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

Phase 1

Not yet recruiting

• Conditions: Alzheimer Disease, Early Onset
• Interventions: Drug: THN391; Drug: Placebo

• Registration Number: NCT06814730
• Lead Sponsor: Therini Bio, Inc.

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.

Study Timeline

• Status Verified: 2024-12
• Study First Submitted: 2024-12-24
• Study First Submitted QC: 2025-02-05
• Last Update Submitted: 2025-02-05
• Study First Posted: 2025-02-07
• Last Update Posted: 2025-02-07
• Study Start: 2025-03-17
• Primary Completion: 2025-12-31
• Study Completion: 2026-06-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 15

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 1	Placebo	THN391 (low dosage) or Placebo, IV-infusion
Cohort 2	THN391	THN391 (medium dosage) or Placebo, IV-infusion
Cohort 2	Placebo	THN391 (medium dosage) or Placebo, IV-infusion
Cohort 3	THN391	THN391 (high dosage) or Placebo, IV infusion
Cohort 3	Placebo	THN391 (high dosage) or Placebo, IV infusion
Cohort 1	THN391	THN391 (low dosage) or Placebo, IV-infusion

Primary Outcome Measures

Name	Time	Method
To assess the safety and tolerability of multiple doses of THN391 in Early AD subjects via AEs	From enrollment to the end of the follow-up period at week 24	Incidence of Adverse Events (AEs)
To assess the safety and tolerability of multiple doses of THN391 in Early AD subjects via SAEs	From enrollment to the end of the follow-up period at week 24	Incidence of Serious Adverse Events (SAEs)
To assess the pharmacokinetics (PK) of multiple doses of THN391 in Early AD subjects	From the first dosing to the end of the follow-up period at week 24	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).
To assess the maximum plasma concentration (Cmax) for THN391 in Early AD subjects	From the first dosing to the end of the follow-up period at week 24	Evaluate Cmax for serum and CSF concentration of THN391 at specified time points
To assess area under the curve concentration (AUC) for THN391 in Early AD subjects	From the first dosing to the end of the follow-up period at week 24	Evaluate AUC for serum and CSF concentration of THN391 at specified time points
To measure the half-life (t1/2) of THN391 in Early AD subjects	From the first dosing to the end of the follow-up period at week 24	Evaluate PK in serum and CSF concentration of THN391 at specified time points

Secondary Outcome Measures

Name	Time	Method
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	Occurrence of antidrug antibodies (ADA) to THN391
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	Changes in activated partial thromboplastin time (aPTT)
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	Changes in international normalized ratio (INR)
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	Changes in prothrombin time (PT)
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	Changes in platelet counts

Trial Locations

Locations (2)

Amsterdam UMC; 🇳🇱 Amsterdam, New Hampshire, Netherlands

Scottish Brain Sciences; 🇬🇧 Edinburgh, United Kingdom