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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03289143




Registration number
NCT03289143
Ethics application status
Date submitted
18/09/2017
Date registered
20/09/2017
Date last updated
16/03/2022

Titles & IDs
Public title
A Study to Evaluate the Efficacy and Safety of Semorinemab in Patients With Prodromal to Mild Alzheimer's Disease
Scientific 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
Secondary ID [1] 0 0
2017-001800-31
Secondary ID [2] 0 0
GN39763
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer's Disease 0 0
Condition category
Condition code
Neurological 0 0 0 0
Alzheimer's disease
Neurological 0 0 0 0
Dementias

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Semorinemab
Treatment: Drugs - Placebo
Treatment: Drugs - [18F]GTP1

Experimental: Dose 1 Semorinemab -

Experimental: Dose 2 Semorinemab -

Experimental: Dose 3 Semorinemab -

Placebo comparator: Placebo -


Treatment: Drugs: Semorinemab
Participants will receive Semorinemab intravenously (IV).

Treatment: Drugs: Placebo
Matching placebo doses of Semorinemab given intravenously (IV).

Treatment: Drugs: [18F]GTP1
\[18F\]GTP1 will be administered as a solution for intravenous (IV) use, as part of positron emission tomography (PET) imaging.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline on the CDR-SB
Assessment method [1] 0 0
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.
Timepoint [1] 0 0
Baseline and 73 Weeks
Primary outcome [2] 0 0
Percentage of Participants With Adverse Events
Assessment method [2] 0 0
Percentage of participants with at least one adverse event
Timepoint [2] 0 0
Up to the data cutoff date 15 January 2021 (up to approximately 39 months)
Primary outcome [3] 0 0
Change From Baseline on the C-SSRS
Assessment method [3] 0 0
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.
Timepoint [3] 0 0
Baseline to data cutoff date 15 January 2021 (up to approximately 39 months)
Primary outcome [4] 0 0
Other Abnormal MRI Findings
Assessment method [4] 0 0
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.
Timepoint [4] 0 0
Baseline, Week 9, Week 49, Week 73, Study Treatment Discontinuation, and Week 89
Secondary outcome [1] 0 0
Change From Baseline on the Repeatable Battery for Assessment of Neuropsychological Status (RBANS)
Assessment method [1] 0 0
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.
Timepoint [1] 0 0
Baseline and 73 weeks
Secondary outcome [2] 0 0
Change From Baseline on the Alzheimer's Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog-13) Subscale Score
Assessment method [2] 0 0
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.
Timepoint [2] 0 0
Baseline and 73 weeks
Secondary outcome [3] 0 0
Change From Baseline on the Amsterdam Instrumental Activity of Daily Living (iADL) Questionnaire
Assessment method [3] 0 0
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.
Timepoint [3] 0 0
Baseline and 73 weeks
Secondary outcome [4] 0 0
Change From Baseline on the Alzheimer's Disease Cooperative Study Group-Activities of Daily Living Inventory
Assessment method [4] 0 0
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.
Timepoint [4] 0 0
Baseline and 73 weeks
Secondary outcome [5] 0 0
Serum Concentrations of Semorinemab at Specified Timepoints
Assessment method [5] 0 0
Serum concentrations of Semorinemab at specified timepoints.
Timepoint [5] 0 0
Up to 109 weeks
Secondary outcome [6] 0 0
Presence of Anti-drug Antibodies During the Study Relative to Their Presence at Baseline
Assessment method [6] 0 0
Presence of anti-drug antibodies during the study relative to their presence at baseline.
Timepoint [6] 0 0
Up to 109 weeks

Eligibility
Key inclusion 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 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
Minimum age
50 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
4/10/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
15/01/2021
Sample size
Target
Accrual to date
Final
457
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
St Vincents Medical Centre - Darlinghurst
Recruitment hospital [2] 0 0
Southern Neurology - Kogarah
Recruitment hospital [3] 0 0
Queensland University of Technology - Mermaid Waters
Recruitment hospital [4] 0 0
Eastern Clinical Research Unit; Pharmacy - Box Hill
Recruitment hospital [5] 0 0
HammondCare Aged Psychiatry Clinical Trials - Malvern
Recruitment hospital [6] 0 0
The Alfred Hospital, Melbourne; Thrombosis and Haemostasis Unit - Melbourne
Recruitment hospital [7] 0 0
Neuro Trials Victoria - Noble Park
Recruitment hospital [8] 0 0
Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2217 - Kogarah
Recruitment postcode(s) [3] 0 0
4218 - Mermaid Waters
Recruitment postcode(s) [4] 0 0
3128 - Box Hill
Recruitment postcode(s) [5] 0 0
3144 - Malvern
Recruitment postcode(s) [6] 0 0
3004 - Melbourne
Recruitment postcode(s) [7] 0 0
3174 - Noble Park
Recruitment postcode(s) [8] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
District of Columbia
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Maine
Country [9] 0 0
United States of America
State/province [9] 0 0
Massachusetts
Country [10] 0 0
United States of America
State/province [10] 0 0
Minnesota
Country [11] 0 0
United States of America
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New Jersey
Country [12] 0 0
United States of America
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New York
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Oregon
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Pennsylvania
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United States of America
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Rhode Island
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United States of America
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Tennessee
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United States of America
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Vermont
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Belgium
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Brussel
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Belgium
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Kortrijk
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Belgium
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Leuven
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Belgium
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Roeselare
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Canada
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Ontario
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Canada
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Quebec
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Denmark
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Aalborg
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Vejle
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Bordeaux
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Bron
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Lille
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Marseille
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Bayreuth
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Hannover
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München
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Siegen
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Tubingen
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Germany
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Ulm
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Italy
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Lazio
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Italy
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Liguria
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Lombardia
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Molise
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'S Hertogenbosch
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Bialystok
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Wroclaw
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Barcelona
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Guipuzcoa
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Navarra
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Palencia
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Vizcaya
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Albacete
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Cordoba
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Madrid
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Sevilla
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Spain
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Valencia
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Sweden
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Jönköping
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Sweden
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Kalmar
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Sweden
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Malmö
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Sweden
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Mölndal
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Sweden
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Stockholm
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United Kingdom
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Glasgow
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London
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United Kingdom
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Surrey

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Genentech, Inc.
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Genentech, Inc.
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT03289143