Clinical trial NCT06079190: Efficacy and Safety of GSK4527226 [AL101] in Participants With Early Alzheimer's Disease
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Alzheimer's Disease
Keywords: Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Mental Disorders
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: Alector Inc.
First posted: 2023-10-12
Enrollment: 367
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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:

  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 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:

  1. \>3 lacunar infarcts.
  2. Stroke involving a major vascular territory, severe small vessel, or white matter disease.
  3. Any territorial /cortical/other infarct \>1 cubic centimetre (cm\^3).
  4. White matter hyperintense lesions on the FLAIR sequence that correspond to an overall 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 greatest diameter.
  8. Vasogenic edema.
  9. Cerebral contusion, encephalomalacia, aneurysms, vascular malformations, or infective 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 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.

Primary outcomes:
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
timeFrame: Baseline, Week 52, 64 and 76
Secondary outcomes:
measure: 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
measure: 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
measure: 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
measure: 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
measure: 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
Other outcomes:
Locations:
city: San Diego
country: United States
facility: GSK Investigational Site
state: California
city: Lake Mary
country: United States
facility: GSK Investigational Site
state: Florida
city: Lake Worth
country: United States
facility: GSK Investigational Site
state: Florida
city: Maitland
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Orlando
country: United States
facility: GSK Investigational Site
state: Florida
city: Orlando
country: United States
facility: GSK Investigational Site
state: Florida
city: Stuart
country: United States
facility: GSK Investigational Site
state: Florida
city: The Villages
country: United States
facility: GSK Investigational Site
state: Florida
city: The Villages
country: United States
facility: GSK Investigational Site
state: Florida
city: Decatur
country: United States
facility: GSK Investigational Site
state: Georgia
city: Elk Grove Village
country: United States
facility: GSK Investigational Site
state: Illinois
city: Chesterfield
country: United States
facility: GSK Investigational Site
state: Missouri
city: Toms River
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Staten Island
country: United States
facility: GSK Investigational Site
state: New York
city: Matthews
country: United States
facility: GSK Investigational Site
state: North Carolina
city: North Canton
country: United States
facility: GSK Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: GSK Investigational Site
state: Oklahoma
city: Portland
country: United States
facility: GSK Investigational Site
state: Oregon
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Fairfax
country: United States
facility: GSK Investigational Site
state: Virginia
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autonoma De Bueno
country: Argentina
facility: GSK Investigational Site
city: Camperdown
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Darlinghurst
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Kogarah
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Macquarie Park
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Gold Coast
country: Australia
facility: GSK Investigational Site
state: Queensland
city: Heidelberg
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Nedlands
country: Australia
facility: GSK Investigational Site
state: Western Australia
city: Melbourne
country: Australia
facility: GSK Investigational Site
city: Ottawa
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Peterborough
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Greenfield Park
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Sherbrooke
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Helsinki
country: Finland
facility: GSK Investigational Site
city: Kuopio
country: Finland
facility: GSK Investigational Site
city: Oulu
country: Finland
facility: GSK Investigational Site
city: Turku
country: Finland
facility: GSK Investigational Site
city: Bron
country: France
facility: GSK Investigational Site
city: Lille Cedex
country: France
facility: GSK Investigational Site
city: Nice
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Saint-Herblain
country: France
facility: GSK Investigational Site
city: Strasbourg
country: France
facility: GSK Investigational Site
city: Toulouse
country: France
facility: GSK Investigational Site
city: Villeurbanne
country: France
facility: GSK Investigational Site
city: Erbach
country: Germany
facility: GSK Investigational Site
city: Koeln
country: Germany
facility: GSK Investigational Site
city: Muenchen
country: Germany
facility: GSK Investigational Site
city: Muenster
country: Germany
facility: GSK Investigational Site
city: Brescia
country: Italy
facility: GSK Investigational Site
city: CefalU PA
country: Italy
facility: GSK Investigational Site
city: Genova
country: Italy
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
city: Modena
country: Italy
facility: GSK Investigational Site
city: Monza
country: Italy
facility: GSK Investigational Site
city: Pavia
country: Italy
facility: GSK Investigational Site
city: Perugia
country: Italy
facility: GSK Investigational Site
city: Jung Gu
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Amsterdam
country: Netherlands
facility: GSK Investigational Site
city: Den Bosch
country: Netherlands
facility: GSK Investigational Site
city: Zwolle
country: Netherlands
facility: GSK Investigational Site
city: Bergen
country: Norway
facility: GSK Investigational Site
city: Oslo
country: Norway
facility: GSK Investigational Site
city: Stavanger
country: Norway
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Getxo - Vizcaya
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Pamplona
country: Spain
facility: GSK Investigational Site
city: Salamanca
country: Spain
facility: GSK Investigational Site
city: Terrassa - Barcelona
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Goteborg
country: Sweden
facility: GSK Investigational Site
city: Malmo
country: Sweden
facility: GSK Investigational Site
city: Stockholm
country: Sweden
facility: GSK Investigational Site
city: Kaohsiung
country: Taiwan
facility: GSK Investigational Site
city: Tainan
country: Taiwan
facility: GSK Investigational Site
city: Tau-Yuan
country: Taiwan
facility: GSK Investigational Site
city: Ankara
country: Turkey
facility: GSK Investigational Site
city: CapaIstanbul
country: Turkey
facility: GSK Investigational Site
city: Birmingham
country: United Kingdom
facility: GSK Investigational Site
city: Bristol
country: United Kingdom
facility: GSK Investigational Site
city: Glasgow
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: