A Study to Learn About the Safety of 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
- Conditions
- Alzheimer's Disease DementiaMild Cognitive Impairment Due to Alzheimer's Disease
- Interventions
- Drug: BIIB080-matching placebo
- Registration Number
- NCT05399888
- Lead Sponsor
- Biogen
- Brief Summary
In this study, researchers will learn more about a study drug called 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 BIIB080 can slow the worsening of AD more than placebo. It will focus on what dose of BIIB080 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 BIIB080.
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 BIIB080, 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 BIIB080, 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 BIIB080 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 BIIB080 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.
- Detailed Description
BIIB080 is an investigational antisense therapy designed to target microtubule-associated protein tau (MAPT) messenger ribonucleic acid (mRNA) and prevent production of tau protein.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 416
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Q12W BIIB080 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. BIIB080 High Dose Q24W BIIB080-matching placebo 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. Placebo Q12W BIIB080-matching placebo 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. BIIB080 Low Dose Q24W BIIB080-matching placebo 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. BIIB080 High Dose Q12W BIIB080 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. BIIB080 Low Dose Q24W BIIB080 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. BIIB080 High Dose Q24W BIIB080 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.
- Primary Outcome Measures
Name Time Method Dose response in Change From Baseline to Week 76 on the CDR-SB 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.
- Secondary Outcome Measures
Name Time Method Change From Baseline to Week 76 on the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog 13) Baseline to Week 76 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.
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) 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.
Change From Baseline to Week 76 on the CDR-SB Baseline to Week 76 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.
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 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.
Change From Baseline to Week 76 on the Modified Integrated Alzheimer's Disease Rating Scale (iADRS) Baseline to Week 76 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.
Change From Baseline to Week 76 on the Mini Mental State Examination (MMSE) Baseline to Week 76 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.
Change From Baseline to Week 76 on the Alzheimer's Disease Composite Score (ADCOMS) Baseline to Week 76 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.
Trial Locations
- Locations (137)
Mary S. Easton Center for Alzheimer's Disease Research, UCLA
🇺🇸Los Angeles, California, United States
University of California San Diego Medical Center
🇺🇸San Diego, California, United States
University of California San Francisco (PARENT)
🇺🇸San Francisco, California, United States
Ålborg Universitets Hospital
🇩🇰Ålborg, Denmark
Charter Research, LLC
🇺🇸Winter Park, Florida, United States
Conquest Research
🇺🇸Winter Park, Florida, United States
Brigham and Women's Hospital Department of Neurology
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Lahey Clinic Medical Center - Burlington
🇺🇸Burlington, Massachusetts, United States
Neurological Associates of Albany, PC
🇺🇸Albany, New York, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
Neurology Consultants of Dallas, PA
🇺🇸Dallas, Texas, United States
Recherches Neuro-Hippocampe Inc., d/b/a Ottawa Memory Clinic
🇨🇦Ottawa, Ontario, Canada
Medical Arts Health Research Group
🇨🇦West Vancouver, British Columbia, Canada
HonorHealth Neurology
🇺🇸Scottsdale, Arizona, United States
The Medical Arts Health Research Group
🇨🇦Kamloops, British Columbia, Canada
Neurology Clinic, PC
🇺🇸Cordova, Tennessee, United States
Jewish General Hospital - NETWORK
🇨🇦Montreal, Quebec, Canada
AZ Groeninge
🇧🇪Kortrijk, Belgium
Azienda Ospedaliera Card. G. Panico
🇮🇹Tricase, Lecce, Italy
Tokyo Metropolitan Institute for Geriatrics and Gerontology
🇯🇵Itabashi-ku, Tokyo-To, Japan
FORBELI s.r.o.
🇨🇿Praha 6, Czechia
Universitaetsklinikum Ulm
🇩🇪Ulm, Baden Wuerttemberg, Germany
Universitaetsmedizin Goettingen
🇩🇪Goettingen, Niedersachsen, Germany
Hospital Universitari de Santa Maria
🇪🇸Lleida, Spain
Spitalzentrum Biel
🇨🇭Biel/Bienne, Switzerland
Kantonsspital St. Gallen
🇨🇭St. Gallen, Switzerland
NeuroClin Limited
🇬🇧Motherwell, Strathclyde, United Kingdom
Re Cognition Health Bristol
🇬🇧Bristol, United Kingdom
Dent Neurologic Institute
🇺🇸Amherst, New York, United States
Rocky Mountain Movement Disorders Center, PC
🇺🇸Englewood, Colorado, United States
Duke University
🇺🇸Durham, North Carolina, United States
Boston Center for Memory
🇺🇸Newton, Massachusetts, United States
Center for Neurosciences
🇺🇸Tucson, Arizona, United States
PNS Clinical Research, LLC dba
🇺🇸Orange, California, United States
Stanford Hospital and Clinics
🇺🇸Palo Alto, California, United States
New York University Medical Center PRIME
🇺🇸New York, New York, United States
South Shore Neurologic Associates, P.C.
🇺🇸Patchogue, New York, United States
Butler Hospital
🇺🇸Providence, Rhode Island, United States
AMC Research, LLC
🇺🇸Matthews, North Carolina, United States
NeuroScience Research Center, LLC.
🇺🇸Canton, Ohio, United States
Kingfisher Cooperative, LLC
🇺🇸Spokane, Washington, United States
University of Cincinnati Physicians Group, LLC
🇺🇸Cincinnati, Ohio, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
EvergreenHealth
🇺🇸Kirkland, Washington, United States
Royal Prince Alfred Hospital
🇦🇺Camperdown, New South Wales, Australia
St Vincent's Hospital Sydney
🇦🇺Darlinghurst, New South Wales, Australia
Liverpool Hospital
🇦🇺Liverpool, New South Wales, Australia
Southern Neurology
🇦🇺Kogarah, New South Wales, Australia
Mater Hospital Brisbane
🇦🇺South Brisbane, Queensland, Australia
UZ Brussel
🇧🇪Brussel, Belgium
Toronto Memory Program (Neurology Research Inc.)
🇨🇦Toronto, Ontario, Canada
Fakultni nemocnice Hradec Kralove
🇨🇿Hradec Kralove, Czechia
Fakultni nemocnice u sv. Anny v Brne
🇨🇿Brno, Czechia
Fakultni nemocnice Ostrava
🇨🇿Ostrava, Czechia
Fakultni nemocnice v Motole
🇨🇿Praha 5, Czechia
Vestra Clinics s.r.o.
🇨🇿Rychnov nad Kneznou, Czechia
Rigshospitalet
🇩🇰Copenhagen, Denmark
Itä-Suomen yliopisto, Kuopion kampus
🇫🇮Kuopio, Finland
CHU Strasbourg - Hôpital Hautepierre
🇫🇷Strasbourg Cedex, Bas Rhin, France
CHU Nantes - Hopital Nord Laënnec
🇫🇷Saint-Herblain, Loire Atlantique, France
Hopital Purpan
🇫🇷Toulouse Cedex 9, Haute Garonne, France
Hopital Gui de Chauliac
🇫🇷Montpellier, Herault, France
Hôpital La Grave
🇫🇷Toulouse Cedex 9, Haute Garonne, France
Hôpital Lariboisière
🇫🇷Paris cedex 10, Paris, France
Universitaetsmedizin Mannheim
🇩🇪Mannheim, Baden Wuerttemberg, Germany
Universitaetsklinikum Tuebingen
🇩🇪Tuebingen, Baden Wuerttemberg, Germany
Groupe Hospitalier Pitie-Salpetriere
🇫🇷Paris, France
CHU de Rouen - Hôpital Charles Nicolle
🇫🇷Rouen Cedex, Seine Maritime, France
Klinikum Bayreuth GmbH- Hohe Warte
🇩🇪Bayreuth, Bayern, Germany
Klinikum der Universität München
🇩🇪München, Bayern, Germany
Neuro Centrum Science GmbH
🇩🇪Erbach, Hessen, Germany
Deutsches Zentrum fuer Neurodegenerative Erkrankungen (DZNE)
🇩🇪Bonn, Nordrhein Westfalen, Germany
Klinikum Altenburger Land GmbH
🇩🇪Altenburg, Thueringen, Germany
Universitaetsklinikum Koeln
🇩🇪Koeln, Nordrhein Westfalen, Germany
Charité - Campus Charité Mitte
🇩🇪Berlin, Germany
Charité - Universitätsmedizin Berlin
🇩🇪Berlin, Germany
Katholisches Klinikum Bochum gGmbH
🇩🇪Bochum, Germany
Fondazione Istituto G.Giglio di Cefalù
🇮🇹Cefalù, Palermo, Italy
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)
🇮🇹Brescia, Italy
Ospedale San Raffaele
🇮🇹Milano, Italy
Azienda Ospedaliera e Universitaria di Perugia
🇮🇹Perugia, Italy
Fondazione IRCCS Istituto Neurologico Carlo Besta
🇮🇹Milano, Italy
Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza
🇮🇹Roma, Italy
Himeji Central Hospital Clinic
🇯🇵Himeji-shi, Hyogo-Ken, Japan
Podlaskie Centrum Psychogeriatrii
🇵🇱Bialystok, Poland
Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie Kliniczny Oddział Neurologii Oddział Udarowy
🇵🇱Lublin, Poland
Centrum Medyczne Senior
🇵🇱Sopot, Poland
Clinica Universidad de Navarra
🇪🇸Pamplona, Navarra, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Fundacio ACE
🇪🇸Barcelona, Spain
CAE Oroitu
🇪🇸Getxo, Vizcaya, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario Reina Sofia
🇪🇸Cordoba, Spain
Hospital Victoria Eugenia
🇪🇸Sevilla, Spain
Sahlgrenska Universitetssjukhuset, Mölndal Sjukhus
🇸🇪Mölndal, Sweden
Hospital Universitario Dr. Peset
🇪🇸Valencia, Spain
Hospital Universitari i Politecnic La Fe
🇪🇸Valencia, Spain
Ospedale Regionale di Lugano
🇨🇭Lugano, Ticino, Switzerland
Karolinska universitetssjukhuset - Huddinge
🇸🇪Stockholm, Sweden
Re:Cognition Health Ltd (London)
🇬🇧London, Greater London, United Kingdom
Institute of Psychiatry, Psychology and Neuroscience
🇬🇧London, Greater London, United Kingdom
The National Hospital for Neurology and Neurosurgery Centre
🇬🇧London, Greater London, United Kingdom
Warneford Hospital
🇬🇧Oxford, Oxfordshire, United Kingdom
Royal Hallamshire Hospital
🇬🇧Sheffield, South Yorkshire, United Kingdom
Re:Cognition Health - Birmingham
🇬🇧Birmingham, West Midlands, United Kingdom
Xenoscience Inc.
🇺🇸Phoenix, Arizona, United States
Sutter Institute for Medical Research
🇺🇸Sacramento, California, United States
K2 Medical Research, LLC
🇺🇸Orlando, Florida, United States
Advent Health
🇺🇸Orlando, Florida, United States
UZ Leuven
🇧🇪Leuven, Belgium
Hopital Roger Salengro - CHU Lille
🇫🇷Lille Cedex, Nord, France
Cliniques Universitaires Saint-Luc
🇧🇪Bruxelles, Belgium
Ehime University Hospital
🇯🇵Toon-shi, Ehime-Ken, Japan
Osaka Metropolitan University Hospital
🇯🇵Osaka-shi, Osaka-Fu, Japan
Osaka University Hospital
🇯🇵Suita-shi, Osaka-Fu, Japan
PROMENTE Sp. z o.o.
🇵🇱Bydgoszcz, Poland
Ospedale di Arzignano
🇮🇹Arzignano VI, Vicenza, Italy
Yokohama City Minato Red Cross Hospital
🇯🇵Yokohama-shi, Kanagawa-Ken, Japan
Brain Research Center Amsterdam
🇳🇱Amsterdam, Netherlands
SPZOZ Centralny Szpital Kliniczny UM w Lodzi
🇵🇱Lodz, Poland
Banner Sun Health Research Institute
🇺🇸Sun City, Arizona, United States
Nzoz Novo-Med
🇵🇱Katowice, Poland
Clinique de la Memoire de l'Outaouais
🇨🇦Gatineau, Quebec, Canada
Montreal Neurological Institute Clinical Research Unit
🇨🇦Montréal, Quebec, Canada
CRST, Clinical Research Services Turku
🇫🇮Turku, Finland
Nippon Medical School Musashi Kosugi Hospital
🇯🇵Kawasaki-shi, Kanagawa-Ken, Japan
SPZOZ Szpital Uniwersytecki w Krakowie
🇵🇱Krakow, Poland
Southampton General Hospital
🇬🇧Southampton, Hampshire, United Kingdom
UBC Hospital
🇨🇦Vancouver, British Columbia, Canada
Care Clinic Centrum Medyczne
🇵🇱Katowice, Poland
NeuroProtect Sp. z o.o.
🇵🇱Warszawa, Poland
Mazowiecki Szpital Wojewódzki w Warszawie Sp z oo
🇵🇱Warszawa, Poland
Hôpitaux Universitaires de Genève - HUG- Centre de la mémoire, Bâtiment A1 - Morier
🇨🇭Geneve, Switzerland
Hawaii Pacific Neuroscience
🇺🇸Honolulu, Hawaii, United States
Charing Cross Hospital
🇬🇧London, Greater London, United Kingdom
Greater Manchester Mental Health NHS Foundation Trust
🇬🇧Manchester, Greater Manchester, United Kingdom