A Study of Gantenerumab in Participants With Prodromal Alzheimer's Disease (Scarlet Road)

Roche

Status and phase: Completed; Phase 3

Conditions: Alzheimer's Disease

Treatments: Drug: Placebo; Drug: Gantenerumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT01224106

WN25203

2010-019895-66 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 799 patients

Sex: All

Ages: 50 to 85 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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799 participants in 5 patient groups, including a placebo group

Placebo (Parts 1 and 2)

Placebo Comparator group

Description:

Participants with Alzheimer's disease received Placebo by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.

Treatment:

Drug: Placebo

Gantenerumab 105 mg (Parts 1 and 2)

Experimental group

Description:

Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.

Treatment:

Drug: Gantenerumab

Gantenerumab 225 mg (Parts 1 and 2)

Experimental group

Description:

Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.

Treatment:

Drug: Gantenerumab

Placebo (Parts 1 and 2) switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE])

Placebo Comparator group

Description:

Participants with Alzheimer's disease who had received Placebo by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.

Treatment:

Drug: Gantenerumab

Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])

Experimental group

Description:

Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.

Treatment:

Drug: Gantenerumab