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

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT06079190
• Collaborator: Alector Inc. (Industry)
• Enrollment: 282
• Locations: 100
• Arms: 3
• Anticipated Duration (Months): 67.2
• Patients Per Site: 2.8
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease	Drug: GSK4527226; Other: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 282 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Click here to enter text.
• Primary Purpose: Treatment
• 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
• Anticipated Study Start Date: Oct 11, 2023
• Anticipated Primary Completion Date: Dec 2, 2026
• Anticipated Study Completion Date: May 16, 2029

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GSK4527226 Dose 1 Participants will receive GSK4527226 Dose 1	Drug: GSK4527226; GSK4527226 will be administered.
Experimental: GSK4527226 Dose 2 Participants will receive GSK4527226 Dose 2	Drug: GSK4527226; GSK4527226 will be administered.
Placebo Comparator: Placebo Participants will receive placebo.	Other: Placebo; Placebo will be administered.

Outcome Measures

Primary Outcome Measures

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 [Baseline, Week 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.

Secondary Outcome Measures

1. 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]

   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).

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

3. 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]

   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.

4. 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]

   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.

5. 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]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 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

• 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.

• 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 90 days before screening and during the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	San Diego	California	United States	92103
2	GSK Investigational Site	DeLand	Florida	United States	32720
3	GSK Investigational Site	Maitland	Florida	United States	32752
4	GSK Investigational Site	Miami	Florida	United States	33176
5	GSK Investigational Site	Orlando	Florida	United States	32804
6	GSK Investigational Site	Stuart	Florida	United States	34997
7	GSK Investigational Site	The Villages	Florida	United States	32159
8	GSK Investigational Site	Wellington	Florida	United States	33414
9	GSK Investigational Site	Decatur	Georgia	United States	30030
10	GSK Investigational Site	Elk Grove Village	Illinois	United States	60007
11	GSK Investigational Site	Wichita	Kansas	United States	67207
12	GSK Investigational Site	Chesterfield	Missouri	United States	63005
13	GSK Investigational Site	Toms River	New Jersey	United States	08755
14	GSK Investigational Site	New York	New York	United States	10016
15	GSK Investigational Site	New York	New York	United States	10032
16	GSK Investigational Site	Staten Island	New York	United States	10314
17	GSK Investigational Site	Matthews	North Carolina	United States	28105
18	GSK Investigational Site	North Canton	Ohio	United States	44720
19	GSK Investigational Site	Oklahoma City	Oklahoma	United States	73112
20	GSK Investigational Site	Portland	Oregon	United States	07210
21	GSK Investigational Site	Capital Federal	Buenos Aires	Argentina	C1428AQK
22	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires	Argentina	C1431FWO
23	GSK Investigational Site	Buenos Aires		Argentina	C1056ABJ
24	GSK Investigational Site	Camperdown	New South Wales	Australia	2050
25	GSK Investigational Site	Darlinghurst	New South Wales	Australia	2010
26	GSK Investigational Site	Kogarah	New South Wales	Australia	2217
27	GSK Investigational Site	Macquarie Park	New South Wales	Australia	2113
28	GSK Investigational Site	Southport	Queensland	Australia	4222
29	GSK Investigational Site	Ivanhoe	Victoria	Australia	3079
30	GSK Investigational Site	Melbourne	Victoria	Australia	3004
31	GSK Investigational Site	Nedlands	Western Australia	Australia	6009
32	GSK Investigational Site	Ottawa	Ontario	Canada	K1Z 1G3
33	GSK Investigational Site	Peterborough	Ontario	Canada	K9H 2P4
34	GSK Investigational Site	Toronto	Ontario	Canada	M3B 2S7
35	GSK Investigational Site	Toronto	Ontario	Canada	M5T 2S8
36	GSK Investigational Site	Greenfield Park	Quebec	Canada	J4V 2J2
37	GSK Investigational Site	Sherbrooke	Quebec	Canada	J1J 2G2
38	GSK Investigational Site	Verdun	Quebec	Canada	H4H 1R3
39	GSK Investigational Site	Helsinki		Finland	00180
40	GSK Investigational Site	Kuopio		Finland	70210
41	GSK Investigational Site	Oulu		Finland	90100
42	GSK Investigational Site	Turku		Finland	20520
43	GSK Investigational Site	Bron		France	69500
44	GSK Investigational Site	Lille Cedex		France	59037
45	GSK Investigational Site	Nice		France	06100
46	GSK Investigational Site	Paris		France	75010
47	GSK Investigational Site	Paris		France	75013
48	GSK Investigational Site	Saint-Herblain		France	44093
49	GSK Investigational Site	Strasbourg		France	67200
50	GSK Investigational Site	Toulouse		France	31300
51	GSK Investigational Site	Villeurbanne		France	69100
52	GSK Investigational Site	Muenchen	Bayern	Germany	80336
53	GSK Investigational Site	Erbach	Hessen	Germany	64711
54	GSK Investigational Site	Koeln	Nordrhein-Westfalen	Germany	50935
55	GSK Investigational Site	Roma	Lazio	Italy	00179
56	GSK Investigational Site	Genova	Liguria	Italy	16132
57	GSK Investigational Site	Baggiovara	Modena	Italy	41126
58	GSK Investigational Site	Cefalù	Palermo	Italy	90015
59	GSK Investigational Site	Mondino	Pavia	Italy	27100
60	GSK Investigational Site	Brescia		Italy	25123
61	GSK Investigational Site	Milano		Italy	20132
62	GSK Investigational Site	Milano		Italy	20133
63	GSK Investigational Site	Monza		Italy	20900
64	GSK Investigational Site	Palermo		Italy	90127
65	GSK Investigational Site	Perugia		Italy	06129
66	GSK Investigational Site	Jung Gu		Korea, Republic of	400711
67	GSK Investigational Site	Seoul		Korea, Republic of	04763
68	GSK Investigational Site	Seoul		Korea, Republic of	138-736
69	GSK Investigational Site	's-Hertogenbosch		Netherlands	5223 LA
70	GSK Investigational Site	Amsterdam		Netherlands	1081 GN
71	GSK Investigational Site	Zwolle		Netherlands	8025 AZ
72	GSK Investigational Site	Bergen		Norway	5009
73	GSK Investigational Site	Drammen		Norway	N-3004
74	GSK Investigational Site	Oslo		Norway	0450
75	GSK Investigational Site	Stavanger		Norway
76	GSK Investigational Site	Pozuelo De Alarcón	Madrid	Spain	28223
77	GSK Investigational Site	Barcelona		Spain	08028
78	GSK Investigational Site	Getxo		Spain	48993
79	GSK Investigational Site	Madrid		Spain	28034
80	GSK Investigational Site	Madrid		Spain	28041
81	GSK Investigational Site	Madrid		Spain	28046
82	GSK Investigational Site	Pamplona		Spain	31008
83	GSK Investigational Site	Salamanca		Spain	37007
84	GSK Investigational Site	Terrassa (Barcelona)		Spain	08221
85	GSK Investigational Site	Valencia		Spain	46026
86	GSK Investigational Site	Jönköping		Sweden	SE-551 85
87	GSK Investigational Site	Malmö		Sweden	21146
88	GSK Investigational Site	Mölndal		Sweden	431 41
89	GSK Investigational Site	Stockholm		Sweden
90	GSK Investigational Site	Kaohsiung		Taiwan	833
91	GSK Investigational Site	Tainan		Taiwan	704
92	GSK Investigational Site	Taoyuan		Taiwan	333
93	GSK Investigational Site	Ankara		Turkey	06230
94	GSK Investigational Site	Capa/Istanbul		Turkey	34093
95	GSK Investigational Site	Birmingham	England	United Kingdom	B16 8LT
96	GSK Investigational Site	Bristol		United Kingdom	BS32 4SY
97	GSK Investigational Site	London		United Kingdom	EC2Y 8EA
98	GSK Investigational Site	London		United Kingdom	W1G 9JF
99	GSK Investigational Site	London		United Kingdom	WC1N 3BG
100	GSK Investigational Site	Motherwell		United Kingdom	ML1 4UF

Sponsors and Collaborators

• GlaxoSmithKline
• Alector Inc.

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT06079190
• Other Study ID Numbers: 219867; 2023-505083-11-00
• First Posted: Oct 12, 2023
• Last Update Posted: Oct 12, 2023
• Last Verified: Oct 1, 2023

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by GlaxoSmithKline: Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders
• Additional relevant MeSH terms: Alzheimer Disease

Study Results

No Results Posted as of Oct 12, 2023