Alzheimer's Disease Clinical Trial
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
Verified date | February 2022 |
Source | Genentech, Inc. |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
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 |
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 |
Lead Sponsor | Collaborator |
---|---|
Genentech, Inc. |
United States, Australia, Belgium, Canada, Denmark, France, Germany, Italy, Netherlands, Poland, Spain, Sweden, United Kingdom,
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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