Alzheimer Disease, Early OnsetPhase 1NCT06814730
A Study to Assess THN391 in Subjects With Alzheimer's Disease
A Phase 1 study testing THN391 in people with Alzheimer Disease, Early Onset, run by Therini Bio, Inc. at 4 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 60 to 85 years
- Conditions the study is for
- Alzheimer Disease, Early Onset
- What is being tested?
- THN391
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 19 participants
- Where
- 4 sitesin 2 countries
- Study dates
- 17 Jul 2025to 31 May 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
Netherlands2 sites
Amsterdam UMC
Amsterdam, New Hampshire
CTC-Netherlands
Groningen, Provincie Groningen, 9713 EZ
United Kingdom2 sites
Scottish Brain Sciences
Edinburgh, EH12 9DQ
University College London Hospitals
London, WC1N 3BG
About this study
Official 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
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.
Read more
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.
Read the 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.
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.
- Conditions
- Alzheimer Disease, Early Onset
- Being tested
- THN391, Placebo
- Keywords
- Early AD, Fibrin, Fibrinogen, amyloid pathology, Alzheimer Disease
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
THN391Drug
THN391, IV infusion, 3*Q4W (every 4 weeks)
PlaceboDrug
Placebo for comparison with THN391, IV infusion, 3*Q4W
THN391Drug
THN391, IV infusion, 6*Q4W (every 4 weeks)
PlaceboDrug
Placebo for comparison with THN391, IV infusion, 6*Q4W
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | THN391 (low dosage) or Placebo, IV-infusion Receives: Drug: THN391; Drug: Placebo |
| Cohort 2 | Experimental | THN391 (medium dosage) or Placebo, IV-infusion Receives: Drug: THN391; Drug: Placebo |
| Cohort 3 | Experimental | THN391 (high dosage) or Placebo, IV infusion Receives: Drug: THN391; Drug: Placebo |
| Cohort 4 | Experimental | THN391 (high dosage) or Placebo, IV infusion - 6 doses Receives: Drug: THN391; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the safety and tolerability of multiple doses of THN391 in Early AD subjects via AEs
Incidence of Adverse Events (AEs)
Measured: From enrollment to the end of the follow-up period (6 months post dosing)
To assess the safety and tolerability of multiple doses of THN391 in Early AD subjects via SAEs
Incidence of Serious Adverse Events (SAEs)
Measured: From enrollment to the end of the follow-up period (6 months post dosing)
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).
Measured: From the first dosing to the end of the follow-up period (6 months post dosing)
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
Measured: From the first dosing to the end of the follow-up period (6 months post dosing)
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
Measured: From the first dosing to the end of the follow-up period (6 months post dosing)
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
Measured: From the first dosing to the end of the follow-up period (6 months post dosing)
Secondary outcomes (5)
To assess the immunogenicity of multiple doses of THN391 in Early AD subjects
Occurrence of antidrug antibodies (ADA) to THN391
Measured: 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
Changes in activated partial thromboplastin time (aPTT)
Measured: 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
Changes in international normalized ratio (INR)
Measured: 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
Changes in prothrombin time (PT)
Measured: 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
Changes in platelet counts
Measured: From enrollment to the end of the follow-up period (6 months post dosing)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2025
- Study start17 Jul 2025
- Primary completion31 Mar 2027 (estimated)
- Study completion31 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer Disease, Early OnsetStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- Multiple Ascending Dose
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Therini Bio, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Nuno Mendonca, MD, Study director, Therini Bio, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06814730
- Sponsor's protocol ID
- THN391-NEU-102
- Other IDs
- 2024-519899-72-00
- Status last verified
- Jul 2026
- First submitted
- 24 Dec 2024
- Last updated
- 8 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT06814730
- Acronym / sponsor ID
- THN391-NEU-102
- Conditions
- Alzheimer Disease, Early Onset
- Keywords
- Early AD, Fibrin, Fibrinogen, amyloid pathology, Alzheimer Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Therini Bio, Inc.Industry (pharma, biotech, devices)
- Study start
- 17 Jul 2025 (actual)
- Primary completion
- 31 Mar 2027 (estimated)
- Study completion
- 31 May 2027 (estimated)
- First posted
- 7 Feb 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- Multiple Ascending Dose
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: THN391, Drug: PlaceboTHN391 (low dosage) or Placebo, IV-infusion |
| Cohort 2 | Experimental | Drug: THN391, Drug: PlaceboTHN391 (medium dosage) or Placebo, IV-infusion |
| Cohort 3 | Experimental | Drug: THN391, Drug: PlaceboTHN391 (high dosage) or Placebo, IV infusion |
| Cohort 4 | Experimental | Drug: THN391, Drug: PlaceboTHN391 (high dosage) or Placebo, IV infusion - 6 doses |
Who may qualify
- Ages
- 60 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| THN391THN391, IV infusion, 3*Q4W (every 4 weeks) | Drug | Cohort 1, Cohort 2, Cohort 3 |
| PlaceboPlacebo for comparison with THN391, IV infusion, 3*Q4W | Drug | Cohort 1, Cohort 2, Cohort 3 |
| THN391THN391, IV infusion, 6*Q4W (every 4 weeks) | Drug | Cohort 4 |
| PlaceboPlacebo for comparison with THN391, IV infusion, 6*Q4W | Drug | Cohort 4 |
Primary outcome
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
5 secondary outcomes
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)
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)
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)
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)
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)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nuno Mendonca, MD study director
Therini Bio, Inc.
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing THN391 in people with Alzheimer Disease, Early Onset, run by Therini Bio, Inc. at 4 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 8 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Netherlands, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2026.