NCT04592341 - A Study to Evaluate the Pharmacodynamic (PD) Effects of Once Weekly Administration of Gantenerumab in Participants With Early Alzheimer's Disease (AD) | Crick

Eligibility

Sex: ALLMin age: 50 YearsMax age: 90 Years

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Inclusion Criteria: * Probable Alzheimer's Disease (AD) dementia or prodromal AD. * Availability of a reliable study partner (non-professional caregiver) who accepts to participate in study procedure throughout the study duration * The participant should be capable of completing all aspects of study assessments including MRI, clinical genotyping, and PET imaging, either alone or with the help of the study partner (non-professional caregiver). * Adequate visual and auditory acuitysufficient to perform the neuropsychological testing (eye glasses and hearing aids are permitted). * Evidence of AD pathological process, as confirmed by amyloid PET scan by qualitative read by the core/central PET laboratory. * Prodromal or mild symptomatology, as defined by a screening Mini-Mental State Examination (MMSE) score \>/=22 and Clinical Dementia Rating global score (CDR-GS) of 0.5 or 1.0, as well as a clinical dementia rating (CDR) memory domain score \>/=0.5. * If the participant is receiving symptomatic AD medications, a stable dosing regimen for at least 3 months prior to screening and until start of study treatment. * Agreement not to donate blood or blood products for transfusion for the duration of the study and for 1 year after final dose of study drug. * Agreement not to participate in other research studies for the duration of this trial, unless these are related Roche-sponsored non-interventional studies. * For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods hat result in a failure rate of \< 1% per year during the treatment period and for at least 16 weeks after the final dose of study drug. Exclusion Criteria: * Any evidence of a condition other than AD that may affect cognition. * History or presence of clinically evident systemic vascular disease that in the opinion of the investigator has the potential to affect cognitive function. * History or presence of clinically evident cerebrovascular disease. * History or presence of posterior reversible encephalopathy syndrome. * History or presence of any stroke with clinical symptoms within the past 12 months, or documented history within the last 6 months of an acute event that is consistent with a transient ischemic attack. * History of severe, clinically significant CNS trauma. * History or presence of intracranial mass that could potentially impair cognition. * Presence of infections that affect brain function or history of infections that resulted in neurologic sequelae. * History or presence of systemic autoimmune disorders that potentially cause progressive neurologic disease with associated cognitive deficits. * History of schizophrenia, schizoaffective disorder, major depression, or bipolar disorder. * At risk for suicide in the opinion of the investigator. * Alcohol and/or substance abuse or dependants in past 2 years.

Outcomes

Primary Outcomes

Change From Baseline in Brain Amyloid Load at Week 104 as Measured by [18F] Florbetaben Positron Emission Tomography (PET) Scan

Screening amyloid PET scan was considered baseline evaluation.Brain amyloid load was quantified in terms of Standardized Uptake Value Ratio (SUVR),defined as ratio of tracer uptake in cortical composite target region of interest(ROI)to tracer uptake in reference ROI.Composite region: frontal,parietal,temporal,posterior cingulate cortex,anterior cingulate cortex. Reference ROI (whole cerebellum) was represented by weighted average of Cerebellum Ventral,Cerebellum Dorsal (left/right), Cerebellar White Matter.SUVR linearly transformed to standardized Centiloid Scale (CL) using formula CL=175.6xSUVR-174.2.CL ranges from \<0 to \>100, anchor points are 0=high-certainty amyloid negative scan and 100=amount of global amyloid deposition found in typical AD scan.

Time frame: Baseline, Week 104

Secondary Outcomes

Number of Caregiver or Study Partner With Responses to Home Administration Questionnaire (HAQ)

HAQ comprised 4 items completed by study partner capturing confidence (Q1), convenience (Q2), ease of use (Q3), and overall satisfaction (Q4) with administering medication. Response options Q1: Not at all confident, somewhat confident, confident, very confident; Q2: Not at all convenient, somewhat convenient, convenient, very convenient; Q3: Not at all easy, somewhat easy, easy, very easy; Q4:Not at all satisfied, somewhat satisfied, satisfied, very satisfied.

Time frame: Weeks 36, 52, 76, 104

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

AE: any untoward medical occurrence in participant administered pharmaceutical product, which does not necessarily have a causal relationship with treatment. Also, any unfavorable, unintended sign, symptom, or disease temporally associated with use of medicinal product, whether or not considered related to it. SAE: any AE that was fatal, life threatening, required prolonged inpatient hospitalization, resulted in significant disability or resulted in a congenital anomaly to mother exposed to study treatment. This was a single-arm study and all participants received gantenerumab according to predefined universal up-titration scheme as follows: 120 mg Q4W (Day 1, Week (W) 4, and W8), then 255 mg Q4W (W 12, 16, and 20), then 255 mg Q2W for 12 weeks (W 24, 26, 28, 30, 32, and 34), followed by target dose of 255 mg Q1W (W 36 to 104). Data was collected and reported in single arm for each participant who started treatment as specified and either completed or discontinued study.