A Study of Semorinemab in Patients With Moderate Alzheimer's Disease
- Conditions
- Alzheimer's Disease
- Interventions
- Registration Number
- NCT03828747
- Lead Sponsor
- Genentech, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 272
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo [18F]GTP1 Placebo will be administered intravenously in the double-blind treatment period and semorinemab will be administered intravenously in the optional open-label extension. Placebo Placebo Placebo will be administered intravenously in the double-blind treatment period and semorinemab will be administered intravenously in the optional open-label extension. Semorinemab [18F]GTP1 Semorinemab will be administered intravenously in the double-blind treatment period, and semorinemab will be administered intravenously in the optional open-label extension period. Semorinemab Semorinemab Semorinemab will be administered intravenously in the double-blind treatment period, and semorinemab will be administered intravenously in the optional open-label extension period.
- Primary Outcome Measures
Name Time Method 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) Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2 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.
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) Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2 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.
- Secondary Outcome Measures
Name Time Method 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 The Clinical Dementia Rating-Sum of Boxes (CDR-SB) is a scale used to quantify the severity of symptoms of dementia. The CDR-SB is obtained through interviews of patients and informants, and disease severity is rated in 6 domains of functioning: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a 5-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment (personal care is scored on a 4-point scale without a 0.5 rating available). The CDR-SB score is obtained by summing each of the domain box scores, with scores ranging from 0 to 18, with the higher values representing more severe impairment.
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 The Mini Mental State Examination (MMSE) is a brief clinical cognitive examination commonly used to screen for dementia and other cognitive deficits that has a total score of 0-30. Higher scores indicate better cognitive function.
Percentage of Participants With Adverse Events Baseline up to end of study (approximately 4 years and 7 months) An Adverse Event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
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. Relationship Between ADA Status and Percentage of Participants With Adverse Events Up to 57 weeks for Cohort 1, and up to 69 weeks for Cohort 2. Descriptive statistics will be used for assessment.
Relationship Between ADA Status and 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) Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2 Descriptive statistics will be used for assessment.
A 70-point scale used to quantify the areas of cognitive function most often affected in Alzheimer's disease. Lower scores indicate better cognitive function.Relationship Between ADA Status and 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) Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2 Descriptive statistics will be used for assessment.
A scale used to quantify performance of activities of daily living. Scores on the ADCS-ADL range from 0-78, with higher scores indicating better ADL function.Relationship Between ADA Status and 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 Descriptive statistics will be used for assessment.
A scale used to quantify the severity of symptoms of dementia. The CDR-SB is obtained through interviews of patients and informants, and disease severity is rated in 6 domains of functioning: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a 5-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment (personal care is scored on a 4-point scale without a 0.5 rating available). The CDR-SOB score is obtained by summing each of the domain box scores, with scores ranging from 0 to 18, with the higher values representing more severe impairment.Relationship Between ADA Status and 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 Descriptive statistics will be used for assessment.
The Mini Mental State Examination (MMSE) is a brief clinical cognitive examination commonly used to screen for dementia and other cognitive deficits that has a total score of 0-30. Higher scores indicate better cognitive function.Relationship Between ADA Status and Serum Concentration of RO7105705 at Specified Timepoints 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. Descriptive statistics will be used for assessment.
Relationship Between ADA Status and 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. Descriptive statistics will be used for assessment.
Trial Locations
- Locations (49)
Miami Jewish Health Systems
🇺🇸Miami, Florida, United States
Pharmacology Research Institute
🇺🇸Los Alamitos, California, United States
Collier Neurologic Specialists
🇺🇸Naples, Florida, United States
Synexus Clinical Research US, Inc. - Orlando
🇺🇸Orlando, Florida, United States
Collaborative Neuroscience Network, Inc.
🇺🇸Garden Grove, California, United States
Alzheimer?s Research and Treatment Center
🇺🇸Wellington, Florida, United States
Pacific Research Network - PRN
🇺🇸San Diego, California, United States
Brain Matters Research, Inc.
🇺🇸Delray Beach, Florida, United States
Stanford University; Stanford Clinical Cancer Ctr
🇺🇸Palo Alto, California, United States
Neuropsychiatric Research; Center of Southwest Florida
🇺🇸Fort Myers, Florida, United States
Southern Illinois University, School of Medicine
🇺🇸Springfield, Illinois, United States
Brigham and Womens Hospital; Center for Alzheimer Research & Treatment
🇺🇸Boston, Massachusetts, United States
Alexian Brothers Neuroscience Institute
🇺🇸Elk Grove Village, Illinois, United States
Alzheimers Disease Center
🇺🇸Quincy, Massachusetts, United States
University of Rochester; AD-CARE
🇺🇸Rochester, New York, United States
Advanced Memory Research Institute of NJ
🇺🇸Toms River, New Jersey, United States
Abington Neurological Associates
🇺🇸Abington, Pennsylvania, United States
Summit Research Network Inc.
🇺🇸Portland, Oregon, United States
Bradenton Research Center
🇺🇸Bradenton, Florida, United States
KI Health Partners, LLC; New England Institute for Clinical Research
🇺🇸Stamford, Connecticut, United States
Rush University Medical Center - Chicago
🇺🇸Chicago, Illinois, United States
Premiere Research Institute
🇺🇸West Palm Beach, Florida, United States
Rhode Island Mood & Memory Research Institute
🇺🇸East Providence, Rhode Island, United States
Butler Hospital; Movement Disorders Program
🇺🇸Providence, Rhode Island, United States
Center for Memory and Aging
🇺🇸Saint Paul, Minnesota, United States
Neurology Clinic PC
🇺🇸Cordova, Tennessee, United States
Chu Toulouse
🇫🇷Bron, France
Empire Neurology PC; MS Center of Northeastern NY
🇺🇸Latham, New York, United States
New Orleans Center for Clinical Research
🇺🇸Knoxville, Tennessee, United States
CHU de la Timone - Hopital d Adultes; Service de Neurologie
🇫🇷Marseille, France
The Memory Clinic
🇺🇸Bennington, Vermont, United States
Centrum Medyczne NeuroProtect
🇵🇱Warszawa, Poland
NZOZ WCA
🇵🇱Wroc?aw, Poland
Groupe Hospitalier Pitie-Salpetriere
🇫🇷Paris, France
Hopital des Charpennes
🇫🇷Villeurbanne, France
Podlaskie Centrum Psychogeriatrii
🇵🇱Bia?ystok, Poland
CHU Rennes - Hopital Pontchaillou
🇫🇷Rennes cedex 09, France
Novo-Med Zielinski i wspolnicy Sp. j.
🇵🇱Katowice, Poland
NZOZ NEURO-KARD Ilkowski i Partnerzy Sp. Partn. Lek
🇵🇱Pozna?, Poland
Osrodek Badan Klinicznych Euromedis
🇵🇱Szczecin, Poland
Centrum Medyczne AMED
🇵🇱Warszawa, Poland
Hospital Mutua de Terrassa
🇪🇸Terrassa, Barcelona, Spain
Fundacio ACE
🇪🇸Barcelona, Spain
Hospital de la Santa Creu i Sant Pau; Servicio de Neurologia
🇪🇸Barcelona, Spain
Hospital Universitario Doctor Peset
🇪🇸Valencia, Spain
Hospital Clinic I Provincial
🇪🇸Barcelona, Spain
Hospital Universitari i Politecnic La Fe
🇪🇸Valencia, Spain
Molecular Neuroimaging; MRI/PET
🇺🇸New Haven, Connecticut, United States
JEM Research LLC
🇺🇸Atlantis, Florida, United States