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A Study of Gantenerumab in Participants With Prodromal Alzheimer's Disease

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01224106
First received: October 14, 2010
Last updated: September 1, 2016
Last verified: September 2016
  Purpose
This multi-center, randomized, double-blind, placebo-controlled parallel-group study will evaluate the effect of gantenerumab (RO4909832) on cognition and functioning and the safety and pharmacokinetics in participants with prodromal Alzheimer's Disease. Participants will be randomized to receive subcutaneous (SC) injections of either gantenerumab or placebo. Participants who consent to be part of the sub study will undergo positron emission tomography (PET) scanning to assess brain amyloid. The anticipated time on study treatment is 104 weeks, with an option for an additional 2 years of treatment.

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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Two Year Study to Evaluate the Effect of Subcutaneous RO4909832 on Cognition and Function in Prodromal Alzheimer's Disease and Up to Three Years of an Open-Label Extension With Active Study Treatment

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Mean Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Total Score at Week 104 [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog-11) Scores at Week 104 [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]
  • Time to Onset of Dementia [ Time Frame: Every 6 months to up to 3 years (1096 days) ] [ Designated as safety issue: No ]
  • Mean Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Composite Score at Week 104 [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]
  • Mean Change from Baseline in Free and Cued Selective Reminding Test (FCSRT) Score at Week 104 [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline in Functional Activities Questionnaire (FAQ) Score at Week 104 [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline in CDR-Global Score at Week 104 [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]
  • Mean Change from Baseline in Neuropsychiatric Inventory (NPI) Questionnaire Score at Week 104 [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]
  • Percent Change from Baseline in Cerebrospinal Fluid Biomarkers (Phosphorylated-tau [p-tau], Amyloid Beta 1-42 [Abeta 1-42], Total tau [t-tau]) at Week 104 [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]
  • Percent Change from Baseline in Hippocampal Volume at Week 104 [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 [ Time Frame: Baseline, Week 156 ] [ Designated as safety issue: No ]
  • Gantenerumab Plasma Concentration at Different Time Points [ Time Frame: Prior to injections at Weeks 1, 8, 20, 44, 53, 68, 100, 101 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline in Mini Mental State Exam (MMSE) Score at Week 104 [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]

Enrollment: 799
Study Start Date: November 2010
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: December 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Gantenerumab 105 mg (Parts 1 and 2)
Participants with Alzheimer's disease will receive gantenerumab 105 milligrams (mg) by SC injection every 4 weeks (q4w) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who complete the Week 104 visit will be given an option to continue the treatment received during Part 1 for 2 additional years in Part 2.
Drug: Gantenerumab
Participants will receive gantenerumab 105 or 225 mg SC injection q4w.
Experimental: Gantenerumab 225 mg (Parts 1 and 2)
Participants with Alzheimer's disease will receive gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who complete the Week 104 visit will be given an option to continue the treatment received during Part 1 for 2 additional years in Part 2.
Drug: Gantenerumab
Participants will receive gantenerumab 105 or 225 mg SC injection q4w.
Placebo Comparator: Placebo (Parts 1 and 2)
Participants with Alzheimer's disease will receive placebo SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who complete the Week 104 visit will be given an option to continue the treatment received during Part 1 for 2 additional years in Part 2.
Drug: Placebo
Participants will receive placebo SC injection q4w.

  Eligibility

Ages Eligible for Study:   50 Years to 85 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult participants, 50-85 years of age
  • Participants with prodromal Alzheimer's disease who are not receiving memantine or cholinesterase inhibitors
  • Has a study partner who in the investigator's judgement has frequent and sufficient contact with the participant as to be able to provide accurate information as to the participant's cognitive and functional abilities, who agrees to provide information at clinic visits which require partner input for scale completion
  • Has had sufficient education or work experience to exclude mental retardation
  • Study partner has noticed a recent gradual decrease in participant's memory (over the last 12 months), which the participant may or may not be aware of
  • Screening Mini Mental State Exam (MMSE) score of 24 or above

Additional inclusion criteria for sub study:

  • Able and willing to travel to PET imaging center and complete the planned scanning sessions
  • Past and planned exposure to ionizing radiation not exceeding safe and permissible levels

Exclusion Criteria:

  • Other prior or current neurologic or medical disorder which may currently or during the course of the study impair cognition or psychiatric functioning
  • A history of stroke
  • A documented history of transient ischemic attack within the last 12 months
  • History of schizophrenia, schizoaffective or bipolar disorder
  • Currently meets criteria for major depression
  • Within the last 2 years, unstable or clinical significant cardiovascular disease (myocardial infarction, angina pectoris)

Additional exclusion criteria for sub study:

  • Inclusion in a research and/or medical protocol involving PET ligands or other radioactive agents within 12 months
  • Present or planned participation in a research and/or medical protocol involving PET ligands or radioactive agents other than study WN25203
  • Have planned or are planning to have exposure to ionizing radiation that in combination with the planned administration with study amyloid PET ligand would result in a cumulative exposure that exceeds local recommended exposure limits
  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: NCT01224106

  Show 156 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01224106     History of Changes
Other Study ID Numbers: WN25203  2010-019895-66 
Study First Received: October 14, 2010
Last Updated: September 1, 2016
Health Authority: United States: Food and Drug Administration

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 September 23, 2016