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

Last updated: February 28, 2025
Sponsor: GlaxoSmithKline
Overall Status: Active - Recruiting

Phase

2

Condition

Alzheimer's Disease

Dementia

Memory Loss

Treatment

GSK4527226

Placebo

Clinical Study ID

NCT06079190
219867
2023-505083-11-00
  • Ages 50-85
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

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:
  1. MMSE score of between 21 and 29 points

  2. CDR-global score (GS) of 0.5 to 1.0.

  3. CDR Memory Box score greater than or equal to (≥) 0.5.

  4. Participants with objective impairment in episodic memory as indicated by atleast 1 standard deviation below age-adjusted mean in the Wechsler MemoryScale-IV Logical Memory II (WMS-IV LMII)

  • If the participant is receiving symptomatic AD medications such as anAcetylcholinesterase inhibitor (AChEI) or memantine, the dosing regimen must havebeen stable for at least 12 weeks prior to screening and is not expected to changeduring study participation.

  • If the participant is receiving other medications for AD related symptoms orassociated conditions, the dosing regimen must have been stable for at least 4 weeksprior to screening and not expected to change during study participation. Symptomsmust be considered adequately and stably controlled by the investigator, withoutmarked 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 massindex (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 orbreastfeeding, and if of child-bearing potential follows contraception requirementsoutlined in the protocol

  • A male participant is eligible to participate if he follows contraceptionrequirements outlined in the protocol

  • Willing and able to give informed consent which includes compliance with therequirements and restrictions listed in the informed consent form (ICF).

  • Availability of an adult person who has frequent and sufficient contact with theparticipant is able to provide accurate information regarding the participant'scognitive and functional abilities, agrees to provide information at clinic visits,and signs the ICF of the study partner.

Exclusion

Exclusion Criteria:

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 cognitivefunction.

  • History or presence of stroke within the past 1 year or recent transient ischemicattack 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 ofinfections that resulted in neurologic sequelae.

  • History of primary psychiatric diagnosis that the investigator considers mayinterfere 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 disorderwithin the past 2 years

  • Magnetic resonance imaging (MRI) evidence based on central read of:

  1. >3 lacunar infarcts.

  2. Stroke involving a major vascular territory, severe small vessel, or whitematter disease.

  3. Any territorial /cortical/other infarct >1 cubic centimetre (cm^3).

  4. White matter hyperintense lesions on the FLAIR sequence that correspond to anoverall Fazekas score of 3

  5. >4 microhaemorrhages.

  6. Any areas of superficial (leptomeningeal) hemosiderosis.

  7. A single macro-hemorrhage greater than 10 millimetres (mm) at greatestdiameter.

  8. Vasogenic edema.

  9. Cerebral contusion, encephalomalacia, aneurysms, vascular malformations, orinfective lesions.

  10. Space occupying lesions or brain tumors.

  11. Significant cerebral vascular pathology

  12. Hydrocephalus/Normal pressure hydrocephalus.

  13. Other MRI findings contraindicating participation in the study such assubarachnoid hemorrhage.

  • History suggestive of exposure to, or past tuberculosis (TB) infection shouldundergo screening for TB disease.

  • Chronic active immune disorder requiring systemic immunosuppressive therapy within 6months prior to Screening.

  • Screening serum vitamin B12 concentration < Lower limit of normal (LLN) or in thelow normal range

  • Folate <LLN or Thyroid-stimulating hormone (TSH) > Upper limit of normal (ULN)

  • Hemoglobin A1c >8 percentage (%) or poorly controlled diabetes during the last 12weeks

  • History of cancer

  • Known history of severe allergic, anaphylactic, or other hypersensitivity reactionsto chimeric, human, or humanized antibodies or fusion proteins

  • Planned surgery during the study which requires general, spinal, or epiduralanesthesia that would take place during the study.

  • Known genetic predisposition for clotting disorder or hemorrhagic disease.

  • Key exclusionary medications include:

  • Antipsychotics, opiates/opioids, cannabinoids, hypnotics, antidepressants, moodstabilizers, or stimulants that are used on a chronic basis, are exclusionaryif not consistent with the following rule: treatment has to have been at astable dose for at least 4 weeks before screening and should remain stableduring the study

  • Any biologic drugs with systemic exposure, whether investigational or approved,used within 6 months before screening Any disease modification drug for AD,such as aducanumab and lecanemab, whether investigational or approved, usedwithin 6 months before screening.

  • Anticoagulation medications within 90 days of screening and during the study

  • Systemic immunosuppressive therapy within 6 months before screening and duringthe study.

Study Design

Total Participants: 282
Treatment Group(s): 2
Primary Treatment: GSK4527226
Phase: 2
Study Start date:
October 20, 2023
Estimated Completion Date:
November 16, 2026

Connect with a study center

  • GSK Investigational Site

    Capital Federal, Buenos Aires C1428AQK
    Argentina

    Site Not Available

  • GSK Investigational Site

    Ciudad Autonoma de Buenos Aires, Buenos Aires C1431FWO
    Argentina

    Site Not Available

  • GSK Investigational Site

    Buenos Aires, C1425AGC
    Argentina

    Active - Recruiting

  • GSK Investigational Site

    Ciudad Autonoma De Bueno, C1056ABJ
    Argentina

    Active - Recruiting

  • GSK Investigational Site

    Ciudad Autonoma de Buenos Aire, C1431FWO
    Argentina

    Active - Recruiting

  • GSK Investigational Site

    Camperdown, New South Wales 2050
    Australia

    Active - Recruiting

  • GSK Investigational Site

    Darlinghurst, New South Wales 2010
    Australia

    Active - Recruiting

  • GSK Investigational Site

    Kogarah, New South Wales 2217
    Australia

    Active - Recruiting

  • GSK Investigational Site

    Macquarie Park, New South Wales 2113
    Australia

    Active - Recruiting

  • GSK Investigational Site

    Gold Coast, Queensland 4222
    Australia

    Active - Recruiting

  • GSK Investigational Site

    Southport, Queensland 4222
    Australia

    Site Not Available

  • GSK Investigational Site

    Heidelberg, Victoria 3079
    Australia

    Active - Recruiting

  • GSK Investigational Site

    Ivanhoe, Victoria 3079
    Australia

    Site Not Available

  • GSK Investigational Site

    Nedlands, Western Australia 6009
    Australia

    Active - Recruiting

  • GSK Investigational Site

    Melbourne,
    Australia

    Active - Recruiting

  • GSK Investigational Site

    Ottawa, Ontario K1Z 1G3
    Canada

    Active - Recruiting

  • GSK Investigational Site

    Peterborough, Ontario K9H 2P4
    Canada

    Active - Recruiting

  • GSK Investigational Site

    Toronto, Ontario M3B 2S7
    Canada

    Active - Recruiting

  • GSK Investigational Site

    Greenfield Park, Quebec J4V 2J2
    Canada

    Active - Recruiting

  • GSK Investigational Site

    Greenfield-Park, Quebec J4V 2J2
    Canada

    Site Not Available

  • GSK Investigational Site

    Sherbrooke, Quebec J1J 2G2
    Canada

    Active - Recruiting

  • GSK Investigational Site

    Verdun, Quebec H4H 1R3
    Canada

    Site Not Available

  • GSK Investigational Site

    Helsinki, 00180
    Finland

    Active - Recruiting

  • GSK Investigational Site

    Kuopio, 70210
    Finland

    Active - Recruiting

  • GSK Investigational Site

    Oulu, 90100
    Finland

    Active - Recruiting

  • GSK Investigational Site

    Turku, 20520
    Finland

    Active - Recruiting

  • GSK Investigational Site

    Bron, 69500
    France

    Active - Recruiting

  • GSK Investigational Site

    Lille Cedex, 59037
    France

    Active - Recruiting

  • GSK Investigational Site

    Nice, 06100
    France

    Active - Recruiting

  • GSK Investigational Site

    Paris, 75010
    France

    Active - Recruiting

  • GSK Investigational Site

    Saint-Herblain, 44093
    France

    Active - Recruiting

  • GSK Investigational Site

    Strasbourg, 67000
    France

    Active - Recruiting

  • GSK Investigational Site

    Toulouse, 31300
    France

    Active - Recruiting

  • GSK Investigational Site

    Villeurbanne, 69100
    France

    Active - Recruiting

  • GSK Investigational Site

    Erbach, 64711
    Germany

    Active - Recruiting

  • GSK Investigational Site

    Koeln, 50935
    Germany

    Active - Recruiting

  • GSK Investigational Site

    Muenchen, 80336
    Germany

    Active - Recruiting

  • GSK Investigational Site

    Muenster, 48149
    Germany

    Active - Recruiting

  • GSK Investigational Site

    Baggiovara, Modena 41126
    Italy

    Site Not Available

  • GSK Investigational Site

    Cefalù, Palermo 90015
    Italy

    Site Not Available

  • GSK Investigational Site

    Mondino, Pavia 27100
    Italy

    Site Not Available

  • GSK Investigational Site

    Brescia, 25123
    Italy

    Active - Recruiting

  • GSK Investigational Site

    CefalU PA, 90015
    Italy

    Active - Recruiting

  • GSK Investigational Site

    Genova, 16132
    Italy

    Active - Recruiting

  • GSK Investigational Site

    Milano, 20133
    Italy

    Active - Recruiting

  • GSK Investigational Site

    Modena, 41126
    Italy

    Active - Recruiting

  • GSK Investigational Site

    Monza, 20900
    Italy

    Active - Recruiting

  • GSK Investigational Site

    Palermo, 90127
    Italy

    Site Not Available

  • GSK Investigational Site

    Pavia, 27100
    Italy

    Active - Recruiting

  • GSK Investigational Site

    Perugia, 06129
    Italy

    Active - Recruiting

  • GSK Investigational Site

    Roma, 00179
    Italy

    Site Not Available

  • GSK Investigational Site

    Jung Gu, 400711
    Korea, Republic of

    Active - Recruiting

  • GSK Investigational Site

    Seoul, 04763
    Korea, Republic of

    Active - Recruiting

  • GSK Investigational Site

    's-Hertogenbosch, 5223 LA
    Netherlands

    Site Not Available

  • GSK Investigational Site

    Amsterdam, 1081 GN
    Netherlands

    Active - Recruiting

  • GSK Investigational Site

    Den Bosch, 5223 LA
    Netherlands

    Active - Recruiting

  • GSK Investigational Site

    Zwolle, 8025 AZ
    Netherlands

    Active - Recruiting

  • GSK Investigational Site

    Bergen, 5009
    Norway

    Active - Recruiting

  • GSK Investigational Site

    Drammen, N-3004
    Norway

    Site Not Available

  • GSK Investigational Site

    Oslo, 0450
    Norway

    Active - Recruiting

  • GSK Investigational Site

    Stavanger,
    Norway

    Active - Recruiting

  • GSK Investigational Site

    Pozuelo De Alarcón, Madrid 28223
    Spain

    Site Not Available

  • GSK Investigational Site

    Barcelona, 08028
    Spain

    Active - Recruiting

  • GSK Investigational Site

    Getxo, 48993
    Spain

    Site Not Available

  • GSK Investigational Site

    Getxo - Vizcaya, 48993
    Spain

    Active - Recruiting

  • GSK Investigational Site

    Madrid, 28223
    Spain

    Active - Recruiting

  • GSK Investigational Site

    Pamplona, 31008
    Spain

    Active - Recruiting

  • GSK Investigational Site

    Salamanca, 37007
    Spain

    Active - Recruiting

  • GSK Investigational Site

    San Sebastian, 20009
    Spain

    Site Not Available

  • GSK Investigational Site

    Terrassa (Barcelona), 08221
    Spain

    Site Not Available

  • GSK Investigational Site

    Terrassa - Barcelona, 08221
    Spain

    Active - Recruiting

  • GSK Investigational Site

    Valencia, 46026
    Spain

    Active - Recruiting

  • GSK Investigational Site

    Goteborg, 431 41
    Sweden

    Active - Recruiting

  • GSK Investigational Site

    Jonkoping, SE-551 85
    Sweden

    Site Not Available

  • GSK Investigational Site

    Jönköping, SE-551 85
    Sweden

    Site Not Available

  • GSK Investigational Site

    Malmo, 21146
    Sweden

    Active - Recruiting

  • GSK Investigational Site

    Malmö, 21146
    Sweden

    Site Not Available

  • GSK Investigational Site

    Mölndal, 431 41
    Sweden

    Site Not Available

  • GSK Investigational Site

    Stockholm,
    Sweden

    Active - Recruiting

  • GSK Investigational Site

    Kaohsiung, 833
    Taiwan

    Active - Recruiting

  • GSK Investigational Site

    Tainan, 704
    Taiwan

    Active - Recruiting

  • GSK Investigational Site

    Taoyuan, 333
    Taiwan

    Site Not Available

  • GSK Investigational Site

    Tau-Yuan, 333
    Taiwan

    Active - Recruiting

  • GSK Investigational Site

    Ankara, 06230
    Turkey

    Active - Recruiting

  • GSK Investigational Site

    Capa/Istanbul, 34093
    Turkey

    Site Not Available

  • GSK Investigational Site

    CapaIstanbul, 34093
    Turkey

    Active - Recruiting

  • GSK Investigational Site

    Birmingham, B16 8LT
    United Kingdom

    Active - Recruiting

  • GSK Investigational Site

    Bristol, BS32 4SY
    United Kingdom

    Active - Recruiting

  • GSK Investigational Site

    Glasgow, ML1 4UF
    United Kingdom

    Active - Recruiting

  • GSK Investigational Site

    London, W1G 8TA
    United Kingdom

    Active - Recruiting

  • GSK Investigational Site

    Motherwell, ML1 4UF
    United Kingdom

    Site Not Available

  • GSK Investigational Site

    San Diego, California 92103
    United States

    Completed

  • GSK Investigational Site

    DeLand, Florida 32720
    United States

    Site Not Available

  • GSK Investigational Site

    Lake Mary, Florida 32720
    United States

    Completed

  • GSK Investigational Site

    Lake Worth, Florida 33462
    United States

    Active - Recruiting

  • GSK Investigational Site

    Maitland, Florida 32752
    United States

    Active - Recruiting

  • GSK Investigational Site

    Miami, Florida 33176
    United States

    Active - Recruiting

  • GSK Investigational Site

    Orlando, Florida 32804
    United States

    Completed

  • GSK Investigational Site

    Stuart, Florida 34997
    United States

    Active - Recruiting

  • GSK Investigational Site

    The Villages, Florida 32162
    United States

    Active - Recruiting

  • GSK Investigational Site

    Wellington, Florida 33414
    United States

    Site Not Available

  • GSK Investigational Site

    Decatur, Georgia 30030
    United States

    Completed

  • GSK Investigational Site

    Elk Grove Village, Illinois 60007
    United States

    Active - Recruiting

  • GSK Investigational Site

    Wichita, Kansas 67207
    United States

    Site Not Available

  • GSK Investigational Site

    Chesterfield, Missouri 63005
    United States

    Active - Recruiting

  • GSK Investigational Site

    Toms River, New Jersey 08755
    United States

    Active - Recruiting

  • GSK Investigational Site

    West Long Branch, New Jersey 07764
    United States

    Active - Recruiting

  • GSK Investigational Site

    New York, New York 10016
    United States

    Site Not Available

  • GSK Investigational Site

    Staten Island, New York 10314
    United States

    Active - Recruiting

  • GSK Investigational Site

    Matthews, North Carolina 28105
    United States

    Active - Recruiting

  • GSK Investigational Site

    North Canton, Ohio 44720
    United States

    Completed

  • GSK Investigational Site

    Oklahoma City, Oklahoma 73112
    United States

    Active - Recruiting

  • GSK Investigational Site

    Portland, Oregon 07210
    United States

    Active - Recruiting

  • GSK Investigational Site

    Charleston, South Carolina 29403
    United States

    Active - Recruiting

  • GSK Investigational Site

    Houston, Texas 77030
    United States

    Active - Recruiting

  • GSK Investigational Site

    Fairfax, Virginia 22031
    United States

    Active - Recruiting

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