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
Trial Snapshot
- Phase
- Phase 1
- Status
- Active, not recruiting
- Sponsor
- Therini Bio, Inc.
- Enrollment
- 19
- Locations
- 7
- Primary Endpoint
- To assess the safety and tolerability of multiple doses of THN391 in Early AD subjects via AEs
Study Overview
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 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.
Detailed Description
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 60 Years to 85 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Cohort 2
THN391 (medium dosage) or Placebo, IV-infusion
Intervention: Placebo (Drug)
Cohort 2
THN391 (medium dosage) or Placebo, IV-infusion
Intervention: THN391 (Drug)
Cohort 1
THN391 (low dosage) or Placebo, IV-infusion
Intervention: THN391 (Drug)
Cohort 3
THN391 (high dosage) or Placebo, IV infusion
Intervention: THN391 (Drug)
Cohort 1
THN391 (low dosage) or Placebo, IV-infusion
Intervention: Placebo (Drug)
Cohort 3
THN391 (high dosage) or Placebo, IV infusion
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
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 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
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)
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)
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).
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
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
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
- 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)
- 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 (6 months post dosing))
- To assess the effects of THN391 on coagulation in Early AD subjects via aPTT(From enrollment to the end of the follow-up period (6 months post dosing))
- To assess the effects of THN391 on coagulation in Early AD subjects via INR(From enrollment to the end of the follow-up period (6 months post dosing))
- To assess the effects of THN391 on coagulation in Early AD subjects via PT(From enrollment to the end of the follow-up period (6 months dosing))
- 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 (6 months post dosing))
Investigators
Bradford Navia, MD, PhD
Scientific
Therini Bio Inc.