Clinical trial NCT03289143: A Study to Evaluate the Efficacy and Safety of Semorinemab in Patients With Prodromal to Mild 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 Prodromal to Mild Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Alzheimer's Disease
Keywords: Alzheimer Disease
Brain Diseases
Dementia
Neurodegenerative Diseases
Neurocognitive Disorders
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2017-09-20
Enrollment: 457
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This was a phase II, randomized, placebo-controlled, double-blind study to evaluate the efficacy and safety of Semorinemab in participants with prodromal to mild Alzheimer's disease. An optional 96-week open-label extension period was available to participants who completed the double-blind treatment period and who, in the judgment of the investigator, would potentially benefit from open-label Semorinemab treatment.


Eligibility criteria: Inclusion criteria

* Age between 50 and 80 years
* National Institute on Aging/Alzheimer's Association core clinical criteria for probable Alzheimer's disease (AD) dementia or mild cognitive impairment (prodromal AD)
* Evidence of the AD pathological process, by a positive amyloid assessment either on cerebrospinal fluid Aβ1-42 OR amyloid positron emission tomography (PET) scan. Historical amyloid PET scans may be accepted in some cases
* Mild AD symptomatology, as defined by a screening Mini-Mental State Examination score of \>= 20 points and Clinical Dementia Rating (CDR) -Global Score of 0.5 or 1
* Abnormal memory function at screening
* Availability of a person with sufficient contact with the participant to be able to provide accurate information on the participant's cognitive and functional ability

Exclusion criteria

* Pregnant or breastfeeding
* Inability to tolerate magnetic resonance imaging (MRI) procedures or contraindication to MRI
* Contraindications to both PET imaging and lumbar dural puncture (must be able to undergo at least one of these procedures to be eligible)
* Residence in a skilled nursing facility
* Any serious medical condition or abnormality in clinical laboratory tests that remains abnormal on retest and, 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
* Alcohol or 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 and any passive immunotherapy (immunoglobulin) against tau, except use of RO7105705 in Genentech Study GN39058, as long as the last dose was at least 90 days prior to screening
* Use of any passive immunotherapy (immunoglobulin) against Aβ, unless the last dose was at least 1 year prior to screening and any active immunotherapy (vaccine) that is under evaluation to prevent or postpone cognitive decline
* Any previous treatment with medications specifically intended to treat Parkinsonian symptoms or any other 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, which is permitted except within 2 days or 5 half-lives (whichever is longer) prior to any COA: atypical antipsychotics, 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 on the CDR-SB
timeFrame: Baseline and 73 Weeks
measure: Percentage of Participants With Adverse Events
timeFrame: Up to the data cutoff date 15 January 2021 (up to approximately 39 months)
measure: Change From Baseline on the C-SSRS
timeFrame: Baseline to data cutoff date 15 January 2021 (up to approximately 39 months)
measure: Other Abnormal MRI Findings
timeFrame: Baseline, Week 9, Week 49, Week 73, Study Treatment Discontinuation, and Week 89
Secondary outcomes:
measure: Change From Baseline on the Repeatable Battery for Assessment of Neuropsychological Status (RBANS)
timeFrame: Baseline and 73 weeks
measure: Change From Baseline on the Alzheimer's Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog-13) Subscale Score
timeFrame: Baseline and 73 weeks
measure: Change From Baseline on the Amsterdam Instrumental Activity of Daily Living (iADL) Questionnaire
timeFrame: Baseline and 73 weeks
measure: Change From Baseline on the Alzheimer's Disease Cooperative Study Group-Activities of Daily Living Inventory
timeFrame: Baseline and 73 weeks
measure: Serum Concentrations of Semorinemab at Specified Timepoints
timeFrame: Up to 109 weeks
measure: Presence of Anti-drug Antibodies During the Study Relative to Their Presence at Baseline
timeFrame: Up to 109 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Glendale
country: United States
facility: California Clinical Trials
state: California
city: Irvine
country: United States
facility: University of California Irvine
state: California
city: Newport Beach
country: United States
facility: Pharmacology Research Inst
state: California
city: Palo Alto
country: United States
facility: Stanford Neuroscience Health Center (SNHC)
state: California
city: San Diego
country: United States
facility: Pacific Research Network - PRN
state: California
city: Santa Monica
country: United States
facility: Neurological Research Inst
state: California
city: Torrance
country: United States
facility: Collaborative Neuroscience Network Inc.
state: California
city: New Haven
country: United States
facility: Invicro, a Konica Minolta company
state: Connecticut
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Stamford
country: United States
facility: KI Health Partners, LLC; New England Institute for Clinical Research
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Hospital
state: District of Columbia
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: Compass Research East, LLC
state: Florida
city: Tampa
country: United States
facility: Stedman Clinical Trials, LLC
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: Atlanta
country: United States
facility: Emory University; Global Health
state: Georgia
city: Chicago
country: United States
facility: Rush Alzheimer's Disease Cntr.
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: Bangor
country: United States
facility: Eastern Maine Medical Center
state: Maine
city: Boston
country: United States
facility: Brigham & Women's Hosp; TIMI Study Grp
state: Massachusetts
city: Quincy
country: United States
facility: Alzheimers Disease Center
state: Massachusetts
city: Saint Paul
country: United States
facility: Health Partners Institute for Education and Research
state: Minnesota
city: Mount Arlington
country: United States
facility: NeuroCognitive Institute
state: New Jersey
city: Toms River
country: United States
facility: Advanced Memory Research Institute of NJ
state: New Jersey
city: Albany
country: United States
facility: Albany Medical College; Neurology
state: New York
city: Latham
country: United States
facility: Empire Neurology PC; MS Center of Northeastern NY
state: New York
city: New York
country: United States
facility: Columbia Univ Medical Center
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
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: Clinical Neuroscience Research Associates, Inc.
state: Vermont
city: Darlinghurst
country: Australia
facility: St Vincents Medical Centre
state: New South Wales
city: Kogarah
country: Australia
facility: Southern Neurology
state: New South Wales
city: Mermaid Waters
country: Australia
facility: Queensland University of Technology
state: Queensland
city: Box Hill
country: Australia
facility: Eastern Clinical Research Unit; Pharmacy
state: Victoria
city: Malvern
country: Australia
facility: HammondCare Aged Psychiatry Clinical Trials
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital, Melbourne; Thrombosis and Haemostasis Unit
state: Victoria
city: Noble Park
country: Australia
facility: Neuro Trials Victoria
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Brussel
country: Belgium
facility: UZ Brussel
city: Kortrijk
country: Belgium
facility: AZ Groeninge
city: Leuven
country: Belgium
facility: UZ Leuven
city: Roeselare
country: Belgium
facility: AZ Delta Campus Westlaan
city: Burlington
country: Canada
facility: JBN Medical Diagnostic Services; Clinical Trials Division
state: Ontario
city: London
country: Canada
facility: Parkwood Institute, Mental Health Care Building
state: Ontario
city: Ottawa
country: Canada
facility: Elisabeth Bruyere Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto Memory Program
state: Ontario
city: Toronto
country: Canada
facility: Centre for Memory and Aging
state: Ontario
city: Toronto
country: Canada
facility: Toronto Sunnybrook Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto Western Hospital
state: Ontario
city: Gatineau
country: Canada
facility: Recherches Neuro-Hippocame
state: Quebec
city: Aalborg
country: Denmark
facility: Center For Clinical and Basic Research (Ccbr); Site Management Organisation
city: Vejle
country: Denmark
facility: CCBR - Vejle - DK
city: Bordeaux
country: France
facility: Groupe Hospitalier Pellegrin; Service de Neurologie - 3ème étage
city: Bron
country: France
facility: Hopital Neurologique Pierre Wertheimer
city: Lille
country: France
facility: Hopital Roger Salengro
city: Marseille
country: France
facility: CHU de la Timone - Hopital d Adultes; Service de Neurologie
city: Montpellier
country: France
facility: Hopital Gui de Chauliac; Neurologie
city: Paris
country: France
facility: Hopital Fernand Widal Centre
city: Paris
country: France
facility: Groupe Hospitalier Pitie-Salpetriere
city: Rennes
country: France
facility: CHU Rennes
city: Strasbourg
country: France
facility: CHU Hautepierre; ACTR Association Recherche Clinique Rhumatologie
city: Strasbourg
country: France
facility: CHU Strasbourg - Hôpital Hautepierre
city: Toulouse
country: France
facility: Hopital de La Grave
city: Villeurbanne
country: France
facility: Hopital des Charpennes
city: Bayreuth
country: Germany
facility: Klinikum Bayreuth; Krankenhaus Hohe Warte
city: Berlin
country: Germany
facility: Praxis Dr. med. Volker Shumann
city: Berlin
country: Germany
facility: Studienambulanz emovis GmbH; St. Joseph Krankenhaus
city: Berlin
country: Germany
facility: Charite Campus Benjamin Franklin
city: Berlin
country: Germany
facility: Neurologisch-psychiatrische Praxis am Brosepark
city: Günzburg
country: Germany
facility: Bezirkskrankenhaus Günzburg
city: Hannover
country: Germany
facility: Klinische Forschung Hannover-Mitte GmbH
city: München
country: Germany
facility: Klinikum rechts der Isar der TU München; Klinik & Poliklinik für Neurologie
city: Siegen
country: Germany
facility: ZNS Siegen im MVZ Weidenau
city: Tubingen
country: Germany
facility: Universitätsklinik Tübingen; Psychiatrie und Psychotherapie
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm; Klinik für Neurologie
city: Roma
country: Italy
facility: Umberto I Policlinico di Roma-Università di Roma La Sapienza
state: Lazio
city: Roma
country: Italy
facility: Ospedale San Giovanni Calibita Fatebenefratell;Neurologia
state: Lazio
city: Genova
country: Italy
facility: Azienda Ospedaliero Universitaria San Martino; Dip. di Neuroscienze Oftalmologia e Genetica
state: Liguria
city: Brescia
country: Italy
facility: IRCCS Centro San Giovanni di Dio FBF
state: Lombardia
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Neurologico Carlo Besta
state: Lombardia
city: Pozzilli
country: Italy
facility: IRCCS Neuromed; Neurologia I-Centro studio e cura delle demenze e UVA
state: Molise
city: Tricase - LE
country: Italy
facility: Az. Osp. C. Panico; Rep. Ematologia E Trapianto
state: Puglia
city: 'S Hertogenbosch
country: Netherlands
facility: Jeroen Bosch Ziekenhuis
city: Amsterdam
country: Netherlands
facility: Brain Research Center B.V
city: Białystok
country: Poland
facility: Podlaskie Centrum Psychogeriatrii
city: Bydgoszcz
country: Poland
facility: PALLMED Sp. z o.o. prowadząca NZOZ DOM SUE RYDER
city: Katowice
country: Poland
facility: M.A. - LEK A.M.Maciejowscy SC.
city: Katowice
country: Poland
facility: Novo-Med Zielinski i wspolnicy Sp. j.
city: Krakow
country: Poland
facility: Malopolskie Centrum Medyczne
city: Poznań
country: Poland
facility: NEURO - KARD Ośrodek Badań Klinicznych
city: Siemianowice Śląskie
country: Poland
facility: NEURO-CARE Sp. z o.o. Sp. Komandytowa
city: Sopot
country: Poland
facility: Senior Sp. Z O.O. Poradnia Psychogeriatryczna
city: Szczecin
country: Poland
facility: EroMedis
city: Warszawa
country: Poland
facility: AMED Medical Center
city: Warszawa
country: Poland
facility: Centrum Medyczne NeuroProtect
city: Wrocław
country: Poland
facility: NZOZ WCA
city: Terrassa
country: Spain
facility: Hospital Mutua de Terrassa
state: Barcelona
city: San Sebastian
country: Spain
facility: Policlinica Guipuzcoa
state: Guipuzcoa
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra; Servicio de Neurología
state: Navarra
city: Plasencia
country: Spain
facility: Hospital Virgen del Puerto
state: Palencia
city: Barakaldo
country: Spain
facility: Hospital de Cruces; Servicio de Neurologia
state: Vizcaya
city: Albacete
country: Spain
facility: Hospital Perpetuo Socorro, Servicio de Geriatria
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Fundación ACE; Servicio de Neurología
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia; Servicio de Neurologia
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital de Cantoblanco; Servicio de Geriatria
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Valencia
country: Spain
facility: Hospital Universitario Dr. Peset; Servicio de Neurologia
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
city: Jönköping
country: Sweden
facility: Länssjukhuset Ryhov
city: Kalmar
country: Sweden
facility: Länssjukhuset Kalmar; Oncology
city: Malmö
country: Sweden
facility: Skane University Hospital Malmo/Lund, Dept.of Hematology and Coagulation Disorders
city: Mölndal
country: Sweden
facility: Sahlgrenska Univ Hospital Mölndal; Department of Nephrology
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset Huddinge
city: Glasgow
country: United Kingdom
facility: Glasgow Memory Clinic
city: London
country: United Kingdom
facility: RE:Cognition Health
city: London
country: United Kingdom
facility: The National Hospital for Neurology & Neurosurgery
city: Surrey
country: United Kingdom
facility: Re:Cognition Health Guildford
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Teng E, Manser PT, Pickthorn K, Brunstein F, Blendstrup M, Sanabria Bohorquez S, Wildsmith KR, Toth B, Dolton M, Ramakrishnan V, Bobbala A, Sikkes SAM, Ward M, Fuji RN, Kerchner GA; Tauriel Investigators. Safety and Efficacy of Semorinemab in Individuals With Prodromal to Mild Alzheimer Disease: A Randomized Clinical Trial. JAMA Neurol. 2022 Aug 1;79(8):758-767. doi: 10.1001/jamaneurol.2022.1375.