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

• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

Brief Summary:

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 in Part 1, with an option for an additional up to 2 years of treatment in Part 2, followed by an open-label extension (Part 3) until July 2020.

The dosing for Parts 1 and 2 was stopped after a planned futility interim analysis showed a low probability of meeting the primary outcome measure with the doses studied. The study has converted to open-label to investigate higher gantenerumab doses.

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 799 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, 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 With Option for up to an Additional Two Years of Treatment and an Open-Label Extension With Active Study Treatment
• Actual Study Start Date: November 30, 2010
• Estimated Primary Completion Date: August 28, 2020
• Estimated Study Completion Date: August 28, 2020

Arms and Interventions

Arm	Intervention/treatment
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 at 105 mg , 225 mg, or at doses up to 1200 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 at 105 mg , 225 mg, or at doses up to 1200 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.
Experimental: Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE]); Participants with Alzheimer's disease that participated in Part 1 or Part 2 will receive open-label gantenerumab by SC injection at doses up to 1200 mg q4w for 3 additional years.	Drug: Gantenerumab; Participants will receive gantenerumab at 105 mg , 225 mg, or at doses up to 1200 mg SC injection q4w.

Outcome Measures

Primary Outcome Measures :

1. Mean Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Total Score at Week 104 [ Time Frame: Baseline, Week 104 ]
2. Part 3: Percentage of Participants with Adverse Events (AEs) or Serious Adverse Events (SAEs) [ Time Frame: Baseline through end of study (up to approximately 4.5 years) ]

Secondary Outcome Measures :

1. Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog-11) Scores at Week 104 [ Time Frame: Baseline, Week 104 ]
2. Time to Onset of Dementia [ Time Frame: Baseline, Week 104 ]
3. Mean Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Composite Score at Week 104 [ Time Frame: Baseline, Week 104 ]
4. Mean Change from Baseline in Free and Cued Selective Reminding Test (FCSRT) Score at Week 104 [ Time Frame: Baseline, Week 104 ]
5. Mean Change From Baseline in Functional Activities Questionnaire (FAQ) Score at Week 104 [ Time Frame: Baseline, Week 104 ]
6. Mean Change From Baseline in CDR-Global Score at Week 104 [ Time Frame: Baseline, Week 104 ]
7. Mean Change from Baseline in Neuropsychiatric Inventory (NPI) Questionnaire Score at Week 104 [ Time Frame: Baseline, Week 104 ]
8. 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 ]
9. Percent Change from Baseline in Hippocampal Volume at Week 104 [ Time Frame: Baseline, Week 104 ]
10. Percent Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 104 [ Time Frame: Baseline, Week 104 ]
11. Gantenerumab Plasma Concentration at Different Time Points [ Time Frame: Prior to injections at Weeks 1, 8, 20, 44, 53, 68, 100, 101 ]
12. Mean Change From Baseline in Mini Mental State Exam (MMSE) Score at Week 104 [ Time Frame: Baseline, Week 104 ]

Eligibility Criteria

• Ages Eligible for Study: 50 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

  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):

Ostrowitzki S, Lasser RA, Dorflinger E, Scheltens P, Barkhof F, Nikolcheva T, Ashford E, Retout S, Hofmann C, Delmar P, Klein G, Andjelkovic M, Dubois B, Boada M, Blennow K, Santarelli L, Fontoura P; SCarlet RoAD Investigators. A phase III randomized trial of gantenerumab in prodromal Alzheimer's disease. Alzheimers Res Ther. 2017 Dec 8;9(1):95. doi: 10.1186/s13195-017-0318-y. Erratum in: Alzheimers Res Ther. 2018 Sep 27;10(1):99.

Delrieu J, Ousset PJ, Vellas B. Gantenerumab for the treatment of Alzheimer's disease. Expert Opin Biol Ther. 2012 Aug;12(8):1077-86. doi: 10.1517/14712598.2012.688022. Epub 2012 May 15. Review.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01224106 History of Changes
• Other Study ID Numbers: WN25203; 2010-019895-66 ( EudraCT Number )
• First Posted: October 19, 2010
• Last Update Posted: August 7, 2019
• Last Verified: August 2019

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