Clinical trial NCT04592341: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Alzheimer Disease
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2020-10-19
Enrollment: 192
Sex: ALL
Minimum age (years): 50
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Change From Baseline in Brain Amyloid Load at Week 104 as Measured by [18F] Florbetaben Positron Emission Tomography (PET) Scan
timeFrame: Baseline, Week 104
Secondary outcomes:
measure: Number of Caregiver or Study Partner With Responses to Home Administration Questionnaire (HAQ)
timeFrame: Weeks 36, 52, 76, 104
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From day of first dose up to 16 weeks after the last dose (up to 120 weeks)
measure: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: From day of first dose up to 16 weeks after the last dose (up to 120 weeks)
measure: Number of Participants With Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Confirmed by Magnetic Resonance Imaging (MRI)
timeFrame: From day of first dose up to 16 weeks after the last dose (up to 120 weeks)
measure: Number of Participants With Amyloid-Related Imaging Abnormalities-Haemosiderin Deposition (ARIA-H) Confirmed by Magnetic Resonance Imaging (MRI)
timeFrame: From day of first dose up to 16 weeks after the last dose (up to 120 weeks)
measure: Number of Participants With Injection-Site Reactions (ISR)
timeFrame: From day of first dose up to 16 weeks after the last dose (up to 120 weeks)
measure: Number of Participants With Treatment-emergent Anti-Drug Antibodies to Gantenerumab
timeFrame: From day of first dose up to 16 weeks after the last dose (up to 120 weeks)
measure: Plasma Concentration of Subcutaneous (SC) Gantenerumab at Specified Timepoints
timeFrame: Day 4 of Week 1, Week 24, 36, 52, and 76
measure: Change in Brain Amyloid Based on Different Dosing Frequency
timeFrame: Baseline up to Week 52
Other outcomes:
Locations:
city: Atlantis
country: United States
facility: JEM Research LLC
state: Florida
city: Maitland
country: United States
facility: ClinCloud, LLC
state: Florida
city: Ocala
country: United States
facility: Renstar Medical Research
state: Florida
city: Wellington
country: United States
facility: Alzheimer?s Research and Treatment Center
state: Florida
city: Gainesville
country: United States
facility: Center for Advanced Research & Education
state: Georgia
city: Portland
country: United States
facility: Summit Research Network Inc.
state: Oregon
city: Willow Grove
country: United States
facility: Abington Neurological Associates Willow Grove
state: Pennsylvania
city: Hasselt
country: Belgium
facility: Jessa Zkh (Campus Virga Jesse)
city: Kortrijk
country: Belgium
facility: AZ Groeninge
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: Bron cedex
country: France
facility: Groupement Hospitalier Est - Hôpital Neurologique; Neurologie A (U502)
city: Paris
country: France
facility: CH Pitie Salpetriere; IM2A
city: Toulouse
country: France
facility: Gerontopole; Centre de Recherche clinique
city: Berlin
country: Germany
facility: Ambulates Gesundheitszentrum der Charité GmbH; MVZ Neurologie Campus Benjamin Franklin
city: Berlin
country: Germany
facility: ECRC Experimental and Clinical Research Center, Charité Campus Berlin Buch, Memory Clinic
city: München
country: Germany
facility: Klinikum rechts der Isar der TU München; Klinik für Psychiatrie und Psychotherapie
city: Roma
country: Italy
facility: Ospedale San Giovanni Calibita Fatebenefratell;Neurologia
state: Lazio
city: Milano
country: Italy
facility: Fondazione San Raffaele Del Monte Tabor; Dipartimento Di Neurologia
state: Lombardia
city: Tricase (LE)
country: Italy
facility: Ospedale Cardinale Panico; Dip.Ricerca Clinica in Neurologia ? UO Malattie Neurodegenerative
state: Puglia
city: Bydgoszcz
country: Poland
facility: NZOZ Vitamed
city: Lublin
country: Poland
facility: Indywidualna Praktyka Lekarska Prof. Dr Hab. N. Med. Konrad Rejdak.
city: Sopot
country: Poland
facility: Senior Sp. Z O.O. Poradnia Psychogeriatryczna
city: Szczecin
country: Poland
facility: Centrum Medyczne Euromedis Sp. z o.o.
city: Warszawa
country: Poland
facility: Centrum Medyczne NeuroProtect
city: Wroc?aw
country: Poland
facility: NZOZ WCA
city: Donostia-san Sebastian
country: Spain
facility: Policlínica Guipuzcoa; Servicio de Neurología
state: Guipuzcoa
city: Pozuelo de Alarcon
country: Spain
facility: Hospital Quiron de Madrid; Servicio de Neurologia
state: Madrid
city: Madrid
country: Spain
facility: Hospital Universitario de la Princesa; Servicio de Neurologia
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre; Servicio de Neurologia
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe; Servicio de Neurología
city: Birmingham
country: United Kingdom
facility: Re-Cognition
city: Cheltenham
country: United Kingdom
facility: Fritchie Centre
city: Dundee
country: United Kingdom
facility: Ninewells Hospital
city: London
country: United Kingdom
facility: Charing Cross Hospital; Imperial Memory Unit, Level 10 West
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: