2023-506873-36-00
进行中（未招募）
3 期
A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of AL001 in Individuals at Risk For or With Frontotemporal Dementia Due to Heterozygous Mutations in the Progranulin Gene
干预措施latozinemab
概览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- Alector LLC
- 入组人数
- 79
- 试验地点
- 22
- 主要终点
- Change from baseline to Weeks 48, 72, and 96 in the CDR® plus NACC FTLD-SB.
概览
简要总结
To evaluate the efficacy of AL001 compared with placebo in symptomatic participants as measured by the CDR plus NACC FTLD-SB
研究设计
- 分配方式
- Non-randomized
- 主要目的
- Part 2
- 盲法
- None
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
- •Is a known carrier of a heterozygous loss-of-function GRN mutation causative of FTD with a global CDR® plus NACC FTLD score of 0 to 2, and: • A CDR® plus NACC FTLD-SB score ≤0.5 with an elevated level of serum NfL, or • A CDR® plus NACC FTLD-SB score of >0.5 with 1 or more of the 6 behavioral/cognitive symptoms required for a diagnosis of possible bvFTD (Rascovsky 2011), or a diagnosis of PPA (Gorno-Tempini 2011).
- •Age 25 to 85 years, inclusive, at Screening. Note: For participants in France, inclusion criterion #2 is:
- •At risk participants (with a CDR® plus NACC FTLD-SB score ≤0.5) who are 45 to 85 years of age, inclusive, at Screening, or symptomatic participants (with a CDR® plus NACC FTLD-SB >0.5) who are 25 to 85 years of age, inclusive, at Screening.
- •At Screening, women must be nonpregnant and nonlactating, and 1 of the following conditions must apply: a. Not a woman of childbearing potential (WOCBP) (either surgically sterilized or physiologically incapable of becoming pregnant, or at least 1-year post-menopausal [amenorrhea duration of 12 consecutive months with no identified cause other than menopause]). b. Is a WOCBP and agrees to use an acceptable contraceptive method from Screening until 10 weeks after the last dose of study treatment. Acceptable contraception is defined as using hormonal contraceptives (eg, combined oral contraceptive pill) or an intrauterine device combined with at least 1 of the following forms of contraception: a diaphragm, cervical cap, or condom. In addition, total abstinence, if in accordance with the lifestyle of the participant, is acceptable. c. WOCBP must have a serum pregnancy test conducted at screening. Additional requirements for pregnancy testing during and after study intervention are described in the Schedules of Assessments.
- •Men must agree to use acceptable contraception and not donate sperm from Day 0 until 10 weeks after the last dose of study treatment. Acceptable contraception for the male participant when having sexual intercourse with a WOCBP who is not currently pregnant is defined as using a condom. In addition, WOCBP partners must use hormonal contraceptives (eg, combined oral contraceptive pill) or an intrauterine device.
- •Agrees not to donate blood or blood products for transfusion for the duration of the study and for 1 year after the final dose of study treatment.
- •Willing to and can comply with the study protocol requirements, in the opinion of the Investigator.
- •Willing and able to give informed consent. If the patient is not competent, a legally authorized representative must provide informed consent on their behalf, and the patient must provide assent, in accordance with local regulations, guidelines, and institutional review board (IRB) or independent ethics committee (IEC). Note: For participants in Germany, inclusion criterion #7 is:
- •Willing and able to give informed consent. Participants who are not capable of comprehending the nature, significance, and implications of the clinical trial cannot participate in the trial.
- •Patient has the availability of a person (“study partner”) who has frequent and sufficient contact with the patient (at least 5 hours per week of in-person contact) and who can provide accurate information to the study site regarding the patient’s behavior, cognitive, and functional abilities, as well as their health, throughout the study. Requirements for the study partner include: a. Willing and able to provide informed consent to participate in the study as a study partner. b. The study partner must have sufficient cognitive capacity to accurately report upon the participant’s behavior, cognitive, and functional abilities, in the opinion of the Investigator. c. The study partner should be in sufficiently good general health to have a high likelihood of maintaining the same level of interaction with the participant and participation in study procedures throughout the study duration. d. The same study partner should participate throughout the duration of Part 1 of the study. If a change in study partner is necessary, the Medical Monitor must be contacted. e. Study partner agrees to provide information at investigational site visits that require partner input for COA completion. f. Study partner agrees to accompany the participant at COA visits, as follows: − At-risk participants (CDR® plus NACC FTLD-SB score ≤0.5) require the study partner at the COA visits only. − Symptomatic participants (CDR® plus NACC FTLD-SB score >0.5) require the study partner at each visit. − At-risk participants who become symptomatic (CDR® plus NACC FTLD-SB >0.5) during the study treatment period require the study partner at each visit moving forward through Study Completion.
排除标准
- •Dementia due to a condition other than FTD including, but not limited to, Alzheimer’s disease, Parkinson’s disease, dementia with Parkinsonism, rapid eye movement (REM) behavior disorder, dementia with Lewy bodies, Huntington disease, or vascular dementia.
- •Participant has a history of cancer except if it: a. Is considered likely to be cured or in remission for at least 12 months, b. Is not being actively treated with anticancer therapy or radiation and, in the opinion of the Investigator, is not likely to require treatment in the ensuing 3 years, c. Is considered to have low probability of recurrence (with supporting documentation from the treating oncologist if possible), including participants with ongoing antihormonal treatment (eg, tamoxifen), d. For prostate cancer, has not had significant progression within the past 2 years, and is stable and adequately controlled, e. For localized skin basal cell carcinoma or squamous cell carcinoma, the participant should continue with screening and seek treatment for the skin carcinoma. Note: For participants in Germany, exclusion criterion #10 is:
- •Participant has a history of cancer.
- •Positive for hepatitis B surface antigen, human immunodeficiency virus 1 or 2 antibodies or antigen, or history of spirochetal infection of the central nervous system (CNS) (eg, syphilis, borreliosis, or Lyme disease). Participants with a positive or equivocal hepatitis C virus antibody will be allowed to enroll if hepatitis C RNA is confirmed negative.
- •Significant kidney disease as indicated by either of the following: a. Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2, according to the re-expressed abbreviated (4-variable) Modification of Diet in Renal Disease (MDRD) Study equation, Note: MDRD equation is as follows: eGFR (mL/min/1.73 m2) = 175 × (standardized serum creatinine) – 1.154 × (Age) – 0.203 × (0.742 if female) × (1.212 if Black)*, or b. Creatinine ≥2 mg/dL Note: *In France, if the participant screened is Black, the coefficient of 1.000 should be utilized where “(1.212 if Black)” is noted. This will result in an additional safety margin for Black participants.
- •Impaired hepatic function as indicated by screening aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥2.5 × the upper limit of normal (ULN), and total bilirubin ≥1.5 × ULN. Note: Participants with Gilbert’s syndrome are eligible to participate if approved by the Medical Monitor. Note: For participants in Germany and France, exclusion criterion #13 is:
- •Impaired hepatic function as indicated by screening aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥2.5 × the upper limit of normal (ULN), and total bilirubin ≥2.0 × ULN. Note: Participants with Gilbert’s syndrome are eligible to participate if approved by the Medical Monitor.
- •Clinically significant hematologic abnormalities as indicated by hemoglobin ≤10 g/dL; white blood cells (WBC) ≤3,000/mm3; absolute neutrophil count ≤1,000/mm3; or platelet count ≤150,000/mm
- •Participants with hypertension who are not adequately and stably controlled as per the American College of Cardiology/American Heart Association (ACC/AHA) guidelines.
- •History or presence of an abnormal electrocardiogram (ECG) that is clinically significant, including complete left bundle branch block, second- or thirddegree atrioventricular block, or evidence of acute or subacute myocardial infarction or ischemia.
研究组 & 干预措施
latozinemab
Experimental
Participants receiving latozinemab
干预措施: latozinemab (Drug)
结局指标
主要结局
Change from baseline to Weeks 48, 72, and 96 in the CDR® plus NACC FTLD-SB.
Change from baseline to Weeks 48, 72, and 96 in the CDR® plus NACC FTLD-SB.
次要结局
- Change from baseline to Weeks 48, 72, and 96 on the CGI-S.
- Actual values at Weeks 48, 72, and 96 on the CGI-I.
- Change from baseline to Weeks 48, 72, and 96 on the RBANS.
研究者
Clinical Trial Information Desk
Scientific
Alector LLC
研究点 (22)
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