A Study to Learn About the Safety of BIIB080 and Whether it 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

Mild Cognitive Impairment Due to Alzheimer's Disease Clinical Trial

— CELIA  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05399888
• Other study ID #: 247AD201
• Secondary ID: 2022-501644-15
• Status: Recruiting
• Phase: Phase 2
• Start date: August 24, 2022
• Est. completion date: February 4, 2030

Study information

• Verified date: June 2024
• Source: Biogen
• Contact: US Biogen Clinical Trial Center
• Phone: 866-633-4636
• Email: clinicaltrials[@]biogen.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 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.

Description:

BIIB080 is an investigational antisense therapy designed to target microtubule-associated protein tau (MAPT) mRNA and prevent production of tau protein.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 735
• Est. completion date: February 4, 2030
• Est. primary completion date: November 19, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 80 Years

Eligibility

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

• 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.

• MMSE score >10 at the Week 76 visit.

• 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 Aß, 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.

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease Dementia
• Cognitive Dysfunction
• Dementia
• Mild Cognitive Impairment Due to Alzheimer's Disease

Intervention

Drug:
• BIIB080
Administered as specified in the treatment arm.
• BIIB080-matching placebo
Administered as specified in the treatment arm.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Czechia,  Denmark,  Finland,  France,  Germany,  Italy,  Japan,  Netherlands,  Poland,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)