study drug
- •Male participants with a partner of child-bearing potential unwilling or unable to use an acceptable method of contraception whilst on trial treatment and up to 12 weeks after the last dose of the study drug.
- •Male participants unwilling to desist from sperm donation during the trial and for 12 weeks after the last dose of trial treatment
- •Current or previous exposure to any of the currently recruiting AD-SMART IMPs ≤26 weeks before randomisation.
- •History of alcohol and/or drug abuse and/or dependence within the 5 years prior to screening visit.
- •Any concurrent medical condition, abnormal laboratory tests or uncontrolled, clinically significant systemic disease that, in the opinion of the Investigator, could cause study participation to be detrimental to the participant.
- •Participants who are not eligible for any of the trial IMPs, according to the eligibility criteria listed in the individual drug appendices. Please note that participants can enter the trial if they are eligible for at least one of the trial treatment arms, but do not need to be eligible for all.
- •Arm-specific eligibility criteria:
- •Atomoxetine-specific exclusion eligibility criteria:
- •In addition to the core inclusion and exclusion criteria, refer to section 2.2 of AD-SMART Appendix 1 Atomoxetine' for the arm-specific exclusion eligibility criteria for the Atomoxetine arm which must also be met.
- •Metformin-specific exclusion eligibility criteria:
- •In addition to the core inclusion and exclusion criteria, refer to section 2.2 of AD-SMART Appendix 2 Metformin' for the arm-specific exclusion eligibility criteria for the metformin arm which must also be met.
结局指标
主要结局
Change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) score
时间窗: Baseline to 18 months
The Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) measures the severity of cognitive impairment in dementia. Scores range from 0 to 70, with higher scores indicating worse cognitive performance (Unit of Measure: ADAS-Cog score (0-70). ADAS-Cog will be administered at baseline, month 6, month 12, and month 18 (end of study), and change over time will be assessed.
Change in Amsterdam Instrumental Activities of Daily Living Questionnaire - Short Version (A-IADL-Q-SV) score
时间窗: Baseline to 18 months
The Amsterdam Instrumental Activities of Daily Living Questionnaire - Short Version (A-IADL-Q-SV) assesses functional impairment in instrumental activities of daily living. Scores range from 0 to 100, with higher scores indicating better functional performance (Unit of Measure: A-IADL-Q-SV score (0-100). The A-IADL-Q-SV will be administered at baseline, month 6, month 12, and month 18 (end of study), and change over time will be evaluated.
次要结局
- Change in Neuropsychiatric Inventory (NPI) total score(Baseline to 18 months)
- Change in EQ-5D-5L health-related quality-of-life score (participant-reported)(Baseline to 18 months)
- Change in EQ-5D-5L health-related quality-of-life score (study partner-reported)(Baseline to 18 months)
- Change in Zarit Burden Interview (ZBI) total score(Baseline to 18 months)
- Incidence of treatment-emergent adverse events and serious adverse events(Baseline to 18 months)
- Change in health and social care resource use and associated costs(Baseline to 18 months)
研究者
研究点 (2)
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