Brainshuttle AD: A Multiple Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7126209 Following Intravenous Infusion in Participants With Prodromal or Mild to Moderate Alzheimer's Disease
- Registration Number
- NCT04639050
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
The purpose of this study is to evaluate the safety, tolerability, immunogenicity, pharmacokinetics, and pharmacodynamics of multiple-ascending intravenous (IV) doses of RO7126209 in participants with prodromal or mild to moderate Alzheimer's disease (AD), who are amyloid positive based on amyloid positron emission tomography (PET) scan.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 285
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1 (Dose Finding) Cohort 1: Dose Level 1 of RO7126209 RO7126209 Participants will receive multiple doses of RO7126209 at dose level 1 once every 4 weeks (Q4W) for 28 weeks followed by a 28-week safety follow-up period. Part 1 (Dose Finding) Cohort 1: Placebo Placebo Participants will receive matching placebo to dose level 1 Q4W for 28 weeks followed by a 28-week safety follow-up period. Part 1 (Dose Finding) Cohort 2: Dose Level 2 of RO7126209 RO7126209 Participants will receive multiple doses of RO7126209 at dose level 2, Q4W, for 28 weeks followed by a 28-week safety follow-up period. Part 1 (Dose Finding) Cohort 2: Placebo Placebo Participants will receive matching placebo to dose level 2, Q4W, for 28 weeks followed by a 28-week safety follow-up period. Part 1 (Dose Finding) Cohort 3: Placebo Placebo Participants will receive matching placebo to dose level 3, Q4W, for 28 weeks followed by a 28-week safety follow-up period. Part 1 (Dose Finding) Cohort 4: Placebo Placebo Participants will receive matching placebo to dose level 4, Q4W, for 28 weeks followed by a 28-week safety follow-up period. Part 1 (Dose Finding) Cohort 5: Dose Level 5 of RO7126209 RO7126209 Participants will receive a total of 2 doses of RO7126209 at dose level 5 Q4W, for 28 weeks followed by an 8-week safety follow-up period. Part 1 (Dose Finding) Cohort 5: Placebo Placebo Participants will receive a total of 2 doses of matching placebo to dose level 5 Q4W, for 28 weeks followed by an 8-week safety follow-up period. Part 2 (Expansion) Cohort 1: Dose Level 1 of RO7126209 RO7126209 Participants will receive multiple doses of RO7126209 at dose level 1, Q4W, for 28 weeks followed by a 28-week safety follow-up period. Part 2 (Expansion) Cohort 1: Placebo Placebo Participants will receive matching placebo to dose level 1, Q4W, for 28 weeks followed by a 28-week safety follow-up period. Part 2 (Expansion) Cohort 2: Placebo Placebo Participants will receive matching placebo to dose level 2, Q4W, for 28 weeks followed by a 28-week safety follow-up period. Part 2 (Expansion) Cohort 3: Dose Level 3 of RO7126209 RO7126209 Participants will receive a total of 2 doses of RO7126209 at dose level 3, Q4W, for 28 weeks followed by an 8-week safety follow-up period. Part 2 (Expansion) Cohort 3: Placebo Placebo Participants will receive a total of 2 doses of matching placebo to dose level 3, Q4W, for 28 weeks followed by an 8-week safety follow-up period. Part 3 (Dose/Frequency/Pharmacodynamic (PD) Relationship): Dose Level 1: RO7126209 RO7126209 Participants will receive multiple doses of RO7126209 in an open-label treatment period at dose level 1, Q4W, for 24 weeks followed by a 28-week safety follow-up period. Part 4 OLE Phase Arm 2: RO7126209 RO7126209 Participants who completed Part 1, 2, or 3 and who are amyloid positive (≥24 centiloids) will receive RO7126209 Q4W for 12 weeks and will have to reach amyloid negativity (≤ 24 centiloids) before they can switch to Q12W dosing in an open-label treatment period of 89 weeks. The dose level will depend on the dose level received in Part 1,2, and 3. Part 1 (Dose Finding) Cohort 3: Dose Level 3 of RO7126209 RO7126209 Participants will receive multiple doses of RO7126209 at dose level 3, Q4W, for 28 weeks followed by a 28-week safety follow-up period. Part 1 (Dose Finding) Cohort 4: Dose Level 4 of RO7126209 RO7126209 Participants will receive multiple doses of RO7126209 at dose level 4, Q4W, for 28 weeks followed by a 28-week safety follow-up period. Part 3 Dose/Frequency/PD Relationship: Dose Level 2: RO7126209 RO7126209 Participants will receive multiple doses of RO7126209 in an open-label treatment period at dose level 2, Q12W, for 24 weeks followed by a 28-week safety follow-up period. Part 4: Open Label Extension (OLE) phase Arm 1: RO7126209 RO7126209 Participants who completed Part 1, 2, or 3 and have reached amyloid negativity (≤ 24 centiloids) in either of the Study Parts or at the OLE baseline visit will receive RO7126209 Q12W for 101 weeks. The dose level will depend on the dose level in Part 1, 2, and 3. Part 4 OLE Phase Arm 3: RO7126209 RO7126209 Participants who completed Part 1, 2, or 3 and who are amyloid positive (≥24 centiloids) at week 12 of OLE will receive RO7126209 Q4W for an additional 12 weeks, before to switch to Q12W dosing for the remaining 77 weeks in an open-label treatment period. The dose level will depend on the dose level received in Part 1,2, and 3. Part 2 (Expansion) Cohort 2: Dose Level 2 of RO7126209 RO7126209 Participants will receive multiple doses of RO7126209 at dose level 2, Q4W, for 28 weeks followed by a 28-week safety follow-up period.
- Primary Outcome Measures
Name Time Method Part 1, 2, 3, and 4: Percentage of Participants With Adverse Events (AEs) Part 1 and 2: Up to approximately 56 weeks; Part 3: Up to approximately 52 weeks; Part 4: Up to approximately 129 weeks Part 3: Change From Baseline in Brain Amyloid Load as Measured by Amyloid Positron Emission Tomography (PET) Scan Up to approximately 24 weeks
- Secondary Outcome Measures
Name Time Method Part 1, 2, and 4: Change From Baseline in Brain Amyloid Load as Measured by Amyloid PET Scan Part 1 and 2: Up to approximately 28 weeks; Part 4: Up to approximately 101 weeks Part 1, 2, 3, and 4: Plasma Concentration of RO7126209 Part 1 and 2: Up to approximately 32 weeks; Part 3: Up to approximately 24 weeks; Part 4: Up to approximately 105 weeks Part 1, 2, 3, and 4: Cerebral Spinal Fluid (CSF) Concentration of RO7126209 Part 1 and 2: Up to approximately 25 weeks; Part 3: Up to approximately 21 weeks; Part 4: Up to approximately 101 weeks Part 1, 2, 3, and 4: Number of Participants With Anti-Drug Antibodies (ADAs) to RO7126209 Part 1 and 2: Up to approximately 56 weeks; Part 3: Up to approximately 52 weeks; Part 4: Up to approximately 129 weeks
Trial Locations
- Locations (45)
JEM Research LLC
🇺🇸Atlantis, Florida, United States
K2 Medical Research-Winter Garden
🇺🇸Clermont, Florida, United States
K2 Medical Research - The Villages
🇺🇸Lady Lake, Florida, United States
K2 Medical Research, LLC
🇺🇸Maitland, Florida, United States
Optimus U Corp
🇺🇸Miami, Florida, United States
Charter Research - Winter Park/Orlando
🇺🇸Orlando, Florida, United States
Advent Health Orlando
🇺🇸Orlando, Florida, United States
Alzheimer's Research and Treatment Center
🇺🇸Stuart, Florida, United States
Charter Research - Lady Lake/The Villages
🇺🇸The Villages, Florida, United States
Alzheimer?s Research and Treatment Center
🇺🇸Wellington, Florida, United States
Conquest Research, LLC
🇺🇸Winter Park, Florida, United States
Columbus Memory Center
🇺🇸Columbus, Georgia, United States
Center for Advanced Research & Education
🇺🇸Gainesville, Georgia, United States
Quest Research Institute
🇺🇸Farmington Hills, Michigan, United States
Summit Research Network Inc.
🇺🇸Portland, Oregon, United States
Abington Neurological Associates
🇺🇸Abington, Pennsylvania, United States
Kerwin Research Center, LLC
🇺🇸Dallas, Texas, United States
Heidelberg Repatriation Hospital
🇦🇺Heidelberg West, Victoria, Australia
Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Okanagan Clinical Trials
🇨🇦Kelowna, British Columbia, Canada
Richmond Clinical Trials
🇨🇦Richmond, British Columbia, Canada
Toronto Memory Program
🇨🇦Toronto, Ontario, Canada
Centro de Investigación Clínica UC-CICUC
🇨🇱Santiago, Chile
Hospital Clinico Univ de Chile
🇨🇱Santiago, Chile
Yokohama City Minato Red Cross Hospital
🇯🇵Kanagawa, Japan
Koseikai Takeda Hospital
🇯🇵Kyoto, Japan
National Hospital Organization Utano National Hospital
🇯🇵Kyoto, Japan
Keio University Hospital
🇯🇵Tokyo, Japan
Tokyo Metropolitan Geriatric Hospital
🇯🇵Tokyo, Japan
Federation of National Public Service Personnel Mutual Aid Associations Tachikawa Hospital
🇯🇵Tokyo, Japan
Inha University Hospital
🇰🇷Incheon, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Osrodek Badan Klinicznych Euromedis
🇵🇱Szczecin, Poland
NZOZ WCA
🇵🇱Wroc?aw, Poland
Hospital General De Catalunya
🇪🇸Sant Cugat del Valles, Barcelona, Spain
Policlínica Guipuzcoa
🇪🇸Donostia-san Sebastian, Guipuzcoa, Spain
Fundación ACE
🇪🇸Barcelona, Spain
Hospital Clinic i Provincial
🇪🇸Barcelona, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario Dr. Peset
🇪🇸Valencia, Spain
Hospital Universitario la Fe
🇪🇸Valencia, Spain
Re-Cognition
🇬🇧Birmingham, United Kingdom
Recognition Health Bristol
🇬🇧Bristol, United Kingdom
RE:Cognition Health
🇬🇧London, United Kingdom
UCL Institute of Neurology
🇬🇧London, United Kingdom