Back to resultsA Study to Evaluate the Pharmacodynamic (PD) Effects of Once Weekly Administration of Gantenerumab in Participants With Early Alzheimer's Disease (AD)
Primary Purpose
Alzheimer Disease
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Gantenerumab
Sponsored by
About this trial
This is an interventional treatment trial for Alzheimer Disease
Eligibility Criteria
Inclusion Criteria:
- Probable Alzheimer's Disease (AD) dementia or prodromal AD.
- Availability of a reliable study partner (non-professional caregiver) who accepts to participate in study procedure throughout the study duration
- The participant should be capable of completing all aspects of study assessments including MRI, clinical genotyping, and PET imaging, either alone or with the help of the study partner (non-professional caregiver).
- Adequate visual and auditory acuitysufficient to perform the neuropsychological testing (eye glasses and hearing aids are permitted).
- Evidence of AD pathological process, as confirmed by amyloid PET scan by qualitative read by the core/central PET laboratory.
- Prodromal or mild symptomatology, as defined by a screening Mini-Mental State Examination (MMSE) score >/=22 and Clinical Dementia Rating global score (CDR-GS) of 0.5 or 1.0, as well as a clinical dementia rating (CDR) memory domain score >/=0.5.
- If the participant is receiving symptomatic AD medications, a stable dosing regimen for at least 3 months prior to screening and until start of study treatment.
- Agreement not to donate blood or blood products for transfusion for the duration of the study and for 1 year after final dose of study drug.
- Agreement not to participate in other research studies for the duration of this trial, unless these are related Roche-sponsored non-interventional studies.
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods hat result in a failure rate of < 1% per year during the treatment period and for at least 16 weeks after the final dose of study drug.
Exclusion Criteria:
- Any evidence of a condition other than AD that may affect cognition.
- History or presence of clinically evident systemic vascular disease that in the opinion of the investigator has the potential to affect cognitive function.
- History or presence of clinically evident cerebrovascular disease.
- History or presence of posterior reversible encephalopathy syndrome.
- History or presence of any stroke with clinical symptoms within the past 12 months, or documented history within the last 6 months of an acute event that is consistent with a transient ischemic attack.
- History of severe, clinically significant CNS trauma.
- History or presence of intracranial mass that could potentially impair cognition.
- Presence of infections that affect brain function or history of infections that resulted in neurologic sequelae.
- History or presence of systemic autoimmune disorders that potentially cause progressive neurologic disease with associated cognitive deficits.
- History of schizophrenia, schizoaffective disorder, major depression, or bipolar disorder.
- At risk for suicide in the opinion of the investigator.
- Alcohol and/or substance abuse or dependants in past 2 years.
Sites / Locations
- JEM Research LLC
- ClinCloud, LLC
- Renstar Medical Research
- Alzheimer?s Research and Treatment Center
- Center for Advanced Research & Education
- Summit Research Network Inc.
- Abington Neurological Associates Willow Grove
- Jessa Zkh (Campus Virga Jesse)
- AZ Groeninge
- UZ Leuven Gasthuisberg
- Groupement Hospitalier Est - Hôpital Neurologique; Neurologie A (U502)
- CH Pitie Salpetriere; IM2A
- Gerontopole; Centre de Recherche clinique
- Ambulates Gesundheitszentrum der Charité GmbH; MVZ Neurologie Campus Benjamin Franklin
- ECRC Experimental and Clinical Research Center, Charité Campus Berlin Buch, Memory Clinic
- Klinikum rechts der Isar der TU München; Klinik für Psychiatrie und Psychotherapie
- Ospedale San Giovanni Calibita Fatebenefratell;Neurologia
- Fondazione San Raffaele Del Monte Tabor; Dipartimento Di Neurologia
- Ospedale Cardinale Panico; Dip.Ricerca Clinica in Neurologia ? UO Malattie Neurodegenerative
- NZOZ Vitamed
- Indywidualna Praktyka Lekarska Prof. Dr Hab. N. Med. Konrad Rejdak.
- Senior Sp. Z O.O. Poradnia Psychogeriatryczna
- Centrum Medyczne Euromedis Sp. z o.o.
- Centrum Medyczne NeuroProtect
- NZOZ WCA
- Policlínica Guipuzcoa; Servicio de Neurología
- Hospital Quiron de Madrid; Servicio de Neurologia
- Hospital Universitario de la Princesa; Servicio de Neurologia
- Hospital Universitario 12 de Octubre; Servicio de Neurologia
- Hospital Universitari i Politecnic La Fe; Servicio de Neurología
- Re-Cognition
- Fritchie Centre
- Ninewells Hospital
- Charing Cross Hospital; Imperial Memory Unit, Level 10 West
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Gantenerumab
Arm Description
Participants will receive gantenerumab by subcutaneous (SC) injection at a dose of 120 mg every 4 weeks (Q4W) for 12 weeks, followed by 255 mg Q4W for 12 weeks, and 255 mg every 2 weeks (Q2W) for another 12 weeks, followed by the target dose 255 mg once weekly (Q1W) for up to Week 103. Participants who complete Week 104 visit will be given an option to take part in 2-year extension of the study to receive gantenerumab 255 mg Q1W for up to Week 207.
Outcomes
Primary Outcome Measures
Change from Baseline in Deposited Amyloid as Measured by Brain Amyloid PET Centiloid (CL) Levels
Secondary Outcome Measures
Responses to Home Administration Questionnaire
The home administration questionnaire will capture confidence, ease of use, convenience, and overall satisfaction.
Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Change in the Columbia-Suicide Severity Rating Scale (C-SSRS) Score
The C-SSRS is an assessment tool used to assess the lifetime suicidality of a patient (C-SSRS at baseline) as well as any new instances of suicidality (C-SSRS since last visit). The structured interview prompts recollection of suicidal ideation, including the intensity of the ideation, behavior, and attempts with actual or potential lethality.
Percentage of Participants with Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Confirmed by Magnetic Resonance Imaging (MRI)
Percentage of Participants with Amyloid-Related Imaging Abnormalities-Haemosiderin deposition (ARIA-H) Confirmed by Magnetic Resonance Imaging (MRI)
Percentage of Participants with Injection-Site Reactions (ISR)
Injection reactions (local and systemic) are defined as adverse events that occur during or within 24 hours after study drug administration that are judged to be related to the study drug injection.
Percentage of Participants with Anti-Drug Antibodies to Gantenerumab
Plasma Concentration of SC Gantenerumab at specified timepoints
Change in Brain Amyloid Based on Different Dosing Frequency
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04592341
Brief Title
A Study to Evaluate the Pharmacodynamic (PD) Effects of Once Weekly Administration of Gantenerumab in Participants With Early Alzheimer's Disease (AD)
Official Title
A Phase II, Multicenter, Open-Label, Single Arm Study to Evaluate the Pharmacodynamic Effects of Once Weekly Administration of Gantenerumab in Participants With Early (Prodromal to Mild) Alzheimer's Disease
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Terminated
Why Stopped
Decision to terminate development of Gantenerumab for treatment of prodromal/mild/early-stage Alzheimer's disease following results of a pre-planned analysis of the safety and efficacy of Gant in Graduate I&II (WN29922/WN39658).
Study Start Date
November 18, 2020 (Actual)
Primary Completion Date
January 11, 2023 (Actual)
Study Completion Date
March 15, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
This is a Phase II, multicenter, open-label, single arm, PD study in participants with early (prodromal to mild) AD to evaluate the effect of a once weekly (Q1W) dosing regimen of gantenerumab on deposited amyloid as measured by change from baseline to Week 104 (primary) and Week 208 in brain amyloid positron emission tomography (PET). The administration of gantenerumab as a single injection of Q1W will be investigated in this study, to simplify the dosing regimen for participants.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
192 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Gantenerumab
Arm Type
Experimental
Arm Description
Participants will receive gantenerumab by subcutaneous (SC) injection at a dose of 120 mg every 4 weeks (Q4W) for 12 weeks, followed by 255 mg Q4W for 12 weeks, and 255 mg every 2 weeks (Q2W) for another 12 weeks, followed by the target dose 255 mg once weekly (Q1W) for up to Week 103. Participants who complete Week 104 visit will be given an option to take part in 2-year extension of the study to receive gantenerumab 255 mg Q1W for up to Week 207.
Intervention Type
Drug
Intervention Name(s)
Gantenerumab
Intervention Description
Gantenerumab will be administered by SC injection at a dose of 120 mg Q4W for 12 weeks, followed by 255 mg Q4W for 12 weeks, and 255 mg Q2W for another 12 weeks, followed by the target dose 255 mg Q1W for up to Week 103 and an optional dose of 255 mg Q1W for up to Week 207.
Primary Outcome Measure Information:
Title
Change from Baseline in Deposited Amyloid as Measured by Brain Amyloid PET Centiloid (CL) Levels
Time Frame
Up to Week 104
Secondary Outcome Measure Information:
Title
Responses to Home Administration Questionnaire
Description
The home administration questionnaire will capture confidence, ease of use, convenience, and overall satisfaction.
Time Frame
Up to Week 208
Title
Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame
Up to Week 224
Title
Change in the Columbia-Suicide Severity Rating Scale (C-SSRS) Score
Description
The C-SSRS is an assessment tool used to assess the lifetime suicidality of a patient (C-SSRS at baseline) as well as any new instances of suicidality (C-SSRS since last visit). The structured interview prompts recollection of suicidal ideation, including the intensity of the ideation, behavior, and attempts with actual or potential lethality.
Time Frame
Up to Week 208
Title
Percentage of Participants with Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Confirmed by Magnetic Resonance Imaging (MRI)
Time Frame
Up to Week 208
Title
Percentage of Participants with Amyloid-Related Imaging Abnormalities-Haemosiderin deposition (ARIA-H) Confirmed by Magnetic Resonance Imaging (MRI)
Time Frame
Up to Week 208
Title
Percentage of Participants with Injection-Site Reactions (ISR)
Description
Injection reactions (local and systemic) are defined as adverse events that occur during or within 24 hours after study drug administration that are judged to be related to the study drug injection.
Time Frame
24 hours after study drug administration, up to Week 208
Title
Percentage of Participants with Anti-Drug Antibodies to Gantenerumab
Time Frame
Up to Week 224
Title
Plasma Concentration of SC Gantenerumab at specified timepoints
Time Frame
Up to Week 224
Title
Change in Brain Amyloid Based on Different Dosing Frequency
Time Frame
Up to Week 208
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Probable Alzheimer's Disease (AD) dementia or prodromal AD.
Availability of a reliable study partner (non-professional caregiver) who accepts to participate in study procedure throughout the study duration
The participant should be capable of completing all aspects of study assessments including MRI, clinical genotyping, and PET imaging, either alone or with the help of the study partner (non-professional caregiver).
Adequate visual and auditory acuitysufficient to perform the neuropsychological testing (eye glasses and hearing aids are permitted).
Evidence of AD pathological process, as confirmed by amyloid PET scan by qualitative read by the core/central PET laboratory.
Prodromal or mild symptomatology, as defined by a screening Mini-Mental State Examination (MMSE) score >/=22 and Clinical Dementia Rating global score (CDR-GS) of 0.5 or 1.0, as well as a clinical dementia rating (CDR) memory domain score >/=0.5.
If the participant is receiving symptomatic AD medications, a stable dosing regimen for at least 3 months prior to screening and until start of study treatment.
Agreement not to donate blood or blood products for transfusion for the duration of the study and for 1 year after final dose of study drug.
Agreement not to participate in other research studies for the duration of this trial, unless these are related Roche-sponsored non-interventional studies.
For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods hat result in a failure rate of < 1% per year during the treatment period and for at least 16 weeks after the final dose of study drug.
Exclusion Criteria:
Any evidence of a condition other than AD that may affect cognition.
History or presence of clinically evident systemic vascular disease that in the opinion of the investigator has the potential to affect cognitive function.
History or presence of clinically evident cerebrovascular disease.
History or presence of posterior reversible encephalopathy syndrome.
History or presence of any stroke with clinical symptoms within the past 12 months, or documented history within the last 6 months of an acute event that is consistent with a transient ischemic attack.
History of severe, clinically significant CNS trauma.
History or presence of intracranial mass that could potentially impair cognition.
Presence of infections that affect brain function or history of infections that resulted in neurologic sequelae.
History or presence of systemic autoimmune disorders that potentially cause progressive neurologic disease with associated cognitive deficits.
History of schizophrenia, schizoaffective disorder, major depression, or bipolar disorder.
At risk for suicide in the opinion of the investigator.
Alcohol and/or substance abuse or dependants in past 2 years.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
JEM Research LLC
City
Atlantis
State/Province
Florida
ZIP/Postal Code
33462
Country
United States
Facility Name
ClinCloud, LLC
City
Maitland
State/Province
Florida
ZIP/Postal Code
32751
Country
United States
Facility Name
Renstar Medical Research
City
Ocala
State/Province
Florida
ZIP/Postal Code
34470
Country
United States
Facility Name
Alzheimer?s Research and Treatment Center
City
Wellington
State/Province
Florida
ZIP/Postal Code
33414
Country
United States
Facility Name
Center for Advanced Research & Education
City
Gainesville
State/Province
Georgia
ZIP/Postal Code
30501
Country
United States
Facility Name
Summit Research Network Inc.
City
Portland
State/Province
Oregon
ZIP/Postal Code
97210
Country
United States
Facility Name
Abington Neurological Associates Willow Grove
City
Willow Grove
State/Province
Pennsylvania
ZIP/Postal Code
19090
Country
United States
Facility Name
Jessa Zkh (Campus Virga Jesse)
City
Hasselt
ZIP/Postal Code
3500
Country
Belgium
Facility Name
AZ Groeninge
City
Kortrijk
ZIP/Postal Code
8500
Country
Belgium
Facility Name
UZ Leuven Gasthuisberg
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Groupement Hospitalier Est - Hôpital Neurologique; Neurologie A (U502)
City
Bron cedex
ZIP/Postal Code
69677
Country
France
Facility Name
CH Pitie Salpetriere; IM2A
City
Paris
ZIP/Postal Code
75651
Country
France
Facility Name
Gerontopole; Centre de Recherche clinique
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
Ambulates Gesundheitszentrum der Charité GmbH; MVZ Neurologie Campus Benjamin Franklin
City
Berlin
ZIP/Postal Code
12200
Country
Germany
Facility Name
ECRC Experimental and Clinical Research Center, Charité Campus Berlin Buch, Memory Clinic
City
Berlin
ZIP/Postal Code
13125
Country
Germany
Facility Name
Klinikum rechts der Isar der TU München; Klinik für Psychiatrie und Psychotherapie
City
München
ZIP/Postal Code
81675
Country
Germany
Facility Name
Ospedale San Giovanni Calibita Fatebenefratell;Neurologia
City
Roma
State/Province
Lazio
ZIP/Postal Code
00186
Country
Italy
Facility Name
Fondazione San Raffaele Del Monte Tabor; Dipartimento Di Neurologia
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20132
Country
Italy
Facility Name
Ospedale Cardinale Panico; Dip.Ricerca Clinica in Neurologia ? UO Malattie Neurodegenerative
City
Tricase (LE)
State/Province
Puglia
ZIP/Postal Code
73039
Country
Italy
Facility Name
NZOZ Vitamed
City
Bydgoszcz
ZIP/Postal Code
85-079
Country
Poland
Facility Name
Indywidualna Praktyka Lekarska Prof. Dr Hab. N. Med. Konrad Rejdak.
City
Lublin
ZIP/Postal Code
20-016
Country
Poland
Facility Name
Senior Sp. Z O.O. Poradnia Psychogeriatryczna
City
Sopot
ZIP/Postal Code
81-855
Country
Poland
Facility Name
Centrum Medyczne Euromedis Sp. z o.o.
City
Szczecin
ZIP/Postal Code
70-111
Country
Poland
Facility Name
Centrum Medyczne NeuroProtect
City
Warszawa
ZIP/Postal Code
01-684
Country
Poland
Facility Name
NZOZ WCA
City
Wroc?aw
ZIP/Postal Code
53-659
Country
Poland
Facility Name
Policlínica Guipuzcoa; Servicio de Neurología
City
Donostia-san Sebastian
State/Province
Guipuzcoa
ZIP/Postal Code
20014
Country
Spain
Facility Name
Hospital Quiron de Madrid; Servicio de Neurologia
City
Pozuelo de Alarcon
State/Province
Madrid
ZIP/Postal Code
28223
Country
Spain
Facility Name
Hospital Universitario de la Princesa; Servicio de Neurologia
City
Madrid
ZIP/Postal Code
28006
Country
Spain
Facility Name
Hospital Universitario 12 de Octubre; Servicio de Neurologia
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Hospital Universitari i Politecnic La Fe; Servicio de Neurología
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Facility Name
Re-Cognition
City
Birmingham
ZIP/Postal Code
B16 8QQ
Country
United Kingdom
Facility Name
Fritchie Centre
City
Cheltenham
ZIP/Postal Code
GL53 9DZ
Country
United Kingdom
Facility Name
Ninewells Hospital
City
Dundee
ZIP/Postal Code
DD12 9SY
Country
United Kingdom
Facility Name
Charing Cross Hospital; Imperial Memory Unit, Level 10 West
City
London
ZIP/Postal Code
W6 8RF
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
Learn more about this trial
A Study to Evaluate the Pharmacodynamic (PD) Effects of Once Weekly Administration of Gantenerumab in Participants With Early Alzheimer's Disease (AD)
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