A Study of Semorinemab in Patients With Moderate 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 Moderate Alzheimer's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03828747
• Other study ID #: GN40040
• Status: Completed
• Phase: Phase 2
• Start date: January 25, 2019
• Est. completion date: August 30, 2023

Study information

• Verified date: September 2023
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This Phase II, multicenter, randomized, double-blind, placebo-controlled, parallel-group study will evaluate the clinical efficacy, safety, pharmacokinetics, and pharmacodynamics of semorinemab in patients with moderate AD. The study consists of a screening period, a double-blind treatment period, an optional open-label extension (OLE) period, and a safety follow-up period. There may be up to two study cohorts.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 272
• Est. completion date: August 30, 2023
• Est. primary completion date: July 20, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 85 Years

Eligibility

Inclusion Criteria:

• National Institute on Aging/Alzheimer's Association core clinical criteria for probable AD dementia

• Evidence of the AD pathological process, by a positive amyloid assessment either on CSF Aß1-42 as measured on Elecsys ß-Amyloid(1-42) Test System OR amyloid PET scan

• AD dementia of moderate severity, as defined by a screening MMSE score of 16-21 points, inclusive, and a CDR-GS of 1 or 2

• Availability of a person with sufficient contact with the participant to be able to provide accurate information on the participant's cognitive, behavioral and functional ability

Exclusion Criteria:

• Pregnant or breastfeeding

• Inability to tolerate MRI procedures or contraindication to MRI

• Contraindication to PET imaging

• Residence in a skilled nursing facility

• Any serious medical condition or abnormality in clinical laboratory tests that, 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

• 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, or any passive immunotherapy against tau

• Use of any passive immunotherapy (immunoglobulin) against Aß, unless the last dose was at least 1 year prior to screening or any active immunotherapy (vaccine) that is under evaluation to prevent or postpone cognitive decline

• Any other biologic therapy or previous treatment with medications specifically intended to treat Parkinsonian symptoms or any other non-AD 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): 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 every 2 weeks (Q2W) for the first three doses of the double-blind treatment period and every 4 weeks (Q4W) thereafter during the double-blind treatment period. Semorinemab will be administered Q4W in the OLE period.
• Placebo
Participants will receive placebo every 2 weeks (Q2W) for the first three doses of the double-blind treatment period and every 4 weeks (Q4W) thereafter during the double-blind treatment period.
• [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
France	Chu Toulouse	Bron
France	CHU de la Timone - Hopital d Adultes; Service de Neurologie	Marseille
France	Groupe Hospitalier Pitie-Salpetriere	Paris
France	CHU Rennes - Hopital Pontchaillou	Rennes cedex 09
France	Hopital des Charpennes	Villeurbanne
Poland	Podlaskie Centrum Psychogeriatrii	Bia?ystok
Poland	Novo-Med Zielinski i wspolnicy Sp. j.	Katowice
Poland	NZOZ NEURO-KARD Ilkowski i Partnerzy Sp. Partn. Lek	Pozna?
Poland	Osrodek Badan Klinicznych Euromedis	Szczecin
Poland	Centrum Medyczne AMED	Warszawa
Poland	Centrum Medyczne NeuroProtect	Warszawa
Poland	NZOZ WCA	Wroc?aw
Spain	Fundacio ACE	Barcelona
Spain	Hospital Clinic I Provincial	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau; Servicio de Neurologia	Barcelona
Spain	Hospital Mutua de Terrassa	Terrassa	Barcelona
Spain	Hospital Universitari i Politecnic La Fe	Valencia
Spain	Hospital Universitario Doctor Peset	Valencia
United States	Abington Neurological Associates	Abington	Pennsylvania
United States	JEM Research LLC	Atlantis	Florida
United States	The Memory Clinic	Bennington	Vermont
United States	Brigham and Womens Hospital; Center for Alzheimer Research & Treatment	Boston	Massachusetts
United States	Bradenton Research Center	Bradenton	Florida
United States	Rush University Medical Center - Chicago	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	Collaborative Neuroscience Network, Inc.	Garden Grove	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	Pharmacology Research Institute	Los Alamitos	California
United States	Miami Jewish Health Systems	Miami	Florida
United States	Collier Neurologic Specialists	Naples	Florida
United States	Molecular Neuroimaging; MRI/PET	New Haven	Connecticut
United States	Synexus Clinical Research US, Inc. - Orlando	Orlando	Florida
United States	Stanford University; Stanford Clinical Cancer Ctr	Palo Alto	California
United States	Summit Research Network Inc.	Portland	Oregon
United States	Butler Hospital; Movement Disorders Program	Providence	Rhode Island
United States	Alzheimers Disease Center	Quincy	Massachusetts
United States	University of Rochester; AD-CARE	Rochester	New York
United States	Center for Memory and Aging	Saint Paul	Minnesota
United States	Pacific Research Network - PRN	San Diego	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	Advanced Memory Research Institute of NJ	Toms River	New Jersey
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,  France,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline to Last Visit of Double-Blind Treatment Period in Cognitive Function as Measured by the Alzheimer's Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11)	The Alzheimer's Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11) is an 11 item cognitive subscale used to quantify the areas of cognitive function most often affected in Alzheimer's disease. The total score ranges from 0-70 with lower scores indicating better cognitive function.	Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2
Primary	Change From Baseline to Last Visit of Double-Blind Treatment Period in Functional Capacities as Measured by the Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL)	The Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL) is a scale used to quantify performance of activities of daily living (ADL). Scores on the ADCS-ADL range from 0-78, with higher scores indicating better ADL function.	Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2
Secondary	Change From Baseline to Last Visit of Double-Blind Treatment Period on the Clinical Dementia Rating-Sum of Boxes (CDR-SB)	The Clinical Dementia Rating-Sum of Boxes (CDR-SB) is a scale used to quantify the severity of symptoms of dementia. The CDR-SB is obtained through interviews of patients and informants, and disease severity is rated in 6 domains of functioning: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a 5-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment (personal care is scored on a 4-point scale without a 0.5 rating available). The CDR-SB score is obtained by summing each of the domain box scores, with scores ranging from 0 to 18, with the higher values representing more severe impairment.	Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2
Secondary	Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE)	The Mini Mental State Examination (MMSE) is a brief clinical cognitive examination commonly used to screen for dementia and other cognitive deficits that has a total score of 0-30. Higher scores indicate better cognitive function.	Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2
Secondary	Percentage of Participants With Adverse Events	An Adverse Event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.	Baseline up to Clinical Cut Off Date (CCOD) of July 20, 2021 (approximately 2.5 years)
Secondary	Serum Concentration of RO7105705 at Specified Timepoints		Weeks 1,3,5,9,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,3,5,9,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2.
Secondary	Incidence of Anti-drug Antibodies (ADAs) During the Study Relative to the Prevalence of ADAs at Baseline		Weeks 1,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2.
Secondary	Relationship Between ADA Status and Percentage of Participants With Adverse Events	Descriptive statistics will be used for assessment.	Up to 57 weeks for Cohort 1, and up to 69 weeks for Cohort 2.
Secondary	Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period in Cognitive Function as Measured by the Alzheimer's Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11)	Descriptive statistics will be used for assessment.; A 70-point scale used to quantify the areas of cognitive function most often affected in Alzheimer's disease. Lower scores indicate better cognitive function.	Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2
Secondary	Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period in Functional Capacities as Measured by the Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL)	Descriptive statistics will be used for assessment.; A scale used to quantify performance of activities of daily living. Scores on the ADCS-ADL range from 0-78, with higher scores indicating better ADL function.	Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2
Secondary	Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period on the Clinical Dementia Rating-Sum of Boxes (CDR-SB)	Descriptive statistics will be used for assessment.; A scale used to quantify the severity of symptoms of dementia. The CDR-SB is obtained through interviews of patients and informants, and disease severity is rated in 6 domains of functioning: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a 5-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment (personal care is scored on a 4-point scale without a 0.5 rating available). The CDR-SOB score is obtained by summing each of the domain box scores, with scores ranging from 0 to 18, with the higher values representing more severe impairment.	Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2
Secondary	Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE)	Descriptive statistics will be used for assessment.; The Mini Mental State Examination (MMSE) is a brief clinical cognitive examination commonly used to screen for dementia and other cognitive deficits that has a total score of 0-30. Higher scores indicate better cognitive function.	Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2
Secondary	Relationship Between ADA Status and Serum Concentration of RO7105705 at Specified Timepoints	Descriptive statistics will be used for assessment.	Weeks 1,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2.
Secondary	Relationship Between ADA Status and Incidence of Anti-Drug Antibodies (ADAs) During the Study Relative to the Prevalence of ADAs at Baseline	Descriptive statistics will be used for assessment.	Weeks 1,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2.