Randomized, Double‑Blind, Placebo‑Controlled Trial of Intrathecal BIIB080 in Adults 50–80 y with MCI due to Alzheimer’s Disease or Mild AD Dementia
- Trial ID
- 2022-501644-15-01
- Protocol
- 247AD201
- Sponsor
- Biogen Idec Research Limited
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to characterize the **dose-response** in change from Baseline to Week 76 using the Clinical Dementia Rating-Sum of Boxes (CDR-SB) in participants with mild cognitive impairment due to Alzheimer's disease or mild Alzheimer's disease dementia. This is clinically relevant as it aims to determine the optimal dosing of BIIB080, potentially leading to improved management of cognitive symptoms in these patients.
Secondary objectives include:
- Testing the superiority of at least one dose arm of BIIB080 versus placebo in change from Baseline to Week 76 using CDR-SB.
- Evaluating the efficacy of BIIB080 versus placebo in change from Baseline to Week 76.
- Assessing the safety and tolerability of BIIB080 in participants with mild cognitive impairment due to Alzheimer's disease or with mild Alzheimer's disease dementia.
Participants
The clinical trial involves a total of **183 participants** diagnosed with **Mild Cognitive Impairment due to Alzheimer's Disease** or **Alzheimer's Disease Dementia**. The study population includes both male and female subjects, with an age range that corresponds to categories 3 and 4, indicating middle-aged to older adults. Participants were selected based on specific clinical criteria, including a Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Delayed Memory Index score of ≤85, a Clinical Dementia Rating (CDR) global score of 0.5 or 1, and a Mini-Mental State Examination (MMSE) score between 21 and 30. The trial population is characterized by individuals who, apart from their clinical diagnosis of Alzheimer's Disease, are in good health as determined by the investigator. Participants are required to have a care partner with sufficient contact to provide accurate information about their cognitive and functional abilities. The study includes a vulnerable population, and evidence of amyloid pathology is a prerequisite for participation. Lifestyle considerations such as diet and physical activity are not specified in the available data.
Plans and Procedures
The clinical trial is designed as a **randomized, double-blind, placebo-controlled, parallel-group study** to evaluate the efficacy, safety, and tolerability of BIIB080 in subjects with mild cognitive impairment due to **Alzheimer's disease** or mild Alzheimer's disease dementia. The trial will span an estimated duration from September 2023 to January 2029. Participants will be randomly assigned to receive either BIIB080, a placebo, or auxiliary treatments such as Neuraceq or Vizamyl, both of which are solutions for injection. The primary endpoint is to assess the dose-response in change from baseline to Week 76 using the Clinical Dementia Rating-Sum of Boxes (CDR-SB). Secondary endpoints include changes in various cognitive and functional assessments and the incidence of treatment-emergent adverse events.
The study involves several key visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Delayed Memory Index score of ≤85 and a CDR global score of 0.5 or 1. Participants will then undergo regular follow-up visits to monitor their response to treatment and any adverse events. The end-of-study visit will occur at Week 76, marking the completion of the placebo-controlled period. Participants who complete this period and meet specific criteria may continue into a long-term extension (LTE) period.
Participant involvement is expected to last up to 105 weeks, with the possibility of early termination if they are unable to adhere to the study protocol, experience significant adverse events, or withdraw consent. The trial is conducted under strict ethical guidelines, ensuring that participants and their legally authorized representatives provide informed consent and understand the study's purpose and risks. The study aims to provide valuable insights into the potential therapeutic benefits of BIIB080 for individuals with Alzheimer's disease-related cognitive impairment.
Treatment
The clinical trial involves the administration of **BIIB080**, an experimental medication formulated as a **solution for injection**. The active substance in BIIB080 is a **2'-O-(2-methoxyethyl) antisense oligonucleotide** targeting microtubule-associated protein tau pre-mRNA. This investigational drug is administered via **intrathecal use**. The dosing schedule is designed for a maximum treatment period of 105 weeks, with the specific dosage amount not explicitly defined in the provided data. Participant compliance with the dosing regimen will be monitored throughout the study.
In addition to the experimental treatment, the study includes the use of **Neuraceq**, a 300 MBq/mL solution for injection containing the active substance **florbetaben (18F)**. Neuraceq is administered **intravenously** and is used as an auxiliary treatment in the trial. The maximum daily and total dose for Neuraceq is 300 MBq, with a treatment period limited to a single day.
The trial also incorporates a **placebo** for BIIB080, which is an artificial cerebrospinal fluid diluent formulated as a solution for injection. The placebo is used to maintain the double-blind nature of the study, ensuring unbiased assessment of BIIB080's efficacy and safety.
Additionally, **VIZAMYL**, a 400 MBq/mL solution for injection containing **flutemetamol (18F)**, is utilized as an auxiliary treatment. VIZAMYL is administered **intravenously**, with a maximum daily and total dose of 185 MBq, also limited to a single day of treatment. This compound is used to support imaging assessments within the trial.
Efficacy
The efficacy of the investigational product BIIB080 in subjects with mild cognitive impairment due to Alzheimer's disease or mild Alzheimer's disease dementia will be assessed using several parameters. The primary endpoint is the **dose-response** in change from Baseline to Week 76 on the Clinical Dementia Rating-Sum of Boxes (CDR-SB). Secondary endpoints include changes from Baseline to Week 76 on the CDR-SB, ADCS-ADL-MCI, ADAS-Cog 13, MMSE, Modified iADRS, and ADCOMS. The number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) will also be evaluated.
Measurements will be collected at specified timepoints, with the primary and secondary endpoints focusing on the change from Baseline to Week 76. The CDR-SB, a validated scale, will be used to assess cognitive and functional performance. Other tools such as ADCS-ADL-MCI, ADAS-Cog 13, MMSE, Modified iADRS, and ADCOMS will provide additional insights into the cognitive and functional abilities of the participants. The study is designed to characterize the dose-response relationship and evaluate the safety and tolerability of BIIB080 over the course of the trial.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Key Inclusion Criteria for Placebo-controlled Period: Must meet all the clinical 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: 1) Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Delayed Memory Index score of ≤85, indicative of objective evidence of memory impairment 2) CDR global score of 0.5 for MCI due to AD or 0.5 or 1 for mild AD dementia 3) MMSE score of 21 to 30 (inclusive) 4) CDR Memory Box score of ≥0.5 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 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 Week 76 visit. • Participants must have taken at least 5 doses of BIIB080 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.
- Evidence of amyloid pathology as measured by positive emission tomography (PET) or cerebrospinal fluid (CSF) sampling
- Note: Other protocol defined Inclusion/Exclusion criteria may apply
Exclusion Criteria
- Known allergy to BIIB080 or a history of hypersensitivity to any of the inactive ingredients in the drug product
- Previous participation in this study or previous studies with BIIB080
- 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 Study Day 1
- 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 an immunotherapy, 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
- Prior participation in a study of any other agent(s) [including gene therapy] not included in exclusion criteria 4, 5, and 6 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 -1. 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 enrolment or a plan to enrol 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
- Note: Other protocol defined Inclusion/Exclusion criteria may apply
- 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 enrolment in and completion of the study.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Recruiting | 11 Sept 2023 | 18 |
 Czechia | Not Recruiting | 11 Sept 2023 | 18 |
 Denmark | Not Recruiting | 11 Sept 2023 | 4 |
 Finland | Not Recruiting | 11 Sept 2023 | 5 |
 France | Not Recruiting | 11 Sept 2023 | 18 |
 Germany | Not Recruiting | 11 Sept 2023 | 39 |
 Italy | Not Recruiting | 11 Sept 2023 | 46 |
 The Netherlands | Not Recruiting | 11 Sept 2023 | — |
 Poland | Not Recruiting | 11 Sept 2023 | 17 |
 Spain | Not Recruiting | 11 Sept 2023 | 52 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
VIZAMYL 400 MBq/mL solution for injection | Other | SOLUTION FOR INJECTION | INTRAVENOUS | 185 | 1 | PRD1651612 |
Neuraceq 300 MBq/mL solution for injection | Other | SOLUTION FOR INJECTION | INTRAVENOUS | 300 | 1 | PRD6020031 |
BIIB080 | Test | SOLUTION FOR INJECTION | INTRATHECAL USE | 00 | 105 | PRD9961667 |
BIIB080 | Test | SOLUTION FOR INJECTION | INTRATHECAL USE | 00 | 105 | PRD9961671 |
Placebo for BIIB080: artificial cerebrospinal fluid diluent, solution for injection. | Placebo | N/A | — | — | — | N/A |
VIZAMYL 400 MBq/mL solution for injection | Other | SOLUTION FOR INJECTION | INTRAVENOUS | 185 | 1 | PRD1651609 |