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

Official title

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

Overview

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.

Interventions

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

Primary outcome measures

• Part A and optional dose 2 cohort: change from baseline to Week 48 in plasma p-tau217 [Time frame: 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 [Time frame: From Week 48 to Week 96]

Secondary outcome measures (8)

• 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]
• 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) [Time frame: 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) [Time frame: 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) [Time frame: 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 [Time frame: From baseline to Week 48]
• Part A and optional dose 2 cohort: Plasma and CSF concentrations of SAR448851 [Time frame: From baseline to Week 48]
• 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]
• 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]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07688213 · ACT23645 · 2025-524581-14 · U1111-1328-4936

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗