Efficacy and Safety of GSK4527226 [AL101] in Participants With Early Alzheimer's Disease

NCT06079190 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2198672023-505083-11-00
• Study Type: interventional
• Target: 367
• Locations: 16 countries
• Sites: 97

Brief Summary

The aim of this study is to assess the efficacy and safety of GSK4527226 in participants with early Alzheimer's Disease (AD) (including mild cognitive impairment \[MCI\] and mild dementia due to AD) of 2 dose levels of GSK4527226 compared to placebo.

Conditions

Alzheimer's Disease

Keywords

Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score for Dose 1 vs Placebo Across Weeks 52, 64 and 76

  The CDR-SB score is a quantitative general index that provides more precision in participants with mild dementia. The CDR scale is a clinician-rated dementia staging system 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 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, Week 52, 64 and 76

Secondary Outcomes (5)

• Change from Baseline in Integrated Alzheimer's Disease Rating Scale (iADRS) Score for Dose 1 vs Placebo Across Weeks 52, 64 and 76

  Baseline, Weeks 52, 64 and 76

• Change from Baseline in ADAS-Cog14 Score for Dose 1 vs Placebo Across Weeks 52, 64 and 76

  Baseline, Weeks 52, 64 and 76

• Change from Baseline in ADCS-ADL-MCI Score for Dose 1 vs Placebo Across Weeks 52, 64 and 76

  Baseline, Weeks 52, 64 and 76

• Change from Baseline in ADCS-iADL component of ADCS-ADL-MCI Score for Dose 1 vs Placebo Across Weeks 52, 64 and 76

  Baseline, Weeks 52, 64 and 76

• Change from Baseline in Alzheimer's Disease Composite Score (ADCOMS) for Dose 1 vs Placebo Across Weeks 52, 64 and 76

  Baseline, Weeks 52, 64 and 76

Study Arms (3)

GSK4527226 Dose 1

EXPERIMENTAL

Participants will receive GSK4527226 Dose 1

Drug: GSK4527226

GSK4527226 Dose 2

EXPERIMENTAL

Participants will receive GSK4527226 Dose 2

Drug: GSK4527226

Placebo

PLACEBO COMPARATOR

Participants will receive placebo.

Other: Placebo

Interventions

GSK4527226 DRUG

GSK4527226 will be administered.

GSK4527226 Dose 1; GSK4527226 Dose 2

Placebo OTHER

Placebo will be administered.

Placebo

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be in the Alzheimer's continuum as defined by the 2018 National Institute on Aging and Alzheimer's Association (NIAAA) Research Framework corresponding to the clinical categories of MCI due to AD and mild AD dementia.
• Participant must have evidence of amyloid positivity either by positive positron emission tomography (PET) result (Amyloid PET scans must be read by a central imaging lab) or cerebrospinal fluid (CSF) amyloid beta (Aβ) test result indicative of amyloid positivity
• Participants must also meet the following criteria for clinical severity:
• MMSE score of between 21 and 29 points
• CDR-global score (GS) of 0.5 to 1.0.
• CDR Memory Box score greater than or equal to (≥) 0.5.
• Participants with objective impairment in episodic memory as indicated by at least 1 standard deviation below age-adjusted mean in the Wechsler Memory Scale-IV Logical Memory II (WMS-IV LMII)
• If the participant is receiving symptomatic AD medications such as an Acetylcholinesterase inhibitor (AChEI) or memantine, the dosing regimen must have been stable for at least 12 weeks prior to screening and is not expected to change during study participation.
• If the participant is receiving other medications for AD related symptoms or associated conditions, the dosing regimen must have been stable for at least 4 weeks prior to screening and not expected to change during study participation. Symptoms must be considered adequately and stably controlled by the investigator, without marked changes in medication anticipated for the duration of the study.
• Body weight ≥ 45 kilogram (kg) to less than or equal to (≤)120 kg with body mass index (BMI) between 17 and 34.9 kilogram per meter square (kg/m\^2), inclusive.
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and if of child-bearing potential follows contraception requirements outlined in the protocol
• A male participant is eligible to participate if he follows contraception requirements outlined in the protocol
• Willing and able to give informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF).
• Availability of an adult person who has frequent and sufficient contact with the participant is able to provide accurate information regarding the participant's cognitive and functional abilities, agrees to provide information at clinic visits, and signs the ICF of the study partner.

You may not qualify if:

• Participant has evidence of any neurological condition other than AD that may contribute to cognitive impairment.
• History or presence of vascular disease that has the potential to affect cognitive function.
• History or presence of stroke within the past 1 year or recent transient ischemic attack within 180 days before screening.
• History of severe, clinically significant central nervous system (CNS) trauma.
• History or presence of intracranial tumor.
• Presence of ongoing infection(s) that may affect brain function, or history of infections that resulted in neurologic sequelae.
• History of primary psychiatric diagnosis that the investigator considers may interfere with study assessments.
• Columbia Suicide Severity Rating Scale (C-SSRS) suicidal ideation Type 4 or 5, suicidal behaviour or has been assessed to be at risk of suicide, in the opinion of the investigator within 6 months before screening, at screening, or at the Baseline visit, or has been hospitalized or treated for suicidal behaviour in the past 2 years.
• Participant has history of alcohol and/or moderate to severe substance use disorder within the past 2 years
• Magnetic resonance imaging (MRI) evidence based on central read of:
• \>3 lacunar infarcts.
• Stroke involving a major vascular territory, severe small vessel, or white matter disease.
• Any territorial /cortical/other infarct \>1 cubic centimetre (cm\^3).
• White matter hyperintense lesions on the FLAIR sequence that correspond to an overall Fazekas score of 3
• \>4 microhaemorrhages.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• Alector Inc.: collaborator

Study Sites (97)

GSK Investigational Site

San Diego, California, 92103, United States

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GSK Investigational Site

Lake Mary, Florida, 32720, United States

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GSK Investigational Site

Lake Worth, Florida, 33462, United States

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GSK Investigational Site

Maitland, Florida, 32752, United States

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GSK Investigational Site

Miami, Florida, 33176, United States

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GSK Investigational Site

Orlando, Florida, 32803, United States

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GSK Investigational Site

Orlando, Florida, 32804, United States

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GSK Investigational Site

Stuart, Florida, 34997, United States

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GSK Investigational Site

The Villages, Florida, 32159, United States

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GSK Investigational Site

The Villages, Florida, 32162, United States

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GSK Investigational Site

Decatur, Georgia, 30030, United States

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GSK Investigational Site

Elk Grove Village, Illinois, 60007, United States

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GSK Investigational Site

Chesterfield, Missouri, 63005, United States

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GSK Investigational Site

Toms River, New Jersey, 08755, United States

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GSK Investigational Site

Staten Island, New York, 10314, United States

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GSK Investigational Site

Matthews, North Carolina, 28105, United States

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GSK Investigational Site

North Canton, Ohio, 44720, United States

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GSK Investigational Site

Oklahoma City, Oklahoma, 73112, United States

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GSK Investigational Site

Portland, Oregon, 07210, United States

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GSK Investigational Site

Houston, Texas, 77030, United States

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GSK Investigational Site

Fairfax, Virginia, 22031, United States

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GSK Investigational Site

Buenos Aires, C1425AGC, Argentina

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GSK Investigational Site

Buenos Aires, C1428AQK, Argentina

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GSK Investigational Site

Ciudad Autonoma de Buenos Aire, C1431FWO, Argentina

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GSK Investigational Site

Ciudad Autonoma de Bueno, C1056ABJ, Argentina

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GSK Investigational Site

Camperdown, New South Wales, 2050, Australia

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GSK Investigational Site

Darlinghurst, New South Wales, 2010, Australia

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GSK Investigational Site

Kogarah, New South Wales, 2217, Australia

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GSK Investigational Site

Macquarie Park, New South Wales, 2113, Australia

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Gold Coast, Queensland, 4222, Australia

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Heidelberg, Victoria, 3079, Australia

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Nedlands, Western Australia, 6009, Australia

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Melbourne, Australia

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Ottawa, Ontario, K1Z 1G3, Canada

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Peterborough, Ontario, K9H 2P4, Canada

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Toronto, Ontario, M3B 2S7, Canada

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Greenfield Park, Quebec, J4V 2J2, Canada

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Sherbrooke, Quebec, J1J 2G2, Canada

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GSK Investigational Site

Helsinki, 00180, Finland

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GSK Investigational Site

Kuopio, 70210, Finland

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GSK Investigational Site

Oulu, 90100, Finland

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GSK Investigational Site

Turku, 20520, Finland

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GSK Investigational Site

Bron, 69500, France

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GSK Investigational Site

Lille, 59037, France

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GSK Investigational Site

Nice, 06100, France

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Paris, 75010, France

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Paris, 75013, France

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GSK Investigational Site

Saint-Herblain, 44093, France

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GSK Investigational Site

Strasbourg, 67000, France

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GSK Investigational Site

Toulouse, 31300, France

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GSK Investigational Site

Villeurbanne, 69100, France

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GSK Investigational Site

Cologne, 50935, Germany

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GSK Investigational Site

Erbach im Odenwald, 64711, Germany

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GSK Investigational Site

München, 80336, Germany

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GSK Investigational Site

Münster, 48149, Germany

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GSK Investigational Site

Brescia, 25123, Italy

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GSK Investigational Site

CefalU PA, 90015, Italy

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GSK Investigational Site

Genova, 16132, Italy

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GSK Investigational Site

Milan, 20132, Italy

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GSK Investigational Site

Milan, 20133, Italy

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GSK Investigational Site

Modena, 41126, Italy

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Monza, 20900, Italy

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Pavia, 27100, Italy

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GSK Investigational Site

Perugia, 06129, Italy

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GSK Investigational Site

's-Hertogenbosch, 5223 LA, Netherlands

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GSK Investigational Site

Amsterdam, 1081 GN, Netherlands

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GSK Investigational Site

Zwolle, 8025 AZ, Netherlands

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GSK Investigational Site

Bergen, 5009, Norway

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GSK Investigational Site

Oslo, 0450, Norway

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GSK Investigational Site

Stavanger, Norway

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GSK Investigational Site

Junggu, 400711, South Korea

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GSK Investigational Site

Seoul, 04763, South Korea

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GSK Investigational Site

Seoul, 138-736, South Korea

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GSK Investigational Site

Barcelona, 08028, Spain

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GSK Investigational Site

Getxo - Vizcaya, 48993, Spain

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GSK Investigational Site

Madrid, 28034, Spain

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GSK Investigational Site

Madrid, 28041, Spain

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GSK Investigational Site

Madrid, 28046, Spain

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GSK Investigational Site

Madrid, 28223, Spain

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GSK Investigational Site

Pamplona, 31008, Spain

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GSK Investigational Site

Salamanca, 37007, Spain

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GSK Investigational Site

Terrassa - Barcelona, 08221, Spain

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GSK Investigational Site

Valencia, 46026, Spain

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GSK Investigational Site

Gothenburg, 431 41, Sweden

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GSK Investigational Site

Malmo, 21146, Sweden

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GSK Investigational Site

Stockholm, Sweden

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GSK Investigational Site

Kaohsiung City, 833, Taiwan

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GSK Investigational Site

Tainan, 704, Taiwan

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GSK Investigational Site

Tau-Yuan, 333, Taiwan

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GSK Investigational Site

Ankara, 06230, Turkey (Türkiye)

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GSK Investigational Site

CapaIstanbul, 34093, Turkey (Türkiye)

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GSK Investigational Site

Birmingham, B16 8LT, United Kingdom

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GSK Investigational Site

Bristol, BS32 4SY, United Kingdom

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GSK Investigational Site

Glasgow, ML1 4UF, United Kingdom

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GSK Investigational Site

London, EC2Y 8EA, United Kingdom

Location

GSK Investigational Site

London, W1G 8TA, United Kingdom

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GSK Investigational Site

London, WC1N 3BG, United Kingdom

Location

MeSH Terms

Conditions

Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders

Condition Hierarchy (Ancestors)

Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Click here to enter text.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2023
• First Posted: October 12, 2023
• Study Start: October 20, 2023
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): November 23, 2026
• Last Updated: November 14, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

ES (10); TU (2); FI (4); GB (6); AR (4); CA (5); IT (9); NO (3); FR (9); SE (3); DE (4); NL (3); TW (3); US (21); KR (3); AU (8)