A first in human trial of AL001 in HV and subjects with a GRN mutation

• Research type

  Research Study

• Full title

  First in Human Phase 1 Study in Healthy Volunteers and Heterozygous Carriers of a Loss-of-function Granulin Mutation Causative of Frontotemporal Dementia to Assess AL001 Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics

• IRAS ID

  251610

• Contact name

  Catherine Mummery

• Contact email

  cath.mummery@nhs.net

• Sponsor organisation

  Alector LLC

• Eudract number

  2018-001813-34

• Clinicaltrials.gov Identifier

  NCT03636204

• Duration of Study in the UK

  1 years, 3 months, 1 days

• Research summary

  This is a Phase 1, First in Human study to see how safe and well-tolerated the experimental drug AL001 is when given intravenously (IV) to healthy volunteers (n/a for the UK) and participants who have a mutation in the gene for Granulin (GRN), which causes frontotemporal dementia (FTD).

  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, as well as behavioural and personality changes, and language problems. Patients with FTD decline rapidly, and may die within as little as 3-5 years. No effective treatment has been approved for the treatment of FTD, and only symptomatic care can be provided.

  Mutations in the GRN gene, which makes the protein Progranulin, account for about 20% of cases of inherited FTD, and 5-10% of cases overall. The study drug AL001, which prevents the breakdown of Progranulin by binding to the SORT1 receptor, consistently produced a significant increase in Progranulin levels in non-clinical studies. This is the first clinical study using AL001; however, non-clinical studies have not identified any potential risks that would prevent the initiation of this study.

  Approximately 60 healthy volunteers and participants with a GRN mutation will be enrolled during the trial, which will use single increasing and multiple doses of AL001 in healthy volunteers and participants with a GRN mutation. Safety assessments will include blood sampling, adverse event monitoring, electrocardiograms, blood pressure, physical examination, lumbar puncture, 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 - Chelsea Research Ethics Committee

• REC reference

  18/LO/2053

• Date of REC Opinion

  24 Jan 2019

• REC opinion

  Further Information Favourable Opinion