A Study to Investigate the Safety and Effectiveness of SAR448851 in Participants With Early Alzheimer's Disease
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age55-85
SponsorSanofi
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Design model
Parallel
Treatments tested in this trial
SAR448851
DrugPharmaceutical form: Capsule Route of administration: Oral
Placebo
DrugPharmaceutical form: Capsule Route of administration: Oral
Treatment groups
160 Participants
are divided into 2 treatment groupsGroup A: SAR448851Experimental treatment 1 intervention
Group B: PlaceboPlacebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
Part A and optional dose 2 cohort: change from baseline to Week 48 in plasma p-tau217
Time frame
From baseline to Week 482
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)
Time frame
From Week 48 to Week 96Secondary outcomes
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 482
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 483
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 484
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 \[C-SSRS\])
Time frame
From baseline to Week 48 Source ClinicalTrials.gov