A Study to Evaluate the Efficacy and Safety of Semorinemab in Patients With Prodromal to Mild Alzheimer's Disease
- Conditions
- Alzheimer's Disease
- Interventions
- Registration Number
- NCT03289143
- Lead Sponsor
- Genentech, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 457
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dose 2 Semorinemab [18F]GTP1 - Placebo Placebo - Dose 3 Semorinemab [18F]GTP1 - Dose 1 Semorinemab [18F]GTP1 - Placebo [18F]GTP1 - Dose 1 Semorinemab Semorinemab - Dose 2 Semorinemab Semorinemab - Dose 3 Semorinemab Semorinemab -
- Primary Outcome Measures
Name Time Method Change From Baseline on the CDR-SB Baseline and 73 Weeks The Clinical Dementia Rating-Sum of Boxes (CDR-SB) rates impairment in 6 categories (memory, orientation, judgement and problem solving, community affairs, home and hobbies and personal care) on a 5-point scale in which no impairment = 0, questionable impairment = 0.5 and mild, moderate and severe impairment = 1, 2 and 3 respectively. The score range is from 0 to 18 with a high score indicating a high disease severity. The difference in mean change from Baseline to Week 73 between Semorinemab doses and Placebo treated participants was estimated. The difference in mean change from Baseline to Week 73 between Semorinemab doses and Placebo treated participants was estimated.
Other Abnormal MRI Findings Baseline, Week 9, Week 49, Week 73, Study Treatment Discontinuation, and Week 89 Other abnormal MRI findings by visit. For the Double Blind Period, baseline is defined as last results prior to initiation of study drug. For the Open Label Extension Period, baseline is defined as last results prior to entering the open label period.
Percentage of Participants With Adverse Events Up to the data cutoff date 15 January 2021 (up to approximately 39 months) Percentage of participants with at least one adverse event
Change From Baseline on the C-SSRS Baseline to data cutoff date 15 January 2021 (up to approximately 39 months) Categories are as defined in the Classification Algorithm for Suicide Assessment (CASA) based on the Columbia Suicide Severity Rating Scale (C-SSRS) questionnaire. SI1: Passive category is "Wish to be dead", SI2: Active-Nonspecific (no method, intent or plan), SI3: Active-Method, but no intent or Plan, SI4: Active-Method and intent, but no plan in C-SSRS. The worst post-baseline suicidal ideation is the highest across post-baseline visits, with highest as SI5 and lowest as SI1. Percentages are based on the total number of subjects in a treatment group. Baseline is the last observation prior to initiation of study drug.
- Secondary Outcome Measures
Name Time Method Change From Baseline on the Repeatable Battery for Assessment of Neuropsychological Status (RBANS) Baseline and 73 weeks The RBANS is a validated neuropsychological assessment has been shown to be a useful tool in both clinical and research settings. The RBANS consists of ten subtests that are combined to provide five indices, one for each of the five domains tested (immediate memory, visuospatial/constructional, language, attention, and delayed memory). Scores range from 40 to 160 and a higher score indicates better cognitive functioning. A decrease in the outcome measure from baseline corresponds to disease worsening. The difference in mean change from Baseline to Week 73 between Semorinemab doses and Placebo treated participants was estimated.
Serum Concentrations of Semorinemab at Specified Timepoints Up to 109 weeks Serum concentrations of Semorinemab at specified timepoints.
Change From Baseline on the Alzheimer's Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog-13) Subscale Score Baseline and 73 weeks The ADAS-Cog-13 assesses multiple cognitive domains including memory, comprehension, praxis, orientation, and spontaneous speech. Most of these are assessed by tests although some are rated by the clinician on a 5-point scale. The ADAS-Cog-13 is the ADAS-Cog-11 with 2 further items: delayed word recall and total digit cancellation. The score range for ADAS-Cog-13 is from 0 to 85 with high scores representing severe dysfunction. The difference in mean change from Baseline to Week 73 between Semorinemab doses and Placebo treated participants was estimated.
Change From Baseline on the Amsterdam Instrumental Activity of Daily Living (iADL) Questionnaire Baseline and 73 weeks The Amsterdam iADL questionnaire is an informant-based instrument for measuring iADL problems in participants with dementia. This instrument consists of 70 items, scored on a 5-point scale, that uses item response theory for scoring. Items presented to the informant are tailored to responses to earlier items; thus each administration of the Amsterdam iADL may consist of less than the total of 70 items. The resulting score ranges from 20 to 80 with lower scores indicating poorer performance. A decrease in the outcome measure from baseline corresponds to disease worsening. The difference in mean change from Baseline to Week 73 between Semorinemab doses and Placebo treated participants was estimated.
Change From Baseline on the Alzheimer's Disease Cooperative Study Group-Activities of Daily Living Inventory Baseline and 73 weeks The ADCS-ADL (Alzheimer's Disease Cooperative Study-Activities of Daily Living) is the scale most widely used to assess functional outcomes in participants with AD. The ADCS-ADL covers both basic ADL (e.g., eating and toileting) and more complex 'instrumental' ADL or iADL (e.g., using the telephone, managing finances and preparing a meal). The ADCS-ADL consists of 23 questions with a score range of 0 to 78 where a higher score represents better function. The difference in mean change from Baseline to Week 73 between Semorinemab doses and Placebo treated participants was estimated.
Presence of Anti-drug Antibodies During the Study Relative to Their Presence at Baseline Up to 109 weeks Presence of anti-drug antibodies during the study relative to their presence at baseline.
Trial Locations
- Locations (133)
M.A. - LEK A.M.Maciejowscy SC.
🇵🇱Katowice, Poland
Novo-Med Zielinski i wspolnicy Sp. j.
🇵🇱Katowice, Poland
AMED Medical Center
🇵🇱Warszawa, Poland
Länssjukhuset Kalmar; Oncology
🇸🇪Kalmar, Sweden
Skane University Hospital Malmo/Lund, Dept.of Hematology and Coagulation Disorders
🇸🇪Malmö, Sweden
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
NEURO-CARE Sp. z o.o. Sp. Komandytowa
🇵🇱Siemianowice Śląskie, Poland
EroMedis
🇵🇱Szczecin, Poland
Hospital de Cantoblanco; Servicio de Geriatria
🇪🇸Madrid, Spain
Hospital Universitario Dr. Peset; Servicio de Neurologia
🇪🇸Valencia, Spain
Fundación ACE; Servicio de NeurologÃa
🇪🇸Barcelona, Spain
NEURO - KARD Ośrodek Badań Klinicznych
🇵🇱Poznań, Poland
Hospital Virgen del Puerto
🇪🇸Plasencia, Palencia, Spain
Länssjukhuset Ryhov
🇸🇪Jönköping, Sweden
RE:Cognition Health
🇬🇧London, United Kingdom
Hospital Perpetuo Socorro, Servicio de Geriatria
🇪🇸Albacete, Spain
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Glasgow Memory Clinic
🇬🇧Glasgow, United Kingdom
Hospital Universitario Reina Sofia; Servicio de Neurologia
🇪🇸Cordoba, Spain
Sahlgrenska Univ Hospital Mölndal; Department of Nephrology
🇸🇪Mölndal, Sweden
Re:Cognition Health Guildford
🇬🇧Surrey, United Kingdom
Policlinica Guipuzcoa
🇪🇸San Sebastian, Guipuzcoa, Spain
Hospital de Cruces; Servicio de Neurologia
🇪🇸Barakaldo, Vizcaya, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Karolinska Universitetssjukhuset Huddinge
🇸🇪Stockholm, Sweden
Hospital Clinic i Provincial de Barcelona
🇪🇸Barcelona, Spain
Hospital Mutua de Terrassa
🇪🇸Terrassa, Barcelona, Spain
Hospital Universitari i Politecnic La Fe de Valencia
🇪🇸Valencia, Spain
The National Hospital for Neurology & Neurosurgery
🇬🇧London, United Kingdom
Clinica Universitaria de Navarra; Servicio de NeurologÃa
🇪🇸Pamplona, Navarra, Spain
Senior Sp. Z O.O. Poradnia Psychogeriatryczna
🇵🇱Sopot, Poland
Centrum Medyczne NeuroProtect
🇵🇱Warszawa, Poland
Center For Clinical and Basic Research (Ccbr); Site Management Organisation
🇩🇰Aalborg, Denmark
CCBR - Vejle - DK
🇩🇰Vejle, Denmark
Parkwood Institute, Mental Health Care Building
🇨🇦London, Ontario, Canada
Elisabeth Bruyere Hospital
🇨🇦Ottawa, Ontario, Canada
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
California Clinical Trials
🇺🇸Glendale, California, United States
University of California Irvine
🇺🇸Irvine, California, United States
Pharmacology Research Inst
🇺🇸Newport Beach, California, United States
Stanford Neuroscience Health Center (SNHC)
🇺🇸Palo Alto, California, United States
Pacific Research Network - PRN
🇺🇸San Diego, California, United States
Neurological Research Inst
🇺🇸Santa Monica, California, United States
Collaborative Neuroscience Network Inc.
🇺🇸Torrance, California, United States
KI Health Partners, LLC; New England Institute for Clinical Research
🇺🇸Stamford, Connecticut, United States
Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
Bradenton Research Center
🇺🇸Bradenton, Florida, United States
Brain Matters Research, Inc.
🇺🇸Delray Beach, Florida, United States
Neuropsychiatric Research; Center of Southwest Florida
🇺🇸Fort Myers, Florida, United States
Miami Jewish Health Systems
🇺🇸Miami, Florida, United States
Premiere Research Institute
🇺🇸West Palm Beach, Florida, United States
Alzheimer's Research and Treatment Center
🇺🇸Wellington, Florida, United States
Emory University; Global Health
🇺🇸Atlanta, Georgia, United States
Rush Alzheimer's Disease Cntr.
🇺🇸Chicago, Illinois, United States
Alexian Brothers Neuroscience Institute
🇺🇸Elk Grove Village, Illinois, United States
Southern Illinois University, School of Medicine
🇺🇸Springfield, Illinois, United States
Brigham & Women's Hosp; TIMI Study Grp
🇺🇸Boston, Massachusetts, United States
NeuroCognitive Institute
🇺🇸Mount Arlington, New Jersey, United States
Eastern Maine Medical Center
🇺🇸Bangor, Maine, United States
Alzheimers Disease Center
🇺🇸Quincy, Massachusetts, United States
Health Partners Institute for Education and Research
🇺🇸Saint Paul, Minnesota, United States
Albany Medical College; Neurology
🇺🇸Albany, New York, United States
Empire Neurology PC; MS Center of Northeastern NY
🇺🇸Latham, New York, United States
Columbia Univ Medical Center
🇺🇸New York, New York, United States
University of Rochester; AD-CARE
🇺🇸Rochester, New York, United States
Abington Neurological Associates
🇺🇸Abington, Pennsylvania, United States
Rhode Island Mood & Memory Research Institute
🇺🇸East Providence, Rhode Island, United States
Butler Hospital
🇺🇸Providence, Rhode Island, United States
Neurology Clinic PC
🇺🇸Cordova, Tennessee, United States
New Orleans Center For Clinical Research
🇺🇸Knoxville, Tennessee, United States
St Vincents Medical Centre
🇦🇺Darlinghurst, New South Wales, Australia
Clinical Neuroscience Research Associates, Inc.
🇺🇸Bennington, Vermont, United States
Southern Neurology
🇦🇺Kogarah, New South Wales, Australia
Queensland University of Technology
🇦🇺Mermaid Waters, Queensland, Australia
Eastern Clinical Research Unit; Pharmacy
🇦🇺Box Hill, Victoria, Australia
HammondCare Aged Psychiatry Clinical Trials
🇦🇺Malvern, Victoria, Australia
The Alfred Hospital, Melbourne; Thrombosis and Haemostasis Unit
🇦🇺Melbourne, Victoria, Australia
Neuro Trials Victoria
🇦🇺Noble Park, Victoria, Australia
UZ Brussel
🇧🇪Brussel, Belgium
AZ Groeninge
🇧🇪Kortrijk, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
JBN Medical Diagnostic Services; Clinical Trials Division
🇨🇦Burlington, Ontario, Canada
Centre for Memory and Aging
🇨🇦Toronto, Ontario, Canada
Toronto Sunnybrook Hospital
🇨🇦Toronto, Ontario, Canada
Recherches Neuro-Hippocame
🇨🇦Gatineau, Quebec, Canada
Hopital Neurologique Pierre Wertheimer
🇫🇷Bron, France
CHU de la Timone - Hopital d Adultes; Service de Neurologie
🇫🇷Marseille, France
Hopital Roger Salengro
🇫🇷Lille, France
Hopital Fernand Widal Centre
🇫🇷Paris, France
Groupe Hospitalier Pitie-Salpetriere
🇫🇷Paris, France
CHU Rennes
🇫🇷Rennes, France
CHU Hautepierre; ACTR Association Recherche Clinique Rhumatologie
🇫🇷Strasbourg, France
Hopital de La Grave
🇫🇷Toulouse, France
Hopital des Charpennes
🇫🇷Villeurbanne, France
Klinikum Bayreuth; Krankenhaus Hohe Warte
🇩🇪Bayreuth, Germany
Praxis Dr. med. Volker Shumann
🇩🇪Berlin, Germany
Studienambulanz emovis GmbH; St. Joseph Krankenhaus
🇩🇪Berlin, Germany
Charite Campus Benjamin Franklin
🇩🇪Berlin, Germany
Neurologisch-psychiatrische Praxis am Brosepark
🇩🇪Berlin, Germany
Bezirkskrankenhaus Günzburg
🇩🇪Günzburg, Germany
Klinische Forschung Hannover-Mitte GmbH
🇩🇪Hannover, Germany
Klinikum rechts der Isar der TU München; Klinik & Poliklinik für Neurologie
🇩🇪München, Germany
Universitätsklinik Tübingen; Psychiatrie und Psychotherapie
🇩🇪Tubingen, Germany
Umberto I Policlinico di Roma-Università di Roma La Sapienza
🇮🇹Roma, Lazio, Italy
Ospedale San Giovanni Calibita Fatebenefratell;Neurologia
🇮🇹Roma, Lazio, Italy
Azienda Ospedaliero Universitaria San Martino; Dip. di Neuroscienze Oftalmologia e Genetica
🇮🇹Genova, Liguria, Italy
IRCCS Centro San Giovanni di Dio FBF
🇮🇹Brescia, Lombardia, Italy
Fondazione IRCCS Istituto Neurologico Carlo Besta
🇮🇹Milano, Lombardia, Italy
IRCCS Neuromed; Neurologia I-Centro studio e cura delle demenze e UVA
🇮🇹Pozzilli, Molise, Italy
Az. Osp. C. Panico; Rep. Ematologia E Trapianto
🇮🇹Tricase - LE, Puglia, Italy
Jeroen Bosch Ziekenhuis
🇳🇱'S Hertogenbosch, Netherlands
Brain Research Center B.V
🇳🇱Amsterdam, Netherlands
Podlaskie Centrum Psychogeriatrii
🇵🇱Białystok, Poland
Groupe Hospitalier Pellegrin; Service de Neurologie - 3ème étage
🇫🇷Bordeaux, France
Hopital Gui de Chauliac; Neurologie
🇫🇷Montpellier, France
CHU Strasbourg - Hôpital Hautepierre
🇫🇷Strasbourg, France
Toronto Memory Program
🇨🇦Toronto, Ontario, Canada
Toronto Western Hospital
🇨🇦Toronto, Ontario, Canada
ZNS Siegen im MVZ Weidenau
🇩🇪Siegen, Germany
Universitätsklinikum Ulm; Klinik für Neurologie
🇩🇪Ulm, Germany
JEM Research LLC
🇺🇸Atlantis, Florida, United States
PALLMED Sp. z o.o. prowadzÄ…ca NZOZ DOM SUE RYDER
🇵🇱Bydgoszcz, Poland
NZOZ WCA
🇵🇱Wrocław, Poland
Advanced Memory Research Institute of NJ
🇺🇸Toms River, New Jersey, United States
Malopolskie Centrum Medyczne
🇵🇱Krakow, Poland
Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia
AZ Delta Campus Westlaan
🇧🇪Roeselare, Belgium
Compass Research East, LLC
🇺🇸Orlando, Florida, United States
Invicro, a Konica Minolta company
🇺🇸New Haven, Connecticut, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Stedman Clinical Trials, LLC
🇺🇸Tampa, Florida, United States
Summit Research Network Inc.
🇺🇸Portland, Oregon, United States
Collier Neurologic Specialists
🇺🇸Naples, Florida, United States