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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT03289143
Other study ID # GN39763
Secondary ID 2017-001800-31
Status Terminated
Phase Phase 2
First received
Last updated
Start date October 4, 2017
Est. completion date January 15, 2021

Study information

Verified date February 2022
Source Genentech, Inc.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Terminated
Enrollment 457
Est. completion date January 15, 2021
Est. primary completion date January 15, 2021
Accepts healthy volunteers No
Gender All
Age group 50 Years to 80 Years
Eligibility 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 Aß1-42 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 Aß, 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Semorinemab
Participants will receive Semorinemab intravenously (IV).
Placebo
Matching placebo doses of Semorinemab given intravenously (IV).
[18F]GTP1
[18F]GTP1 will be administered as a solution for intravenous (IV) use, as part of positron emission tomography (PET) imaging.

Locations

Country Name City State
Australia Eastern Clinical Research Unit; Pharmacy Box Hill Victoria
Australia St Vincents Medical Centre Darlinghurst New South Wales
Australia Southern Neurology Kogarah New South Wales
Australia HammondCare Aged Psychiatry Clinical Trials Malvern Victoria
Australia The Alfred Hospital, Melbourne; Thrombosis and Haemostasis Unit Melbourne Victoria
Australia Queensland University of Technology Mermaid Waters Queensland
Australia Neuro Trials Victoria Noble Park Victoria
Australia Royal Melbourne Hospital Parkville Victoria
Belgium UZ Brussel Brussel
Belgium AZ Groeninge Kortrijk
Belgium UZ Leuven Leuven
Belgium AZ Delta Campus Westlaan Roeselare
Canada JBN Medical Diagnostic Services; Clinical Trials Division Burlington Ontario
Canada Recherches Neuro-Hippocame Gatineau Quebec
Canada Parkwood Institute, Mental Health Care Building London Ontario
Canada Elisabeth Bruyere Hospital Ottawa Ontario
Canada Centre for Memory and Aging Toronto Ontario
Canada Toronto Memory Program Toronto Ontario
Canada Toronto Sunnybrook Hospital Toronto Ontario
Canada Toronto Western Hospital Toronto Ontario
Denmark Center For Clinical and Basic Research (Ccbr); Site Management Organisation Aalborg
Denmark CCBR - Vejle - DK Vejle
France Groupe Hospitalier Pellegrin; Service de Neurologie - 3ème étage Bordeaux
France Hopital Neurologique Pierre Wertheimer Bron
France Hopital Roger Salengro Lille
France CHU de la Timone - Hopital d Adultes; Service de Neurologie Marseille
France Hopital Gui de Chauliac; Neurologie Montpellier
France Groupe Hospitalier Pitie-Salpetriere Paris
France Hopital Fernand Widal Centre Paris
France CHU Rennes Rennes
France CHU Hautepierre; ACTR Association Recherche Clinique Rhumatologie Strasbourg
France CHU Strasbourg - Hôpital Hautepierre Strasbourg
France Hopital de La Grave Toulouse
France Hopital des Charpennes Villeurbanne
Germany Klinikum Bayreuth; Krankenhaus Hohe Warte Bayreuth
Germany Charite Campus Benjamin Franklin Berlin
Germany Neurologisch-psychiatrische Praxis am Brosepark Berlin
Germany Praxis Dr. med. Volker Shumann Berlin
Germany Studienambulanz emovis GmbH; St. Joseph Krankenhaus 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 ZNS Siegen im MVZ Weidenau Siegen
Germany Universitätsklinik Tübingen; Psychiatrie und Psychotherapie Tubingen
Germany Universitätsklinikum Ulm; Klinik für Neurologie Ulm
Italy IRCCS Centro San Giovanni di Dio FBF Brescia Lombardia
Italy Azienda Ospedaliero Universitaria San Martino; Dip. di Neuroscienze Oftalmologia e Genetica Genova Liguria
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 Ospedale San Giovanni Calibita Fatebenefratell;Neurologia Roma Lazio
Italy Umberto I Policlinico di Roma-Università di Roma La Sapienza Roma Lazio
Italy Az. Osp. C. Panico; Rep. Ematologia E Trapianto Tricase - LE Puglia
Netherlands Jeroen Bosch Ziekenhuis 'S Hertogenbosch
Netherlands Brain Research Center B.V Amsterdam
Poland Podlaskie Centrum Psychogeriatrii Bialystok
Poland PALLMED Sp. z o.o. prowadzaca NZOZ DOM SUE RYDER Bydgoszcz
Poland M.A. - LEK A.M.Maciejowscy SC. Katowice
Poland Novo-Med Zielinski i wspolnicy Sp. j. Katowice
Poland Malopolskie Centrum Medyczne Krakow
Poland NEURO - KARD Osrodek Badan Klinicznych Poznan
Poland NEURO-CARE Sp. z o.o. Sp. Komandytowa Siemianowice Slaskie
Poland Senior Sp. Z O.O. Poradnia Psychogeriatryczna Sopot
Poland EroMedis Szczecin
Poland AMED Medical Center Warszawa
Poland Centrum Medyczne NeuroProtect Warszawa
Poland NZOZ WCA Wroclaw
Spain Hospital Perpetuo Socorro, Servicio de Geriatria Albacete
Spain Hospital de Cruces; Servicio de Neurologia Barakaldo Vizcaya
Spain Fundación ACE; Servicio de Neurología Barcelona
Spain Hospital Clinic i Provincial de Barcelona Barcelona
Spain Hospital de la Santa Creu i Sant Pau Barcelona
Spain Hospital Universitario Reina Sofia; Servicio de Neurologia Cordoba
Spain Hospital de Cantoblanco; Servicio de Geriatria Madrid
Spain Hospital Universitario Ramon y Cajal Madrid
Spain Clinica Universitaria de Navarra; Servicio de Neurología Pamplona Navarra
Spain Hospital Virgen del Puerto Plasencia Palencia
Spain Policlinica Guipuzcoa San Sebastian Guipuzcoa
Spain Hospital Universitario Virgen Macarena Sevilla
Spain Hospital Mutua de Terrassa Terrassa Barcelona
Spain Hospital Universitari i Politecnic La Fe de Valencia Valencia
Spain Hospital Universitario Dr. Peset; Servicio de Neurologia Valencia
Sweden Länssjukhuset Ryhov Jönköping
Sweden Länssjukhuset Kalmar; Oncology Kalmar
Sweden Skane University Hospital Malmo/Lund, Dept.of Hematology and Coagulation Disorders Malmö
Sweden Sahlgrenska Univ Hospital Mölndal; Department of Nephrology Mölndal
Sweden Karolinska Universitetssjukhuset Huddinge Stockholm
United Kingdom Glasgow Memory Clinic Glasgow
United Kingdom RE:Cognition Health London
United Kingdom The National Hospital for Neurology & Neurosurgery London
United Kingdom Re:Cognition Health Guildford Surrey
United States Abington Neurological Associates Abington Pennsylvania
United States Albany Medical College; Neurology Albany New York
United States Emory University; Global Health Atlanta Georgia
United States JEM Research LLC Atlantis Florida
United States Eastern Maine Medical Center Bangor Maine
United States Clinical Neuroscience Research Associates, Inc. Bennington Vermont
United States University of Alabama at Birmingham Birmingham Alabama
United States Brigham & Women's Hosp; TIMI Study Grp Boston Massachusetts
United States Bradenton Research Center Bradenton Florida
United States Rush Alzheimer's Disease Cntr. Chicago Illinois
United States Neurology Clinic PC Cordova Tennessee
United States Brain Matters Research, Inc. Delray Beach Florida
United States Rhode Island Mood & Memory Research Institute East Providence Rhode Island
United States Alexian Brothers Neuroscience Institute Elk Grove Village Illinois
United States Neuropsychiatric Research; Center of Southwest Florida Fort Myers Florida
United States California Clinical Trials Glendale California
United States University of California Irvine Irvine California
United States New Orleans Center For Clinical Research Knoxville Tennessee
United States Empire Neurology PC; MS Center of Northeastern NY Latham New York
United States Miami Jewish Health Systems Miami Florida
United States NeuroCognitive Institute Mount Arlington New Jersey
United States Collier Neurologic Specialists Naples Florida
United States Invicro, a Konica Minolta company New Haven Connecticut
United States Yale University New Haven Connecticut
United States Columbia Univ Medical Center New York New York
United States Pharmacology Research Inst Newport Beach California
United States Compass Research East, LLC Orlando Florida
United States Stanford Neuroscience Health Center (SNHC) Palo Alto California
United States Summit Research Network Inc. Portland Oregon
United States Butler Hospital Providence Rhode Island
United States Alzheimers Disease Center Quincy Massachusetts
United States University of Rochester; AD-CARE Rochester New York
United States Health Partners Institute for Education and Research Saint Paul Minnesota
United States Pacific Research Network - PRN San Diego California
United States Neurological Research Inst Santa Monica California
United States Southern Illinois University, School of Medicine Springfield Illinois
United States KI Health Partners, LLC; New England Institute for Clinical Research Stamford Connecticut
United States Stedman Clinical Trials, LLC Tampa Florida
United States Advanced Memory Research Institute of NJ Toms River New Jersey
United States Collaborative Neuroscience Network Inc. Torrance California
United States Georgetown University Hospital Washington District of Columbia
United States Alzheimer's Research and Treatment Center Wellington Florida
United States Premiere Research Institute West Palm Beach Florida

Sponsors (1)

Lead Sponsor Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Denmark,  France,  Germany,  Italy,  Netherlands,  Poland,  Spain,  Sweden,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Change From Baseline on the CDR-SB 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. Baseline and 73 Weeks
Primary Percentage of Participants With Adverse Events Percentage of participants with at least one adverse event Up to the data cutoff date 15 January 2021 (up to approximately 39 months)
Primary Change From Baseline on the C-SSRS 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. Baseline to data cutoff date 15 January 2021 (up to approximately 39 months)
Primary Other Abnormal MRI Findings 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. Baseline, Week 9, Week 49, Week 73, Study Treatment Discontinuation, and Week 89
Secondary Change From Baseline on the Repeatable Battery for Assessment of Neuropsychological Status (RBANS) 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. Baseline and 73 weeks
Secondary Change From Baseline on the Alzheimer's Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog-13) Subscale Score 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. Baseline and 73 weeks
Secondary Change From Baseline on the Amsterdam Instrumental Activity of Daily Living (iADL) Questionnaire 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. Baseline and 73 weeks
Secondary Change From Baseline on the Alzheimer's Disease Cooperative Study Group-Activities of Daily Living Inventory 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. Baseline and 73 weeks
Secondary Serum Concentrations of Semorinemab at Specified Timepoints Serum concentrations of Semorinemab at specified timepoints. Up to 109 weeks
Secondary Presence of Anti-drug Antibodies During the Study Relative to Their Presence at Baseline Presence of anti-drug antibodies during the study relative to their presence at baseline. Up to 109 weeks
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