Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01224106




Registration number
NCT01224106
Ethics application status
Date submitted
14/10/2010
Date registered
19/10/2010
Date last updated
13/12/2021

Titles & IDs
Public title
A Study of Gantenerumab in Participants With Prodromal Alzheimer's Disease
Scientific 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
Secondary ID [1] 0 0
2010-019895-66
Secondary ID [2] 0 0
WN25203
Universal Trial Number (UTN)
Trial acronym
Scarlet Road
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer's Disease 0 0
Condition category
Condition code
Neurological 0 0 0 0
Alzheimer's disease
Neurological 0 0 0 0
Dementias

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Gantenerumab
Treatment: Drugs - Placebo

Placebo comparator: Placebo (Parts 1 and 2) - 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.

Experimental: Gantenerumab 105 mg (Parts 1 and 2) - 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.

Experimental: Gantenerumab 225 mg (Parts 1 and 2) - 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.

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

Experimental: Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE]) - 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: Drugs: Gantenerumab
Participants received Gantenerumab at 105 mg , 225 mg, or at doses up to 1200 mg SC injection Q4W.

Treatment: Drugs: Placebo
Participants received Placebo SC injection Q4W.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Mean Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Total Score at Week 104 (Double-Blind Treatment Phase)
Timepoint [1] 0 0
Baseline, Week 104
Primary outcome [2] 0 0
Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) (OLE Phase)
Timepoint [2] 0 0
Baseline up until a maximum of 5 years
Secondary outcome [1] 0 0
Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog-11) Scores at Week 104 (Double-Blind Treatment Phase)
Timepoint [1] 0 0
Baseline, Week 104
Secondary outcome [2] 0 0
Time to Onset of Dementia at Week 104 (Double-Blind Treatment Phase)
Timepoint [2] 0 0
Baseline, Week 104
Secondary outcome [3] 0 0
Mean Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Composite Score at Week 104 (Double-Blind Treatment Phase)
Timepoint [3] 0 0
Baseline, Week 104
Secondary outcome [4] 0 0
Mean Change From Baseline in Free and Cued Selective Reminding Test (FCSRT) Score at Week 104 (Double-Blind Treatment Phase)
Timepoint [4] 0 0
Baseline, Week 104
Secondary outcome [5] 0 0
Mean Change From Baseline in Functional Activities Questionnaire (FAQ) Score at Week 104 (Double-Blind Treatment Phase)
Timepoint [5] 0 0
Baseline, Week 104
Secondary outcome [6] 0 0
Mean Change From Baseline in CDR-Global Score at Week 104 (Double-Blind Treatment Phase)
Timepoint [6] 0 0
Baseline, Week 104
Secondary outcome [7] 0 0
Mean Change From Baseline in Neuropsychiatric Inventory (NPI) Questionnaire Score at Week 104 (Double-Blind Treatment Phase)
Timepoint [7] 0 0
Baseline, Week 104
Secondary outcome [8] 0 0
Percentage 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 (Double-Blind Treatment Phase)
Timepoint [8] 0 0
Baseline, Week 104
Secondary outcome [9] 0 0
Percentage Change From Baseline in Hippocampal Volume at Week 104 (Double-Blind Treatment Phase)
Timepoint [9] 0 0
Baseline, Week 104
Secondary outcome [10] 0 0
Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase)
Timepoint [10] 0 0
Baseline, Week 156
Secondary outcome [11] 0 0
Gantenerumab Plasma Concentrations at Different Time Points (Double-Blind Treatment Phase)
Timepoint [11] 0 0
Pre-Dose: Weeks 8, 20, 44, 68 and 100; Post-Dose: Weeks 1, 53 and 101
Secondary outcome [12] 0 0
Mean Change From Baseline in Mini Mental State Exam (MMSE) Score at Week 104 (Double-Blind Treatment Phase)
Timepoint [12] 0 0
Baseline, Week 104
Secondary outcome [13] 0 0
Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) (Double-Blind Treatment Phase)
Timepoint [13] 0 0
Baseline up until a maximum of 4.5 years
Secondary outcome [14] 0 0
Percentage of Participants With Anti-Drug Antibodies (ADAs) (Double-Blind Treatment Phase)
Timepoint [14] 0 0
Baseline up until a maximum of 4.5 years
Secondary outcome [15] 0 0
Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog-11) Scores at Week 156 (OLE Phase)
Timepoint [15] 0 0
Baseline, Week 156
Secondary outcome [16] 0 0
Mean Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Total Score at Week 156 (OLE Phase)
Timepoint [16] 0 0
Baseline, Week 156
Secondary outcome [17] 0 0
Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog-13) Scores at Week 156 (OLE Phase)
Timepoint [17] 0 0
Baseline, Week 156
Secondary outcome [18] 0 0
Time to Onset of Dementia at Week 156 (OLE Phase)
Timepoint [18] 0 0
Baseline, Week 156
Secondary outcome [19] 0 0
Mean Change From Baseline in Free and Cued Selective Reminding Test (FCSRT) Score at Week 156 (OLE Phase)
Timepoint [19] 0 0
Baseline, Week 156
Secondary outcome [20] 0 0
Mean Change From Baseline in Functional Activities Questionnaire (FAQ) Score at Week 156 (OLE Phase)
Timepoint [20] 0 0
Baseline, Week 156
Secondary outcome [21] 0 0
Mean Change From Baseline in CDR-Global Score at Week 156 (OLE Phase)
Timepoint [21] 0 0
Baseline, Week 156
Secondary outcome [22] 0 0
Percentage Change From Baseline in Hippocampal Volume at Week 152 (OLE Phase)
Timepoint [22] 0 0
Baseline, Week 152
Secondary outcome [23] 0 0
Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (OLE Phase)
Timepoint [23] 0 0
Baseline, Week 156
Secondary outcome [24] 0 0
Gantenerumab Plasma Concentrations at Different Time Points (OLE Phase)
Timepoint [24] 0 0
Pre-Dose: Weeks 64, 100, 104, 136, 156 and 208; Post-Dose: Week 101
Secondary outcome [25] 0 0
Mean Change From Baseline in Mini Mental State Exam (MMSE) Score at Week 156 (OLE Phase)
Timepoint [25] 0 0
Baseline, Week 156
Secondary outcome [26] 0 0
Percentage of Participants With Anti-Drug Antibodies (ADAs) (OLE Phase)
Timepoint [26] 0 0
Baseline up until a maximum of 5 years

Eligibility
Key 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
Minimum age
50 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/11/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
10/09/2020
Sample size
Target
Accrual to date
Final
799
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC,WA
Recruitment hospital [1] 0 0
Hornsby Ku-ring-gai Hospital; Division of Rehabilitation & Aged Care - Hornsby
Recruitment hospital [2] 0 0
Prince of Wales Hospital, Academic Department for Old Age Psychiatry - Randwick
Recruitment hospital [3] 0 0
Royal Adelaide Hospital; Memory Trials Centre - Adelaide
Recruitment hospital [4] 0 0
The Queen Elizabeth Hospital; Neurology - Woodville
Recruitment hospital [5] 0 0
Heidelberg Repatriation Hospital; Medical and Cognitive Research Centre - Heidelberg West
Recruitment hospital [6] 0 0
Australian Alzheimer's Research Foundation - Nedlands
Recruitment postcode(s) [1] 0 0
2077 - Hornsby
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
5011 - Woodville
Recruitment postcode(s) [5] 0 0
3081 - Heidelberg West
Recruitment postcode(s) [6] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
Mississippi
Country [9] 0 0
United States of America
State/province [9] 0 0
New Jersey
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
North Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Oregon
Country [13] 0 0
United States of America
State/province [13] 0 0
Pennsylvania
Country [14] 0 0
United States of America
State/province [14] 0 0
Rhode Island
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
United States of America
State/province [16] 0 0
Vermont
Country [17] 0 0
Argentina
State/province [17] 0 0
Buenos Aires
Country [18] 0 0
Argentina
State/province [18] 0 0
Caba
Country [19] 0 0
Argentina
State/province [19] 0 0
Córdoba
Country [20] 0 0
Argentina
State/province [20] 0 0
La Plata
Country [21] 0 0
Belgium
State/province [21] 0 0
Leuven
Country [22] 0 0
Brazil
State/province [22] 0 0
PR
Country [23] 0 0
Brazil
State/province [23] 0 0
RS
Country [24] 0 0
Brazil
State/province [24] 0 0
SP
Country [25] 0 0
Canada
State/province [25] 0 0
Nova Scotia
Country [26] 0 0
Canada
State/province [26] 0 0
Ontario
Country [27] 0 0
Canada
State/province [27] 0 0
Quebec
Country [28] 0 0
Chile
State/province [28] 0 0
Santiago
Country [29] 0 0
Czechia
State/province [29] 0 0
Brno
Country [30] 0 0
Czechia
State/province [30] 0 0
Rychnov nad Kneznou
Country [31] 0 0
Denmark
State/province [31] 0 0
Aarhus N
Country [32] 0 0
Denmark
State/province [32] 0 0
Koebenhavn Oe
Country [33] 0 0
Finland
State/province [33] 0 0
Turku
Country [34] 0 0
France
State/province [34] 0 0
Bobigny
Country [35] 0 0
France
State/province [35] 0 0
Bordeaux
Country [36] 0 0
France
State/province [36] 0 0
Bron
Country [37] 0 0
France
State/province [37] 0 0
Caen
Country [38] 0 0
France
State/province [38] 0 0
Lille
Country [39] 0 0
France
State/province [39] 0 0
Paris
Country [40] 0 0
France
State/province [40] 0 0
Rouen
Country [41] 0 0
France
State/province [41] 0 0
St Herblain
Country [42] 0 0
France
State/province [42] 0 0
Strasbourg
Country [43] 0 0
France
State/province [43] 0 0
Toulouse
Country [44] 0 0
Germany
State/province [44] 0 0
Berlin
Country [45] 0 0
Germany
State/province [45] 0 0
Bonn
Country [46] 0 0
Germany
State/province [46] 0 0
Frankfurt
Country [47] 0 0
Germany
State/province [47] 0 0
Leipzig
Country [48] 0 0
Germany
State/province [48] 0 0
Mannheim
Country [49] 0 0
Germany
State/province [49] 0 0
Mittweida
Country [50] 0 0
Germany
State/province [50] 0 0
München
Country [51] 0 0
Germany
State/province [51] 0 0
Nürnberg
Country [52] 0 0
Germany
State/province [52] 0 0
Rostock
Country [53] 0 0
Germany
State/province [53] 0 0
Ulm
Country [54] 0 0
Italy
State/province [54] 0 0
Emilia-Romagna
Country [55] 0 0
Italy
State/province [55] 0 0
Lombardia
Country [56] 0 0
Italy
State/province [56] 0 0
Marche
Country [57] 0 0
Italy
State/province [57] 0 0
Toscana
Country [58] 0 0
Korea, Republic of
State/province [58] 0 0
Gyeonggi-do
Country [59] 0 0
Korea, Republic of
State/province [59] 0 0
Seoul
Country [60] 0 0
Mexico
State/province [60] 0 0
Mexico CITY (federal District)
Country [61] 0 0
Mexico
State/province [61] 0 0
Nuevo LEON
Country [62] 0 0
Mexico
State/province [62] 0 0
Culiacan
Country [63] 0 0
Mexico
State/province [63] 0 0
Guadalajara
Country [64] 0 0
Mexico
State/province [64] 0 0
Mexico City
Country [65] 0 0
Mexico
State/province [65] 0 0
Monterrey
Country [66] 0 0
Mexico
State/province [66] 0 0
Saltillo
Country [67] 0 0
Netherlands
State/province [67] 0 0
'S Hertogenbosch
Country [68] 0 0
Netherlands
State/province [68] 0 0
Amsterdam
Country [69] 0 0
Poland
State/province [69] 0 0
Bialystok
Country [70] 0 0
Poland
State/province [70] 0 0
Bydgoszcz
Country [71] 0 0
Poland
State/province [71] 0 0
Poznan
Country [72] 0 0
Poland
State/province [72] 0 0
Warszawa
Country [73] 0 0
Portugal
State/province [73] 0 0
Amadora
Country [74] 0 0
Portugal
State/province [74] 0 0
Lisboa
Country [75] 0 0
Russian Federation
State/province [75] 0 0
Ekaterinburg
Country [76] 0 0
Russian Federation
State/province [76] 0 0
Kazan
Country [77] 0 0
Russian Federation
State/province [77] 0 0
Saint Petersburg
Country [78] 0 0
Russian Federation
State/province [78] 0 0
Saratov
Country [79] 0 0
Russian Federation
State/province [79] 0 0
St. Petersburg
Country [80] 0 0
Spain
State/province [80] 0 0
Barcelona
Country [81] 0 0
Spain
State/province [81] 0 0
Vizcaya
Country [82] 0 0
Spain
State/province [82] 0 0
Madrid
Country [83] 0 0
Spain
State/province [83] 0 0
Valencia
Country [84] 0 0
Sweden
State/province [84] 0 0
Malmö
Country [85] 0 0
Switzerland
State/province [85] 0 0
Basel
Country [86] 0 0
Switzerland
State/province [86] 0 0
Chêne-Bourg
Country [87] 0 0
Turkey
State/province [87] 0 0
Antalya
Country [88] 0 0
Turkey
State/province [88] 0 0
Istanbul
Country [89] 0 0
Turkey
State/province [89] 0 0
Samsun
Country [90] 0 0
United Kingdom
State/province [90] 0 0
Cambridge
Country [91] 0 0
United Kingdom
State/province [91] 0 0
Cardiff
Country [92] 0 0
United Kingdom
State/province [92] 0 0
Epping
Country [93] 0 0
United Kingdom
State/province [93] 0 0
Glasgow
Country [94] 0 0
United Kingdom
State/province [94] 0 0
London
Country [95] 0 0
United Kingdom
State/province [95] 0 0
Newcastle
Country [96] 0 0
United Kingdom
State/province [96] 0 0
Southampton
Country [97] 0 0
United Kingdom
State/province [97] 0 0
Swindon
Country [98] 0 0
United Kingdom
State/province [98] 0 0
Warrington

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT01224106
Trial related presentations / publications
Klein G, Delmar P, Voyle N, Rehal S, Hofmann C, Abi-Saab D, Andjelkovic M, Ristic S, Wang G, Bateman R, Kerchner GA, Baudler M, Fontoura P, Doody R. Gantenerumab reduces amyloid-beta plaques in patients with prodromal to moderate Alzheimer's disease: a PET substudy interim analysis. Alzheimers Res Ther. 2019 Dec 12;11(1):101. doi: 10.1186/s13195-019-0559-z.
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. doi: 10.1186/s13195-018-0409-4.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01224106