A Study to Evaluate the Pharmacodynamic (PD) Effects of Once Weekly Administration of Gantenerumab in Participants With Early Alzheimer's Disease (AD)
- Registration Number
- NCT04592341
- Lead Sponsor
- Hoffmann-La Roche
- 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 ...
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 192
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Gantenerumab Gantenerumab 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.
- Primary Outcome Measures
Name Time Method Change From Baseline in Brain Amyloid Load at Week 104 as Measured by [18F] Florbetaben Positron Emission Tomography (PET) Scan Baseline, Week 104 Screening amyloid PET scan was considered baseline evaluation.Brain amyloid load was quantified in terms of Standardized Uptake Value Ratio (SUVR),defined as ratio of tracer uptake in cortical composite target region of interest(ROI)to tracer uptake in reference ROI.Composite region: frontal,parietal,temporal,posterior cingulate cortex,anterior cingulate cor...
- Secondary Outcome Measures
Name Time Method Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) From day of first dose up to 16 weeks after the last dose (up to 120 weeks) AE: any untoward medical occurrence in participant administered pharmaceutical product, which does not necessarily have a causal relationship with treatment. Also, any unfavorable, unintended sign, symptom, or disease temporally associated with use of medicinal product, whether or not considered related to it. SAE: any AE that was fatal, life threatening, re...
Number of Participants With Amyloid-Related Imaging Abnormalities-Haemosiderin Deposition (ARIA-H) Confirmed by Magnetic Resonance Imaging (MRI) From day of first dose up to 16 weeks after the last dose (up to 120 weeks) ARIA are an identified risk with anti-amyloid antibodies, including gantenerumab. These changes can be identified on brain MRI. ARIA-H (H for hemosiderosis) are small foci of signal loss observed on MRI sequences sensitive for paramagnetic tissue properties and comprise cerebral microbleeds (small foci of bleeding in the brain parenchyma) and leptomeningeal ...
Number of Participants With Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Confirmed by Magnetic Resonance Imaging (MRI) From day of first dose up to 16 weeks after the last dose (up to 120 weeks) ARIA are an identified risk with anti-amyloid antibodies, including gantenerumab. These changes can be identified on brain MRI. The occurrences of imaging abnormalities in vasogenic edema and sulcal effusions (ARIA-E) were evaluated.
Number of Caregiver or Study Partner With Responses to Home Administration Questionnaire (HAQ) Weeks 36, 52, 76, 104 HAQ comprised 4 items completed by study partner capturing confidence (Q1), convenience (Q2), ease of use (Q3), and overall satisfaction (Q4) with administering medication. Response options Q1: Not at all confident, somewhat confident, confident, very confident; Q2: Not at all convenient, somewhat convenient, convenient, very convenient; Q3: Not at all easy,...
Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) From day of first dose up to 16 weeks after the last dose (up to 120 weeks) C-SSRS=assessment tool used to assess lifetime suicidality of a participant (at baseline) as well as any new instances of suicidality (C-SSRS since last visit). Structured interview prompts recollection of suicidal ideation, including intensity of ideation, behavior, \& attempts with actual/potential lethality. Categories have binary responses (yes/no) \& in...
Number of Participants With Injection-Site Reactions (ISR) From day of first dose up to 16 weeks after the last dose (up to 120 weeks) An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product or other protocol-imposed intervention, regardless of attribution. Injection reactions (local and systemic) were defined as AEs that occured during or within 24 hours after study drug administration that were judged to be related...
Number of Participants With Treatment-emergent Anti-Drug Antibodies to Gantenerumab From day of first dose up to 16 weeks after the last dose (up to 120 weeks) A participant with an ADA assay result from at least one post-baseline sample was defined as a post-baseline evaluable participant. Treatment Emergent ADA was defined as a participant with a negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result, or a participant with a positive ADA result at baseline who has at least o...
Plasma Concentration of Subcutaneous (SC) Gantenerumab at Specified Timepoints Day 4 of Week 1, Week 24, 36, 52, and 76 Change in Brain Amyloid Based on Different Dosing Frequency Baseline up to Week 52 The change from baseline at Week 52 using the once-weekly dosing frequency was analysed using the centiloid scale. The centiloid scale anchor points are 0 and 100, where 0 represents a high-certainty amyloid negative scan and 100 represents the amount of global amyloid deposition found in a typical AD scan. The range of centiloid values can be below 0 (negat...
Trial Locations
- Locations (34)
UZ Leuven Gasthuisberg
🇧🇪Leuven, Belgium
Senior Sp. Z O.O. Poradnia Psychogeriatryczna
🇵🇱Sopot, Poland
Gerontopole; Centre de Recherche clinique
🇫🇷Toulouse, France
ECRC Experimental and Clinical Research Center, Charité Campus Berlin Buch, Memory Clinic
🇩🇪Berlin, Germany
Alzheimer?s Research and Treatment Center
🇺🇸Wellington, Florida, United States
Renstar Medical Research
🇺🇸Ocala, Florida, United States
Center for Advanced Research & Education
🇺🇸Gainesville, Georgia, United States
CH Pitie Salpetriere; IM2A
🇫🇷Paris, France
Ambulates Gesundheitszentrum der Charité GmbH; MVZ Neurologie Campus Benjamin Franklin
🇩🇪Berlin, Germany
Jessa Zkh (Campus Virga Jesse)
🇧🇪Hasselt, Belgium
Groupement Hospitalier Est - Hôpital Neurologique; Neurologie A (U502)
🇫🇷Bron cedex, France
Klinikum rechts der Isar der TU München; Klinik für Psychiatrie und Psychotherapie
🇩🇪München, Germany
Centrum Medyczne Euromedis Sp. z o.o.
🇵🇱Szczecin, Poland
Policlínica Guipuzcoa; Servicio de Neurología
🇪🇸Donostia-san Sebastian, Guipuzcoa, Spain
Centrum Medyczne NeuroProtect
🇵🇱Warszawa, Poland
Hospital Quiron de Madrid; Servicio de Neurologia
🇪🇸Pozuelo de Alarcon, Madrid, Spain
Hospital Universitario de la Princesa; Servicio de Neurologia
🇪🇸Madrid, Spain
Charing Cross Hospital; Imperial Memory Unit, Level 10 West
🇬🇧London, United Kingdom
Ninewells Hospital
🇬🇧Dundee, United Kingdom
Fondazione San Raffaele Del Monte Tabor; Dipartimento Di Neurologia
🇮🇹Milano, Lombardia, Italy
Ospedale Cardinale Panico; Dip.Ricerca Clinica in Neurologia ? UO Malattie Neurodegenerative
🇮🇹Tricase (LE), Puglia, Italy
Re-Cognition
🇬🇧Birmingham, United Kingdom
Fritchie Centre
🇬🇧Cheltenham, United Kingdom
Hospital Universitari i Politecnic La Fe; Servicio de Neurología
🇪🇸Valencia, Spain
Ospedale San Giovanni Calibita Fatebenefratell;Neurologia
🇮🇹Roma, Lazio, Italy
NZOZ WCA
🇵🇱Wroc?aw, Poland
Abington Neurological Associates Willow Grove
🇺🇸Willow Grove, Pennsylvania, United States
Summit Research Network Inc.
🇺🇸Portland, Oregon, United States
JEM Research LLC
🇺🇸Atlantis, Florida, United States
ClinCloud, LLC
🇺🇸Maitland, Florida, United States
Hospital Universitario 12 de Octubre; Servicio de Neurologia
🇪🇸Madrid, Spain
NZOZ Vitamed
🇵🇱Bydgoszcz, Poland
Indywidualna Praktyka Lekarska Prof. Dr Hab. N. Med. Konrad Rejdak.
🇵🇱Lublin, Poland
AZ Groeninge
🇧🇪Kortrijk, Belgium