THN391-NEU-102 - A Double-Blind, Randomized, Placebo-Controlled, Phase 1b Study to Assess the Safety, Tolerability, and Pharmacokinetics of Multiple Ascending Doses of THN391 in Early Alzheimer’s Disease Subjects
Recipient organisationNIHR Wellcome Trust UCL Clinical Research Facility
NIHR supportRecorded as supported by this research centre
PeriodFeb 2025 — Ongoing
In plain English
AI plain-English summary
A laboratory-made antibody called THN391 is being infused into people with early Alzheimer’s to see if it safely clears a blood-clotting protein called fibrin from their brains. This matters because fibrin deposits are abnormally high in the brains of people with dementia, and they are linked to cerebral small vessel disease (cSVD)—a condition that damages tiny blood vessels and worsens cognitive decline. No existing Alzheimer’s treatment targets fibrin directly. This phase 1b trial, conducted at four sites across the UK and Netherlands, will enroll men and women aged 65 to 85 with early Alzheimer’s and cSVD. Participants receive three doses of THN391 or a placebo via 60-minute infusions every four weeks, with neither they nor staff knowing who gets which. Safety monitoring includes brain MRIs, spinal taps, electrocardiograms, and cognitive tests over 169 days. If THN391 proves safe and tolerable, it would open a fundamentally new treatment avenue for Alzheimer’s—one that targets vascular damage rather than amyloid plaques. That could eventually slow disease progression in the many patients whose dementia is driven by blood-brain barrier breakdown and clotting abnormalities.
View original technical description
THN391 is an antibody that was produced in the laboratory and is now in development for treatment of neurodegenerative disorders, including Alzheimer’s disease (AD). It is intended to target the protein fibrin, an important protein involved in clotting. Fibrin deposits are increased in brains of people with dementia. The primary objectives are to assess the safety, tolerability, and pharmacokinetics of multiple doses of THN391 in people with Early AD with cerebral small vessel disease (cSVD). cSVD is an indicator of deposition of fibrin in the brain. In approximately 2 sites in UK and 2 in The Netherlands, male and female subjects will be enrolled, aged 65 to 85 years with Early AD and cSVD. Subjects will be randomized to receive 3 doses of THN391 or placebo. Placebo is an inactive drug that looks just like THN391. Neither the subject nor the staff will know who is getting THN391 and who is getting placebo. However, if the subject experiences any important side effects, the doctor can find out whether the subject is getting THN391 or placebo. Study drug will be administered over an approximately 60-minute infusion, once every 4 weeks. Subjects will remain in the clinical unit for at least 24 hours following the first administration of study drug. They will return to the clinic for the second and third doses and for multiple evaluations up to the End of Study (Day 169). Subjects will undergo clinical and laboratory-based safety-related assessments, as well as blood collections at different time points. Assessments will include brain MRIs, spinal taps, electrocardiograms, vital signs, physical and neurological examinations, blood draws, adverse event recordings, monitoring of mental health, and tests to determine the severity of AD. Informed consent will be obtained from all subjects before any study-related procedures are conducted.
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