Clinical trial NCT06814730: A Study to Assess THN391 in Subjects with Alzheimer's Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Alzheimer Disease, Early Onset
Keywords: Early AD
Fibrin
Fibrinogen
amyloid pathology
Alzheimer Disease
Lead sponsor: Therini Bio, Inc.
Sponsor class: INDUSTRY
First posted: 2025-02-07
Enrollment: 15
Sex: ALL
Minimum age (years): 65
Maximum age (years): 85
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Multiple Ascending Dose
Primary purpose: TREATMENT

Brief summary: This is a Phase 1b study to evaluate different doses of the drug and see whether a drug is safe and how it behaves in the body.

THN391 has already been assessed in healthy people without Alzheimer's disease. This is the first study of THN391 in patients with Early Alzheimer's disease. Later studies will evaluate THN391 to see if it is effective for the treatment of Alzheimer's disease.

In this study, THN391 will be compared with a placebo (a look-alike substance that contains no drug). The study duration is approximately 6 months in which the participants will visit the clinic approximately 13 times and have 2 telephone calls with the site.

Patients who fulfill all criteria to participate in the study, will receive 3 times a monthly dose of THN391 or placebo in the clinic.

Assessments that will be done at several timepoints during the study will be blood collection, physical examinations and neurological examinations, 4x an MRI-scan of the head, 2x a spinal tap and some testing of the memory and thinking skills.

Detailed description: This is a Phase 1b, randomized, double-blind, multi-center, placebo-controlled, multiple ascending dose trial in male and female participants, aged 65 to 85 years with Early Alzheimer's disease and cSVD.

The study duration is 6-8 months: first screening to assess eligibility, then 2 months' treatment period (3 monthly doses), followed by a 4 month follow-up period.

The trial will investigate THN391 in at least 3 dose cohorts, Depending on preliminary, blinded results of the first two cohorts, the sample sizes of the following dose cohort may be increased and/or additional dose cohorts may be added.

Eligible participants will be randomized to receive either THN391 or placebo.

Three dose administrations will be provided monthly. Participants will undergo clinical and laboratory-based safety-related assessments, as well as Pharmacodynamics (PD), immunogenicity, and blood Pharmacokinetic (PK) collections at different time points.

Assessments will include 4 brain MRIs (Magnetic Resonance Imaging), 2 spinal taps, electrocardiograms (ECGs), vital signs, physical and neurological examinations, adverse event recordings, monitoring of mental health, and tests to determine the severity of Alzheimer's disease.

Eligibility criteria: Inclusion Criteria:

* Be willing and able to understand the study procedures and the risks involved and provide written informed consent before the first study-related activity
* 65 to 85 years of age (inclusive at the time of informed consent).
* Diagnosis of Early Alzheimer's Disease (AD)
* Diagnosis of cerebral Small Vessel Disease (cSVD), and having at least one of the following vascular risk factors: hypertension, Type 2 diabetes mellitus, or hyperlipidemia

Exclusion criteria:

* Diagnosis of moderate or severe dementia
* Any other medical condition except for early AD (e.g. any clinically significant neurological, psychiatric or large vessel disease) that could affect interpretation of study assessments
* Use of anticoagulant, except for either clopidogrel or low dose aspirin, unless taken simultaneously

Primary outcomes:
measure: To assess the safety and tolerability of multiple doses of THN391 in Early AD subjects via AEs
timeFrame: From enrollment to the end of the follow-up period at week 24
measure: To assess the safety and tolerability of multiple doses of THN391 in Early AD subjects via SAEs
timeFrame: From enrollment to the end of the follow-up period at week 24
measure: To assess the pharmacokinetics (PK) of multiple doses of THN391 in Early AD subjects
timeFrame: From the first dosing to the end of the follow-up period at week 24
measure: To assess the maximum plasma concentration (Cmax) for THN391 in Early AD subjects
timeFrame: From the first dosing to the end of the follow-up period at week 24
measure: To assess area under the curve concentration (AUC) for THN391 in Early AD subjects
timeFrame: From the first dosing to the end of the follow-up period at week 24
measure: To measure the half-life (t1/2) of THN391 in Early AD subjects
timeFrame: From the first dosing to the end of the follow-up period at week 24
Secondary outcomes:
measure: To assess the immunogenicity of multiple doses of THN391 in Early AD subjects
timeFrame: From the first dosing to the end of the follow-up period at week 24
measure: To assess the effects of THN391 on coagulation in Early AD subjects via aPTT
timeFrame: From enrollment to the end of the follow-up period at week 24
measure: To assess the effects of THN391 on coagulation in Early AD subjects via INR
timeFrame: From enrollment to the end of the follow-up period at week 24
measure: To assess the effects of THN391 on coagulation in Early AD subjects via PT
timeFrame: From enrollment to the end of the follow-up period at week 24
measure: To assess the effects of THN391 on coagulation in Early AD subjects via platelet counts
timeFrame: From enrollment to the end of the follow-up period at week 24
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
state: New Hampshire
city: Edinburgh
country: United Kingdom
facility: Scottish Brain Sciences
Study officials:
affiliation: Therini Bio, Inc.
name: Bradford Navia, MD, PhD
role: STUDY_DIRECTOR
References: