A Study of Semorinemab in Patients With Moderate Alzheimer's Disease
A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy, and Safety Study of MTAU9937A in Patients With Moderate Alzheimer's Disease
1 other identifier
interventional
272
4 countries
49
Brief Summary
This Phase II, multicenter, randomized, double-blind, placebo-controlled, parallel-group study will evaluate the clinical efficacy, safety, pharmacokinetics, and pharmacodynamics of semorinemab in patients with moderate AD. The study consists of a screening period, a double-blind treatment period, an optional open-label extension (OLE) period, and a safety follow-up period. There may be up to two study cohorts.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jan 2019
Typical duration for phase_2
49 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
January 25, 2019
CompletedFirst Submitted
Initial submission to the registry
January 29, 2019
CompletedFirst Posted
Study publicly available on registry
February 4, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 20, 2021
CompletedResults Posted
Study results publicly available
October 3, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
August 30, 2023
CompletedSeptember 24, 2024
August 1, 2024
2.5 years
January 29, 2019
July 15, 2022
August 29, 2024
Conditions
Outcome Measures
Primary Outcomes (2)
Change From Baseline to Last Visit of Double-Blind Treatment Period in Cognitive Function as Measured by the Alzheimer's Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11)
The Alzheimer's Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11) is an 11 item cognitive subscale used to quantify the areas of cognitive function most often affected in Alzheimer's disease. The total score ranges from 0-70 with lower scores indicating better cognitive function.
Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2
Change From Baseline to Last Visit of Double-Blind Treatment Period in Functional Capacities as Measured by the Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL)
The Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL) is a scale used to quantify performance of activities of daily living (ADL). Scores on the ADCS-ADL range from 0-78, with higher scores indicating better ADL function.
Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2
Secondary Outcomes (12)
Change From Baseline to Last Visit of Double-Blind Treatment Period on the Clinical Dementia Rating-Sum of Boxes (CDR-SB)
Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2
Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE)
Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2
Percentage of Participants With Adverse Events
Baseline up to end of study (approximately 4 years and 7 months)
Serum Concentration of RO7105705 at Specified Timepoints
Weeks 1,3,5,9,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,3,5,9,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2.
Incidence of Anti-drug Antibodies (ADAs) During the Study Relative to the Prevalence of ADAs at Baseline
Weeks 1,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2.
- +7 more secondary outcomes
Study Arms (2)
Semorinemab
EXPERIMENTALSemorinemab will be administered intravenously in the double-blind treatment period, and semorinemab will be administered intravenously in the optional open-label extension period.
Placebo
PLACEBO COMPARATORPlacebo will be administered intravenously in the double-blind treatment period and semorinemab will be administered intravenously in the optional open-label extension.
Interventions
Participants will receive semorinemab every 2 weeks (Q2W) for the first three doses of the double-blind treatment period and every 4 weeks (Q4W) thereafter during the double-blind treatment period. Semorinemab will be administered Q4W in the OLE period.
Participants will receive placebo every 2 weeks (Q2W) for the first three doses of the double-blind treatment period and every 4 weeks (Q4W) thereafter during the double-blind treatment period.
\[18F\]GTP1 will be administered as a solution for intravenous (IV) use, as part of positron emission tomography (PET) imaging.
Eligibility Criteria
You may qualify if:
- National Institute on Aging/Alzheimer's Association core clinical criteria for probable AD dementia
- Evidence of the AD pathological process, by a positive amyloid assessment either on CSF Aβ1-42 as measured on Elecsys β-Amyloid(1-42) Test System OR amyloid PET scan
- AD dementia of moderate severity, as defined by a screening MMSE score of 16-21 points, inclusive, and a CDR-GS of 1 or 2
- Availability of a person with sufficient contact with the participant to be able to provide accurate information on the participant's cognitive, behavioral and functional ability
You may not qualify if:
- Pregnant or breastfeeding
- Inability to tolerate MRI procedures or contraindication to MRI
- Contraindication to PET imaging
- Residence in a skilled nursing facility
- Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study, or bias the assessment of the clinical or mental status of the participant to a significant degree
- Any evidence of a condition other than AD that may affect cognition
- Substance abuse within the past 2 years
- Use of any experimental therapy within 90 days or 5 half-lives prior to screening, whichever is greater, or any passive immunotherapy against tau
- Use of any passive immunotherapy (immunoglobulin) against Aβ, unless the last dose was at least 1 year prior to screening or any active immunotherapy (vaccine) that is under evaluation to prevent or postpone cognitive decline
- Any other biologic therapy or previous treatment with medications specifically intended to treat Parkinsonian symptoms or any other non-AD neurodegenerative disorder within 1 year of screening
- Systemic immunosuppressive therapy within 12 months of screening through the entire study period
- Typical antipsychotic or neuroleptic medication within 6 months of screening
- Daily treatment with any of the following classes of medication (except for intermittent short-term use): opiates or opioids, benzodiazepines, barbiturates, hypnotics, or any medication with clinically significant centrally-acting antihistamine or anticholinergic activity
- Stimulant medications, unless the dose has been stable within the 6 months prior to screening and is expected to be stable throughout the study
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Genentech, Inc.lead
Study Sites (49)
Collaborative Neuroscience Network, Inc.
Garden Grove, California, 92845, United States
Pharmacology Research Institute
Los Alamitos, California, 90720, United States
Stanford University; Stanford Clinical Cancer Ctr
Palo Alto, California, 94305, United States
Pacific Research Network - PRN
San Diego, California, 92103, United States
Molecular Neuroimaging; MRI/PET
New Haven, Connecticut, 06510, United States
KI Health Partners, LLC; New England Institute for Clinical Research
Stamford, Connecticut, 06905, United States
JEM Research LLC
Atlantis, Florida, 33462, United States
Bradenton Research Center
Bradenton, Florida, 34205, United States
Brain Matters Research, Inc.
Delray Beach, Florida, 33445, United States
Neuropsychiatric Research; Center of Southwest Florida
Fort Myers, Florida, 33912, United States
Miami Jewish Health Systems
Miami, Florida, 33137, United States
Collier Neurologic Specialists
Naples, Florida, 34105, United States
Synexus Clinical Research US, Inc. - Orlando
Orlando, Florida, 32806, United States
Alzheimer?s Research and Treatment Center
Wellington, Florida, 33414, United States
Premiere Research Institute
West Palm Beach, Florida, 33407, United States
Rush University Medical Center - Chicago
Chicago, Illinois, 60612, United States
Alexian Brothers Neuroscience Institute
Elk Grove Village, Illinois, 60007, United States
Southern Illinois University, School of Medicine
Springfield, Illinois, 62702, United States
Brigham and Womens Hospital; Center for Alzheimer Research & Treatment
Boston, Massachusetts, 02115, United States
Alzheimers Disease Center
Quincy, Massachusetts, 02169, United States
Center for Memory and Aging
Saint Paul, Minnesota, 55130, United States
Advanced Memory Research Institute of NJ
Toms River, New Jersey, 08755, United States
Empire Neurology PC; MS Center of Northeastern NY
Latham, New York, 12110, United States
University of Rochester; AD-CARE
Rochester, New York, 14642, United States
Summit Research Network Inc.
Portland, Oregon, 97210, United States
Abington Neurological Associates
Abington, Pennsylvania, 19001, United States
Rhode Island Mood & Memory Research Institute
East Providence, Rhode Island, 02914, United States
Butler Hospital; Movement Disorders Program
Providence, Rhode Island, 02906, United States
Neurology Clinic PC
Cordova, Tennessee, 38018, United States
New Orleans Center for Clinical Research
Knoxville, Tennessee, 37920, United States
The Memory Clinic
Bennington, Vermont, 05201, United States
Chu Toulouse
Bron, 69500, France
CHU de la Timone - Hopital d Adultes; Service de Neurologie
Marseille, 13005, France
Groupe Hospitalier Pitie-Salpetriere
Paris, 75651, France
CHU Rennes - Hopital Pontchaillou
Rennes, 35033, France
Hopital des Charpennes
Villeurbanne, 69100, France
Podlaskie Centrum Psychogeriatrii
Bia?ystok, 15-756, Poland
Novo-Med Zielinski i wspolnicy Sp. j.
Katowice, 40-650, Poland
NZOZ NEURO-KARD Ilkowski i Partnerzy Sp. Partn. Lek
Późna, 61-853, Poland
Osrodek Badan Klinicznych Euromedis
Szczecin, 70-111, Poland
Centrum Medyczne NeuroProtect
Warsaw, 01-684, Poland
Centrum Medyczne AMED
Warsaw, 03-291, Poland
NZOZ WCA
Wroc?aw, 53-659, Poland
Hospital Mutua de Terrassa
Terrassa, Barcelona, 08221, Spain
Fundacio ACE
Barcelona, 08028, Spain
Hospital Clinic I Provincial
Barcelona, 08036, Spain
Hospital de la Santa Creu i Sant Pau; Servicio de Neurologia
Barcelona, 08041, Spain
Hospital Universitario Doctor Peset
Valencia, 46017, Spain
Hospital Universitari i Politecnic La Fe
Valencia, 46026, Spain
Related Publications (3)
Chandler JM, Lansdall CJ, Ye W, McDougall F, Belger M, Toth B, Mi X, Sink KM, Atkins AS. The Alzheimer's Disease Cooperative Study - Activities of Daily Living dependence score: revision and validation of an algorithm evaluating patient dependence across the spectrum of AD severity. J Prev Alzheimers Dis. 2025 Sep;12(8):100261. doi: 10.1016/j.tjpad.2025.100261. Epub 2025 Jul 1.
PMID: 40603145DERIVEDSchauer SP, Toth B, Lee J, Honigberg LA, Ramakrishnan V, Jiang J, Kollmorgen G, Bayfield A, Wild N, Hoffman J, Ceniceros R, Dolton M, Bohorquez SMS, Hoogenraad CC, Wildsmith KR, Teng E, Monteiro C, Anania V, Yeh FL. Pharmacodynamic effects of semorinemab on plasma and CSF biomarkers of Alzheimer's disease pathophysiology. Alzheimers Dement. 2024 Dec;20(12):8855-8866. doi: 10.1002/alz.14346. Epub 2024 Nov 8.
PMID: 39513754DERIVEDMonteiro C, Toth B, Brunstein F, Bobbala A, Datta S, Ceniceros R, Sanabria Bohorquez SM, Anania VG, Wildsmith KR, Schauer SP, Lee J, Dolton MJ, Ramakrishnan V, Abramzon D, Teng E; Lauriet investigators. Randomized Phase II Study of the Safety and Efficacy of Semorinemab in Participants With Mild-to-Moderate Alzheimer Disease: Lauriet. Neurology. 2023 Oct 3;101(14):e1391-e1401. doi: 10.1212/WNL.0000000000207663. Epub 2023 Aug 29.
PMID: 37643887DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Communications
- Organization
- Hoffmann-La Roche
Study Officials
- STUDY DIRECTOR
Clinical Trials
Hoffmann-La Roche
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 29, 2019
First Posted
February 4, 2019
Study Start
January 25, 2019
Primary Completion
July 20, 2021
Study Completion
August 30, 2023
Last Updated
September 24, 2024
Results First Posted
October 3, 2022
Record last verified: 2024-08
Data Sharing
- IPD Sharing
- Will share
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). 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)