Clinical trial NCT05399888: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Mild Cognitive Impairment Due to Alzheimer's Disease
Alzheimer's Disease Dementia
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2022-06-01
Enrollment: 416
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 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.

Key Exclusion Criteria for Placebo-controlled Period:

* 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 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.

Primary outcomes:
measure: Dose response in Change From Baseline to Week 76 on the CDR-SB
timeFrame: Baseline to Week 76
Secondary outcomes:
measure: Change From Baseline to Week 76 on the CDR-SB
timeFrame: Baseline to Week 76
measure: Change From Baseline to Week 76 on the Alzheimer's Disease Cooperative Study Activities of Daily Living for Mild Cognitive Impairment (ADCS-ADL-MCI)
timeFrame: Baseline to Week 76
measure: Change From Baseline to Week 76 on the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog 13)
timeFrame: Baseline to Week 76
measure: Change From Baseline to Week 76 on the Mini Mental State Examination (MMSE)
timeFrame: Baseline to Week 76
measure: Change From Baseline to Week 76 on the Modified Integrated Alzheimer's Disease Rating Scale (iADRS)
timeFrame: Baseline to Week 76
measure: Change From Baseline to Week 76 on the Alzheimer's Disease Composite Score (ADCOMS)
timeFrame: Baseline to Week 76
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: From first dose of study drug up to end of study of placebo-controlled period (up to Week 96)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Xenoscience Inc.
state: Arizona
city: Scottsdale
country: United States
facility: HonorHealth Neurology
state: Arizona
city: Sun City
country: United States
facility: Banner Sun Health Research Institute
state: Arizona
city: Tucson
country: United States
facility: Center for Neurosciences
state: Arizona
city: Los Angeles
country: United States
facility: Mary S. Easton Center for Alzheimer's Disease Research, UCLA
state: California
city: Orange
country: United States
facility: PNS Clinical Research, LLC dba
state: California
city: Palo Alto
country: United States
facility: Stanford Hospital and Clinics
state: California
city: Sacramento
country: United States
facility: Sutter Institute for Medical Research
state: California
city: San Diego
country: United States
facility: University of California San Diego Medical Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco (PARENT)
state: California
city: Englewood
country: United States
facility: Rocky Mountain Movement Disorders Center, PC
state: Colorado
city: Lady Lake
country: United States
facility: Charter Research, LLC
state: Florida
city: Orlando
country: United States
facility: K2 Medical Research, LLC
state: Florida
city: Orlando
country: United States
facility: Advent Health
state: Florida
city: Winter Park
country: United States
facility: Conquest Research
state: Florida
city: Winter Park
country: United States
facility: Charter Research, LLC
state: Florida
city: Honolulu
country: United States
facility: Hawaii Pacific Neuroscience
state: Hawaii
city: Boston
country: United States
facility: Brigham and Women's Hospital Department of Neurology
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Burlington
country: United States
facility: Lahey Clinic Medical Center - Burlington
state: Massachusetts
city: Newton
country: United States
facility: Boston Center for Memory
state: Massachusetts
city: Albany
country: United States
facility: Neurological Associates of Albany, PC
state: New York
city: Amherst
country: United States
facility: Dent Neurologic Institute
state: New York
city: New York
country: United States
facility: New York University Medical Center PRIME
state: New York
city: Patchogue
country: United States
facility: South Shore Neurologic Associates, P.C.
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Matthews
country: United States
facility: AMC Research, LLC
state: North Carolina
city: Canton
country: United States
facility: NeuroScience Research Center, LLC.
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati Physicians Group, LLC
state: Ohio
city: Providence
country: United States
facility: Butler Hospital
state: Rhode Island
city: Cordova
country: United States
facility: Neurology Clinic, PC
state: Tennessee
city: Dallas
country: United States
facility: Neurology Consultants of Dallas, PA
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Kirkland
country: United States
facility: EvergreenHealth
state: Washington
city: Spokane
country: United States
facility: Kingfisher Cooperative, LLC
state: Washington
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Darlinghurst
country: Australia
facility: St Vincent's Hospital Sydney
state: New South Wales
city: Kogarah
country: Australia
facility: Southern Neurology
state: New South Wales
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: South Brisbane
country: Australia
facility: Mater Hospital Brisbane
state: Queensland
city: Brussel
country: Belgium
facility: UZ Brussel
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Kortrijk
country: Belgium
facility: AZ Groeninge
city: Leuven
country: Belgium
facility: UZ Leuven
city: Kamloops
country: Canada
facility: The Medical Arts Health Research Group
state: British Columbia
city: Vancouver
country: Canada
facility: UBC Hospital
state: British Columbia
city: West Vancouver
country: Canada
facility: Medical Arts Health Research Group
state: British Columbia
city: Ottawa
country: Canada
facility: Recherches Neuro-Hippocampe Inc., d/b/a Ottawa Memory Clinic
state: Ontario
city: Toronto
country: Canada
facility: Toronto Memory Program (Neurology Research Inc.)
state: Ontario
city: Gatineau
country: Canada
facility: Clinique de la Memoire de l'Outaouais
state: Quebec
city: Montreal
country: Canada
facility: Jewish General Hospital - NETWORK
state: Quebec
city: Montréal
country: Canada
facility: Montreal Neurological Institute Clinical Research Unit
state: Quebec
city: Brno
country: Czechia
facility: Fakultni nemocnice u sv. Anny v Brne
city: Hradec Kralove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
city: Ostrava
country: Czechia
facility: Fakultni nemocnice Ostrava
city: Praha 5
country: Czechia
facility: Fakultni nemocnice v Motole
city: Praha 6
country: Czechia
facility: FORBELI s.r.o.
city: Rychnov nad Kneznou
country: Czechia
facility: Vestra Clinics s.r.o.
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Ålborg
country: Denmark
facility: Ålborg Universitets Hospital
city: Kuopio
country: Finland
facility: Itä-Suomen yliopisto, Kuopion kampus
city: Turku
country: Finland
facility: CRST, Clinical Research Services Turku
city: Strasbourg Cedex
country: France
facility: CHU Strasbourg - Hôpital Hautepierre
state: Bas Rhin
city: Toulouse Cedex 9
country: France
facility: Hopital Purpan
state: Haute Garonne
city: Toulouse Cedex 9
country: France
facility: Hôpital La Grave
state: Haute Garonne
city: Montpellier
country: France
facility: Hopital Gui de Chauliac
state: Herault
city: Saint-Herblain
country: France
facility: CHU Nantes - Hopital Nord Laënnec
state: Loire Atlantique
city: Lille Cedex
country: France
facility: Hopital Roger Salengro - CHU Lille
state: Nord
city: Paris cedex 10
country: France
facility: Hôpital Lariboisière
state: Paris
city: Rouen Cedex
country: France
facility: CHU de Rouen - Hôpital Charles Nicolle
state: Seine Maritime
city: Paris
country: France
facility: Groupe Hospitalier Pitie-Salpetriere
city: Mannheim
country: Germany
facility: Universitaetsmedizin Mannheim
state: Baden Wuerttemberg
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen
state: Baden Wuerttemberg
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm
state: Baden Wuerttemberg
city: Bayreuth
country: Germany
facility: Klinikum Bayreuth GmbH- Hohe Warte
state: Bayern
city: München
country: Germany
facility: Klinikum der Universität München
state: Bayern
city: Erbach
country: Germany
facility: Neuro Centrum Science GmbH
state: Hessen
city: Goettingen
country: Germany
facility: Universitaetsmedizin Goettingen
state: Niedersachsen
city: Bonn
country: Germany
facility: Deutsches Zentrum fuer Neurodegenerative Erkrankungen (DZNE)
state: Nordrhein Westfalen
city: Koeln
country: Germany
facility: Universitaetsklinikum Koeln
state: Nordrhein Westfalen
city: Altenburg
country: Germany
facility: Klinikum Altenburger Land GmbH
state: Thueringen
city: Berlin
country: Germany
facility: Charité - Campus Charité Mitte
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Bochum
country: Germany
facility: Katholisches Klinikum Bochum gGmbH
city: Tricase
country: Italy
facility: Azienda Ospedaliera Card. G. Panico
state: Lecce
city: Cefalù
country: Italy
facility: Fondazione Istituto G.Giglio di Cefalù
state: Palermo
city: Arzignano VI
country: Italy
facility: Ospedale di Arzignano
state: Vicenza
city: Brescia
country: Italy
facility: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Neurologico Carlo Besta
city: Perugia
country: Italy
facility: Azienda Ospedaliera e Universitaria di Perugia
city: Roma
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza
city: Toon-shi
country: Japan
facility: Ehime University Hospital
state: Ehime-Ken
city: Himeji-shi
country: Japan
facility: Himeji Central Hospital Clinic
state: Hyogo-Ken
city: Kawasaki-shi
country: Japan
facility: Nippon Medical School Musashi Kosugi Hospital
state: Kanagawa-Ken
city: Yokohama-shi
country: Japan
facility: Yokohama City Minato Red Cross Hospital
state: Kanagawa-Ken
city: Osaka-shi
country: Japan
facility: Osaka Metropolitan University Hospital
state: Osaka-Fu
city: Suita-shi
country: Japan
facility: Osaka University Hospital
state: Osaka-Fu
city: Itabashi-ku
country: Japan
facility: Tokyo Metropolitan Institute for Geriatrics and Gerontology
state: Tokyo-To
city: Amsterdam
country: Netherlands
facility: Brain Research Center Amsterdam
city: Bialystok
country: Poland
facility: Podlaskie Centrum Psychogeriatrii
city: Bydgoszcz
country: Poland
facility: PROMENTE Sp. z o.o.
city: Katowice
country: Poland
facility: Nzoz Novo-Med
city: Katowice
country: Poland
facility: Care Clinic Centrum Medyczne
city: Krakow
country: Poland
facility: SPZOZ Szpital Uniwersytecki w Krakowie
city: Lodz
country: Poland
facility: SPZOZ Centralny Szpital Kliniczny UM w Lodzi
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie Kliniczny Oddział Neurologii Oddział Udarowy
city: Sopot
country: Poland
facility: Centrum Medyczne Senior
city: Warszawa
country: Poland
facility: NeuroProtect Sp. z o.o.
city: Warszawa
country: Poland
facility: Mazowiecki Szpital Wojewódzki w Warszawie Sp z oo
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
city: Getxo
country: Spain
facility: CAE Oroitu
state: Vizcaya
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Fundacio ACE
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Lleida
country: Spain
facility: Hospital Universitari de Santa Maria
city: Sevilla
country: Spain
facility: Hospital Victoria Eugenia
city: Valencia
country: Spain
facility: Hospital Universitario Dr. Peset
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: Mölndal
country: Sweden
facility: Sahlgrenska Universitetssjukhuset, Mölndal Sjukhus
city: Stockholm
country: Sweden
facility: Karolinska universitetssjukhuset - Huddinge
city: Lugano
country: Switzerland
facility: Ospedale Regionale di Lugano
state: Ticino
city: Biel/Bienne
country: Switzerland
facility: Spitalzentrum Biel
city: Geneve
country: Switzerland
facility: Hôpitaux Universitaires de Genève - HUG- Centre de la mémoire, Bâtiment A1 - Morier
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
city: London
country: United Kingdom
facility: Institute of Psychiatry, Psychology and Neuroscience
state: Greater London
city: London
country: United Kingdom
facility: Re:Cognition Health Ltd (London)
state: Greater London
city: London
country: United Kingdom
facility: Charing Cross Hospital
state: Greater London
city: London
country: United Kingdom
facility: The National Hospital for Neurology and Neurosurgery Centre
state: Greater London
city: Manchester
country: United Kingdom
facility: Greater Manchester Mental Health NHS Foundation Trust
state: Greater Manchester
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
state: Hampshire
city: Oxford
country: United Kingdom
facility: Warneford Hospital
state: Oxfordshire
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital
state: South Yorkshire
city: Motherwell
country: United Kingdom
facility: NeuroClin Limited
state: Strathclyde
city: Birmingham
country: United Kingdom
facility: Re:Cognition Health - Birmingham
state: West Midlands
city: Bristol
country: United Kingdom
facility: Re Cognition Health Bristol
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References: