Safety and Efficacy Study of Gantenerumab in Participants With Early Alzheimer's Disease (AD)

• Register: ClinicalTrials.gov
• Last refreshed on: 16 January 2023
• Main ID: NCT03443973
• Date of registration: 19/02/2018
• Prospective Registration: Yes
• Primary sponsor: Hoffmann-La Roche
• Public title: Safety and Efficacy Study of Gantenerumab in Participants With Early Alzheimer's Disease (AD)
• Scientific title: A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy, and Safety Study of Gantenerumab in Patients With Early (Prodromal to Mild) Alzheimer's Disease
• Date of first enrolment: August 22, 2018
• Target sample size: 982
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT03443973
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

Argentina, Belgium, Chile, Croatia, Denmark, Finland, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Portugal, Puerto Rico, Singapore, Spain, Sweden, Turkey, United Kingdom, United States

Contacts

• Name: Clinical Trials
• Affiliation: Hoffmann-La Roche

Key inclusion & exclusion criteria

Key Inclusion criteria:

- Meets National Institute on Aging/Alzheimer's Association (NIAAA) core clinical
criteria for probable AD dementia or prodromal AD (consistent with the NIAAA
diagnostic criteria and guidelines for mild cognitive impairment)

- Evidence of the AD pathological process, as confirmed by CSF tau/A-beta42or amyloid
PET scan

- Demonstrated abnormal memory function

- MMSE score greater than or equal to 22 (= 22)

- Clinical dementia rating-global score (CDR-GS) of 0.5 or 1.0

- Availability of a reliable study partner who accepts to participate in study
procedures throughout the 2 years duration of study

- If receiving symptomatic AD medications, the dosing regimen must have been stable for
3 months prior to screening and until randomization

- For enrollment in the China extension, patients must have residence in mainland China,
Hong Kong, or Taiwan and be of Chinese ancestry

- For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraceptive methods

Key Exclusion criteria:

- Any evidence of a condition other than AD that may affect cognition

- History of schizophrenia, schizoaffective disorder, major depression, or bipolar
disorder

- 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 (e.g., glioma, meningioma) 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

- At risk for suicide in the opinion of the investigator

- Alcohol and/or substance abuse or dependants in past 2 years

- Relevant brain hemorrhage, bleeding disorder and cerebrovascular abnormalities

- Any contraindications to brain MRI

- Unstable or clinically significant cardiovascular, kidney or liver disease

- Uncontrolled hypertension

- Unstable or clinically significant cardiovascular disease

- Abnormal thyroid function

- Patients with evidence of folic acid deficiency

Exclusion for Open-Label Extension (OLE):

- Discontinued from study treatment during the double-blind treatment period

- Received any other investigational medication during the double-blind treatment period
or after the end of double-blind treatment

- Participation in the OLE deemed inappropriate by the investigator

- Presence of ARIA-E findings at the Week 116 MRI scan



Age minimum: 50 Years
Age maximum: 90 Years
Gender: All

Health Condition(s) or Problem(s) studied

Alzheimer Disease

Intervention(s)

Drug: Gantenerumab

Drug: Placebo

Primary Outcome(s)

Change From Baseline to Week 116 in Global Outcome, as Measured by Clinical Dementia Rating-Sum of Boxes (CDR-SOB) [Time Frame: Baseline up to Week 116]

Secondary Outcome(s)

Change From Baseline in CSF Marker of Disease in a Subset of Patients - Total Tau up to Week 116 [Time Frame: Baseline up to Week 116]

Change From Baseline to Week 116 in Coding [Time Frame: Change from baseline to Week 116 in the Wechsler Adult Intelligence Scale - Fourth Edition (WAIS-IV) coding subtest.]

Change From Baseline to Week 116 in Mini-Mental State Examination (MMSE) Total Score [Time Frame: Baseline up to Week 116]

Change From Baseline to Week 116 in Verbal Fluency Task Score [Time Frame: Baseline up to Week 116]

Percentage of Participants with Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Confirmed by Magnetic Resonance Imaging (MRI) [Time Frame: Baseline up to end of study (week 164) or Week 35 (Open label extension)]

Change From Baseline to Week 116 in Alzheimer Disease Assessment Scale-Cognition Subscale 11 (ADAS-Cog11) Subscale Score [Time Frame: Baseline up to Week 116]

Percentage of Participants With Adverse Events (AEs) [Time Frame: Baseline up to end of study (week 164) or Week 35 (Open label extension)]

Change in Columbia-Suicide Severity Rating Scale (C-SSRS) Score [Time Frame: Baseline up to Week 116 or Week 24 in Open label extension]

Percentage of Participants With Anti-Drug Antibodies (ADA) to Gantenerumab [Time Frame: Baseline up to end of study (week 164) or Week 35 (Open label extension)]

Change from Baseline to Week 116 in Alzheimer Disease Assessment Scale-Cognition, Subscale 13 (ADAS-Cog13) [Time Frame: Baseline up to Week 116]

Percentage of Participants with Injection-Site Reactions [Time Frame: Baseline up to end of study (week 164) or Week 35 (Open label extension)]

Change From Baseline to Week 116 in Alzheimer Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL) Total Score [Time Frame: Baseline up to Week 116]

Change from Baseline in Brain Amyloid Load as Measured by Amyloid Positron Emission Tomography (PET) Scan in a subset of patients up to Week 116 [Time Frame: Baseline up to Week 116]

Change From Baseline in CSF Marker of Disease in a Subset of Patients - Phosphorylated Tau up to Week 116 [Time Frame: Baseline up to Week 116]

Percentage of Participants with Amyloid-Related Imaging Abnormalities-Haemosiderin deposition (ARIA-H) Confirmed by Magnetic Resonance Imaging (MRI) [Time Frame: Baseline up to end of study (week 164) or Week 35 (Open label extension)]

Change From Baseline in Brain Tau Load, as Measured by Tau PET Scan in a Subset of Patients up to Week 116 [Time Frame: Baseline up to Week 116]

Change From Baseline to Week 116 in Functional Activities Questionnaire (FAQ) Score [Time Frame: Baseline to Week 116]

Secondary ID(s)

WN39658

2017-001365-24

Source(s) of Monetary Support

Please refer to primary and secondary sponsors