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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

A study to investigate the safety and effectiveness of SAR448851 in participants with early Alzheimer's disease
(TREMHANCE)

Obara Kentaro

Sanofi K.K.

Tokyo Opera City Tower, 3-20-2, Nishi Shinjuku, Shinjuku-ku, Tokyo 163-1488, Japan

clinical-trials-jp@sanofi.com

Clinical Study Unit

Sanofi K.K.

Tokyo Opera City Tower, 3-20-2, Nishi Shinjuku, Shinjuku-ku, Tokyo 163-1488, Japan

+81-3-6301-3670

clinical-trials-jp@sanofi.com

Pending

Sept. 15, 2026

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

- 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.

- 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 (TREM2) 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.

Both

Dementia Alzheimer's type

Drug: SAR448851
Pharmaceutical form: Capsule, Route of administration: Oral
Drug: Placebo
Pharmaceutical form: Capsule, Route of administration: Oral

Study Arms:
Experimental: SAR448851
- Participants will receive SAR448851 dose 1 or dose 2 oral daily for 48 weeks.
- - Interventions: SAR448851
Placebo Comparator: Placebo
- Participants will receive placebo oral daily for 48 weeks.
- - Interventions: Placebo

1. Part A and optional dose 2 cohort: change from baseline to Week 48 in plasma p-tau217
[Time Frame: From baseline to Week 48]
2. Part B: Number of participants with treatment-emergent adverse events (TEAE), including amyloid-related imaging abnormalities-edema (ARIA-E) and amyloid-related imaging abnormalities-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
[Time Frame: From Week 48 to Week 96]
Number of participants experiencing at least one TEAE.

1. 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)
[Time Frame: From baseline to Week 48]
2. Part A and optional dose 2 cohort: Change from baseline to Week 48 in brain amyloid plaque deposition as measured by amyloid PET
[Time Frame: From baseline to Week 48]
3. Part A and optional dose 2 cohort: Change from baseline to Week 48 in CSF soluble triggering receptor expressed on myeloid cells 2 (sTREM2)
[Time Frame: From baseline to Week 48]
4. 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)
[Time Frame: From baseline to Week 48]
Number of participants experiencing at least one TEAE, SAE or discontinuation due to TEAEs and SAEs.
5. Part A and optional dose 2 cohort: Number of participants with ARIA-E and ARIA-H assessed by brain MRIs
[Time Frame: From baseline to Week 48]
Number of participants with at least one ARIA event: adverse event causing brain swelling or bleeding that requires close monitoring.
6. Part A and optional dose 2 cohort: Plasma and CSF concentrations of SAR448851
[Time Frame: From baseline to Week 48]
7. Part B: Change from baseline to Week 96 in AD biomarkers: plasma p-tau217, plasma GFAP, CSF Ng
[Time Frame: From baseline to Week 96]
8. Part B: Change from Week 48 to Week 96 in AD biomarkers: plasma p-tau217, plasma GFAP, CSF Ng
[Time Frame: From Week 48 to Week 96]

Yes

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

United States