Open-Label Study to Evaluate Safety of long-term AL001 dosing in FTD
Research type
Research Study
Full title
A Phase 2, Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AL001 in Heterozygous Carriers of Granulin or C9orf72 Mutations Causative of Frontotemporal Dementia
IRAS ID
264080
Contact name
Catherine Mummery
Contact email
Sponsor organisation
Alector Inc.
Eudract number
2019-000138-20
Duration of Study in the UK
1 years, 8 months, 8 days
Research summary
This is a Phase 2 Open-Label study to see how safe and well-tolerated the experimental drug AL001 is when given intravenously to participants with a mutation in the gene for Granulin (GRN) or C9orf72, which causes frontotemporal dementia (FTD). This study will enrol symptomatic and asymptomatic participants with a GRN mutation who completed the AL001-1 study, as well as symptomatic patients with a GRN or C9orf72 mutation who have not had AL001 before.
FTD is the second most common early-onset form of dementia after Alzheimer’s Disease and leads to cognitive dysfunction, e.g. issues with attention and memory, behavioural and personality changes, as well as language problems. Patients with FTD decline rapidly, and may die within 3-5 years. No effective treatment has been approved for the treatment of FTD, and only symptomatic care can be provided.
Mutations such as GRN and C9orf72 cause accumulation of a protein called TDP-43 in the brain, leading to disruption of brain activity, and neurodegeneration. Al001 prevents the breakdown of another protein, Progranulin, which has been found to reduce TDP-43 in non-clinical studies. Therapeutics targeted at reducing TDP-43 may slow the progression of disease in FTD. This is the second clinical study using AL001; however, non-clinical studies have not identified any potential risks that would prevent the initiation of this study.
Approximately 32 participants will be enrolled during the trial to receive up to 13 doses of AL001 over a 48 week period. Study procedures will include blood sampling, adverse event monitoring, ECG, blood pressure, physical and neurological examinations, lumbar puncture, questionnaires, and MRI. The effects of AL001 on the body, and how the body processes AL001 will be measured, and the study will also look at whether AL001 affects markers of disease progression, or if there is any effect on cognitive function in participants with a GRN mutation.
REC name
London - Central Research Ethics Committee
REC reference
19/LO/1134
Date of REC Opinion
18 Nov 2019
REC opinion
Further Information Favourable Opinion