NCT06814730

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.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
15

participants targeted

Target at below P25 for phase_1

Timeline
6mo left

Started Jul 2025

Geographic Reach
2 countries

4 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress62%
Jul 2025Sep 2026

First Submitted

Initial submission to the registry

December 24, 2024

Completed
2 months until next milestone

First Posted

Study publicly available on registry

February 7, 2025

Completed
5 months until next milestone

Study Start

First participant enrolled

July 17, 2025

Completed
11 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 31, 2026

Expected
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

September 30, 2026

Last Updated

September 11, 2025

Status Verified

September 1, 2025

Enrollment Period

11 months

First QC Date

December 24, 2024

Last Update Submit

September 4, 2025

Conditions

Alzheimer Disease, Early Onset

Keywords

Early ADFibrinFibrinogenamyloid pathologyAlzheimer Disease

Outcome Measures

Primary Outcomes (6)

  • 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 Outcomes (5)

  • To assess the immunogenicity of multiple doses of THN391 in Early AD subjects

    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

    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

    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

    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

    From enrollment to the end of the follow-up period at week 24

Study Arms (3)

Cohort 1

EXPERIMENTAL

THN391 (low dosage) or Placebo, IV-infusion

Drug: THN391Drug: Placebo

Cohort 2

EXPERIMENTAL

THN391 (medium dosage) or Placebo, IV-infusion

Drug: THN391Drug: Placebo

Cohort 3

EXPERIMENTAL

THN391 (high dosage) or Placebo, IV infusion

Drug: THN391Drug: Placebo

Interventions

THN391DRUG

THN391, IV infusion, 3\*Q4W (every 4 weeks)

Cohort 1Cohort 2Cohort 3
PlaceboDRUG

Placebo for comparison with THN391, IV infusion, 3\*Q4W

Cohort 1Cohort 2Cohort 3

Eligibility Criteria

Age65 Years - 85 Years
Sexall
Healthy VolunteersNo
Age GroupsOlder Adult (65+)

You may qualify if:

  • Be willing and able to understand the study procedures and the risks involved and provide written informed consent before the first study-related activity
  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Amsterdam UMC

Amsterdam, New Hampshire, Netherlands

RECRUITING

CTC-Netherlands

Groningen, 9713 EZ, Netherlands

RECRUITING

Scottish Brain Sciences

Edinburgh, EH12 9DQ, United Kingdom

RECRUITING

University College London Hospitals

London, WC1N 3BG, United Kingdom

RECRUITING

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

DementiaBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesTauopathiesNeurodegenerative DiseasesNeurocognitive DisordersMental Disorders

Study Officials

  • Bradford Navia, MD, PhD

    Therini Bio, Inc.

    STUDY DIRECTOR

Central Study Contacts

Bradford Navia, MD, PhD

CONTACT

+16173205611bnavia@therinibio.com

Tanja Hoffman

CONTACT

+31615083285thoffman@therinibio.com

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Model Details: Multiple Ascending Dose
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 24, 2024

First Posted

February 7, 2025

Study Start

July 17, 2025

Primary Completion (Estimated)

May 31, 2026

Study Completion (Estimated)

September 30, 2026

Last Updated

September 11, 2025

Record last verified: 2025-09

Data Sharing

IPD Sharing
Will not share

Locations

GB(2)NL(2)