A Study to Investigate the Safety and Effectiveness of SAR448851 in Participants With Early Alzheimer's Disease (TREMHANCE)

A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of 48-week SAR448851 Treatment Followed by Open-label Extension in Participants With Early Alzheimer's Disease

This is a randomized, placebo-controlled Phase 2 study to evaluate the efficacy and safety of SAR448851 in early Alzheimer's disease (AD) participants. The purpose of this study is to measure efficacy and safety with once daily oral SAR448851 compared to placebo in participants with mild cognitive impairment due to AD or mild AD dementia and with evidence of cerebral amyloid pathology.

This Phase 2 study has 2 parts: Part A is a randomized, double-blind, parallel-group, placebo-controlled study with SAR448851 oral once daily. Part B is an open-label extension. All participants who complete Part A may continue to Part B. An optional dose 2 cohort will be considered to evaluate the efficacy and safety of SAR448851 dose 2 oral once daily.

The study duration will be up to 111 weeks for Part A and B, and up to 63 weeks for the dose 2 cohort. The treatment duration will be up to 96 weeks for Part A and B, and up to 48 weeks for the dose 2 cohort.

Up to 160 participants will be included in this study.

Study Overview

• Status: Not yet recruiting
• Conditions: Alzheimer's Disease; Dementia, Alzheimer's Type
• Intervention / Treatment: Drug: Placebo; Drug: SAR448851

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Trial Transparency email recommended (Toll free for US & Canada); Phone Number: option 6 800-633-1610; Email: Contact-US@sanofi.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant must be 55 to 85 years (inclusive) of age, at the time of signing the informed consent.
• Diagnosis of mild cognitive impairment (MCI) due to Alzheimer's disease (AD) (National Institute on Aging-Alzheimer's Association [NIA-AA] Stage 3) or mild AD dementia (NIA-AA Stage 4).
• Have a global Clinical Dementia Rating (CDR) score 0.5 to 1.0 and a CDR-Memory Box score ≥ 0.5 at screening.
• Have a study partner who must provide separate written informed consent at screening. Study partner should be >18 years of age, have known participant for at least 1 year, and have a minimum of 8 hours per week contact with participant.
• The participant has evidence of cerebral amyloid pathology confirmed by positive visual read on amyloid positron emission tomography (PET) at screening.

Exclusion Criteria:

• The participant has any history of significant neurological disease including but not limited to, frontotemporal dementia, Lewy body dementia, Huntington's disease, serious infection of the brain, Parkinson's disease, multiple concussions, multiple sclerosis, or epilepsy or recurrent seizures (except febrile childhood seizures).
• The participant has evidence of more than 4 microhemorrhages (<10 mm in diameter) or superficial siderosis.
• The participant carries two copies of the apolipoprotein-E epsilon 4 (APOE4) allele (APOE4/4).
• The participant is currently receiving or has previously received any anti-amyloid immunotherapy (including, but not limited to, aducanumab, lecanemab, or donanemab) or triggering receptor expressed on myeloid cells 2 (TREM-2) targeting therapy.
• The participant is currently receiving anticoagulant therapies.
• The participant has had malignancy in the 3 years prior to Screening, excluding basal cell carcinoma, squamous cell carcinoma of the skin, melanoma in situ, Stage 1 or 2 prostate cancer, fully resected renal cell cancers, or cervical carcinoma in situ that has been successfully treated.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SAR448851; Participants will receive SAR448851 dose 1 or dose 2 oral daily for 48 weeks	Drug: SAR448851; Pharmaceutical form: Capsule Route of administration: Oral
Placebo Comparator: Placebo; Participants will receive placebo oral daily for 48 weeks	Drug: Placebo; Pharmaceutical form: Capsule Route of administration: Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A and optional dose 2 cohort: change from baseline to Week 48 in plasma p-tau217		From baseline to Week 48
Part B: Number of participants with treatment-emergent adverse events (TEAE), including ARIA-E and ARIA-H by brain MRI, laboratory assessments, vital sign measurements, ECGs and the C-SSRS	Number of participants experiencing at least one treatment-emergent adverse event (TEAE), including amyloid-related imaging abnormalities with edema (ARIA-E) and amyloid-related imaging abnormalities with hemosiderin (ARIA-H) by brain magnetic resonance imaging (MRI), laboratory assessments, vital sign measurements, electrocardiograms (ECGs) and the Columbia-Suicide Severity Rating Scale (C-SSRS)	From Week 48 to Week 96

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A and optional dose 2 cohort: Change from baseline to Week 48 in plasma glial fibrillary acidic protein (GFAP) and cerebrospinal fluid (CSF) neurogranin (Ng)		From baseline to Week 48
Part A and optional dose 2 cohort: Change from baseline to Week 48 in brain amyloid plaque deposition as measured by amyloid positron emission tomography (PET)		From baseline to Week 48
Part A and optional dose 2 cohort: Change from baseline to Week 48 in CSF soluble triggering receptor expressed on myeloid cells 2 (sTREM2)		From baseline to Week 48
Part A and optional dose 2 cohort: Number of participants with TEAEs and serious adverse events (SAEs), and discontinuations due to TEAEs and SAEs (including laboratory assessments, vital sign measurements, ECGs and the C-SSRS)	Number of participants experiencing at least one treatment-emergent adverse event (TEAE), serious adverse event (SAE) or discontinuation due to TEAEs and SAEs (including laboratory assessments, vital sign measurements, electrocardiograms [ECGs] and the Columbia-Suicide Severity Rating Scale [C-SSRS])	From baseline to Week 48
Part A and optional dose 2 cohort: Number of participants with ARIA-E and ARIA-H assessed by brain MRIs	Number of participants with amyloid-related imaging abnormalities with edema (ARIA-E) and amyloid-related imaging abnormalities with hemosiderin (ARIA-H) assessed by brain magnetic resonance imaging (MRI). ARIA event: adverse event causing brain swelling or bleeding that requires close monitoring.	From baseline to Week 48
Part A and optional dose 2 cohort: Plasma and CSF concentrations of SAR448851		From baseline to Week 48
Part B: Change from baseline to Week 96 in AD biomarkers: plasma p-tau217, plasma GFAP, CSF Ng	Change in Alzheimer's disease (AD) biomarkers: plasma p-tau217, plasma glial fibrillary acidic protein (GFAP) and cerebrospinal fluid (CSF) neurogranin (Ng)	From baseline to Week 96
Part B: Change from Week 48 to Week 96 in AD biomarkers: plasma p-tau217, plasma GFAP, CSF Ng	Change in Alzheimer's disease (AD) biomarkers: plasma p-tau217, plasma glial fibrillary acidic protein (GFAP) and cerebrospinal fluid (CSF) neurogranin (Ng)	From Week 48 to Week 96

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 31, 2029
• Study Completion (Estimated): July 31, 2029

Study Registration Dates

• First Submitted: June 30, 2026
• First Submitted That Met QC Criteria: June 30, 2026
• First Posted (Actual): July 7, 2026

Study Record Updates

• Last Update Posted (Actual): July 7, 2026
• Last Update Submitted That Met QC Criteria: June 30, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease
• Other Study ID Numbers: ACT23645; 2025-524581-14 (Registry Identifier: CTIS); U1111-1328-4936 (Registry Identifier: ICTRP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No