A Study to Evaluate the Efficacy and Safety of Semorinemab in Patients With Prodromal to Mild Alzheimer's Disease
- Conditions
- Alzheimer's Disease
- Interventions
- Registration Number
- NCT03289143
- Lead Sponsor
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 457
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dose 2 Semorinemab [18F]GTP1 - Placebo Placebo - Dose 3 Semorinemab [18F]GTP1 - Dose 1 Semorinemab [18F]GTP1 - Placebo [18F]GTP1 - Dose 1 Semorinemab Semorinemab - Dose 2 Semorinemab Semorinemab - Dose 3 Semorinemab Semorinemab -
- Primary Outcome Measures
Name Time Method Change From Baseline on the CDR-SB 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.
Other Abnormal MRI Findings 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.
Percentage of Participants With Adverse Events Up to the data cutoff date 15 January 2021 (up to approximately 39 months) Percentage of participants with at least one adverse event
Change From Baseline on the C-SSRS 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.
- Secondary Outcome Measures
Name Time Method Change From Baseline on the Repeatable Battery for Assessment of Neuropsychological Status (RBANS) 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.
Serum Concentrations of Semorinemab at Specified Timepoints Up to 109 weeks Serum concentrations of Semorinemab at specified timepoints.
Change From Baseline on the Alzheimer's Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog-13) Subscale Score 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.
Change From Baseline on the Amsterdam Instrumental Activity of Daily Living (iADL) Questionnaire 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.
Change From Baseline on the Alzheimer's Disease Cooperative Study Group-Activities of Daily Living Inventory 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.
Presence of Anti-drug Antibodies During the Study Relative to Their Presence at Baseline Up to 109 weeks Presence of anti-drug antibodies during the study relative to their presence at baseline.
Trial Locations
- Locations (133)
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
California Clinical Trials
🇺🇸Glendale, California, United States
University of California Irvine
🇺🇸Irvine, California, United States
Pharmacology Research Inst
🇺🇸Newport Beach, California, United States
Stanford Neuroscience Health Center (SNHC)
🇺🇸Palo Alto, California, United States
Pacific Research Network - PRN
🇺🇸San Diego, California, United States
Neurological Research Inst
🇺🇸Santa Monica, California, United States
Collaborative Neuroscience Network Inc.
🇺🇸Torrance, California, United States
Invicro, a Konica Minolta company
🇺🇸New Haven, Connecticut, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Scroll for more (123 remaining)University of Alabama at Birmingham🇺🇸Birmingham, Alabama, United States