Last updated: 11/12/2025 13:30:11
Efficacy and Safety of GSK4527226 [AL101] in Participants with Early Alzheimer’s DiseasePROGRESS-AD
GSK study ID
219867
Clinicaltrials.gov ID
EudraCT ID
Not applicable
EU CT Number
Trial status
Recruitment complete
Recruitment complete
Trial overview
Official title: A Phase 2, Parallel Group, Randomized, Double- Blind, Placebo-Controlled, 3-Arm, Multicenter Treatment Study to Evaluate the Efficacy and Safety of GSK4527226 [AL101] Intravenous Infusion Compared with Placebo in Patients with Early Alzheimer’s Disease
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:
Randomized
Primary outcomes:
Change from Baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score for Dose 1 vs Placebo Across Weeks 52, 64 and 76
Timeframe: Baseline, Week 52, 64 and 76
Secondary outcomes:
Change from Baseline in Integrated Alzheimer’s Disease Rating Scale (iADRS) Score for Dose 1 vs Placebo Across Weeks 52, 64 and 76
Timeframe: Baseline, Weeks 52, 64 and 76
Change from Baseline in ADAS-Cog14 Score for Dose 1 vs Placebo Across Weeks 52, 64 and 76
Timeframe: 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
Timeframe: 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
Timeframe: 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
Timeframe: Baseline, Weeks 52, 64 and 76
Interventions:
Enrollment:
367
Primary completion date:
2026-30-09
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Alzheimer's Disease
Product
GSK4527226
Collaborators
Alector
Study date(s)
October 2023 to November 2026
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
50 - 85 Years
Accepts healthy volunteers
No
- 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
- 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.
Inclusion and exclusion criteria
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: a. MMSE score of between 21 and 29 points b. CDR-global score (GS) of 0.5 to 1.0. c. CDR Memory Box score greater than or equal to (≥) 0.5. d. 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.
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 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: a. >3 lacunar infarcts. b. Stroke involving a major vascular territory, severe small vessel, or white matter disease. c. Any territorial /cortical/other infarct >1 cubic centimetre (cm^3). d. White matter hyperintense lesions on the FLAIR sequence that correspond to an overall Fazekas score of 3 e. >4 microhaemorrhages. f. Any areas of superficial (leptomeningeal) hemosiderosis. g. A single macro-hemorrhage greater than 10 millimetres (mm) at greatest diameter. h. Vasogenic edema. i. Cerebral contusion, encephalomalacia, aneurysms, vascular malformations, or infective lesions. j. Space occupying lesions or brain tumors. k. Significant cerebral vascular pathology l. Hydrocephalus/Normal pressure hydrocephalus. m. Other MRI findings contraindicating participation in the study such as subarachnoid hemorrhage.
- History suggestive of exposure to, or past tuberculosis (TB) infection should undergo screening for TB disease.
- Chronic active immune disorder requiring systemic immunosuppressive therapy within 6 months prior to Screening.
- Screening serum vitamin B12 concentration < Lower limit of normal (LLN) or in the low normal range
- Folate
Upper limit of normal (ULN) - Hemoglobin A1c >8 percentage (%) or poorly controlled diabetes during the last 12 weeks
- History of cancer
- Known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins
- Planned surgery during the study which requires general, spinal, or epidural anesthesia 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, mood stabilizers, or stimulants that are used on a chronic basis, are exclusionary if not consistent with the following rule: treatment has to have been at a stable dose for at least 4 weeks before screening and should remain stable during 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, used within 6 months before screening. * Anticoagulation medications within 90 days of screening and during the study * Systemic immunosuppressive therapy within 6 months before screening and during the study.
Trial location(s)
Location
GSK Investigational Site
Birmingham, United Kingdom, B16 8LT
Status
Recruitment Complete
Location
GSK Investigational Site
Camperdown, NSW, Australia, 2050
Status
Recruitment Complete
Location
GSK Investigational Site
Darlinghurst, NSW, Australia, 2010
Status
Recruitment Complete
Location
GSK Investigational Site
Heidelberg, VIC, Australia, 3079
Status
Recruitment Complete
Location
GSK Investigational Site
London, United Kingdom, EC2Y 8EA
Status
Recruitment Complete
Location
GSK Investigational Site
London, United Kingdom, WC1N 3BG
Status
Recruitment Complete
Location
GSK Investigational Site
Macquarie Park, NSW, Australia, 2113
Status
Recruitment Complete
Location
GSK Investigational Site
Glasgow, United Kingdom, ML1 4UF
Status
Recruitment Complete
Location
GSK Investigational Site
Gold Coast, QLD, Australia, 4222
Status
Recruitment Complete
Location
GSK Investigational Site
Buenos Aires, Argentina, C1428AQK
Status
Recruitment Complete
Location
GSK Investigational Site
Chesterfield, MO, United States, 63005
Status
Study Complete
Location
GSK Investigational Site
Ciudad Autonoma de Bueno, Argentina, C1056ABJ
Status
Recruitment Complete
Location
GSK Investigational Site
Ciudad Autonoma de Buenos Aire, Argentina, C1431FWO
Status
Recruitment Complete
Location
GSK Investigational Site
Elk Grove Village, IL, United States, 60007
Status
Recruitment Complete
Location
GSK Investigational Site
North Canton, OH, United States, 44720
Status
Study Complete
Location
GSK Investigational Site
Oklahoma City, OK, United States, 73112
Status
Recruitment Complete
Location
GSK Investigational Site
Portland, OR, United States, 07210
Status
Recruitment Complete
Location
GSK Investigational Site
Staten Island, NY, United States, 10314
Status
Recruitment Complete
Location
GSK Investigational Site
Stuart, Florida, United States, 34997
Status
Recruitment Complete
Location
GSK Investigational Site
Toms River, NJ, United States, 08755
Status
Recruitment Complete
Location
GSK Investigational Site
Greenfield Park, QC, Canada, J4V 2J2
Status
Recruitment Complete
Location
GSK Investigational Site
Peterborough, ON, Canada, K9H 2P4
Status
Recruitment Complete
Location
GSK Investigational Site
Bristol, United Kingdom, BS32 4SY
Status
Recruitment Complete
Location
GSK Investigational Site
Maitland, FL, United States, 32752
Status
Recruitment Complete
Location
GSK Investigational Site
Matthews, NC, United States, 28105
Status
Recruitment Complete
Location
GSK Investigational Site
The Villages, FL, United States, 32159
Status
Study Complete
Location
GSK Investigational Site
Terrassa - Barcelona, Spain, 08221
Status
Recruitment Complete
Location
GSK Investigational Site
Fairfax, VA, United States, 22031
Status
Recruitment Complete
Location
GSK Investigational Site
Houston, TX, United States, 77030
Status
Recruitment Complete
Location
GSK Investigational Site
Wichita, KS, United States, 67207
Status
Terminated/Withdrawn
Location
GSK Investigational Site
The Villages, FL, United States, 32162
Status
Recruitment Complete
Location
GSK Investigational Site
Lake Worth, FL, United States, 33462
Status
Recruitment Complete
Location
GSK Investigational Site
Charleston, SC, United States, 29403
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Stuart, FL, United States, 33414
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Stuart, FL, United States, 34997
Status
Terminated/Withdrawn
Location
GSK Investigational Site
West Long Branch, NJ, United States, 07764
Status
Terminated/Withdrawn
Study documents
No study documents available.
Results overview
Study Results yet to be posted
Recruitment status
Recruitment complete
Actual primary completion date
Not applicable
Actual study completion date
Not applicable
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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