A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Assess the Efficacy, Safety, and Tolerability of BIIB080 in Subjects With Mild Cognitive Impairment Due to Alzheimer's Disease or Mild Alzheimer's Disease Dementia
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- Biogen
- 入组人数
- 416
- 试验地点
- 274
- 主要终点
- Dose response in Change From Baseline to Week 76 on the CDR-SB
研究概览
简要总结
In this study, researchers will learn more about a study drug called diranersen (BIIB080). The study will focus on participants with mild cognitive impairment or mild dementia due to AD.
The main question researchers are trying to answer is if diranersen can slow the worsening of AD more than placebo. It will focus on what dose of diranersen slows worsening of AD the most.
To help answer this question, researchers will use the Clinical Dementia Rating-Sum of Boxes, also known as the CDR-SB.
- Clinicians use the CDR-SB to measure several categories of dementia symptoms.
- The results for each category are added together for a total score. Lower scores are better.
Researchers will also learn more about the safety of diranersen.
The study will be split into 2 parts. The 1st part is the Placebo-Controlled Period. The 2nd part is the Long-Term Extension (LTE) Period. The 2nd part of the study will help researchers learn about the long-term safety of diranersen, and how it affects the participant's daily life, thinking, and memory abilities in the longer term.
A description of how the study will be done is given below.
- After screening, participants will first receive either a low dose or high dose of diranersen, or a placebo, as an injection into the fluid around the spinal cord (cerebrospinal fluid). A placebo looks like the study drug but contains no real medicine.
- Participants will receive diranersen or placebo once every 12 weeks or 24 weeks.
- After 76 weeks of treatment in the Placebo-Controlled Period, eligible participants will move onto the Extension Treatment period, which will last 96 weeks.
- In the extension period, participants who received placebo will be switched to high dose diranersen every 12 or 24 weeks.
- Participants may be in the study for up to 201 weeks, or about 4 years. This includes the screening and follow-up periods.
- Participants can continue to take certain medications for AD. Participants must be on the same dose of medication for at least 8 weeks before the screening period.
- After the screening period, most participants will visit the clinic every 6 weeks.
详细描述
Diranersen is an investigational antisense therapy designed to target microtubule-associated protein tau (MAPT) messenger ribonucleic acid (mRNA) and prevent production of tau protein.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •for Placebo-controlled Period:
- •Must meet all the clinical staging criteria for MCI due to AD (Stage 3) or mild AD dementia (Stage 4) according to the National Institute on Aging at National Institutes of Health and the Alzheimer's Association (NIA-AA) and must have the following at Screening Visit 1:
- •Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Delayed Memory Index score of ≤85, indicative of objective evidence of memory impairment.
- •CDR global score of 0.5 for MCI due to AD or 0.5 or 1 for mild AD dementia
- •MMSE score of 21 to 30 (inclusive).
- •CDR Memory Box score of ≥0.
- •Evidence of amyloid pathology as measured by positive emission tomography (PET) or cerebrospinal fluid (CSF) sampling.
- •Must have 1 care partner who, in the Investigator's judgment, has frequent and sufficient contact with the participant (at least 10 hours/week) to be able to provide accurate information about the participant's cognitive and functional abilities.
- •Key Inclusion Criteria for LTE Period
- •Ability of the participant and/or his/her legally authorized representative (e.g., parent, spouse, or legal guardian), where local regulations and institutional practices permit, as appropriate and applicable, to understand the purpose and risks of the study, to provide informed consent, and to authorize the use of confidential health information in accordance with national and local privacy regulations. Incapacitated individuals will not be enrolled in the EU (European Union) and other countries where local laws, regulations, and practices do not permit their inclusion.
- •Participants must have completed the placebo-controlled period of the study, including the Week 76 visit.
- •Participants must have taken at least 5 doses of diranersen or placebo during the placebo-controlled period.
- •Medically able to undergo the study procedures (including LP [lumbar puncture]) and to adhere to the visit schedule at the time of study entry into the LTE period, as determined by the Investigator.
- •Apart from a clinical diagnosis of AD, the participant must be in good health as determined by the Investigator, based on medical history.
- •Must have 1 care partner who, in the Investigator's judgment, has frequent and sufficient contact with the participant (at least 10 hours/week) to be able to provide accurate information about the participant's cognitive and functional abilities.
排除标准
- •for Placebo-controlled Period:
- •Known allergy to diranersen or a history of hypersensitivity to any of the inactive ingredients in the drug product.
- •Previous participation in this study or previous studies with diranersen.
- •Use of non-disease-modifying AD medications (including but not limited to donepezil, rivastigmine, galantamine, tacrine, and memantine) at doses that have not been stable for at least 8 weeks prior to Screening Visit 1 and during the screening period up to Day
- •Use of any commercially available disease-modifying AD medications such as anti-amyloid monoclonal antibodies.
- •Prior participation in any active or passive immunotherapy study targeting Aβ, unless documentation of receipt of placebo is available.
- •Prior participation in any passive immunotherapy study targeting tau, unless the last administration occurred 6 months or 5 half-lives, whichever is sooner, prior to Screening or documentation of receipt of placebo is available.
- •Prior participation in any study involving an investigational treatment targeting tau that is not a passive immunotherapy, unless documentation of receipt of placebo is available.
- •Prior participation in a study of any other agent(s) not included in exclusion criteria 5, 6, and 7 with a purported disease-modifying effect in AD within 12 months, unless documentation of receipt of placebo is available.
- •Prior participation in a study of any gene therapy with a purported disease-modifying effect in AD, unless documentation of receipt of placebo is available.
- •Current use or previous use of medications with a purported disease-modifying effect in AD, outside of investigational studies.
- •Any vaccination given within 10 days prior to Day -
- •Coronavirus disease 2019 (COVID-19) vaccinations using RNA or deoxyribonucleic acid (DNA) technology are allowed during the study, as well as other types of immunization/vaccination/booster, except during the 10 days before and after clinic visits.
- •Contraindications to having a brain magnetic resonance imaging (MRI) [e.g., MRI-incompatible pacemaker; MRI-incompatible aneurysm clips, artificial heart valves, or other metal foreign body; claustrophobia that cannot be medically managed]. If the MRI compatibility of implanted devices is unknown, the participant must be excluded from the study.
- •Current enrollment or a plan to enroll in any interventional clinical study in which an investigational treatment or approved therapy for investigational use is administered within 52 weeks prior to the Baseline Visit.
- •Key Exclusion Criteria for LTE Period
- •Any medical or psychiatric contraindication or clinically significant abnormality that, in the opinion of the Investigator, will substantially increase the risk associated with the participant's enrollment in and completion of the study.
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
BIIB080 High Dose Q12W
Participants will receive a high dose of BIIB080, IT injection, once on Day 1 and then Q12W for up to 72 weeks during the placebo-controlled period. Eligible participants will enter the LTE period, during which they will continue to receive BIIB080 high dose, IT injection, Q12W for an additional 96 weeks.
干预措施: BIIB080 (Drug)
BIIB080 Low Dose Q24W
Participants will receive a low dose of BIIB080, IT injection, Q24W from Week 1 up to 72 weeks and BIIB080-matching placebo, IT injection, once at Weeks 12, 36, and 60 during the placebo-controlled period. Eligible participants will enter the LTE period, during which they will continue to receive BIIB080 low dose, IT injection, Q24W for an additional 96 weeks.
干预措施: BIIB080 (Drug)
BIIB080 High Dose Q24W
Participants will receive a high dose of BIIB080, IT injection, Q24W from Week 1 up to 72 weeks and BIIB080-matching placebo, IT injection, once at Weeks 12, 36, and 60 during the placebo-controlled period. Eligible participants will enter the LTE period, during which they will continue to receive BIIB080 high dose, IT injection, Q24W for an additional 96 weeks.
干预措施: BIIB080 (Drug)
Placebo Q12W
Participants will receive BIIB080-matching placebo, intrathecal (IT) injection, once on Day 1 and then once every 12 weeks (Q12W) for up to 72 weeks, during the placebo-controlled period. Eligible participants will enter the LTE period, during which they will be randomized to receive BIIB080 high dose, IT injection, either Q12W or once every 24 weeks (Q24W) for an additional 96 weeks.
干预措施: BIIB080 (Drug)
结局指标
主要结局
Dose response in Change From Baseline to Week 76 on the CDR-SB
时间窗: Baseline to Week 76
The Clinical Dementia Rating (CDR) scale is a clinician-rated dementia staging system that tracks the progression of cognitive impairment in 6 categories (memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care). Each category is scored on a 5-point scale in which None=0, Questionable=0.5, Mild=1, Moderate=2, and Severe=3. The global CDR score is established by clinical scoring rules and has values of 0 (no dementia), 0.5, (questionable dementia), 1 (mild dementia), 2 (moderate dementia), and 3 (severe dementia). The CDR-SB is obtained by adding the ratings in each of the 6 categories and ranges from 0 to 18 with higher scores indicative of greater impairment.
次要结局
- Change From Baseline to Week 76 on the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog 13)(Baseline to Week 76)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(From first dose of study drug up to end of study of placebo-controlled period (up to Week 96))
- Change From Baseline to Week 76 on the CDR-SB(Baseline to Week 76)
- Change From Baseline to Week 76 on the Alzheimer's Disease Cooperative Study Activities of Daily Living for Mild Cognitive Impairment (ADCS-ADL-MCI)(Baseline to Week 76)
- Change From Baseline to Week 76 on the Modified Integrated Alzheimer's Disease Rating Scale (iADRS)(Baseline to Week 76)
- Change From Baseline to Week 76 on the Mini Mental State Examination (MMSE)(Baseline to Week 76)
- Change From Baseline to Week 76 on the Alzheimer's Disease Composite Score (ADCOMS)(Baseline to Week 76)