Clinical trial NCT03828747: A Study of Semorinemab in Patients With Moderate Alzheimer's Disease
Official title: A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy, and Safety Study of MTAU9937A in Patients With Moderate Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alzheimer's Disease
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2019-02-04
Enrollment: 272
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: 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)
timeFrame: Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2
measure: 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)
timeFrame: Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2
Secondary outcomes:
measure: Change From Baseline to Last Visit of Double-Blind Treatment Period on the Clinical Dementia Rating-Sum of Boxes (CDR-SB)
timeFrame: Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2
measure: Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE)
timeFrame: Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2
measure: Percentage of Participants With Adverse Events
timeFrame: Baseline up to end of study (approximately 4 years and 7 months)
measure: Serum Concentration of RO7105705 at Specified Timepoints
timeFrame: 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.
measure: Incidence of Anti-drug Antibodies (ADAs) During the Study Relative to the Prevalence of ADAs at Baseline
timeFrame: 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.
measure: Relationship Between ADA Status and Percentage of Participants With Adverse Events
timeFrame: Up to 57 weeks for Cohort 1, and up to 69 weeks for Cohort 2.
measure: 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)
timeFrame: Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2
measure: 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)
timeFrame: Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2
measure: 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)
timeFrame: Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2
measure: Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE)
timeFrame: Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2
measure: Relationship Between ADA Status and Serum Concentration of RO7105705 at Specified Timepoints
timeFrame: 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.
measure: Relationship Between ADA Status and Incidence of Anti-Drug Antibodies (ADAs) During the Study Relative to the Prevalence of ADAs at Baseline
timeFrame: 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.
Other outcomes:
Locations:
city: Garden Grove
country: United States
facility: Collaborative Neuroscience Network, Inc.
state: California
city: Los Alamitos
country: United States
facility: Pharmacology Research Institute
state: California
city: Palo Alto
country: United States
facility: Stanford University; Stanford Clinical Cancer Ctr
state: California
city: San Diego
country: United States
facility: Pacific Research Network - PRN
state: California
city: New Haven
country: United States
facility: Molecular Neuroimaging; MRI/PET
state: Connecticut
city: Stamford
country: United States
facility: KI Health Partners, LLC; New England Institute for Clinical Research
state: Connecticut
city: Atlantis
country: United States
facility: JEM Research LLC
state: Florida
city: Bradenton
country: United States
facility: Bradenton Research Center
state: Florida
city: Delray Beach
country: United States
facility: Brain Matters Research, Inc.
state: Florida
city: Fort Myers
country: United States
facility: Neuropsychiatric Research; Center of Southwest Florida
state: Florida
city: Miami
country: United States
facility: Miami Jewish Health Systems
state: Florida
city: Naples
country: United States
facility: Collier Neurologic Specialists
state: Florida
city: Orlando
country: United States
facility: Synexus Clinical Research US, Inc. - Orlando
state: Florida
city: Wellington
country: United States
facility: Alzheimer?s Research and Treatment Center
state: Florida
city: West Palm Beach
country: United States
facility: Premiere Research Institute
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center - Chicago
state: Illinois
city: Elk Grove Village
country: United States
facility: Alexian Brothers Neuroscience Institute
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University, School of Medicine
state: Illinois
city: Boston
country: United States
facility: Brigham and Womens Hospital; Center for Alzheimer Research & Treatment
state: Massachusetts
city: Quincy
country: United States
facility: Alzheimers Disease Center
state: Massachusetts
city: Saint Paul
country: United States
facility: Center for Memory and Aging
state: Minnesota
city: Toms River
country: United States
facility: Advanced Memory Research Institute of NJ
state: New Jersey
city: Latham
country: United States
facility: Empire Neurology PC; MS Center of Northeastern NY
state: New York
city: Rochester
country: United States
facility: University of Rochester; AD-CARE
state: New York
city: Portland
country: United States
facility: Summit Research Network Inc.
state: Oregon
city: Abington
country: United States
facility: Abington Neurological Associates
state: Pennsylvania
city: East Providence
country: United States
facility: Rhode Island Mood & Memory Research Institute
state: Rhode Island
city: Providence
country: United States
facility: Butler Hospital; Movement Disorders Program
state: Rhode Island
city: Cordova
country: United States
facility: Neurology Clinic PC
state: Tennessee
city: Knoxville
country: United States
facility: New Orleans Center for Clinical Research
state: Tennessee
city: Bennington
country: United States
facility: The Memory Clinic
state: Vermont
city: Bron
country: France
facility: Chu Toulouse
city: Marseille
country: France
facility: CHU de la Timone - Hopital d Adultes; Service de Neurologie
city: Paris
country: France
facility: Groupe Hospitalier Pitie-Salpetriere
city: Rennes cedex 09
country: France
facility: CHU Rennes - Hopital Pontchaillou
city: Villeurbanne
country: France
facility: Hopital des Charpennes
city: Bia?ystok
country: Poland
facility: Podlaskie Centrum Psychogeriatrii
city: Katowice
country: Poland
facility: Novo-Med Zielinski i wspolnicy Sp. j.
city: Pozna?
country: Poland
facility: NZOZ NEURO-KARD Ilkowski i Partnerzy Sp. Partn. Lek
city: Szczecin
country: Poland
facility: Osrodek Badan Klinicznych Euromedis
city: Warszawa
country: Poland
facility: Centrum Medyczne NeuroProtect
city: Warszawa
country: Poland
facility: Centrum Medyczne AMED
city: Wroc?aw
country: Poland
facility: NZOZ WCA
city: Terrassa
country: Spain
facility: Hospital Mutua de Terrassa
state: Barcelona
city: Barcelona
country: Spain
facility: Fundacio ACE
city: Barcelona
country: Spain
facility: Hospital Clinic I Provincial
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau; Servicio de Neurologia
city: Valencia
country: Spain
facility: Hospital Universitario Doctor Peset
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: