GSK4527226 (AL101) is a monoclonal antibody therapeutic candidate developed by GlaxoSmithKline (GSK) in collaboration with Alector Inc. that targets progranulin (PGRN) for the treatment of early Alzheimer's disease.
This open-label extension (OLE) study allows participants who completed the parent Phase 2 trial (NCT06079190) to continue receiving AL101 treatment in an unblinded manner. The OLE provides:
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Overview
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GSK4527226 (AL101) is a monoclonal antibody therapeutic candidate developed by GlaxoSmithKline (GSK) in collaboration with Alector Inc. that targets progranulin (PGRN) for the treatment of early Alzheimer's disease.
This open-label extension (OLE) study allows participants who completed the parent Phase 2 trial (NCT06079190) to continue receiving AL101 treatment in an unblinded manner. The OLE provides:
Long-term safety data: Monitoring of adverse events with extended exposure to AL101
Efficacy durability: Assessment of whether treatment benefits are maintained over time
Open-label access: Participants previously on placebo may now receive active treatment
Study Design
Study Type
Allocation: Non-randomized (all participants receive active treatment)
Intervention Model: Single Group
Masking: None (Open-Label)
Purpose: Treatment
Treatment
Participants receive AL101 via intravenous infusion according to the dosing schedule established in the parent trial. The specific dose administered in the OLE will depend on the dose received during the parent study.
Current Status (as of March 2026)
The extension study is actively recruiting participants who have completed participation in the parent Phase 2 trial. No published results are currently available.
Anticipated Outcomes
When results become available, this extension study will provide:
Primary Endpoints
Long-term safety and tolerability
Incidence of treatment-emergent adverse events
Secondary Endpoints
Maintenance of cognitive benefits (CDR-SB, iADRS, ADAS-Cog14)
Change in functional abilities (ADCS-ADL-MCI)
Biomarker changes over extended treatment duration
Scientific Context
Progranulin Mechanism
AL101 is designed to elevate progranulin (PGRN) levels in the brain. Progranulin is a multifunctional growth factor that plays critical roles in:
Lysosomal function: Essential for proper lysosomal activity and autophagy
Neuronal survival: Supports neuronal viability and function
The therapeutic approach is supported by human genetics: heterozygous mutations in the GRN gene that reduce progranulin levels by ~50% are associated with increased risk of Alzheimer's disease.
Timeline
| Milestone | Date | |-----------|------| | Parent trial start (NCT06079190) | October 2023 | | OLE start date | Ongoing (2025-2026) | | Parent trial completion | November 2026 (estimated) | | OLE completion | To be determined |
Expected Outcomes Based on Mechanism
Primary Expected Outcomes
Based on the progranulin mechanism:
Long-term Safety: Sustained acceptable safety profile over extended treatment duration
Cognitive Durability: Maintenance of cognitive benefits observed in parent trial
Biomarker Stability: Continued normalization of progranulin levels
Mechanistic Rationale
Progranulin Elevation: Sustained increases in CSF progranulin levels expected
Lysosomal Function: Continued enhancement of lysosomal activity
Microglial Modulation: Long-term anti-inflammatory effects via microglial regulation
The open-label extension provides critical long-term data for a novel therapeutic approach targeting progranulin. Unlike amyloid-targeting antibodies (lecanemab, donanemab), AL101 addresses a different pathway implicated in neurodegeneration through modulation of lysosomal function and microglial biology.
References
[ClinicalTrials.gov. NCT06079190: Efficacy and Safety of GSK4527226 [AL101] in Participants With Early Alzheimer's Disease](https://clinicaltrials.gov/study/NCT06079190)
[ClinicalTrials.gov. NCT07105709: A Study to Evaluate the Long-term Safety and Efficacy of GSK4527226 [AL101] in Participants With Early Alzheimer's Disease (OLE)](https://clinicaltrials.gov/study/NCT07105709)