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A Study of Gantenerumab in Participants With Mild Alzheimer Disease

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02051608
First received: January 30, 2014
Last updated: January 31, 2017
Last verified: January 2017
  Purpose

Part 1 is a multicenter, randomized, double-blind, placebo-controlled, parallel-group study will evaluate the efficacy and safety of gantenerumab in participants with mild Alzheimer disease. Participants will be randomized to receive either gantenerumab subcutaneously every 4 weeks or placebo subcutaneously every 4 weeks. Approved Alzheimer medication is allowed if on stable dose for 3 months prior to screening. Part 2 is an open-label extension (OLE).

A positron emission tomography (PET) imaging substudy will be conducted within the main study. Eligible participants who provide separate informed consent will undergo PET imaging scans using the radioligand florbetapir as a pharmacodynamic measure of changes in brain amyloid load over time. The substudy's target sample size is 100 participants in each arm of the main study.


Condition Intervention Phase
Alzheimer's Disease
Drug: Florbetapir
Drug: Gantenerumab
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Investigator
Primary Purpose: Treatment
Official Title: A Phase III, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter, Efficacy and Safety Study of Gantenerumab in Patients With Mild Alzheimer's Disease; Part II: Open-Label Extension For Participating Patients

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Mean Change From Baseline in Alzheimer's Disease Activity Scale-Cognitive subscale 13 (ADAS-Cog13) scores at Week 104 [ Time Frame: Baseline, Week 104 ]
  • Mean Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scores at week 104 [ Time Frame: Baseline, Week 104 ]
  • Part 2: Percentage of Participants with Adverse Events (AEs) or Serious Adverse Events (SAEs) [ Time Frame: Baseline, Week 104 ]

Secondary Outcome Measures:
  • PET Imaging Substudy: Change From Baseline in Brain Amyloid Load Over Time Using Florbetapir [ Time Frame: Baseline up to Week 104 ]
  • Change From Baseline in Total Tau (t-tau) in CSF at Week 104 [ Time Frame: Baseline, Week 104 ]
  • Change From Baseline in phosphorylated tau [p-tau]in CSF at Week 104 [ Time Frame: Baseline, Week 104 ]
  • Change From Baseline in Abeta 1-42 levels in CSF at Week 104 [ Time Frame: Baseline, Week 104 ]
  • Change From Baseline in Hippocampal Volume, as Assessed by Magnetic Resonance Image (MRI) at Week 104 [ Time Frame: Baseline, Week 104 ]
  • Change From Baseline in Whole Brain Volume, as assessed by MRI at Week 104 [ Time Frame: Baseline, Week 104 ]
  • Change From Baseline in Cortical thickness, as assessed by MRI at Week 104 [ Time Frame: Baseline, Week 104 ]
  • Change From Baseline in Ventricular Volume, as Assessed by MRI at Week 104 [ Time Frame: Baseline, Week 104 ]
  • Change From Baseline in Clinical Dementia Rating Global Score (CDR-GS) at Week 104 [ Time Frame: Baseline, Week 104 ]
  • Change From Baseline in CDR Sum of Boxes (SB) at Week 104 [ Time Frame: Baseline, Week 104 ]
  • Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Week 104 [ Time Frame: Baseline, Week 104 ]
  • Change From Baseline in NPI Domain Score at Week 104 [ Time Frame: Baseline, Week 104 ]
  • Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Week 104 [ Time Frame: Baseline, Week 104 ]
  • Safety: Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) [ Time Frame: Baseline up to Week 152 ]
  • Percentage of Participants with anti-gantenerumab antibodies [ Time Frame: Baseline up to Week 152 ]
  • Change From Baseline in Columbia - Suicide Severity Rating Scale (C-SSRS) Over Week 152 [ Time Frame: Baseline up to Week 152 ]
  • Pharmacokinetics: Apparent Oral Clearance (CL/F) of gantenerumab [ Time Frame: Part 1: Predose (0 hour) at Baseline, Weeks 4, 8, 12, 24, 48, 72, 104, 116; Day 4; at unscheduled visits (up to Week 152) Part 2: Predose (0 hour) at Week 4, 12, 20, 104, 116; Weeks 53, 101; at unscheduled visits (up to Week 152) ]
  • Pharmacokinetics: Apparent Volume of Distribution (V/F) of gantenerumab [ Time Frame: Part 1: Predose (0 hour) at Baseline, Weeks 4, 8, 12, 24, 48, 72, 104, 116; Day 4; at unscheduled visits (up to Week 152) Part 2: Predose (0 hour) at Week 4, 12, 20, 104, 116; Weeks 53, 101; at unscheduled visits (up to Week 152) ]
  • Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of gantenerumab [ Time Frame: Part 1: Predose (0 hour) at Baseline, Weeks 4, 8, 12, 24, 48, 72, 104, 116; Day 4; at unscheduled visits (up to Week 152) Part 2: Predose (0 hour) at Week 4, 12, 20, 104, 116; Weeks 53, 101; at unscheduled visits (up to Week 152) ]
  • Pharmacokinetics: Time to Reach Maximum Plasma Concentrations (Tmax) of gantenerumab [ Time Frame: Part 1: Predose (0 hour) at Baseline, Weeks 4, 8, 12, 24, 48, 72, 104, 116; Day 4; at unscheduled visits (up to Week 152) Part 2: Predose (0 hour) at Week 4, 12, 20, 104, 116; Weeks 53, 101; at unscheduled visits (up to Week 152) ]
  • Pharmacokinetics: Minimum Observed Plasma Concentration (Cmin) of gantenerumab [ Time Frame: Part 1: Predose (0 hour) at Baseline, Weeks 4, 8, 12, 24, 48, 72, 104, 116; Day 4; at unscheduled visits (up to Week 152) Part 2: Predose (0 hour) at Week 4, 12, 20, 104, 116; Weeks 53, 101; at unscheduled visits (up to Week 152) ]
  • Pharmacokinetics: Area Under Plasma Concentration (AUC) -Time Curve of gantenerumab [ Time Frame: Part 1: Predose (0 hour) at Baseline, Weeks 4, 8, 12, 24, 48, 72, 104, 116; Day 4; at unscheduled visits (up to Week 152) Part 2: Predose (0 hour) at Week 4, 12, 20, 104, 116; Weeks 53, 101; at unscheduled visits (up to Week 152) ]
  • Quality of Life - Change From Baseline in Alzheimer's Dementia (QoL-AD) Global Score at Week 104 [ Time Frame: Baseline, Week 104 ]
  • Efficacy: Change From Baseline in Symptom Guide Facilitated (GAS) at Week 104 [ Time Frame: Baseline, Week 104 ]
  • Efficacy: Change from Baseline in Dependence Scale (DS) at Week 104 [ Time Frame: Baseline, Week 104 ]
  • Efficacy: Change From Baseline in Resource Utilization Dementia-Lite (RUD - Life) Scale at Week 104 [ Time Frame: Baseline, Week 104 ]
  • Change From Baseline in Zarit Caregiver Interview for Alzheimer's Disease (ZCI-AD) at Week 104 [ Time Frame: Baseline, Week 104 ]
  • Time to Clinical Decline (as measured by Confirmed greater than of equal to [>=] 2-point decline on MMSE, Loss of >= 1 or 2 points on one or more ADL and I ADL, respectively) [ Time Frame: Baseline up to Week 104 ]
  • Change from Baseline in Clinical Composite Score (Prespecified Items From The ADAS-Cog, MMSE, and CDR) at Week 104 [ Time Frame: Baseline, Week 104 ]

Estimated Enrollment: 1000
Study Start Date: March 2014
Estimated Study Completion Date: November 2019
Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Double-blind: Part 1
Participants will receive either gantenerumab or placebo-matched to gantenerumab.
Drug: Gantenerumab
Participants will receive gantenerumab as SC injection q4w up to Week 100
Drug: Placebo
Participants will receive placebo as SC injection q4w up to Week 100q4w
Experimental: Open - Label Extension: Part 2
Participants will receive open label gantenerumab.
Drug: Gantenerumab
Participants will receive gantenerumab as SC injection q4w up to Week 100
Drug: Placebo
Participants will receive placebo as SC injection q4w up to Week 100q4w
Experimental: PET Imaging Substudy
Participants will undergo PET imaging scans using the PET radioligand, a florbetapir F 18 injection.
Drug: Florbetapir
IV injection of florbetapir [Amyvid] up to 370 mega Becquerel (MBq) (10 millicurie [mCi]) of florbetapir and imaging for up to 15 minutes per PET scan conducted at screening and on 3 subsequent time points per protocol
Other Name: Amyvid

  Eligibility

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

Inclusion Criteria:

  • Clinical diagnosis of probable mild Alzheimer disease (AD) based on National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria or major NCD based whether or not receiving AD approved medication
  • Cerebral spinal fluid (CSF) result consistent with the presence of amyloid pathology
  • Availability of a person ('caregiver') who in the investigator's judgment has frequent and sufficient contact with the participant, and is able to provide accurate information regarding the participant's cognitive and functional abilities
  • Fluency in the language of the tests used at the study site
  • Willingness and ability to complete all aspects of the study
  • Adequate visual and auditory acuity, in the investigator's judgment, sufficient to perform the neuropsychological testing (eye glasses and hearing aids are permitted)
  • If currently receiving approved medications for AD, the dosing regimen must have been stable for 3 months prior to screening
  • Agreement not to participate in other research studies for the duration of this trial and its associated substudies

PART 2 - All participants who have been randomized and are actively participating in the study are eligible for Part 2

Exclusion Criteria:

  • Dementia or neurocognitive disorder (NCD) due to a condition other than AD, including, but not limited to, frontotemporal dementia, Parkinson disease, dementia with Lewy bodies, Huntington disease, or vascular dementia
  • History or presence of clinically evident vascular disease potentially affecting the brain that in the opinion of the investigator has the potential to affect cognitive function
  • History or presence of stroke within the past 2 years or documented history of transient ischemic attack within the last 12 months
  • History or presence of systemic autoimmune disorders potentially causing progressive neurologic disease with associated cognitive deficits
  • History of schizophrenia, schizoaffective disorder, or bipolar disorder
  • Alcohol and/or substance use disorder (according to the DSM-5) within the past 2 years (nicotine use is allowed)
  • History or presence of atrial fibrillation
  • Within the last 2 years, unstable or clinically significant cardiovascular disease (e.g., myocardial infarction, angina pectoris, cardiac failure New York Heart Association Class II or higher)
  • Uncontrolled hypertension
  • Chronic kidney disease
  • Impaired hepatic function

PET imaging substudy, in addition to above:

- Prior participation in other research study or clinical care within the last year such that the total radiation exposure would exceed the local or national annual limits

Part 2 Participants who have been discontinued from the study

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02051608

  Show 131 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02051608     History of Changes
Other Study ID Numbers: WN28745
2013-003390-95 ( EudraCT Number )
Study First Received: January 30, 2014
Last Updated: January 31, 2017

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

ClinicalTrials.gov processed this record on May 22, 2017