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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03289143
Recruitment Status : Terminated (Study was terminated during Open Label Extension period because analyses of placebo-controlled Blinded portion of study did not show any evidence of clinical efficacy or modulation of accumulation of tau PET signal at any of the doses studied.)
First Posted : September 20, 2017
Results First Posted : March 16, 2022
Last Update Posted : March 16, 2022
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Brief 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.

Condition or disease Intervention/treatment Phase
Alzheimer's Disease Drug: Semorinemab Drug: Placebo Drug: [18F]GTP1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 457 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description: Additional blinded personnel will include study site personnel who will evaluate participant status, contract research organization (CRO) personnel who will review case report forms (CRFs), and other sponsor agents (with the exception of the interactive voice or web-based response system [IxRS] vendor).
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 Prodromal to Mild Alzheimer's Disease
Actual Study Start Date : October 4, 2017
Actual Primary Completion Date : January 15, 2021
Actual Study Completion Date : January 15, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Dose 1 Semorinemab Drug: Semorinemab
Participants will receive Semorinemab intravenously (IV).
Other Names:
  • RG6100
  • 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.
Other Name: RO6880276

Experimental: Dose 2 Semorinemab Drug: Semorinemab
Participants will receive Semorinemab intravenously (IV).
Other Names:
  • RG6100
  • 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.
Other Name: RO6880276

Experimental: Dose 3 Semorinemab Drug: Semorinemab
Participants will receive Semorinemab intravenously (IV).
Other Names:
  • RG6100
  • 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.
Other Name: RO6880276

Placebo Comparator: Placebo Drug: Placebo
Matching placebo doses of Semorinemab given intravenously (IV).

Drug: [18F]GTP1
[18F]GTP1 will be administered as a solution for intravenous (IV) use, as part of positron emission tomography (PET) imaging.
Other Name: RO6880276




Primary Outcome Measures :
  1. Change From Baseline on the CDR-SB [ Time Frame: Baseline and 73 Weeks ]
    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.

  2. Percentage of Participants With Adverse Events [ Time Frame: Up to the data cutoff date 15 January 2021 (up to approximately 39 months) ]
    Percentage of participants with at least one adverse event

  3. Change From Baseline on the C-SSRS [ Time Frame: Baseline to data cutoff date 15 January 2021 (up to approximately 39 months) ]
    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.

  4. Other Abnormal MRI Findings [ Time Frame: Baseline, Week 9, Week 49, Week 73, Study Treatment Discontinuation, and Week 89 ]
    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.


Secondary Outcome Measures :
  1. Change From Baseline on the Repeatable Battery for Assessment of Neuropsychological Status (RBANS) [ Time Frame: Baseline and 73 weeks ]
    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.

  2. Change From Baseline on the Alzheimer's Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog-13) Subscale Score [ Time Frame: Baseline and 73 weeks ]
    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.

  3. Change From Baseline on the Amsterdam Instrumental Activity of Daily Living (iADL) Questionnaire [ Time Frame: Baseline and 73 weeks ]
    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.

  4. Change From Baseline on the Alzheimer's Disease Cooperative Study Group-Activities of Daily Living Inventory [ Time Frame: Baseline and 73 weeks ]
    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.

  5. Serum Concentrations of Semorinemab at Specified Timepoints [ Time Frame: Up to 109 weeks ]
    Serum concentrations of Semorinemab at specified timepoints.

  6. Presence of Anti-drug Antibodies During the Study Relative to Their Presence at Baseline [ Time Frame: Up to 109 weeks ]
    Presence of anti-drug antibodies during the study relative to their presence at baseline.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   50 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 Aβ1-42 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 Aβ, 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03289143


Locations
Show Show 133 study locations
Sponsors and Collaborators
Genentech, Inc.
Investigators
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Study Director: Clinical Trials Genentech, Inc.
  Study Documents (Full-Text)

Documents provided by Genentech, Inc.:
Study Protocol  [PDF] June 11, 2019
Statistical Analysis Plan  [PDF] August 16, 2020

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT03289143    
Other Study ID Numbers: GN39763
2017-001800-31 ( EudraCT Number )
First Posted: September 20, 2017    Key Record Dates
Results First Posted: March 16, 2022
Last Update Posted: March 16, 2022
Last Verified: February 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Genentech, Inc.:
Alzheimer Disease
Brain Diseases
Dementia
Neurodegenerative Diseases
Neurocognitive Disorders
Additional relevant MeSH terms:
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Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders