A Study to Learn About the Safety of Diranersen (BIIB080) Injections and Whether They Can Improve Symptoms of Participants With Mild Cognitive Impairment Due to Alzheimer's Disease (AD) or Mild AD Dementia Between 50 to 80 Years of Age (CELIA)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Mild Cognitive Impairment Due to Alzheimer's Disease; Alzheimer's Disease Dementia
• Intervention / Treatment: Drug: Diranersen; Drug: Diranersen-matching placebo

Detailed Description

Diranersen is an investigational antisense therapy designed to target microtubule-associated protein tau (MAPT) messenger ribonucleic acid (mRNA) and prevent production of tau protein.

• Study Type: Interventional
• Enrollment (Actual): 416
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
    • Darlinghurst, New South Wales, Australia, 2010
      • St Vincent's Hospital Sydney
    • Kogarah, New South Wales, Australia, 2217
      • Southern Neurology
    • Liverpool, New South Wales, Australia, 2170
      • Liverpool Hospital
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Mater Hospital Brisbane
• Belgium
  • Brussels, Belgium, 1200
    • Cliniques Universitaires Saint-Luc
  • Brussels, Belgium, 1090
    • UZ Brussel
  • Kortrijk, Belgium, 8500
    • Az Groeninge
  • Leuven, Belgium, 3000
    • UZ Leuven
• Canada
  • British Columbia
    • Kamloops, British Columbia, Canada, V2C 5T1
      • The Medical Arts Health Research Group
    • Vancouver, British Columbia, Canada, V6T 2B5
      • UBC Hospital
    • West Vancouver, British Columbia, Canada, V7T 1C5
      • Medical Arts Health Research Group
  • Ontario
    • Ottawa, Ontario, Canada, K1Z 1G3
      • Recherches Neuro-Hippocampe Inc., d/b/a Ottawa Memory Clinic
    • Toronto, Ontario, Canada, M3B 2S7
      • Toronto Memory Program (Neurology Research Inc.)
  • Quebec
    • Gatineau, Quebec, Canada, J8T 8J1
      • Clinique de la Mémoire de l'Outaouais
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital - NETWORK
    • Montreal, Quebec, Canada, H3A 2B4
      • Montreal Neurological Institute Clinical Research Unit
• Czechia
  • Brno, Czechia, 65691
    • Fakultni nemocnice u sv. Anny v Brne
  • Hradec Králové, Czechia, 50005
    • Fakultni nemocnice Hradec Kralove
  • Ostrava, Czechia, 70852
    • Fakultni Nemocnice Ostrava
  • Prague, Czechia, 150 06
    • Fakultni nemocnice v Motole
  • Prague, Czechia, 16000
    • FORBELI s.r.o.
  • Rychnov nad Kněžnou, Czechia, 516 01
    • Vestra Clinics s.r.o.
• Denmark
  • Aalborg, Denmark, 9100
    • Ålborg Universitets Hospital
  • Copenhagen, Denmark, 2100
    • Rigshospitalet
• Finland
  • Kuopio, Finland, 70210
    • Itä-Suomen yliopisto, Kuopion kampus
  • Turku, Finland, 20520
    • CRST, Clinical Research Services Turku
• France
  • Paris, France, 75013
    • Groupe Hospitalier Pitié-Salpêtrière
  • Bas Rhin
    • Strasbourg, Bas Rhin, France, 67000
      • CHU Strasbourg - Hôpital Hautepierre
  • Haute Garonne
    • Toulouse, Haute Garonne, France, 31059
      • Hopital Purpan
    • Toulouse, Haute Garonne, France, 31059
      • Hôpital La Grave
  • Herault
    • Montpellier, Herault, France, 34295
      • Hopital Gui de Chauliac
  • Loire Atlantique
    • Saint-Herblain, Loire Atlantique, France, 44800
      • CHU Nantes - Hopital Nord Laënnec
  • Nord
    • Lille, Nord, France, 59037
      • Hopital Roger Salengro - CHU Lille
  • Paris
    • Paris, Paris, France, 75010
      • Hopital Lariboisiere
  • Seine Maritime
    • Rouen, Seine Maritime, France, 76031
      • CHU de Rouen - Hôpital Charles Nicolle
• Germany
  • Berlin, Germany, 13125
    • Charité - Universitätsmedizin Berlin
  • Berlin, Germany, 10117
    • Charité - Campus Charité Mitte
  • Bochum, Germany, 44791
    • Katholisches Klinikum Bochum gGmbH
  • Baden-Wurttemberg
    • Mannheim, Baden-Wurttemberg, Germany, 68167
      • Universitaetsmedizin Mannheim
    • Tübingen, Baden-Wurttemberg, Germany, 72076
      • Universitaetsklinikum Tuebingen
    • Ulm, Baden-Wurttemberg, Germany, 89081
      • Universitaetsklinikum Ulm
  • Bavaria
    • Bayreuth, Bavaria, Germany, 95445
      • Klinikum Bayreuth GmbH- Hohe Warte
    • München, Bavaria, Germany, 81377
      • Klinikum der Universität München
  • Hesse
    • Erbach im Odenwald, Hesse, Germany, 64711
      • Neuro Centrum Science GmbH
  • Lower Saxony
    • Göttingen, Lower Saxony, Germany, 37075
      • Universitaetsmedizin Goettingen
  • North Rhine-Westphalia
    • Bonn, North Rhine-Westphalia, Germany, 53127
      • Deutsches Zentrum fuer Neurodegenerative Erkrankungen (DZNE)
    • Cologne, North Rhine-Westphalia, Germany, 50937
      • Universitaetsklinikum Koeln
  • Thuringia
    • Altenburg, Thuringia, Germany, 4600
      • Klinikum Altenburger Land GmbH
• Italy
  • Brescia, Italy, 25123
    • Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)
  • Milan, Italy, 20132
    • Ospedale San Raffaele
  • Milan, Italy, 20133
    • Fondazione IRCCS Istituto Neurologico Carlo BEsta
  • Perugia, Italy, 06156
    • Azienda Ospedaliera e Universitaria di Perugia
  • Roma, Italy, 185
    • Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza
  • Lecce
    • Tricase, Lecce, Italy, 73039
      • Azienda Ospedaliera Card. G. Panico
  • Palermo
    • Cefalù, Palermo, Italy, 90015
      • Fondazione Istituto G.Giglio di Cefalù
  • Vicenza
    • Arzignano VI, Vicenza, Italy, 36071
      • Ospedale di Arzignano
• Japan
  • Ehime
    • Toon-shi, Ehime, Japan, 791-0295
      • Ehime University Hospital
  • Hyōgo
    • Himeji-shi, Hyōgo, Japan, 672-8043
      • Himeji Central Hospital Clinic
  • Kanagawa
    • Kawasaki-shi, Kanagawa, Japan, 211-8533
      • Nippon Medical School Musashi Kosugi Hospital
    • Yokohama, Kanagawa, Japan, 231-8682
      • Yokohama City Minato Red Cross Hospital
  • Osaka
    • Osaka, Osaka, Japan, 545-8586
      • Osaka Metropolitan University Hospital
    • Suita-shi, Osaka, Japan, 565-0871
      • Osaka University Hospital
  • Tokyo-To
    • Itabashi-ku, Tokyo-To, Japan, 173-0015
      • Tokyo Metropolitan Institute for Geriatrics and Gerontology
• Netherlands
  • Amsterdam, Netherlands, Amsterdam
    • Brain Research Center Amsterdam
• Poland
  • Bialystok, Poland, 15-756
    • Podlaskie Centrum Psychogeriatrii
  • Bydgoszcz, Poland, 85-133
    • PROMENTE Sp. z o.o.
  • Katowice, Poland, 40-650
    • Nzoz Novo-Med
  • Katowice, Poland, 40568
    • Care Clinic Centrum Medyczne
  • Krakow, Poland, 30-688
    • SPZOZ Szpital Uniwersytecki w Krakowie
  • Lodz, Poland, 92-213
    • SPZOZ Centralny Szpital Kliniczny UM w Lodzi
  • Lublin, Poland, 20-954
    • Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie Kliniczny Oddział Neurologii Oddział Udarowy
  • Sopot, Poland, 81-855
    • Centrum Medyczne SENIOR
  • Warsaw, Poland, 01-684
    • NeuroProtect Sp. z o.o.
  • Warsaw, Poland, 03-242
    • Mazowiecki Szpital Wojewódzki w Warszawie Sp z oo
• Spain
  • Barcelona, Spain, 8025
    • Hospital de La Santa Creu I Sant Pau
  • Barcelona, Spain, 8036
    • Hospital Clinic de Barcelona
  • Barcelona, Spain, 8028
    • Fundacio ACE
  • Córdoba, Spain, 14004
    • Hospital Universitario Reina Sofia
  • Lleida, Spain, 25198
    • Hospital Universitari de Santa Maria
  • Seville, Spain, 41009
    • Hospital Victoria Eugenia
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe
  • Valencia, Spain, 46017
    • Hospital Universitario Dr. Peset
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Clinica Universidad de Navarra
  • Vizcaya
    • Getxo, Vizcaya, Spain, 48993
      • CAE Oroitu
• Sweden
  • Mölndal, Sweden, 43180
    • Sahlgrenska Universitetssjukhuset, Mölndal Sjukhus
  • Stockholm, Sweden, 14186
    • Karolinska universitetssjukhuset - Huddinge
• Switzerland
  • Biel/Bienne, Switzerland, 2501
    • Spitalzentrum Biel
  • Geneva, Switzerland, 1205
    • Hôpitaux Universitaires de Genève - HUG- Centre de la mémoire, Bâtiment A1 - Morier
  • Sankt Gallen, Switzerland, 9007
    • Kantonsspital St. Gallen
  • Canton Ticino
    • Lugano, Canton Ticino, Switzerland, 6903
      • Ospedale Regionale di Lugano
• United Kingdom
  • Bristol, United Kingdom, BS32 4SY
    • Re Cognition Health Bristol
  • Greater London
    • London, Greater London, United Kingdom, W6 8RF
      • Charing Cross Hospital
    • London, Greater London, United Kingdom, WC1N 3BG
      • The National Hospital for Neurology and Neurosurgery Centre
    • London, Greater London, United Kingdom, SE5 8AF
      • Institute of Psychiatry, Psychology and Neuroscience
    • London, Greater London, United Kingdom, W1G 9RU
      • Re:Cognition Health Ltd (London)
  • Greater Manchester
    • Manchester, Greater Manchester, United Kingdom, M13 9WL
      • Greater Manchester Mental Health NHS Foundation Trust
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO16 6YD
      • Southampton General Hospital
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 7JX
      • Warneford Hospital
  • South Yorkshire
    • Sheffield, South Yorkshire, United Kingdom, S10 2JF
      • Royal Hallamshire Hospital
  • Strathclyde
    • Motherwell, Strathclyde, United Kingdom, ML1 4UF
      • NeuroClin Limited
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B16 8LT
      • Re:Cognition Health - Birmingham
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85004
      • Xenoscience Inc.
    • Scottsdale, Arizona, United States, 85251
      • HonorHealth Neurology
    • Sun City, Arizona, United States, 85351
      • Banner Sun Health Research Institute
    • Tucson, Arizona, United States, 85718
      • Center For Neurosciences
  • California
    • Los Angeles, California, United States, 90095
      • Mary S. Easton Center for Alzheimer's Disease Research, UCLA
    • Orange, California, United States, 92868
      • PNS Clinical Research, LLC dba
    • Palo Alto, California, United States, 94304
      • Stanford Hospital and Clinics
    • Sacramento, California, United States, 95816
      • Sutter Institute for Medical Research
    • San Diego, California, United States, 92103
      • University of California San Diego Medical Center
    • San Francisco, California, United States, 94143
      • University of California San Francisco (PARENT)
  • Colorado
    • Englewood, Colorado, United States, 80113
      • Rocky Mountain Movement Disorders Center, PC
  • Florida
    • Lady Lake, Florida, United States, 32159
      • Charter Research, LLC
    • Orlando, Florida, United States, 32804
      • Advent Health
    • Orlando, Florida, United States, 32751
      • K2 Medical Research, LLC
    • Winter Park, Florida, United States, 32789
      • Conquest Research
    • Winter Park, Florida, United States, 32792
      • Charter Research, LLC
  • Hawaii
    • Honolulu, Hawaii, United States, 96817
      • Hawaii Pacific Neuroscience
  • Massachusetts
    • Boston, Massachusetts, United States, 02216
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02115-5804
      • Brigham and Women's Hospital Department of Neurology
    • Burlington, Massachusetts, United States, 01805
      • Lahey Clinic Medical Center - Burlington
    • Newton, Massachusetts, United States, 02459
      • Boston Center for Memory
  • New York
    • Albany, New York, United States, 12208
      • Neurological Associates of Albany, PC
    • Amherst, New York, United States, 14226
      • Dent Neurologic Institute
    • New York, New York, United States, 10016
      • New York University Medical Center PRIME
    • Patchogue, New York, United States, 11772
      • South Shore Neurologic Associates, P.C.
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University
    • Matthews, North Carolina, United States, 28105
      • AMC Research, LLC
  • Ohio
    • Canton, Ohio, United States, 44718
      • NeuroScience Research Center, LLC.
    • Cincinnati, Ohio, United States, 45206-0829
      • University of Cincinnati Physicians Group, LLC
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Butler Hospital
  • Tennessee
    • Cordova, Tennessee, United States, 38018
      • Neurology Clinic, PC
  • Texas
    • Dallas, Texas, United States, 75243
      • Neurology Consultants of Dallas, PA
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio
  • Washington
    • Kirkland, Washington, United States, 98034
      • EvergreenHealth
    • Spokane, Washington, United States, 99202
      • Kingfisher Cooperative, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria 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:

  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.
• 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.

Key Exclusion Criteria 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 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 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 -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 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Q12W; Participants will receive diranersen-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 diranersen high dose, IT injection, either Q12W or once every 24 weeks (Q24W) for an additional 96 weeks.	Drug: Diranersen; Administered as specified in the treatment arm.; Other Names: ISIS 814907; BIIB080; Drug: Diranersen-matching placebo; Administered as specified in the treatment arm.
Experimental: Diranersen Low Dose Q24W; Participants will receive a low dose of diranersen, IT injection, Q24W from Week 1 up to 72 weeks and diranersen-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 diranersen low dose, IT injection, Q24W for an additional 96 weeks.	Drug: Diranersen; Administered as specified in the treatment arm.; Other Names: ISIS 814907; BIIB080; Drug: Diranersen-matching placebo; Administered as specified in the treatment arm.
Experimental: Diranersen High Dose Q24W; Participants will receive a high dose of diranersen, IT injection, Q24W from Week 1 up to 72 weeks and diranersen-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 diranersen high dose, IT injection, Q24W for an additional 96 weeks.	Drug: Diranersen; Administered as specified in the treatment arm.; Other Names: ISIS 814907; BIIB080; Drug: Diranersen-matching placebo; Administered as specified in the treatment arm.
Experimental: Diranersen High Dose Q12W; Participants will receive a high dose of diranersen, 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 diranersen high dose, IT injection, Q12W for an additional 96 weeks.	Drug: Diranersen; Administered as specified in the treatment arm.; Other Names: ISIS 814907; BIIB080

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose response in Change From Baseline to Week 76 on the CDR-SB	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.	Baseline to Week 76

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 76 on the CDR-SB	The 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. Positive change from baseline indicates clinical decline.	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)	The ADCS-ADL-MCI consists of 17 instrumental items (e.g., shopping, preparing meals, using household appliances) and 1 basic item (getting dressed). Ratings reflect caregiver observations about the participant's actual functioning and provide an assessment of change in the functional state of the participant over time. The total score ranges from 0 to 53, with lower values over time reflecting functional deterioration. Positive change from baseline indicates clinical improvement.	Baseline to Week 76
Change From Baseline to Week 76 on the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog 13)	ADAS-Cog13 comprises both cognitive tasks and clinical ratings of cognitive performance. The scale items capture word recall, ability to follow commands, the ability to correctly copy or draw an image, naming, the ability to interact with everyday objects, orientation, word recognition, memory, comprehension of spoken language, word-finding, and language ability, with a measure for delayed word recall and concentration/distractibility. The total score ranges from 0 to 85. An increase in score over time indicates increasing cognitive impairment. Positive change from baseline indicates clinical decline.	Baseline to Week 76
Change From Baseline to Week 76 on the Mini Mental State Examination (MMSE)	The MMSE is a widely used performance-based test of global cognitive status. It consists of 11 tasks that assess orientation, word recall, attention and calculation, language abilities, and visuospatial functions. The scores from the 11 tests are combined to obtain the total score, which ranges from 0 to 30, with lower scores over time indicating increasing cognitive impairment. Positive change from baseline indicates clinical improvement.	Baseline to Week 76
Change From Baseline to Week 76 on the Modified Integrated Alzheimer's Disease Rating Scale (iADRS)	iADRS is a composite and is calculated as a linear combination of total scores of ADAS-Cog13 and Alzheimer's Disease Cooperative Study Instrumental Activities of Daily Living Inventory (ADCS-iADL) that measures cognition and daily function. ADCS-iADL is calculated from a subset of questions from ADCS-ADL. Range for ADCS-iADL is 0-59 and higher scores reflect better performance. ADAS-Cog13 comprises cognitive tasks and clinical ratings of cognitive performance. Scale items capture word recall, ability to follow commands, ability to correctly copy/draw, naming, ability to interact with everyday objects, orientation, word recognition, memory, spoken language comprehension, word-finding, and language ability, with a measure for delayed word recall and concentration/distractibility. Score ranges from 0 to 85 with higher scores reflecting cognitive impairment. iADRS score range is 0-144 and higher scores indicate greater impairment. Positive change from baseline indicates clinical decline.	Baseline to Week 76
Change From Baseline to Week 76 on the Alzheimer's Disease Composite Score (ADCOMS)	ADCOMS is a composite score comprised of ADAS-cog (4 items), MMSE (2 items) and CDR-SB (6 items). The total scores on the scale range from 0 to 1.97 with higher scores indicating greater impairment. Positive change from baseline indicates clinical decline.	Baseline to Week 76
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal (investigational) product, whether or not related to medicinal (investigational) product. TEAE is any AE that started or worsened on or after the administration of the first dose of study drug through the end of follow-up period. SAE is any untoward medical occurrence that at any dose results in death, in the view of investigator, places the participant at immediate risk of death (life-threatening event), requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in congenital anomaly/birth defect or is medically important event.	From first dose of study drug up to end of study of placebo-controlled period (up to Week 96)

Collaborators and Investigators

• Sponsor: Biogen
• Investigators: Study Director: Medical Director, Biogen

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2022
• Primary Completion (Actual): March 11, 2026
• Study Completion (Estimated): June 6, 2028

Study Registration Dates

• First Submitted: May 27, 2022
• First Submitted That Met QC Criteria: May 27, 2022
• First Posted (Actual): June 1, 2022

Study Record Updates

• Last Update Posted (Actual): June 30, 2026
• Last Update Submitted That Met QC Criteria: June 26, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Tauopathies; Neurodegenerative Diseases; Cognitive Dysfunction; Alzheimer Disease; Dementia
• Other Study ID Numbers: 247AD201; 2022-501644-15 (Other Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No