NCT07758595招募中1 期
A Phase 1/1b, Multicenter, Randomized, Placebo-Controlled, Double-Blind, Single-Dose and Multiple-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL921 in Healthy Participants and Participants With Alzheimer's Disease
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 178
- 试验地点
- 1
- 主要终点
- Part A: Incidence and severity of treatment-emergent averse events (TEAEs)
研究概览
简要总结
This is a Phase 1/1b, multicenter, randomized, placebo-controlled, double-blind study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple doses of DNL921 in healthy participants and participants with Alzheimer's disease (AD). The principal aim of this study is to obtain safety and tolerability data. This information, together with PK and PD data, will inform dose selection and design of future studies.
详细描述
This clinical trial information was submitted voluntarily under the applicable law and, therefore, certain submission deadlines may not apply. (That is, clinical trial information for this applicable clinical trial was submitted under section 402(j)(4)(A) of the Public Health Service Act and 42 CFR 11.60 and is not subject to the deadlines established by sections 402(j)(2) and (3) of the Public Health Service Act or 42 CFR 11.24 and 11.44.).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •(Healthy Participants):
- •Are male or female of non-childbearing potential and are aged 18 through 60 years at the time of screening
- •Have a BMI of 18 through 32 kg/m2 and a body weight of at least 50 kg
- •For female participants: Are of non-childbearing potential
- •For male participants: Are surgically sterile by bilateral orchidectomy, or are abstinent, or agree to use two acceptable forms of contraception
排除标准
- •(Healthy Participants):
- •Have any history of clinically significant neurological, psychiatric, endocrine, pulmonary, cardiovascular, gastrointestinal, hepatic, pancreatic, renal, metabolic, hematological, immunological, or allergic disease, or other major disorders
- •Have a positive serum pregnancy test or are currently lactating or breastfeeding
- •Have been hospitalized during the 4 weeks prior to screening
- •Key Inclusion Criteria (Participants with AD):
- •Are male or female of non-childbearing potential and aged 50 to 75 years at the time of screening
- •Have a BMI between 18 and 32 kg/m2 and a body weight of at least 45 kg
- •Have a diagnosis of probable mild to moderate AD dementia based on NIA AA 2011 criteria, including amnestic or nonamnestic presentation at screening or prodromal AD (consistent with the NIA-AA diagnostic criteria and guidelines for mild cognitive impairment due to AD)
- •Have supportive evidence of AD pathology by the following:
- •Plasma ptau217/Abeta42 positive
- •Positive amyloid PET scan
- •For female participants: Are of non-childbearing potential
- •For male participants: Are surgically sterile by bilateral orchidectomy, or are abstinent, or agree to use two acceptable forms of contraception
- •Key Exclusion Criteria (Participants with AD):
- •Have other clinically significant neurological or cognitive disorders affecting the CNS, as determined by the investigator, other than AD
- •Have specific psychiatric conditions
- •Have any history of unstable or poorly controlled endocrine, pulmonary, cardiovascular, gastrointestinal, hepatic, hematological, or other significant medical condition that, in the opinion of the investigator, may interfere with the completion or interpretation of study assessment
- •Have had a malignancy within 5 years before screening, except fully resected basal cell carcinoma or other malignancies treated with curative intent (such as prostate cancer) at low risk of recurrence
- •Have a positive serum pregnancy test or are currently lactating or breastfeeding
- •Have been hospitalized during the 4 weeks prior to screening
- •Have had previous anti-amyloid or anti-tau immunotherapy (including active immunization) or have participated in experimental gene therapy or cell therapy at any time
研究组 & 干预措施
Placebo Arm
Placebo Comparator
干预措施: Placebo (Drug)
Experimental Arm
Experimental
干预措施: DNL921 (Drug)
结局指标
主要结局
Part A: Incidence and severity of treatment-emergent averse events (TEAEs)
时间窗: 46 days
Parts B and C: Incidence and severity of TEAEs in participants with AD
时间窗: 242 days
次要结局
- PK Parameter: Maximum concentration (Cmax) of DNL921 in serum(Up to 242 Days)
- PK Parameter: Time to reach maximum concentration (tmax) of DNL921 in serum(Up to 242 Days)
- Parts B and C: PK Parameter: Accumulation ratio of DNL921 in serum(242 Days)
- PK Parameter: Area under the concentration-time curve (AUC) from time zero to time of last measurable concentration (AUClast) of DNL921 in serum(Up to 242 Days)
- Part A: PK Parameter: AUC from time zero to infinity of DNL921 in serum(46 Days)
- PK Parameter: Elimination half-life (t1/2) of DNL921 in serum(Up to 242 Days)
- Parts B and C: PK Parameter: Time to reach minimum concentration (Cmin) of DNL921 in serum(242 Days)
- Parts B and C: PK Parameter: AUC during a dosing interval (AUCtau) of DNL921 in serum(242 Days)
- Parts B and C: Change from baseline in brain amyloid load at Weeks 12 and 28 as measured by amyloid PET scan(28 Weeks)
- Parts B and C: Amyloid clearance at Weeks 12 and 28 as measured by amyloid PET scan(28 Weeks)
研究者
研究点 (1)
Loading locations...
相似试验
招募中
1 期
A Randomized, Phase Ib, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of SKB575 (HBM7575) in Participants With AsthmaAsthma (Diagnosis)NCT07732023Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.36
招募中
2 期
Intra-Articular Allocetra in Patients With Primary Knee OsteoarthritisPrimary Knee OsteoarthritisNCT07580716Enlivex Therapeutics Ltd.270
招募中
2 期
A Phase II Study With Exploratory Outcomes of Fucose Supplementation in GLUT1 Deficiency SyndromeGlut1 DeficiencyGLUT1DS1NCT07432490Oregon Health and Science University16
招募中
2 期
A Study of Praliciguat in Participants With Focal Segmental Glomerulosclerosis (FSGS)Focal Segmental GlomerulosclerosisNCT07268638Akebia Therapeutics60
招募中
2 期
A Study to Investigate the Clinical Effect and the Safety of PRX-115 Infused Intravenously at Different Dosing Regimens, With and Without Methotrexate, Versus Placebo in Adults Gout Patients (RELEASE)GoutNCT07280156Protalix150