A Study to Evaluate the Efficacy and Safety of Semorinemab in Patients With Prodromal to Mild Alzheimer's Disease

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03289143
• Other study ID #: GN39763
• Secondary ID: 2017-001800-31
• Status: Terminated
• Phase: Phase 2
• 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
• 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

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

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