NCT05399888

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
416

participants targeted

Target at P75+ for phase_2

Timeline
33mo left

Started Aug 2022

Longer than P75 for phase_2

Geographic Reach
17 countries

138 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress58%
Aug 2022Jan 2029

First Submitted

Initial submission to the registry

May 27, 2022

Completed
5 days until next milestone

First Posted

Study publicly available on registry

June 1, 2022

Completed
3 months until next milestone

Study Start

First participant enrolled

August 24, 2022

Completed
3.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 14, 2026

Expected
2.7 years until next milestone

Study Completion

Last participant's last visit for all outcomes

January 8, 2029

Last Updated

May 18, 2025

Status Verified

May 1, 2025

Enrollment Period

3.7 years

First QC Date

May 27, 2022

Last Update Submit

May 16, 2025

Conditions

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (7)

  • 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 Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog 13)

    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 Modified Integrated Alzheimer's Disease Rating Scale (iADRS)

    Baseline to Week 76

  • +2 more secondary outcomes

Study Arms (4)

Placebo Q12W

PLACEBO COMPARATOR

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.

Drug: BIIB080Drug: BIIB080-matching placebo

BIIB080 Low Dose Q24W

EXPERIMENTAL

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.

Drug: BIIB080Drug: BIIB080-matching placebo

BIIB080 High Dose Q24W

EXPERIMENTAL

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.

Drug: BIIB080Drug: BIIB080-matching placebo

BIIB080 High Dose Q12W

EXPERIMENTAL

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.

Drug: BIIB080

Interventions

Administered as specified in the treatment arm.

Also known as: ISIS 814907
BIIB080 High Dose Q12WBIIB080 High Dose Q24WBIIB080 Low Dose Q24WPlacebo Q12W

Administered as specified in the treatment arm.

BIIB080 High Dose Q24WBIIB080 Low Dose Q24WPlacebo Q12W

Eligibility Criteria

Age50 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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 ≥0.5.
  • 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.
  • 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 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.

You may not qualify if:

  • 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 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 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.
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (138)

Xenoscience Inc.

Phoenix, Arizona, 85004, United States

Location

HonorHealth Neurology

Scottsdale, Arizona, 85251, United States

Location

Banner Sun Health Research Institute

Sun City, Arizona, 85351, United States

Location

Center for Neurosciences

Tucson, Arizona, 85718, United States

Location

Mary S. Easton Center for Alzheimer's Disease Research, UCLA

Los Angeles, California, 90095, United States

Location

PNS Clinical Research, LLC dba

Orange, California, 92868, United States

Location

Stanford Hospital and Clinics

Palo Alto, California, 94304, United States

Location

Sutter Institute for Medical Research

Sacramento, California, 95816, United States

Location

University of California San Diego Medical Center

San Diego, California, 92103, United States

Location

University of California San Francisco (PARENT)

San Francisco, California, 94143, United States

Location

Rocky Mountain Movement Disorders Center, PC

Englewood, Colorado, 80113, United States

Location

Charter Research, LLC

Lady Lake, Florida, 32159, United States

Location

K2 Medical Research, LLC

Orlando, Florida, 32751, United States

Location

Advent Health

Orlando, Florida, 32804, United States

Location

Conquest Research

Winter Park, Florida, 32789, United States

Location

Charter Research, LLC

Winter Park, Florida, 32792, United States

Location

Hawaii Pacific Neuroscience

Honolulu, Hawaii, 96817, United States

Location

Brigham and Women's Hospital Department of Neurology

Boston, Massachusetts, 02115-5804, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02216, United States

Location

Lahey Clinic Medical Center - Burlington

Burlington, Massachusetts, 01805, United States

Location

Boston Center for Memory

Newton, Massachusetts, 02459, United States

Location

Neurological Associates of Albany, PC

Albany, New York, 12208, United States

Location

Dent Neurologic Institute

Amherst, New York, 14226, United States

Location

New York University Medical Center PRIME

New York, New York, 10016, United States

Location

South Shore Neurologic Associates, P.C.

Patchogue, New York, 11772, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

AMC Research, LLC

Matthews, North Carolina, 28105, United States

Location

NeuroScience Research Center, LLC.

Canton, Ohio, 44718, United States

Location

University of Cincinnati Physicians Group, LLC

Cincinnati, Ohio, 45206-0829, United States

Location

Butler Hospital

Providence, Rhode Island, 02906, United States

Location

Neurology Clinic, PC

Cordova, Tennessee, 38018, United States

Location

Neurology Consultants of Dallas, PA

Dallas, Texas, 75243, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

EvergreenHealth

Kirkland, Washington, 98034, United States

Location

Kingfisher Cooperative, LLC

Spokane, Washington, 99202, United States

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

St Vincent's Hospital Sydney

Darlinghurst, New South Wales, 2010, Australia

Location

Southern Neurology

Kogarah, New South Wales, 2217, Australia

Location

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

Location

Mater Hospital Brisbane

South Brisbane, Queensland, 4101, Australia

Location

UZ Brussel

Brussels, 1090, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

AZ Groeninge

Kortrijk, 8500, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

The Medical Arts Health Research Group

Kamloops, British Columbia, V2C 5T1, Canada

Location

UBC Hospital

Vancouver, British Columbia, V6T 2B5, Canada

Location

Medical Arts Health Research Group

West Vancouver, British Columbia, V7T 1C5, Canada

Location

Recherches Neuro-Hippocampe Inc., d/b/a Ottawa Memory Clinic

Ottawa, Ontario, K1Z 1G3, Canada

Location

Toronto Memory Program (Neurology Research Inc.)

Toronto, Ontario, M3B 2S7, Canada

Location

Clinique de la Memoire de l'Outaouais

Gatineau, Quebec, J8T 8J1, Canada

Location

Montreal Neurological Institute Clinical Research Unit

Montreal, Quebec, H3A 2B4, Canada

Location

Jewish General Hospital - NETWORK

Montreal, Quebec, H3T 1E2, Canada

Location

Fakultni nemocnice u sv. Anny v Brne

Brno, 65691, Czechia

Location

Fakultni nemocnice Hradec Kralove

Hradec Králové, 50005, Czechia

Location

Fakultni nemocnice Ostrava

Ostrava, 70852, Czechia

Location

Fakultni nemocnice v Motole

Prague, 150 06, Czechia

Location

FORBELI s.r.o.

Prague, 16000, Czechia

Location

Vestra Clinics s.r.o.

Rychnov nad Kněžnou, 516 01, Czechia

Location

Ålborg Universitets Hospital

Aalborg, 9100, Denmark

Location

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Itä-Suomen yliopisto, Kuopion kampus

Kuopio, 70210, Finland

Location

CRST, Clinical Research Services Turku

Turku, 20520, Finland

Location

CHU Strasbourg - Hôpital Hautepierre

Strasbourg, Bas Rhin, 67000, France

Location

Hopital Purpan

Toulouse, Haute Garonne, 31059, France

Location

Hôpital La Grave

Toulouse, Haute Garonne, 31059, France

Location

Hopital Gui de Chauliac

Montpellier, Herault, 34295, France

Location

CHU Nantes - Hopital Nord Laënnec

Saint-Herblain, Loire Atlantique, 44800, France

Location

Hopital Roger Salengro - CHU Lille

Lille, Nord, 59037, France

Location

Hôpital Lariboisière

Paris, Paris, 75010, France

Location

CHU de Rouen - Hôpital Charles Nicolle

Rouen, Seine Maritime, 76031, France

Location

Groupe Hospitalier Pitie-Salpetriere

Paris, 75013, France

Location

Universitaetsmedizin Mannheim

Mannheim, Baden-Wurttemberg, 68167, Germany

Location

Universitaetsklinikum Tuebingen

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

Universitaetsklinikum Ulm

Ulm, Baden-Wurttemberg, 89081, Germany

Location

Klinikum Bayreuth GmbH- Hohe Warte

Bayreuth, Bavaria, 95445, Germany

Location

Klinikum der Universität München

München, Bavaria, 81377, Germany

Location

Neuro Centrum Science GmbH

Erbach im Odenwald, Hesse, 64711, Germany

Location

Universitaetsmedizin Goettingen

Göttingen, Lower Saxony, 37075, Germany

Location

Deutsches Zentrum fuer Neurodegenerative Erkrankungen (DZNE)

Bonn, North Rhine-Westphalia, 53127, Germany

Location

Universitaetsklinikum Koeln

Cologne, North Rhine-Westphalia, 50937, Germany

Location

Klinikum Altenburger Land GmbH

Altenburg, Thuringia, 4600, Germany

Location

Charité - Campus Charité Mitte

Berlin, 10117, Germany

Location

Charité - Universitätsmedizin Berlin

Berlin, 13125, Germany

Location

Katholisches Klinikum Bochum gGmbH

Bochum, 44791, Germany

Location

Azienda Ospedaliera Card. G. Panico

Tricase, Lecce, 73039, Italy

Location

Fondazione Istituto G.Giglio di Cefalù

Cefalù, Palermo, 90015, Italy

Location

Ospedale di Arzignano

Arzignano VI, Vicenza, 36071, Italy

Location

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)

Brescia, 25123, Italy

Location

Ospedale San Raffaele

Milan, 20132, Italy

Location

Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, 20133, Italy

Location

Azienda Ospedaliera e Universitaria di Perugia

Perugia, 06156, Italy

Location

Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza

Roma, 185, Italy

Location

Ehime University Hospital

Toon-shi, Ehime, 791-0295, Japan

Location

Himeji Central Hospital Clinic

Himeji-shi, Hyōgo, 672-8043, Japan

Location

Nippon Medical School Musashi Kosugi Hospital

Kawasaki-shi, Kanagawa, 211-8533, Japan

Location

Yokohama City Minato Red Cross Hospital

Yokohama, Kanagawa, 231-8682, Japan

Location

Osaka Metropolitan University Hospital

Osaka, Osaka, 545-8586, Japan

Location

Osaka University Hospital

Suita-shi, Osaka, 565-0871, Japan

Location

Tokyo Metropolitan Institute for Geriatrics and Gerontology

Itabashi-ku, Tokyo-To, 173-0015, Japan

Location

Brain Research Center Amsterdam

Amsterdam, Amsterdam, Netherlands

Location

Podlaskie Centrum Psychogeriatrii

Bialystok, 15-756, Poland

Location

PROMENTE Sp. z o.o.

Bydgoszcz, 85-133, Poland

Location

Nzoz Novo-Med

Katowice, 40-650, Poland

Location

Care Clinic Centrum Medyczne

Katowice, 40568, Poland

Location

SPZOZ Szpital Uniwersytecki w Krakowie

Krakow, 30-688, Poland

Location

SPZOZ Centralny Szpital Kliniczny UM w Lodzi

Lodz, 92-213, Poland

Location

Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie Kliniczny Oddział Neurologii Oddział Udarowy

Lublin, 20-954, Poland

Location

Centrum Medyczne Senior

Sopot, 81-855, Poland

Location

NeuroProtect Sp. z o.o.

Warsaw, 01-684, Poland

Location

Mazowiecki Szpital Wojewódzki w Warszawie Sp z oo

Warsaw, 03-242, Poland

Location

Clinica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

Location

CAE Oroitu

Getxo, Vizcaya, 48993, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 8025, Spain

Location

Fundacio ACE

Barcelona, 8028, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 8036, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, 14004, Spain

Location

Hospital Universitari de Santa Maria

Lleida, 25198, Spain

Location

Hospital Victoria Eugenia

Seville, 41009, Spain

Location

Hospital Universitario Dr. Peset

Valencia, 46017, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

Location

Sahlgrenska Universitetssjukhuset, Mölndal Sjukhus

Mölndal, 43180, Sweden

Location

Karolinska universitetssjukhuset - Huddinge

Stockholm, 14186, Sweden

Location

Ospedale Regionale di Lugano

Lugano, Canton Ticino, 6903, Switzerland

Location

Spitalzentrum Biel

Biel/Bienne, 2501, Switzerland

Location

Hôpitaux Universitaires de Genève - HUG- Centre de la mémoire, Bâtiment A1 - Morier

Geneva, 1205, Switzerland

Location

Kantonsspital St. Gallen

Sankt Gallen, 9007, Switzerland

Location

Institute of Psychiatry, Psychology and Neuroscience

London, Greater London, SE5 8AF, United Kingdom

Location

Re:Cognition Health Ltd (London)

London, Greater London, W1G 9RU, United Kingdom

Location

Charing Cross Hospital

London, Greater London, W6 8RF, United Kingdom

Location

The National Hospital for Neurology and Neurosurgery Centre

London, Greater London, WC1N 3BG, United Kingdom

Location

Greater Manchester Mental Health NHS Foundation Trust

Manchester, Greater Manchester, M13 9WL, United Kingdom

Location

Southampton General Hospital

Southampton, Hampshire, SO16 6YD, United Kingdom

Location

Warneford Hospital

Oxford, Oxfordshire, OX3 7JX, United Kingdom

Location

Royal Hallamshire Hospital

Sheffield, South Yorkshire, S10 2JF, United Kingdom

Location

NeuroClin Limited

Motherwell, Strathclyde, ML1 4UF, United Kingdom

Location

Re:Cognition Health - Birmingham

Birmingham, West Midlands, B16 8LT, United Kingdom

Location

Re Cognition Health Bristol

Bristol, BS32 4SY, United Kingdom

Location

Study Officials

  • Medical Director

    Biogen

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 27, 2022

First Posted

June 1, 2022

Study Start

August 24, 2022

Primary Completion (Estimated)

May 14, 2026

Study Completion (Estimated)

January 8, 2029

Last Updated

May 18, 2025

Record last verified: 2025-05

Data Sharing

IPD Sharing
Will share

In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/

More information

Locations