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Alzheimer's DiseasePhase 2PROGRESS-ADNCT06079190

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

A Phase 2 study testing GSK4527226 in people with Alzheimer's Disease, run by GlaxoSmithKline at 97 sites in 16 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 50 to 85 years
Conditions the study is for
Alzheimer's Disease
What is being tested?
GSK4527226
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
367 participants
Where
97 sitesin 16 countries
Study dates
20 Oct 2023to 18 Aug 2026
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 14Show fewer
  • 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.

Who cannot join

  • 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.
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  • 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.
  • Any areas of superficial (leptomeningeal) hemosiderosis.
  • A single macro-hemorrhage greater than 10 millimetres (mm) at greatest diameter.
  • Vasogenic edema.
  • Cerebral contusion, encephalomalacia, aneurysms, vascular malformations, or infective lesions.
  • Space occupying lesions or brain tumors.
  • Significant cerebral vascular pathology
  • Hydrocephalus/Normal pressure hydrocephalus.
  • 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 <LLN or Thyroid-stimulating hormone (TSH) > 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 locations and contacts

97 sites in 16 countries.

97 sites in 16 countries

United States21 sites
  • GSK Investigational Site

    Chesterfield, Missouri, 63005

  • GSK Investigational Site

    Decatur, Georgia, 30030

  • GSK Investigational Site

    Elk Grove Village, Illinois, 60007

  • GSK Investigational Site

    Fairfax, Virginia, 22031

  • GSK Investigational Site

    Houston, Texas, 77030-1312

  • GSK Investigational Site

    Lake Mary, Florida, 32720

  • GSK Investigational Site

    Lake Worth, Florida, 33462

  • GSK Investigational Site

    Maitland, Florida, 32752

  • GSK Investigational Site

    Matthews, North Carolina, 28105-8335

  • GSK Investigational Site

    Miami, Florida, 33176-7947

  • GSK Investigational Site

    North Canton, Ohio, 44720

  • GSK Investigational Site

    Oklahoma City, Oklahoma, 73112

  • GSK Investigational Site

    Orlando, Florida, 32803

  • GSK Investigational Site

    Orlando, Florida, 32804

  • GSK Investigational Site

    Portland, Oregon, 97210-5311

  • GSK Investigational Site

    San Diego, California, 92103

  • GSK Investigational Site

    Staten Island, New York, 10314

  • GSK Investigational Site

    Stuart, Florida, 34997

  • GSK Investigational Site

    The Villages, Florida, 32159

  • GSK Investigational Site

    The Villages, Florida, 32162

  • GSK Investigational Site

    Toms River, New Jersey, 08755-5043

Other trials in United States

Spain10 sites
  • GSK Investigational Site

    Barcelona, 08028

  • GSK Investigational Site

    Getxo, Vizcaya, 48993

  • GSK Investigational Site

    Madrid, 28034

  • GSK Investigational Site

    Madrid, 28041

  • GSK Investigational Site

    Madrid, 28046

  • GSK Investigational Site

    Pamplona, 31008

  • GSK Investigational Site

    Pozuelo de Alarcón, Madrid, 28223

  • GSK Investigational Site

    Salamanca, 37007

  • GSK Investigational Site

    Terrassa - Barcelona, 08221

  • GSK Investigational Site

    Valencia, 46026

Other trials in Spain

France9 sites
  • GSK Investigational Site

    Bron, 69500

  • GSK Investigational Site

    Lille, 59037

  • GSK Investigational Site

    Nice, 06100

  • GSK Investigational Site

    Paris, 75010

  • GSK Investigational Site

    Paris, 75013

  • GSK Investigational Site

    Saint-Herblain, 44093

  • GSK Investigational Site

    Strasbourg, 67000

  • GSK Investigational Site

    Toulouse, 31300

  • GSK Investigational Site

    Villeurbanne, 69100

Other trials in France

Italy9 sites
  • GSK Investigational Site

    Brescia, 25123

  • GSK Investigational Site

    CefalU PA, 90015

  • GSK Investigational Site

    Genova, 16132

  • GSK Investigational Site

    Milan, 20132

  • GSK Investigational Site

    Milan, 20133

  • GSK Investigational Site

    Modena, 41126

  • GSK Investigational Site

    Monza, 20900

  • GSK Investigational Site

    Pavia, 27100

  • GSK Investigational Site

    Perugia, 06129

Other trials in Italy

Australia8 sites
  • GSK Investigational Site

    Camperdown, New South Wales, 2050

  • GSK Investigational Site

    Darlinghurst, New South Wales, 2010

  • GSK Investigational Site

    Gold Coast, Queensland, 4222

  • GSK Investigational Site

    Heidelberg, Victoria, 3079

  • GSK Investigational Site

    Kogarah, New South Wales, 2217

  • GSK Investigational Site

    Macquarie Park, New South Wales, 2113

  • GSK Investigational Site

    Melbourne

  • GSK Investigational Site

    Nedlands, Western Australia, 6009

Other trials in Australia

United Kingdom6 sites
  • GSK Investigational Site

    Birmingham, B16 8LT

  • GSK Investigational Site

    Bristol, BS32 4SY

  • GSK Investigational Site

    Glasgow, ML1 4UF

  • GSK Investigational Site

    London, EC2Y 8EA

  • GSK Investigational Site

    London, W1G 8TA

  • GSK Investigational Site

    London, WC1N 3BG

Other trials in United Kingdom

Canada5 sites
  • GSK Investigational Site

    Greenfield Park, Quebec, J4V 2J2

  • GSK Investigational Site

    Ottawa, Ontario, K1Z 1G3

  • GSK Investigational Site

    Peterborough, Ontario, K9H 2P4

  • GSK Investigational Site

    Sherbrooke, Quebec, J1J 2G2

  • GSK Investigational Site

    Toronto, Ontario, M3B 2S7

Other trials in Canada

Argentina4 sites
  • GSK Investigational Site

    Buenos Aires, C1425AGC

  • GSK Investigational Site

    Buenos Aires, C1428AQK

  • GSK Investigational Site

    Ciudad Autonoma de Bueno, C1056ABJ

  • GSK Investigational Site

    Ciudad Autonoma de Buenos Aire, C1431FWO

Other trials in Argentina

Finland4 sites
  • GSK Investigational Site

    Helsinki, 00180

  • GSK Investigational Site

    Kuopio, 70210

  • GSK Investigational Site

    Oulu, 90100

  • GSK Investigational Site

    Turku, 20520

Other trials in Finland

Germany4 sites
  • GSK Investigational Site

    Cologne, 50935

  • GSK Investigational Site

    Erbach im Odenwald, Hesse, 64711

  • GSK Investigational Site

    München, 80336

  • GSK Investigational Site

    Münster, 48149

Other trials in Germany

Netherlands3 sites
  • GSK Investigational Site

    's-Hertogenbosch, North Brabant, 5223 LA

  • GSK Investigational Site

    Amsterdam, North Holland, 1081 GN

  • GSK Investigational Site

    Zwolle, Overijssel, 8025 AZ

Other trials in Netherlands

Norway3 sites
  • GSK Investigational Site

    Bergen, 5009

  • GSK Investigational Site

    Oslo, 0450

  • GSK Investigational Site

    Stavanger

Other trials in Norway

South Korea3 sites
  • GSK Investigational Site

    Junggu, 400711

  • GSK Investigational Site

    Seoul, 04763

  • GSK Investigational Site

    Seoul, 138-736

Other trials in South Korea

Sweden3 sites
  • GSK Investigational Site

    Gothenburg, 431 41

  • GSK Investigational Site

    Malmö, 21146

  • GSK Investigational Site

    Stockholm

Other trials in Sweden

Taiwan3 sites
  • GSK Investigational Site

    Kaohsiung City, 833

  • GSK Investigational Site

    Tainan, 704

  • GSK Investigational Site

    Tau-Yuan, 333

Other trials in Taiwan

Turkey (Türkiye)2 sites
  • GSK Investigational Site

    Ankara, 06230

  • GSK Investigational Site

    CapaIstanbul, 34093

Other trials in Turkey (Türkiye)

About this study

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

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.

Being tested
GSK4527226, Placebo
Keywords
Alzheimer Disease, Dementia, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Mental Disorders
Medical subject headings
Alzheimer Disease, Dementia, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Mental Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GSK4527226Drug

    GSK4527226 will be administered.

  • PlaceboOther

    Placebo will be administered.

Study groups in NCT06079190
Study groupRoleWhat they receive
GSK4527226 Dose 1ExperimentalParticipants will receive GSK4527226 Dose 1
Receives: Drug: GSK4527226
GSK4527226 Dose 2ExperimentalParticipants will receive GSK4527226 Dose 2
Receives: Drug: GSK4527226
PlaceboPlacebo comparatorParticipants will receive placebo.
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline, Week 52, 64 and 76

Secondary outcomes (5)
  1. Change from Baseline in Integrated Alzheimer's Disease Rating Scale (iADRS) Score for Dose 1 vs Placebo Across Weeks 52, 64 and 76

    The iADRS is a composite score that measures both cognition and function. The iADRS comprises scores from the AD Assessment Scale-Cognitive subscale (ADAS-Cog) and the Alzheimers Disease Cooperative Study-instrumental Activities of Daily Living (ADCS-iADL). The iADRS is calculated as a linear combination of the total scores of the ADAS-Cog14 (14-item version of the test that assesses immediate and delayed memory, confrontational naming, ability to follow commands, ideational and constructional praxis, orientation, language, and attention. Higher scores indicate greater impairment) and the ADCS-iADL (score range from 0-49 with higher scores reflecting better performance and lower scores indicating greater functional impairment).

    Measured: Baseline, Weeks 52, 64 and 76

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

    The AD Assessment Scale-Cognitive subscale (ADAS-Cog14) is a 14-item version of the test that assesses immediate and delayed memory, confrontational naming, ability to follow commands, ideational and constructional praxis, orientation, language, and attention. Score ranges from 0 to 90 and higher scores indicate greater impairment.

    Measured: Baseline, Weeks 52, 64 and 76

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

    The AD Cooperative Study - Activities of Daily Living Scale for use in Mild Cognitive Impairment (ADCS-ADL-MCI). The ADCS-ADL for MCI is a 23-item scale that measures the competence of participants in basic and instrumental activities of daily living. Total scores on the ADCS-ADL-MCI range from 0 to 53 where lower scores indicates greater functional impairment.

    Measured: Baseline, Weeks 52, 64 and 76

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

    The ADCS-iADL is a subscale which measures instrumental activities of daily living. The ADCS-iADL is derived from the ADCS-ADL-MCI. It has a total score ranging from 0 to 49 with lower scores indicating greater functional impairment.

    Measured: Baseline, Weeks 52, 64 and 76

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

    The ADCOMS is a composite score comprising scores from various items of the Mini-Mental Status Examination (MMSE), ADAS-Cog14, and CDR domains. The MMSE is a brief test used to screen for cognitive impairment. It is routinely used for estimating the severity of cognitive impairment and tracking cognitive changes in an individual over time. It assesses orientation (time and place), registration, attention and calculation, recent memory, language (naming, comprehension, and repetition), and constructional praxis (copying a figure). For ADCOMS a higher score is indicative of greater impairment.

    Measured: Baseline, Weeks 52, 64 and 76

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Oct 2023
  2. Study start20 Oct 2023
  3. Primary completion14 May 2026
  4. Study completion18 Aug 2026

Why it stopped: The study was terminated early due to meeting pre-specified efficacy futility criteria at planned interim analysis.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
367 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06079190
Sponsor's protocol ID
219867
Other IDs
2023-505083-11-00, 2023
Acronym
PROGRESS-AD
Status last verified
Sep 2026
First submitted
6 Oct 2023
Last updated
17 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing GSK4527226 in people with Alzheimer's Disease, run by GlaxoSmithKline at 97 sites in 16 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 17 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 97 sites in United States, Spain, France, Italy, Australia and 11 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: The study was terminated early due to meeting pre-specified efficacy futility criteria at planned interim analysis.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change from Baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score for Dose 1 vs Placebo Across Weeks 52, 64 and 76 (time frame: Baseline, Week 52, 64 and 76). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2026.

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