NCT05738486进行中（未招募）3 期
Investigating the Effect of Different Donanemab Dosing Regimens on ARIA-E and Amyloid Lowering in Adults With Early Symptomatic Alzheimer's Disease
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 1,175
- 试验地点
- 95
- 主要终点
- Percentage of Participants With Any Occurrence of Amyloid-Related Imaging Abnormality-Edema/Effusion (ARIA-E)
研究概览
简要总结
This study will investigate different donanemab dosing regimens and their effect on the frequency and severity of ARIA-E in adults with early symptomatic Alzheimer's disease (AD) and explore participant characteristics that might predict risk of ARIA.
Approximately 375 additional participants will be enrolled in addendum 2.
Addendum 3 includes a subset of participants from the main study to receive a single dose.
The study will last approximately 91 weeks and include up to 26 visits in the main study.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 60 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Gradual and progressive change in memory function reported by the participant or informant for ≥6 months.
- •A mini mental state examination (MMSE) score of 20 to 28 (inclusive) at screening.
- •Have an amyloid PET scan result from central read, consistent with the presence of amyloid pathology.
排除标准
- •Have significant neurological disease affecting the central nervous system other than AD, that may affect cognition or ability to complete the study, including but not limited to, other dementias, serious infection of the brain, Parkinson's disease, multiple concussions, or epilepsy or recurrent seizures, except febrile childhood seizures.
- •Has current serious or unstable illnesses including cardiovascular, hepatic, renal, gastroenterologic, respiratory, endocrinologic, neurologic (other than AD), psychiatric, immunologic, or hematologic disease and other conditions that, in the investigator's opinion, could interfere with the analyses in this study.
- •A life expectancy of <24 months.
- •Contraindication to MRI or PET scans
- •Have had prior treatment with a passive anti-amyloid immunotherapy.
- •Have a presence or history of malignant neoplasms within the past 5 years prior to Visit
- •Exceptions:
- •non-metastatic basal- or squamous-cell skin cancer
- •Stage 0 non-invasive carcinoma of the cervix
- •Stage 0 non-invasive prostate cancer, or
- •other cancers with low risk of recurrence or spread
研究组 & 干预措施
1400 mg Donanemab - Standard Regimen
Experimental
Participants received:
- 700 milligrams (mg) donanemab administered intravenously (IV) at baseline, week 4, and 8.
- placebo administered IV at week 2, 6, 10, and 14.
- 1400 mg of donanemab administered IV at week 12, 16, 20, and 24.
Participants enrolled to addendum 3 will receive a single dose at least 12 months after their last dose
干预措施: Placebo (Drug)
1400 mg Donanemab - Dose Skipping
Experimental
Participants received:
- 700 mg donanemab administered IV at baseline.
- placebo administered IV at week 2, 4, 6, 10, and 14.
- 1400 mg of donanemab administered IV at week 8, 12, 16, 20, and 24.
Participants enrolled to addendum 3 will receive a single dose at least 12 months after their last dose
干预措施: Placebo (Drug)
1400 mg Donanemab - Titration
Experimental
Participants received:
- 350 mg donanemab administered IV at baseline.
- placebo administered IV at week 2, 6, 10, and 14.
- 700 mg donanemab administered IV at week 4.
- 1050 mg of donanemab administered IV at week 8.
- 1400 mg of donanemab administered IV at week 12, 16, 20, and 24.
Participants enrolled to addendum 3 will receive a single dose at least 12 months after their last dose
干预措施: Placebo (Drug)
1400 mg Donanemab - Maximum Concentration (Cmax)
Experimental
Participants received:
- 350 mg donanemab administered IV at baseline, weeks 2, 4, 6, 8, and 10.
- 700 mg donanemab administered IV at weeks 12 and 14.
- 1400 mg of donanemab administered IV at weeks 16, 20, and 24.
Participants enrolled to addendum 3 will receive a single dose at least 12 months after their last dose
干预措施: Placebo (Drug)
1400 mg Donanemab - Standard Regimen
Experimental
Participants received:
- 700 milligrams (mg) donanemab administered intravenously (IV) at baseline, week 4, and 8.
- placebo administered IV at week 2, 6, 10, and 14.
- 1400 mg of donanemab administered IV at week 12, 16, 20, and 24.
Participants enrolled to addendum 3 will receive a single dose at least 12 months after their last dose
干预措施: Donanemab (Drug)
1400 mg Donanemab - Dose Skipping
Experimental
Participants received:
- 700 mg donanemab administered IV at baseline.
- placebo administered IV at week 2, 4, 6, 10, and 14.
- 1400 mg of donanemab administered IV at week 8, 12, 16, 20, and 24.
Participants enrolled to addendum 3 will receive a single dose at least 12 months after their last dose
干预措施: Donanemab (Drug)
1400 mg Donanemab - Titration
Experimental
Participants received:
- 350 mg donanemab administered IV at baseline.
- placebo administered IV at week 2, 6, 10, and 14.
- 700 mg donanemab administered IV at week 4.
- 1050 mg of donanemab administered IV at week 8.
- 1400 mg of donanemab administered IV at week 12, 16, 20, and 24.
Participants enrolled to addendum 3 will receive a single dose at least 12 months after their last dose
干预措施: Donanemab (Drug)
1400 mg Donanemab - Maximum Concentration (Cmax)
Experimental
Participants received:
- 350 mg donanemab administered IV at baseline, weeks 2, 4, 6, 8, and 10.
- 700 mg donanemab administered IV at weeks 12 and 14.
- 1400 mg of donanemab administered IV at weeks 16, 20, and 24.
Participants enrolled to addendum 3 will receive a single dose at least 12 months after their last dose
干预措施: Donanemab (Drug)
结局指标
主要结局
Percentage of Participants With Any Occurrence of Amyloid-Related Imaging Abnormality-Edema/Effusion (ARIA-E)
时间窗: 24 Weeks
Percentage of participants with occurrence of ARIA-E at Week 24 is reported here.
次要结局
- Percentage of Participants With Any Occurrence of ARIA-E(52 Weeks)
- Change From Baseline in Brain Amyloid Plaque Deposition As Measured By Amyloid Positron Emission Tomography (PET) Scan(Baseline, 76 Weeks)
- Percentage of Participants With Any Occurrence of Amyloid-Related Imaging Abnormality-Hemorrhage/Hemosiderin Deposits (ARIA-H)(24 Weeks)
- Percentage of Participants With ARIA-H(52 Weeks)
- Percentage of Participants With Maximum Severity of ARIA-E or ARIA-H(76 Weeks)
- Pharmacokinetics (PK): Average Serum Concentration of Donanemab(Baseline to 76 Weeks)
- Number of Participants With Anti-Drug Antibodies (ADAs) Against Donanemab, Including Treatment Emergent ADAs and Neutralizing Antibodies(Baseline to End of Follow-Up (91 Weeks))
研究者
研究点 (95)
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相关资讯
Key Neurology Advances of 2024: From Novel Therapies to Trial Innovations• Donanemab's enhanced titration method significantly reduces ARIA-E frequency and severity while maintaining amyloid reduction in Alzheimer's patients.
• Liraglutide demonstrates neuroprotective effects against Alzheimer's disease dementia, highlighting the potential of GLP-1 analogues in AD treatment.
• Tolebrutinib shows promise in slowing disability progression in non-relapsing secondary progressive multiple sclerosis patients in the HERCULES trial.last yearModified Donanemab Dosing Reduces ARIA-E Risk in Early Alzheimer's Patients- A modified dosing regimen of donanemab, shifting one vial from the first to the third infusion, significantly reduces the risk of ARIA-E in early Alzheimer's patients.
- The adjusted dosing led to a 41% relative risk reduction in ARIA-E occurrence compared to the standard regimen used in the TRAILBLAZER-ALZ 2 study.
- In patients with two copies of the ApoE4 gene variant, the modified dosing reduced ARIA-E risk by 67%, showing a substantial benefit in this high-risk group.
- Amyloid plaque reduction remained similar between the modified and standard dosing regimens, suggesting maintained efficacy with improved safety.last yearAlzheimer's Disease Therapeutics: Donanemab Dosing, Anti-Tau Antibody E2814, and Combination Intranasal Insulin/Empagliflozin Show Promise• Enhanced titration dosing of donanemab in the TRAILBLAZER-ALZ-6 trial significantly reduced the frequency and severity of ARIA-E in early symptomatic Alzheimer's disease patients.
• Phase 1b/2 study data of E2814, an anti-tau therapeutic antibody, demonstrated a significant impact on early and late tau biomarkers in patients with dominantly inherited Alzheimer's disease.
• A phase 2 trial showed that combination treatment with intranasal insulin and empagliflozin improved cognition and modulated immune/inflammatory biomarkers in mild cognitive impairment or early Alzheimer's disease.last year