A Study to Assess THN391 in Subjects With Alzheimer's Disease

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

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.

Study Overview

• Status: Recruiting
• Conditions: Alzheimer Disease, Early Onset
• Intervention / Treatment: Drug: THN391; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Bradford Navia, MD, PhD; Phone Number: +16173205611; Email: bnavia@therinibio.com
• Study Contact Backup: Name: Tanja Hoffman; Phone Number: +31615083285; Email: thoffman@therinibio.com

Study Locations

• Netherlands
  • Groningen, Netherlands, 9713 EZ
    • Recruiting
    • CTC-Netherlands
    • Contact: M. Beukers; Phone Number: +3150 305 5488; Email: vrijwilligers@ctc-netherlands.com
    • Contact: P. Schuilenga; Phone Number: +3150 305 5488; Email: vrijwilligers@ctc-netherlands.com
    • Principal Investigator: Khalid Abdelaziz, MD
    • Sub-Investigator: J. de Vries, MD
  • New Hampshire
    • Amsterdam, New Hampshire, Netherlands
      • Recruiting
      • Amsterdam UMC
      • Contact: E. (Jort) G.B. Vijverberg, Professor, MD, PhD; Phone Number: +31205669111; Email: e.vijverberg@amsterdamumc.nl
      • Principal Investigator: E. (Jort) G.B. Vijverberg, Professor, MD, PhD
• United Kingdom
  • Edinburgh, United Kingdom, EH12 9DQ
    • Recruiting
    • Scottish Brain Sciences
    • Contact: Craig Ritchie, Professor, MD, PhD; Email: C.Ritchie@brainsciences.scot
    • Principal Investigator: Craig Ritchie, Professor, MD, PhD
  • London, United Kingdom, WC1N 3BG
    • Recruiting
    • University College London Hospitals
    • Contact: C. Mummery, Prof., MD, PhD
    • Contact: Phone Number: +4420 3456 7890; Email: cath.mummery@nhs.net
    • Principal Investigator: C. Mummery, Prof., MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; THN391 (low dosage) or Placebo, IV-infusion	Drug: THN391; THN391, IV infusion, 3*Q4W (every 4 weeks); Drug: Placebo; Placebo for comparison with THN391, IV infusion, 3*Q4W
Experimental: Cohort 2; THN391 (medium dosage) or Placebo, IV-infusion	Drug: THN391; THN391, IV infusion, 3*Q4W (every 4 weeks); Drug: Placebo; Placebo for comparison with THN391, IV infusion, 3*Q4W
Experimental: Cohort 3; THN391 (high dosage) or Placebo, IV infusion	Drug: THN391; THN391, IV infusion, 3*Q4W (every 4 weeks); Drug: Placebo; Placebo for comparison with THN391, IV infusion, 3*Q4W

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the safety and tolerability of multiple doses of THN391 in Early AD subjects via AEs	Incidence of Adverse Events (AEs)	From enrollment to the end of the follow-up period at week 24
To assess the safety and tolerability of multiple doses of THN391 in Early AD subjects via SAEs	Incidence of Serious Adverse Events (SAEs)	From enrollment to the end of the follow-up period at week 24
To assess the pharmacokinetics (PK) of multiple doses of THN391 in Early AD subjects	Serum and CSF concentration of THN391 using validated analytical method at specified timepoints The PK parameters will be determined or calculated using non-compartmental analysis from the serum concentration time data for THN391. A complete list of PK parameters will be provided in the statistical analysis plan (SAP).	From the first dosing to the end of the follow-up period at week 24
To assess the maximum plasma concentration (Cmax) for THN391 in Early AD subjects	Evaluate Cmax for serum and CSF concentration of THN391 at specified time points	From the first dosing to the end of the follow-up period at week 24
To assess area under the curve concentration (AUC) for THN391 in Early AD subjects	Evaluate AUC for serum and CSF concentration of THN391 at specified time points	From the first dosing to the end of the follow-up period at week 24
To measure the half-life (t1/2) of THN391 in Early AD subjects	Evaluate PK in serum and CSF concentration of THN391 at specified time points	From the first dosing to the end of the follow-up period at week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the immunogenicity of multiple doses of THN391 in Early AD subjects	Occurrence of antidrug antibodies (ADA) to THN391	From the first dosing to the end of the follow-up period at week 24
To assess the effects of THN391 on coagulation in Early AD subjects via aPTT	Changes in activated partial thromboplastin time (aPTT)	From enrollment to the end of the follow-up period at week 24
To assess the effects of THN391 on coagulation in Early AD subjects via INR	Changes in international normalized ratio (INR)	From enrollment to the end of the follow-up period at week 24
To assess the effects of THN391 on coagulation in Early AD subjects via PT	Changes in prothrombin time (PT)	From enrollment to the end of the follow-up period at week 24
To assess the effects of THN391 on coagulation in Early AD subjects via platelet counts	Changes in platelet counts	From enrollment to the end of the follow-up period at week 24

Collaborators and Investigators

• Sponsor: Therini Bio, Inc.
• Investigators: Study Director: Bradford Navia, MD, PhD, Therini Bio, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 17, 2025
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: December 24, 2024
• First Submitted That Met QC Criteria: February 5, 2025
• First Posted (Actual): February 7, 2025

Study Record Updates

• Last Update Posted (Estimated): September 11, 2025
• Last Update Submitted That Met QC Criteria: September 4, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Alzheimer Disease; Fibrin; Fibrinogen; Early AD; amyloid pathology
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: THN391-NEU-102; 2024-519899-72-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes