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

Sponsor
Genentech, Inc. (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03828747
Collaborator
(none)
272
Enrollment
49
Locations
2
Arms
54.7
Anticipated Duration (Months)
5.6
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
272 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jan 30, 2019
Actual Primary Completion Date :
Jul 20, 2021
Anticipated Study Completion Date :
Aug 23, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Semorinemab

Semorinemab will be administered intravenously in the double-blind treatment period, and semorinemab will be administered intravenously in the optional open-label extension period.

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.
Other Names:
  • MTAU9937A
  • RO7105705

    • Drug: [18F]GTP1
    [18F]GTP1 will be administered as a solution for intravenous (IV) use, as part of positron emission tomography (PET) imaging.
    Placebo Comparator: Placebo

    Placebo will be administered intravenously in the double-blind treatment period.

    Drug: 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.

    Drug: [18F]GTP1
    [18F]GTP1 will be administered as a solution for intravenous (IV) use, as part of positron emission tomography (PET) imaging.

    Outcome Measures

    Primary Outcome Measures

    1. 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) [Baseline to Week 49 for Cohort 1, and Baseline to Week 61 for Cohort 2]

      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.

    2. 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) [Baseline to Week 49 for Cohort 1, and Baseline to Week 61 for Cohort 2]

      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.

    Secondary Outcome Measures

    1. Change From Baseline to Last Visit of Double-Blind Treatment Period on the Clinical Dementia Rating-Sum of Boxes (CDR-SB) [Baseline to Week 49 for Cohort 1, and Baseline to Week 61 for Cohort 2]

      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.

    2. Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE) [Baseline to Week 49 for Cohort 1, and Baseline to Week 61 for Cohort 2]

      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.

    3. Percentage of Participants with Adverse Events [Up to 57 weeks for Cohort 1, and up to 69 weeks for Cohort 2.]

    4. 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.]

    5. 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.]

    6. Relationship between ADA Status and Percentage of Participants with Adverse Events [Up to 57 weeks for Cohort 1, and up to 69 weeks for Cohort 2.]

      Descriptive statistics will be used for assessment.

    7. 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) [Baseline to Week 49 for Cohort 1, and Baseline to Week 61 for Cohort 2]

      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.

    8. 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) [Baseline to Week 49 for Cohort 1, and Baseline to Week 61 for Cohort 2]

      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.

    9. 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) [Baseline to Week 49 for Cohort 1, and Baseline to Week 61 for Cohort 2]

      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.

    10. Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE) [Baseline to Week 49 for Cohort 1, and Baseline to Week 61 for Cohort 2]

      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.

    11. Relationship Between ADA Status and Serum Concentration of RO7105705 at Specified Timepoints [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.]

      Descriptive statistics will be used for assessment.

    12. Relationship Between ADA Status and 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.]

      Descriptive statistics will be used for assessment.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    50 Years to 85 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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 Aβ1-42 as measured on Elecsys β-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 Aβ, 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Collaborative Neuroscience Network, Inc. Garden Grove California United States 92845
    2 Pharmacology Research Institute Los Alamitos California United States 90720
    3 Stanford University; Stanford Clinical Cancer Ctr Palo Alto California United States 94305
    4 Pacific Research Network - PRN San Diego California United States 92103
    5 Molecular Neuroimaging; MRI/PET New Haven Connecticut United States 06510
    6 KI Health Partners, LLC; New England Institute for Clinical Research Stamford Connecticut United States 06905
    7 JEM Research LLC Atlantis Florida United States 33462
    8 Bradenton Research Center Bradenton Florida United States 34205
    9 Brain Matters Research, Inc. Delray Beach Florida United States 33445
    10 Neuropsychiatric Research; Center of Southwest Florida Fort Myers Florida United States 33912
    11 Miami Jewish Health Systems Miami Florida United States 33137
    12 Collier Neurologic Specialists Naples Florida United States 34105
    13 Synexus Clinical Research US, Inc. - Orlando Orlando Florida United States 32806
    14 Alzheimer's Research and Treatment Center Wellington Florida United States 33414
    15 Premiere Research Institute West Palm Beach Florida United States 33407
    16 Rush University Medical Center - Chicago Chicago Illinois United States 60612
    17 Alexian Brothers Neuroscience Institute Elk Grove Village Illinois United States 60007
    18 Southern Illinois University, School of Medicine Springfield Illinois United States 62702
    19 Brigham and Womens Hospital; Center for Alzheimer Research & Treatment Boston Massachusetts United States 02115
    20 Alzheimers Disease Center Quincy Massachusetts United States 02169
    21 Center for Memory and Aging Saint Paul Minnesota United States 55130
    22 Advanced Memory Research Institute of NJ Toms River New Jersey United States 08755
    23 Empire Neurology PC; MS Center of Northeastern NY Latham New York United States 12110
    24 University of Rochester; AD-CARE Rochester New York United States 14642
    25 Summit Research Network Inc. Portland Oregon United States 97210
    26 Abington Neurological Associates Abington Pennsylvania United States 19001
    27 Rhode Island Mood & Memory Research Institute East Providence Rhode Island United States 02914
    28 Butler Hospital; Movement Disorders Program Providence Rhode Island United States 02906
    29 Neurology Clinic PC Cordova Tennessee United States 38018
    30 New Orleans Center for Clinical Research Knoxville Tennessee United States 37920
    31 The Memory Clinic Bennington Vermont United States 05201
    32 Chu Toulouse Bron France 69500
    33 CHU de la Timone - Hopital d Adultes; Service de Neurologie Marseille France 13005
    34 Groupe Hospitalier Pitie-Salpetriere Paris France 75651
    35 CHU Rennes - Hopital Pontchaillou Rennes cedex 09 France 35033
    36 Hopital des Charpennes Villeurbanne France 69100
    37 Podlaskie Centrum Psychogeriatrii Białystok Poland 15-756
    38 Novo-Med Zielinski i wspolnicy Sp. j. Katowice Poland 40-650
    39 NZOZ NEURO-KARD Ilkowski i Partnerzy Sp. Partn. Lek Poznań Poland 61-853
    40 Osrodek Badan Klinicznych Euromedis Szczecin Poland 70-111
    41 Centrum Medyczne NeuroProtect Warszawa Poland 01-684
    42 Centrum Medyczne AMED Warszawa Poland 03-291
    43 NZOZ WCA Wrocław Poland 53-659
    44 Hospital Mutua de Terrassa Terrassa Barcelona Spain 08221
    45 Fundacio ACE Barcelona Spain 08028
    46 Hospital Clinic I Provincial Barcelona Spain 08036
    47 Hospital de la Santa Creu i Sant Pau; Servicio de Neurologia Barcelona Spain 08041
    48 Hospital Universitario Doctor Peset Valencia Spain 46017
    49 Hospital Universitari i Politecnic La Fe Valencia Spain 46026

    Sponsors and Collaborators

    • Genentech, Inc.

    Investigators

    • Study Director: Clinical Trials, Hoffmann-La Roche

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Genentech, Inc.
    ClinicalTrials.gov Identifier:
    NCT03828747
    Other Study ID Numbers:
    • GN40040
    First Posted:
    Feb 4, 2019
    Last Update Posted:
    Mar 15, 2022
    Last Verified:
    Feb 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Alzheimer Disease

    Study Results

    No Results Posted as of Mar 15, 2022