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Active, Not Recruiting

NCT Number: NCT06814730

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

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 depends on the number of dose administrations: for the 3 doses administration, the duration is approx. 8 months, in which the participants will visit the clinic approximately 13 times and have 2 telephone calls with the site. For the 6 doses administration group (starting in Jan 2026), the duration is approx. 11 months, with 19 clinic visits and 5 telephone calls with the site.

Patients who fulfill all criteria to participate in the study, will receive 3 or 6 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, 5-7x an MRI-scan of the head, 3x a spinal tap and some testing of the memory and thinking skills.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Alzheimer Disease, Early Onset Alzheimer Disease Brain Diseases Central Nervous System Diseases Dementia Mental Disorders Nervous System Diseases Neurocognitive Disorders Neurodegenerative Diseases Tauopathies

Age range

60 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Amsterdam UMC, Amsterdam, New Hampshire, Netherlands

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About this study

This is a Phase 1b, randomized, double-blind, multi-center, placebo-controlled, multiple ascending dose trial in male and female participants, aged 60 to 85 years with Early Alzheimer's disease and cSVD.

For the 3 dose administration group, the study duration is approximately 8 months: first screening to assess eligibility, then 2 months' treatment period (3 monthly doses), followed by a 6 month follow-up period. For the 6 dose administration group (starting in January 2026), the study duration is approximately 11 months: first screening to assess eligibility, then 5 months' treatment period (6 monthly doses), followed by a 6 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 or six 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 5-7 brain MRIs (Magnetic Resonance Imaging), 3 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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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
  • 60 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

Treatment and study plan

THN391

Drug

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

Placebo

Drug

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

Primary outcomes

  1. To assess the safety and tolerability of multiple doses of THN391 in Early AD subjects via AEs

    Time frame: From enrollment to the end of the follow-up period (6 months post dosing)

    Incidence of Adverse Events (AEs)

  2. To assess the safety and tolerability of multiple doses of THN391 in Early AD subjects via SAEs

    Time frame: From enrollment to the end of the follow-up period (6 months post dosing)

    Incidence of Serious Adverse Events (SAEs)

  3. To assess the pharmacokinetics (PK) of multiple doses of THN391 in Early AD subjects

    Time frame: From the first dosing to the end of the follow-up period (6 months post dosing)

    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).

  4. To assess the maximum plasma concentration (Cmax) for THN391 in Early AD subjects

    Time frame: From the first dosing to the end of the follow-up period (6 months post dosing)

    Evaluate Cmax for serum and CSF concentration of THN391 at specified time points

  5. To assess area under the curve concentration (AUC) for THN391 in Early AD subjects

    Time frame: From the first dosing to the end of the follow-up period (6 months post dosing)

    Evaluate AUC for serum and CSF concentration of THN391 at specified time points

  6. To measure the half-life (t1/2) of THN391 in Early AD subjects

    Time frame: From the first dosing to the end of the follow-up period (6 months post dosing)

    Evaluate PK in serum and CSF concentration of THN391 at specified time points

Secondary outcomes

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

    Time frame: From the first dosing to the end of the follow-up period (6 months post dosing)

    Occurrence of antidrug antibodies (ADA) to THN391

  2. To assess the effects of THN391 on coagulation in Early AD subjects via aPTT

    Time frame: From enrollment to the end of the follow-up period (6 months post dosing)

    Changes in activated partial thromboplastin time (aPTT)

  3. To assess the effects of THN391 on coagulation in Early AD subjects via INR

    Time frame: From enrollment to the end of the follow-up period (6 months post dosing)

    Changes in international normalized ratio (INR)

  4. To assess the effects of THN391 on coagulation in Early AD subjects via PT

    Time frame: From enrollment to the end of the follow-up period (6 months dosing)

    Changes in prothrombin time (PT)

  5. To assess the effects of THN391 on coagulation in Early AD subjects via platelet counts

    Time frame: From enrollment to the end of the follow-up period (6 months post dosing)

    Changes in platelet counts

Sponsors and collaborators

Lead sponsor

Therini Bio, Inc.

Industry

Registry information

Official study 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

Important dates

Study start
2025
Primary completion
2027
Study completion
2027
First posted
Feb 7, 2025
Registry last updated
Jul 8, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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