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

Study Description

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Brief Summary:

This randomized, double-blind, placebo-controlled, parallel group study will evaluate the efficacy and safety of gantenerumab versus placebo in participants with early (prodromal to mild) AD. All participants must show evidence of beta-amyloid pathology. Eligible participants will be randomized 1:1 to receive either subcutaneous (SC) injection of gantenerumab or placebo. The primary efficacy assessment will be performed at the end of the double blind period at week 104. Participants will then be offered to enter into an open-label extension (OLE). Participants not willing to go to the OLE will participate in a long term follow-up period for up to 50 weeks after the last gantenerumab dose.

Condition or disease	Intervention/treatment	Phase
Alzheimer's Disease	Drug: Gantenerumab; Drug: Placebo	Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	760 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Treatment
Official 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
Actual Study Start Date :	June 6, 2018
Estimated Primary Completion Date :	May 31, 2022
Estimated Study Completion Date :	May 2, 2023

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Gantenerumab; Gantenerumab will be administered as SC injections with gradual uptitration.	Drug: Gantenerumab; Gantenerumab will be administered as per the schedule specified in the respective arm.; Other Name: RO4909832
Placebo Comparator: Placebo; Placebo will be administered as SC injections with gradual uptitration.	Drug: Placebo; Placebo matching to gantenerumab will be administered as per the schedule specified in the respective arm.

Outcome Measures

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Primary Outcome Measures :

1. Change From Baseline to Week 104 in Global Outcome, as Measured by Clinical Dementia Rating−Sum of Boxes (CDR-SOB) [ Time Frame: Baseline up to Week 104 ]

Secondary Outcome Measures :

1. Change From Baseline to Week 104 in Alzheimer Disease Assessment Scale-Cognition Subscale 11 (ADAS-Cog11) Subscale Score [ Time Frame: Baseline up to Week 104 ]
2. Change From Baseline to Week 104 in Mini-Mental State Examination (MMSE) Total Score [ Time Frame: Baseline up to Week 104 ]
3. Change from Baseline to Week 104 in Alzheimer Disease Assessment Scale-Cognition, Subscale 13 (ADAS-Cog13) [ Time Frame: Baseline up to Week 104 ]
4. Change From Baseline to Week 104 in Verbal Fluency Task Score [ Time Frame: Baseline up to Week 104 ]
5. Change From Baseline to Week 104 in Functional Activities Questionnaire (FAQ) Score [ Time Frame: Baseline to Week 104 ]
6. Change From Baseline to Week 104 in Coding [ Time Frame: Change from baseline to Week 104 in the Wechsler Adult Intelligence Scale - Fourth Edition (WAIS-IV) coding subtest. ]
7. Change From Baseline to Week 104 in Alzheimer Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL) Total Score [ Time Frame: Baseline up to Week 104 ]
8. Percentage of Participants With Adverse Events (AEs) [ Time Frame: Baseline up to end of study (up to Week 152) ]
9. Percentage of Participants With Anti-Drug Antibodies (ADA) to Gantenerumab [ Time Frame: Baseline up to end of study (up to Week 152) ]
10. Plasma Concentration of Gantenerumab [ Time Frame: Pre-dose (0 hour [hr]) at Baseline (Day 1), Weeks 24, 52, 76; and at Weeks 2, 41, 103, 116, 152, early termination visit ]
11. Change from Baseline in Brain Amyloid Load as Measured by Amyloid Positron Emission Tomography (PET) Scan in a subset of patients up to Week 104 [ Time Frame: Baseline up to Week 104 ]
12. Change From Baseline in Brain Tau Load, as Measured by Tau PET Scan in a Subset of Patients up to Week 104 [ Time Frame: Baseline up to Week 104 ]
13. Change From Baseline in Cerebral Spinal Fluid (CSF) Marker of Disease in a Subset of Patients - Amyloid-beta 1−42 (Aβ1−42) up to Week 104 [ Time Frame: Baseline up to Week 104 ]
14. Change From Baseline in CSF Marker of Disease in a Subset of Patients - Total Tau up to Week 104 [ Time Frame: Baseline up to Week 104 ]
15. Change From Baseline in CSF Marker of Disease in a Subset of Patients - Phosphorylated Tau up to Week 104 [ Time Frame: Baseline up to Week 104 ]
16. Change From Baseline in Volumetric Magnetic Resonance Imaging (MRI) up to Week 104 [ Time Frame: Baseline up to Week 104 ]
    MRI will be used to assess the effect of treatment on volume of whole brain, ventricles, hippocampus, or other structures.
17. Change from Baseline to Week 104 in Instrumental Score [ Time Frame: Baseline Up to Week 104 ]

Eligibility Criteria

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Ages Eligible for Study:	50 Years to 90 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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 [MCI])
• Evidence of the AD pathological process, as confirmed by CSF or amyloid PET scan
• Demonstrated abnormal memory function
• MMSE score great 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 baseline 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.

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
• At risk for suicide in the opinion of the investigator
• Patients with evidence of folic acid deficiency
• 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

Contacts and Locations

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Contacts

Contact: Reference Study ID Number: WN39658 www.roche.com/about_roche/roche_worldwide.htm	888-662-6728 (U.S. and Canada)	global-roche-genentech-trials@gene.com

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Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director:	Clinical Trials	Hoffmann-La Roche

More Information

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Additional Information:

US residents may click here to find out more about participation in this study 

Responsible Party:	Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT03443973 History of Changes
Other Study ID Numbers:	WN39658; 2017-001365-24 ( EudraCT Number )
First Posted:	February 23, 2018
Last Update Posted:	January 10, 2019
Last Verified:	January 2019

Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Additional relevant MeSH terms:

Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies	Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Antibodies, Monoclonal; Immunologic Factors; Physiological Effects of Drugs