CREAD: A Study Evaluating the Efficacy and Safety of Crenezumab Versus Placebo in Participants With Prodromal to Mild Alzheimer's Disease (AD).
Study Details
Study Description
Brief Summary
This randomized, double-blind, placebo-controlled, parallel group study will evaluate the efficacy and safety of crenezumab versus placebo in participants with prodromal to mild AD. Participants will be randomized 1:1 to receive either intravenous (IV) infusion of crenezumab or placebo every 4 weeks (Q4W) for 100 weeks. The final efficacy and safety assessment will be performed 52 weeks after the last crenezumab dose. Participants will then have the option to enter the Open Label Extension (OLE) study if eligible. Participants who do not enter the OLE study will have additional follow-up visits at 16 and 52 weeks after the last dose, primarily for safety and also for limited efficacy assessments.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks. |
Drug: Placebo
Placebo was administered by intravenous (IV) infusion at 60mg/kg as per the dosing schedule described above.
|
| Experimental: Crenezumab Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks. |
Drug: Crenezumab
Crenezumab was administered by intravenous (IV) infusion at 60mg/kg as per the dosing schedule described above.
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline to Week 105 in Clinical Dementia Rating-Sum of Boxes (CDR-SB) Score [Baseline, Week 105]
The 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 105 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline for this primary endpoint. Data after 29 January 2019 are censored for the primary and secondary efficacy analyses to avoid potential biases due to investigators, participants, raters, etc. being potentially influenced by early closure of the study due to lack of efficacy.
Secondary Outcome Measures
- Change From Baseline to Week 105 on Cognition, as Assessed by Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog) (Subscale) 13 (ADAS-Cog-13) [Baseline, Week 105]
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 105 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.
- Change From Baseline to Week 105 on Cognition, as Assessed by Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog) (Subscale) 11 (ADAS-Cog-11) [Baseline, Week 105]
The ADAS-Cog-11 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 score range for ADAS-Cog-11 is from 0 to 70 with high scores representing severe dysfunction. The difference in mean change from Baseline to Week 105 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.
- Change From Baseline to Week 105 on Severity of Dementia, Assessed Using the CDR-Global Score (CDR-GS) [Baseline, Week 105]
The CDR-GS represents a semi-structured interview which 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 CDR 0 = no dementia and CDR 0.5, 1, 2 or 3 = questionable, mild, moderate or severe dementia respectively. The range in scores for the CDR-GS is from 0 to 3 and a high score on the CDR-GS would indicate a high disease severity. The difference in mean change from Baseline to Week 105 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.
- Change From Baseline to Week 105 on Severity of Dementia, Assessed Using the Mini Mental State Evaluation (MMSE) [Baseline, Week 105]
The MMSE is a set of standardized questions used to evaluate possible cognitive impairment and help stage the severity level of this impairment. The questions target 6 areas: orientation, registration, attention, short-term recall, language and constructional praxis/visuospatial abilities. The scores on the MMSE range from 0 to 30, with higher scores indicating better function. The difference in mean change from Baseline to Week 105 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.
- Change From Baseline to Week 105 on Function as Assessed by the ADCS-ADL Total Score [Baseline, Week 105]
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 105 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.
- Change From Baseline to Week 105 on Function as Assessed by the ADCS-instrumental (ADCS-iADL) Subscore [Baseline, Week 105]
The ADCS-iADL (Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living) measures activities such as using the telephone, managing finances and preparing a meal. The ADCS-iADL consists of 16 questions with a score range of 0 to 56 where a higher score represents better function. The difference in mean change from Baseline to Week 105 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.
- Change From Baseline to Week 105 on a Measure of Dependence Derived From the ADCS-ADL Score [Baseline, Week 105]
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 105 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.
- Change From Baseline to Week 105 Assessed Using the Neuropsychiatric Inventory Questionnaire (NPI-Q) [Baseline, Week 105]
The NPI-Q is an informant-based instrument that evaluates 12 neuropsychiatric disturbances common in dementia: delusions, hallucinations, agitation, dysphoria, anxiety, apathy, irritability, euphoria, disinhibition, aberrant motor behavior, night-time behavioral disturbances and appetite and eating abnormalities. The severity of each neuropsychiatric symptom is rated on a 3-point scale (mild, moderate and marked). The total severity score range is from 0 to 36 with higher scores representing higher severity. The difference in mean change from Baseline to Week 105 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.
- Quality of Life-Alzheimer's Disease (QoL-AD) Scale Score [Baseline up to Week 105]
The QoL-AD (Quality of Life - Alzheimer's Disease) scale assesses QoL in participants who have dementia. The QoL-AD consists of 13 items covering aspects of participants' relationships with friends and family, physical condition, mood, concerns about finances and overall assessment of QoL. Items are rated on 4-point Likert-type scales ranging from 1 [poor] to 4 [excellent]. The score range is from 13 to 52, with higher scores indicating a better QoL. The difference in mean change from Baseline to Week 105 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.
- Zarit Caregiver Interview for Alzheimer's Disease (ZCI-AD) Scale Score [Baseline up to Week 105]
The ZCI-AD is a modified version of the Zarit Burden Interview, which was originally designed to reflect the stresses experienced by caregivers of people with dementia. This modified version includes slight modifications in item and title wording (e.g., removal of "your relative" to refer directly to the patient, removal of "burden" from title) and the use of 11-point numerical rating scales. The ZCI-AD scale consists of a total of 30 items. Total scores will be calculated with a total score range from 0 to 300 (higher scores indicate a higher burden on the caregiver). The difference in mean change from Baseline to Week 105 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.
- EQ-5D Questionnaire Domain Score for Participants [Baseline up to Week 105]
The EQ-5D is a standardized measure of health status designed to provide a simple generic measure of health for clinical and economic appraisal. It is broadly applicable across a wide range of health conditions and treatment. The EQ-5D assesses five domains to provide a health state index. These are anxiety/depression, pain/discomfort, usual activities, mobility, and self-care. The scores on the EQ-5D ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). The difference in mean change from Baseline to Week 105 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.
- EQ-5D Questionnaire Domain Score for Caregivers [Baseline up to Week 105]
The EQ-5D is a standardized measure of health status designed to provide a simple generic measure of health for clinical and economic appraisal. It is broadly applicable across a wide range of health conditions and treatment. The EQ-5D assesses five domains to provide a health state index. These are anxiety/depression, pain/discomfort, usual activities, mobility, and self-care. The scores on the EQ-5D ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). The difference in mean change from Baseline to Week 105 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.
- Percentage of Participants With Adverse Event (AEs) and Serious Adverse Event (SAEs) [Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).]
An Adverse Event is any untoward medical occurrence in a participant 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.
- Percentage of Participants With Anti-Crenezumab Antibodies [Baseline up to Week 105]
Participants were considered positive or negative for ADA based on their baseline and post-baseline sample results. The number and percentage of participants with confirmed positive ADA levels were determined for Crenezumab and Placebo groups. The prevalence of ADA at baseline was calculated as the proportion of participants with confirmed positive ADA levels at baseline relative to the total number of participants with a sample available at baseline. The incidence of treatment-emergent ADAs was determined as the proportion of participants with confirmed post-baseline positive ADAs relative to the total number of participants that had at least one post-baseline sample available for ADA analysis.
- Serum Concentration of Crenezumab [Pre-infusion (0 hour), 60-90 minutes post-infusion on Day 1 Week 1 and on Week 25; Weeks 13, 37 (Pre-dose), 53, 77 and 105 (infusion length = as per the Pharmacy Manual)]
Serum concentration data for Crenezumab will be tabulated and summarized. Descriptive summary statistics will include the arithmetic mean and SD. Since a sparse PK sampling design is being used, population (non-linear mixed-effects) modeling will be used to analyze the dose concentration-time data of crenezumab. Information from other clinical studies may be incorporated to establish the PK model. Please note that Post-dose samples were not collected at Weeks 37 and 105.
- Plasma Amyloid Beta (Abeta) 40 Concentrations [Week 1 Day 1; Weeks 13, 25, 53, 77 and 105]
Plasma Abeta 40 concentrations will be measured over time and descriptive summary statistics will include the arithmetic mean and SD. Please note that a Post-dose sample was only collected at Week 13.
- Plasma Amyloid Beta (Abeta) 42 Concentrations [Week 1 Day 1; Weeks 13, 25, 53, 77 and 105]
Plasma Abeta 42 concentrations will be measured over time and descriptive summary statistics will include the arithmetic mean and SD. Please note that a Post-dose sample was only collected at Week 13.
- Percentage Change From Baseline to Week 105 in Whole Brain Volume as Determined by Magnetic Resonance Imaging (MRI) [Baseline, Week 105]
Percentage Change in Whole Brain Volume will be measured over time and descriptive summary statistics will include the arithmetic mean, median, range, SD, and coefficient of variation, as appropriate. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.
- Percentage Change From Baseline to Week 105 in Ventricle Volume as Determined by Magnetic Resonance Imaging (MRI) [Baseline, Week 105]
Percentage Change in Ventricle Volume will be measured over time and descriptive summary statistics will include the arithmetic mean, median, range, SD, and coefficient of variation, as appropriate. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.
- Percentage Change From Baseline to Week 105 in Hippocampal Volume as Determined by Magnetic Resonance Imaging (MRI) [Baseline, Week 105]
Percentage Change in Hippocampal Volume will be measured over time and descriptive summary statistics will include the arithmetic mean, median, range, SD, and coefficient of variation, as appropriate. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Weight between 40 and 120 kilograms (Kg) inclusive
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Availability of a person (referred to as the "caregiver") who in the investigator's judgment:
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Has frequent and sufficient contact with the participant to be able to provide accurate information regarding the participant's cognitive and functional abilities, agrees to provide information at clinic visits (which require partner input for scale completion), signs the necessary consent form, and has sufficient cognitive capacity to accurately report upon the participant's behavior and cognitive and functional abilities
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Fluency in the language of the tests used at the study site
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Adequate visual and auditory acuity, in the investigator's judgment, sufficient to perform the neuropsychological testing (eye glasses and hearing aids are permitted)
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Evidence of the AD pathological process, by a positive amyloid assessment either on cerebrospinal fluid (CSF) amyloid beta 1-42 levels as measured on the Elecsys beta-amyloid(1-42) test system or amyloid PET scan by qualitative read by the core/central PET laboratory
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Demonstrated abnormal memory function at screening (up to 4 weeks before screening begins) or screening (FCSRT cueing index =<0.67 AND free recall =<27)
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Screening mini mental state examination (MMSE) score of greater than or equal to (>=) 22 points and Clinical Dementia Rating-Global Score (CDR-GS) of 0.5 or 1.0
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Meets National Institute on Aging/Alzheimer's Association (NIAAA) core clinical criteria for probable AD dementia or prodromal AD (consistent with the NIAAA diagnostic criteria and guidelines for mild cognitive impairment (MCI)
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If receiving symptomatic AD medications, the dosing regimen must have been stable for 3 months prior to screening
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Participant must have completed at least 6 years of formal education after the age of 5 years
Exclusion Criteria:
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Any evidence of a condition other than AD that may affect cognition such as other dementias, stroke, brain damage, autoimmune disorders (e.g. multiple sclerosis) or infections with neurological sequelae.
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History of major psychiatric illness such as schizophrenia or major depression (if not considered in remission)
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At risk of suicide in the opinion of the investigator
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Any abnormal MRI findings, such as presence of cerebral vascular pathology, cortical stroke, etc or inability to tolerate MRI procedures or contraindication to MRI
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Unstable or clinically significant cardiovascular (e.g., myocardial infarction), kidney or liver disease
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Uncontrolled hypertension
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Screening hemoglobin A1c (HbA1C) >8%
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Poor peripheral venous access
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History of cancer except:
If considered to be cured or If not being actively treated with anti-cancer therapy or radiotherapy
- Known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Banner Alzheimer's Institute | Phoenix | Arizona | United States | 85006 |
| 2 | Pharmacology Research Inst | Encino | California | United States | 91316 |
| 3 | Collaborative Neuroscience Network Inc. | Long Beach | California | United States | 90502 |
| 4 | Alliance for Wellness, dba Alliance for Research | Long Beach | California | United States | 90807 |
| 5 | Pharmacology Research Institute | Los Alamitos | California | United States | 90720 |
| 6 | USC Keck School Of Medicine | Los Angeles | California | United States | 90033 |
| 7 | UCLA Medical Center, Department of Neurology | Los Angeles | California | United States | 90095 |
| 8 | Pharmacology Research Inst | Newport Beach | California | United States | 92660 |
| 9 | Shankle Clinic | Newport Beach | California | United States | 92663 |
| 10 | Stanford Univ Medical Center | Palo Alto | California | United States | 94304 |
| 11 | Anderson Clinical Research, Inc. | Redlands | California | United States | 92374 |
| 12 | University of California, Davis; Alzheimers Disease Center, Department of Neurology | Sacramento | California | United States | 95817 |
| 13 | UCSF - Memory and Aging Center | San Francisco | California | United States | 94158 |
| 14 | Neurological Research Inst | Santa Monica | California | United States | 90404 |
| 15 | North Bay Neuro Science Institute | Sebastopol | California | United States | 95472 |
| 16 | Associated Neurologists PC - Danbury | Danbury | Connecticut | United States | 06810 |
| 17 | Institute for Neurodegenerative Disorders | New Haven | Connecticut | United States | 06510 |
| 18 | Yale University School Of Medicine | New Haven | Connecticut | United States | 06510 |
| 19 | Research Center for Clinical Studies, Inc. | Norwalk | Connecticut | United States | 06851 |
| 20 | Bradenton Research Center | Bradenton | Florida | United States | 34205 |
| 21 | Quantum Laboratories | Deerfield Beach | Florida | United States | 33064 |
| 22 | Brain Matters Research, Inc. | Delray Beach | Florida | United States | 33445 |
| 23 | Galiz Research, LLC | Hialeah | Florida | United States | 33016 |
| 24 | Jacksonville Center For Clinical Research | Jacksonville | Florida | United States | 32216 |
| 25 | Alzheimer's Research and Treatment Center | Lake Worth | Florida | United States | 33414 |
| 26 | Merritt - Island Medical Research | Merritt Island | Florida | United States | 32952 |
| 27 | Miami Jewish Health Systems | Miami | Florida | United States | 33137 |
| 28 | Renstar Medical Research | Ocala | Florida | United States | 34470 |
| 29 | Bioclinica Research | Orlando | Florida | United States | 32806 |
| 30 | Progressive Medical Research | Port Orange | Florida | United States | 32127 |
| 31 | Johnnie B. Byrd Sr. Alzheimer's Center & Research Institute | Tampa | Florida | United States | 33613 |
| 32 | Stedman Clinical Trials, LLC | Tampa | Florida | United States | 33613 |
| 33 | Compass Research | The Villages | Florida | United States | 32162 |
| 34 | Emory University | Atlanta | Georgia | United States | 30329 |
| 35 | NeuroStudies.net, LLC | Decatur | Georgia | United States | 30033 |
| 36 | Alexian Brothers Neurosci Inst | Elk Grove Village | Illinois | United States | 60007 |
| 37 | Southern Illinois University, School of Medicine | Springfield | Illinois | United States | 62702 |
| 38 | Indiana University | Indianapolis | Indiana | United States | 46202 |
| 39 | MidAmerica Neuroscience Institute | Prairie Village | Kansas | United States | 66206 |
| 40 | Maine Research Associates | Auburn | Maine | United States | 04210 |
| 41 | MMP Neurology | Scarborough | Maine | United States | 04074 |
| 42 | Springfield Neurology Associates | Springfield | Massachusetts | United States | 01104 |
| 43 | Precise Research Centers | Flowood | Mississippi | United States | 39232 |
| 44 | The Cognitive and Research Center of New Jersey | Springfield | New Jersey | United States | 07081 |
| 45 | Advanced Memory Research Institute of NJ | Toms River | New Jersey | United States | 08755 |
| 46 | Albany Medical Faculty Physicians COmmunity Division. The Neurology Group | Albany | New York | United States | 12206 |
| 47 | Neurological Associates of Albany, PC | Albany | New York | United States | 12208 |
| 48 | Dent Neurological Institute | Amherst | New York | United States | 14226 |
| 49 | Columbia University Medical Center | New York | New York | United States | 10032 |
| 50 | South Shore Neurologic Associates P.C. | Patchogue | New York | United States | 11772 |
| 51 | Behavioral Health Research | Charlotte | North Carolina | United States | 28211 |
| 52 | Guilford Neurologic Associates | Greensboro | North Carolina | United States | 27401 |
| 53 | Valley Medical Primary Care | Centerville | Ohio | United States | 45459 |
| 54 | Insight Clinical Trials LLC | Shaker Heights | Ohio | United States | 44122 |
| 55 | Oklahoma Clinical Research | Oklahoma City | Oklahoma | United States | 73112 |
| 56 | Cutting Edge Research Group | Oklahoma City | Oklahoma | United States | 73116 |
| 57 | Central States Research | Tulsa | Oklahoma | United States | 74136 |
| 58 | Summit Research Network Inc. | Portland | Oregon | United States | 97210 |
| 59 | Drexel Univ College of Med; Clinical Research Group | Philadelphia | Pennsylvania | United States | 19102 |
| 60 | Abington Neurological Associates | Willow Grove | Pennsylvania | United States | 19090 |
| 61 | Senior Adults Specialty Research | Austin | Texas | United States | 78757 |
| 62 | Kerwin Research Center, LLC | Dallas | Texas | United States | 75231 |
| 63 | University of North Texas Health Science Center; Fort Worth Patient Care Center | Fort Worth | Texas | United States | 76107 |
| 64 | Sentara Medical Group | Norfolk | Virginia | United States | 23507 |
| 65 | National Clinical Research Inc.-Richmond | Richmond | Virginia | United States | 23294 |
| 66 | Medical College of Wisconsin | Milwaukee | Wisconsin | United States | 53226 |
| 67 | The Queen Elizabeth Hospital; Neurology | Woodville | South Australia | Australia | 5011 |
| 68 | Caulfield Hospital; Aged Psychiatry Research Unit | Caulfield | Victoria | Australia | 3162 |
| 69 | Heidelberg Repatriation Hospital; Medical and Cognitive Research Centre | Heidelberg West | Victoria | Australia | 3081 |
| 70 | Neurodegenerative Disorders Research; Neurology | West Perth | Western Australia | Australia | 6005 |
| 71 | Konventhospital Barmherzige Brüder; Neurologie I | Linz | Austria | 4021 | |
| 72 | UZ Gent | Gent | Belgium | 9000 | |
| 73 | ACIBADEM CITY CLINIC TOKUDA HOSPITAL EAD; Clinic of Neurology and Sleep Medicine | Sofia | Bulgaria | 1407 | |
| 74 | Alexandrovska hospital; Neurology Department | Sofia | Bulgaria | 1431 | |
| 75 | Vancouver Hospital - UBC Hospital Site | Vancouver | British Columbia | Canada | V6Z 1Y6 |
| 76 | Vancouver Island Health Authority | Victoria | British Columbia | Canada | V8R 1J8 |
| 77 | Parkwood Hospital; Geriatric Medicine | London | Ontario | Canada | N6C 5J1 |
| 78 | Bruyere Continuing Care | Ottawa | Ontario | Canada | K1N 5C8 |
| 79 | Kawartha Centre - Redefining Healthy Aging | Peterborough | Ontario | Canada | K9H 2P4 |
| 80 | The Centre for Memory and Aging | Toronto | Ontario | Canada | M4G 3E8 |
| 81 | Toronto Western Hospital | Toronto | Ontario | Canada | M5T 2S8 |
| 82 | Devonshire Clinical Research Inc. | Woodstock | Ontario | Canada | N4S 5P5 |
| 83 | CHA Hopital de I enfant-Jesus | Quebec City | Quebec | Canada | G1J 1Z4 |
| 84 | ICIMED Instituto de Investigación en Ciencias Médicas | San Jose | Costa Rica | 10108 | |
| 85 | Hospital Clínica Biblica | San José | Costa Rica | 10101 | |
| 86 | Clinical Hospital Centre Zagreb;Clinic for Neurology | Zagreb | Croatia | 10000 | |
| 87 | Charles University, Medical faculty, Hradec Kralove ;Department of Neurology | Hradec Králové | Czechia | 500 05 | |
| 88 | General Teaching Hospital, Departmetn of Neurology | Praha | Czechia | 110 00 | |
| 89 | Aarhus Universitetshospital, Neurologisk Afdeling F, Demensklinikken | Aarhus N | Denmark | 8200 | |
| 90 | Rigshospitalet, Hukommelsesklinikken | København Ø | Denmark | 2100 | |
| 91 | Terveystalo Tampere | Tampere | Finland | 33100 | |
| 92 | CRST Oy | Turku | Finland | 20520 | |
| 93 | Hopital Avicenne; Neurologie | Bobigny | France | 93009 | |
| 94 | Hopital neurologique Pierre Wertheimer - CHU Lyon; Neurologie | Bron | France | 69677 | |
| 95 | Hopital Gui de Chauliac; Neurologie | Montpellier | France | 34295 | |
| 96 | Hopital Lariboisiere | Paris | France | 75475 | |
| 97 | CHU Poitiers - Hopital La Miletrie | Poitiers | France | 86000 | |
| 98 | Hopital Hautepierre; Centre dInvestigation Clinique | Strasbourg | France | 67098 | |
| 99 | CHU Toulouse - La Grave | Toulouse | France | 31059 | |
| 100 | Neurologische Praxis Dr. Andrej Pauls | München | Germany | 80331 | |
| 101 | Klinikum rechts der Isar der TU München; Klinik für Psychiatrie und Psychotherapie | München | Germany | 81675 | |
| 102 | Universitätsklinikum Münster; Klinik und Poliklinik für Neurologie | Münster | Germany | 48149 | |
| 103 | Steinwachs Klaus; Arztpraxis fur Neurologie u. Psychiatrie | Nürnberg | Germany | 90402 | |
| 104 | Universitätsklinikum Rostock Zentrum für Nervenheilkunde | Rostock | Germany | 18147 | |
| 105 | Universitätsklinikum Ulm; Klinik für Neurologie | Ulm | Germany | 89081 | |
| 106 | Studienzentrum Nordwest, Dr. med. Joachim Springub / Herr Wolfgang Schwarz | Westerstede | Germany | 26655 | |
| 107 | Forschungszentrum Ruhr | Witten | Germany | 58455 | |
| 108 | Prince of Wales Hospital; Dept. of Medicine & Therapeutics | Hong Kong | Hong Kong | ||
| 109 | Queen Mary Hospital, Division of Geriatric Medicine | Hong Kong | Hong Kong | ||
| 110 | Semmelweis University; Department of Neurology | Budapest | Hungary | 1083 | |
| 111 | Szabolcs-Szatmár-Bereg Megyei Kórházak - Jósa András Oktatókórház; Pszichiátria | Nyíregyháza | Hungary | 4400 | |
| 112 | University of Szeged; Department of Psychiatry | Szeged | Hungary | 6725 | |
| 113 | Szent Borbala Korhaz; Neurologiai es Stroke Osztaly | Tatabánya | Hungary | 2800 | |
| 114 | Jávorszky Ödön Kórház, Neurológia és stroke osztály | VAC | Hungary | 2600 | |
| 115 | Fondazione Santa Lucia IRCCS; Neurologia e Riabilitazione Neurologica | Roma | Lazio | Italy | 00179 |
| 116 | Ospedale San Giovanni Calibita Fatebenefratell;Neurologia | Roma | Lazio | Italy | 00186 |
| 117 | Ente Ospedaliero Ospedali Galliera; Ambulatorio di Neurologia | Genova | Liguria | Italy | 16128 |
| 118 | Casa di Cura Policlinico; Dipartimento di Scienze Neuroriabilitative | Milano | Lombardia | Italy | 20144 |
| 119 | Ospedale S. Maria Nascente; Fondazione Don Gnocchi; Dip. Neurologia Riabilitativa | Milano | Lombardia | Italy | 20148 |
| 120 | Ospedale Casati Passirana di Rho; Centro Regionale Alzheimer | Passirana | Lombardia | Italy | 20017 |
| 121 | Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia; S.C. Geriatria | Perugia | Umbria | Italy | 06129 |
| 122 | Miyoshi Clinic of Neurology, Hananosato | Hiroshima | Japan | 728-0013 | |
| 123 | National Hospital Organization Hiroshima-Nishi Medical Center | Hiroshima | Japan | 739-0696 | |
| 124 | Rakuwakai Otowarehabilitation Hospital | Kyoto | Japan | 607-8113 | |
| 125 | Mie University Hospital | Mie | Japan | 514-8507 | |
| 126 | National Hospital Organization Matsumoto Medical Center | Nagano | Japan | 399-8701 | |
| 127 | Saigata Medical Center | Niigata | Japan | 949-3193 | |
| 128 | Katayama Medical Clinic | Okayama | Japan | 710-0813 | |
| 129 | Tokyo Medical University Hospital | Tokyo | Japan | 160-0023 | |
| 130 | Tokyo Metropolitan Geriatric Hospital | Tokyo | Japan | 173-0015 | |
| 131 | National Center of Neurology and Psychiatry | Tokyo | Japan | 187-8551 | |
| 132 | Chonnam National University Hospital | Gwangju | Korea, Republic of | 61469 | |
| 133 | Inha University Hospital | Incheon | Korea, Republic of | 22332 | |
| 134 | Konkuk University Medical Center | Seoul | Korea, Republic of | 05030 | |
| 135 | Asan Medical Center | Seoul | Korea, Republic of | 05505 | |
| 136 | KyungHee Medical Center | Seoul | Korea, Republic of | 130-702 | |
| 137 | Ewha Womans University Mokdong Hospital; Dept of Neurology | Seoul | Korea, Republic of | 158-710 | |
| 138 | Vilnius University Hospital Santariskiu Clinic | Vilnius | Lithuania | 08661 | |
| 139 | Hospital Angeles de Culiacán, Neurociencias Estudios Clínicos SC | Culiacan | Mexico | 80020 | |
| 140 | Hospital Uni; Dr. Jose E. Gonzalez | Monterrey | Mexico | 64460 | |
| 141 | AVIX Investigación Clínica S.C | Monterrey | Mexico | 64710 | |
| 142 | Hospital Universitario de Saltillo | Saltillo | Mexico | 25000 | |
| 143 | Podlaskie Centrum Psychogeriatrii | Białystok | Poland | 15-756 | |
| 144 | NZOZ NEURO-KARD Ilkowski i Partnerzy Sp. Partn. Lek | Poznań | Poland | 61-853 | |
| 145 | NEURO-CARE Sp. z o.o. Sp. Komandytowa | Siemianowice Śląskie | Poland | 41-100 | |
| 146 | Przychodnia Specjalistyczna PROSEN | Warszawa | Poland | 01-231 | |
| 147 | Centrum Medyczne NeuroProtect | Warszawa | Poland | 01-684 | |
| 148 | Optimum | Warszawa | Poland | 01-785 | |
| 149 | Hospital Prof. Dr. Fernando Fonseca; Servico de Neurologia | Amadora | Portugal | 2720-276 | |
| 150 | Hospital Beatriz Angelo; Servico de Neurologia | Loures | Portugal | 2674-514 | |
| 151 | State Autonomous Healthcare Institution "Republican Clinical Neurological Center | Kazan | Russian Federation | 420021 | |
| 152 | State autonomous institution of healthcare Inter-regional clinical and diagnostic center | Kazan | Russian Federation | 420101 | |
| 153 | Institution of RAMS (Mental Health Research Center of RAMS) | Moscow | Russian Federation | 115522 | |
| 154 | SBEI of HPI The 1st Moscow State Medical University n.a. I.M. Sechenov of MOH of RF | Moscow | Russian Federation | 119021 | |
| 155 | City Clinical Hospital # 2 n.a. V.I. Razumovsky | Saratov | Russian Federation | 410028 | |
| 156 | SHI City Psychoneurological Dispensary #7 | St Petersburg | Russian Federation | 190005 | |
| 157 | Russian Medical Military Academy n.a. S.M.Kirov; Neurology Department | St. Petersburg | Russian Federation | 194044 | |
| 158 | University Medical Centre Maribor | Maribor | Slovenia | 2000 | |
| 159 | Fundació ACE | BArcelon | Barcelona | Spain | 08034 |
| 160 | Hospital Universitari de Bellvitge; Servicio de Neurologia | L'Hospitalet de Llobregat | Barcelona | Spain | 08907 |
| 161 | Hospital Sant Joan de Deu; Servicio de Neurología | Manresa | Barcelona | Spain | |
| 162 | Hospital General De Catalunya; Servicio de Neurologia | Sant Cugat del Valles | Barcelona | Spain | 8195 |
| 163 | Hospital Mutua De Terrasa; Servicio de Neurologia | Terrassa | Barcelona | Spain | 08222 |
| 164 | Hospital Virgen del Puerto. Servicio de Neurología | Plasencia | Caceres | Spain | 10600 |
| 165 | Hospital Universitario Marques de Valdecilla; Servicio de Neurología | Santander | Cantabria | Spain | |
| 166 | Clinica Universitaria de Navarra; Servicio de Neurología | Pamplona | Navarra | Spain | 31008 |
| 167 | Complejo Asistencial Universitario de Salamanca; Servicio de Psiquiatría | Salamaca | Salamanca | Spain | 37007 |
| 168 | Hospital General Universitario de Albacete; Servicio de Neurología | Albacete | Spain | ||
| 169 | Hospital Vall d'Hebron; Servicio de Neurología | Barcelona | Spain | 08035 | |
| 170 | Hospital Universitario de Burgos. Servicio de Neurología | Burgos | Spain | 09006 | |
| 171 | Clinica Ruber, 4 planta; Servicio de Neurologia | Madrid | Spain | 28006 | |
| 172 | Universitario de La Princesa; Servicio de Neurología | Madrid | Spain | 28006 | |
| 173 | Hospital Universitario 12 de Octubre; Servicio de Neurologia | Madrid | Spain | 28041 | |
| 174 | Hospital Regional Universitario Carlos Haya; Servicio de Neurologia | Malaga | Spain | 29010 | |
| 175 | Hospital Universitario Virgen de Arrixaca; Servicio de Neurología | Murcia | Spain | ||
| 176 | Hospital Universitario la Fe; Servicio de Neurologia | Valencia | Spain | 46026 | |
| 177 | Servicio de Neurología Hospital Viamed Montecanal. | Zaragoza | Spain | 50012 | |
| 178 | Skånes Universitetssjukhus Malmö, Minneskliniken | Malmö | Sweden | 211 46 | |
| 179 | Sahlgrenska Academy University,Neuroscience and Physiology;Departmt of Psychiatry and Neurochemistry | Mölndal | Sweden | 431 41 | |
| 180 | Karolinska Uni Hospital, Huddinge; Dept. of Geriatric Med | Stockholm | Sweden | 14186 | |
| 181 | Universitäres Zentrum für Altersmedizin und Rehabilitation | Basel | Switzerland | 4002 | |
| 182 | Hacettepe University School of Medicine; Neurology | Ankara | Turkey | 06100 | |
| 183 | Osmangazi University School of Medicine,Neurology Department | Eskişehir | Turkey | 26480 | |
| 184 | Istanbul University Istanbul School of Medicine; Neurology | Istanbul | Turkey | 34093 | |
| 185 | Ondokuz Mayis University School of Medicine; Neurology | Samsun | Turkey | 55139 | |
| 186 | Regional mental hospital; Department of psychiatry, psychology and sexology | Lviv | KIEV Governorate | Ukraine | 79021 |
| 187 | National Medical Academy of Postgraduate Education named after P.L.Shupik; Neurology Department #1 | Kiev | Ukraine | 04112 | |
| 188 | D.F.Chebotarev Institute of Gerontology NAMS;Depart of Age Physiology&Pathology of Nervous System | Kiev | Ukraine | 04114 | |
| 189 | Royal Preston Hospital | Blackburn | United Kingdom | PR2 9HT | |
| 190 | Surrey and Borders NHS Foundation Trust; Brain Science Research Unit | Chertsey | United Kingdom | KT16 0AE | |
| 191 | Coventry and Warwickshire Partnership NHS Trust | Coventry | United Kingdom | CV6 6NY | |
| 192 | St George's Hospital | London | United Kingdom | SW17 0QT | |
| 193 | Charing Cross Hospital | London | United Kingdom | W6 8RF | |
| 194 | Manchester Royal Infirmary | Manchester | United Kingdom | M13 9WL | |
| 195 | Campus for Ageing and Vitality | Newcastle Upon Tyne | United Kingdom | NE4 6BE | |
| 196 | John Radcliffe Hospital | Oxford | United Kingdom | OX3 9DU |
Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
More Information
Publications
None provided.- BN29552
- 2015-003034-27
Study Results
Participant Flow
| Recruitment Details | The study was conducted at 249 centers in 30 countries. |
|---|---|
| Pre-assignment Detail | A total of 813 participants were enrolled at 249 centers. 4 participants did not receive any study treatment meaning that the modified intent-to-treat and safety populations both consisted of 809 participants. |
| Arm/Group Title | Placebo | Crenezumab |
|---|---|---|
| Arm/Group Description | Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks. | Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks. |
| Period Title: Overall Study | ||
| STARTED | 409 | 404 |
| COMPLETED | 88 | 85 |
| NOT COMPLETED | 321 | 319 |
Baseline Characteristics
| Arm/Group Title | Placebo | Crenezumab | Total |
|---|---|---|---|
| Arm/Group Description | Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks. | Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks. | Total of all reporting groups |
| Overall Participants | 409 | 404 | 813 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
70.3
(8.4)
|
71.0
(7.9)
|
70.7
(8.2)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
247
60.4%
|
236
58.4%
|
483
59.4%
|
| Male |
162
39.6%
|
168
41.6%
|
330
40.6%
|
| Race/Ethnicity, Customized (Number) [Number] | |||
| Hispanic or Latino |
39
9.5%
|
32
7.9%
|
71
8.7%
|
| Not Hispanic or Latino |
361
88.3%
|
369
91.3%
|
730
89.8%
|
| Not Stated |
7
1.7%
|
2
0.5%
|
9
1.1%
|
| Unknown |
2
0.5%
|
1
0.2%
|
3
0.4%
|
| Race/Ethnicity, Customized (Number) [Number] | |||
| American Indian or Alaska Native |
5
1.2%
|
10
2.5%
|
15
1.8%
|
| Asian |
28
6.8%
|
28
6.9%
|
56
6.9%
|
| Black or African American |
3
0.7%
|
5
1.2%
|
8
1%
|
| Multiple |
0
0%
|
1
0.2%
|
1
0.1%
|
| Unknown |
13
3.2%
|
8
2%
|
21
2.6%
|
| White |
360
88%
|
352
87.1%
|
712
87.6%
|
Outcome Measures
| Title | Change From Baseline to Week 105 in Clinical Dementia Rating-Sum of Boxes (CDR-SB) Score |
|---|---|
| Description | The 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 105 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline for this primary endpoint. Data after 29 January 2019 are censored for the primary and secondary efficacy analyses to avoid potential biases due to investigators, participants, raters, etc. being potentially influenced by early closure of the study due to lack of efficacy. |
| Time Frame | Baseline, Week 105 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent-To-Treat population (Placebo (n = 407); Cren (n = 402)) was defined as all randomized participants who received at least 1 dose of study drug, with participants grouped according to the treatment assigned at randomization. Data presented below is only for participants that were included in the actual analysis. |
| Arm/Group Title | Placebo | Crenezumab |
|---|---|---|
| Arm/Group Description | Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks. | Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks. |
| Measure Participants | 88 | 86 |
| Least Squares Mean (Standard Error) [Units on a Scale] |
3.42
(0.263)
|
3.59
(0.264)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Crenezumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference |
| Estimated Value | -0.17 | |
| Confidence Interval |
(2-Sided) 95% -0.86 to 0.53 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.354 |
|
| Estimation Comments | ||
| Title | Change From Baseline to Week 105 on Cognition, as Assessed by Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog) (Subscale) 13 (ADAS-Cog-13) |
|---|---|
| Description | 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 105 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline. |
| Time Frame | Baseline, Week 105 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent-To-Treat population (Placebo (n = 407); Cren (n = 402)) was defined as all randomized participants who received at least 1 dose of study drug, with participants grouped according to the treatment assigned at randomization. Data presented below is only for participants that were included in the actual analysis. |
| Arm/Group Title | Placebo | Crenezumab |
|---|---|---|
| Arm/Group Description | Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks. | Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks. |
| Measure Participants | 86 | 80 |
| Least Squares Mean (Standard Error) [Units on a Scale] |
9.55
(0.824)
|
9.82
(0.841)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Crenezumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference |
| Estimated Value | -0.26 | |
| Confidence Interval |
(2-Sided) 95% -2.39 to 1.87 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.083 |
|
| Estimation Comments | ||
| Title | Change From Baseline to Week 105 on Cognition, as Assessed by Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog) (Subscale) 11 (ADAS-Cog-11) |
|---|---|
| Description | The ADAS-Cog-11 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 score range for ADAS-Cog-11 is from 0 to 70 with high scores representing severe dysfunction. The difference in mean change from Baseline to Week 105 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline. |
| Time Frame | Baseline, Week 105 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent-To-Treat population (Placebo (n = 407); Cren (n = 402)) was defined as all randomized participants who received at least 1 dose of study drug, with participants grouped according to the treatment assigned at randomization. Data presented below is only for participants that were included in the actual analysis. |
| Arm/Group Title | Placebo | Crenezumab |
|---|---|---|
| Arm/Group Description | Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks. | Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks. |
| Measure Participants | 86 | 80 |
| Least Squares Mean (Standard Error) [Units on a Scale] |
8.43
(0.758)
|
8.53
(0.773)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Crenezumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference |
| Estimated Value | -0.10 | |
| Confidence Interval |
(2-Sided) 95% -2.08 to 1.88 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.006 |
|
| Estimation Comments | ||
| Title | Change From Baseline to Week 105 on Severity of Dementia, Assessed Using the CDR-Global Score (CDR-GS) |
|---|---|
| Description | The CDR-GS represents a semi-structured interview which 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 CDR 0 = no dementia and CDR 0.5, 1, 2 or 3 = questionable, mild, moderate or severe dementia respectively. The range in scores for the CDR-GS is from 0 to 3 and a high score on the CDR-GS would indicate a high disease severity. The difference in mean change from Baseline to Week 105 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline. |
| Time Frame | Baseline, Week 105 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent-To-Treat population (Placebo (n = 407); Cren (n = 402)) was defined as all randomized participants who received at least 1 dose of study drug, with participants grouped according to the treatment assigned at randomization. Data presented below is only for participants that were included in the actual analysis. |
| Arm/Group Title | Placebo | Crenezumab |
|---|---|---|
| Arm/Group Description | Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks. | Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks. |
| Measure Participants | 88 | 86 |
| Least Squares Mean (Standard Error) [Units on a Scale] |
0.55
(0.056)
|
0.50
(0.056)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Crenezumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference |
| Estimated Value | 0.05 | |
| Confidence Interval |
(2-Sided) 95% -0.10 to 0.20 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.076 |
|
| Estimation Comments | ||
| Title | Change From Baseline to Week 105 on Severity of Dementia, Assessed Using the Mini Mental State Evaluation (MMSE) |
|---|---|
| Description | The MMSE is a set of standardized questions used to evaluate possible cognitive impairment and help stage the severity level of this impairment. The questions target 6 areas: orientation, registration, attention, short-term recall, language and constructional praxis/visuospatial abilities. The scores on the MMSE range from 0 to 30, with higher scores indicating better function. The difference in mean change from Baseline to Week 105 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline. |
| Time Frame | Baseline, Week 105 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent-To-Treat population (Placebo (n = 407); Cren (n = 402)) was defined as all randomized participants who received at least 1 dose of study drug, with participants grouped according to the treatment assigned at randomization. Data presented below is only for participants that were included in the actual analysis. |
| Arm/Group Title | Placebo | Crenezumab |
|---|---|---|
| Arm/Group Description | Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks. | Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks. |
| Measure Participants | 90 | 87 |
| Least Squares Mean (Standard Error) [Units on a Scale] |
-4.63
(0.377)
|
-4.96
(0.383)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Crenezumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference |
| Estimated Value | 0.33 | |
| Confidence Interval |
(2-Sided) 95% -0.62 to 1.29 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.486 |
|
| Estimation Comments | ||
| Title | Change From Baseline to Week 105 on Function as Assessed by the ADCS-ADL Total Score |
|---|---|
| Description | 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 105 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline. |
| Time Frame | Baseline, Week 105 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent-To-Treat population (Placebo (n = 407); Cren (n = 402)) was defined as all randomized participants who received at least 1 dose of study drug, with participants grouped according to the treatment assigned at randomization. Data presented below is only for participants that were included in the actual analysis. |
| Arm/Group Title | Placebo | Crenezumab |
|---|---|---|
| Arm/Group Description | Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks. | Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks. |
| Measure Participants | 90 | 88 |
| Least Squares Mean (Standard Error) [Units on a Scale] |
-11.51
(1.226)
|
-13.39
(1.242)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Crenezumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference |
| Estimated Value | 1.88 | |
| Confidence Interval |
(2-Sided) 95% -1.43 to 5.18 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.679 |
|
| Estimation Comments | ||
| Title | Change From Baseline to Week 105 on Function as Assessed by the ADCS-instrumental (ADCS-iADL) Subscore |
|---|---|
| Description | The ADCS-iADL (Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living) measures activities such as using the telephone, managing finances and preparing a meal. The ADCS-iADL consists of 16 questions with a score range of 0 to 56 where a higher score represents better function. The difference in mean change from Baseline to Week 105 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline. |
| Time Frame | Baseline, Week 105 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent-To-Treat population (Placebo (n = 407); Cren (n = 402)) was defined as all randomized participants who received at least 1 dose of study drug, with participants grouped according to the treatment assigned at randomization. Data presented below is only for participants that were included in the actual analysis. |
| Arm/Group Title | Placebo | Crenezumab |
|---|---|---|
| Arm/Group Description | Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks. | Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks. |
| Measure Participants | 90 | 88 |
| Least Squares Mean (Standard Error) [Units on a Scale] |
-9.22
(0.967)
|
-10.44
(0.979)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Crenezumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference |
| Estimated Value | 1.22 | |
| Confidence Interval |
(2-Sided) 95% -1.35 to 3.79 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.306 |
|
| Estimation Comments | ||
| Title | Change From Baseline to Week 105 on a Measure of Dependence Derived From the ADCS-ADL Score |
|---|---|
| Description | 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 105 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline. |
| Time Frame | Baseline, Week 105 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Please note that for this Outcome Measure, no participants were evaluated at all as the derivation of this endpoint was not pre-specified before the Sponsor terminated the study and therefore it was not reported. |
| Arm/Group Title | Placebo | Crenezumab |
|---|---|---|
| Arm/Group Description | Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks. | Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks. |
| Measure Participants | 0 | 0 |
| Title | Change From Baseline to Week 105 Assessed Using the Neuropsychiatric Inventory Questionnaire (NPI-Q) |
|---|---|
| Description | The NPI-Q is an informant-based instrument that evaluates 12 neuropsychiatric disturbances common in dementia: delusions, hallucinations, agitation, dysphoria, anxiety, apathy, irritability, euphoria, disinhibition, aberrant motor behavior, night-time behavioral disturbances and appetite and eating abnormalities. The severity of each neuropsychiatric symptom is rated on a 3-point scale (mild, moderate and marked). The total severity score range is from 0 to 36 with higher scores representing higher severity. The difference in mean change from Baseline to Week 105 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline. |
| Time Frame | Baseline, Week 105 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent-To-Treat population (Placebo (n = 407); Cren (n = 402)) was defined as all randomized participants who received at least 1 dose of study drug, with participants grouped according to the treatment assigned at randomization. Data presented below is only for participants that were included in the actual analysis. |
| Arm/Group Title | Placebo | Crenezumab |
|---|---|---|
| Arm/Group Description | Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks. | Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks. |
| Measure Participants | 84 | 87 |
| Least Squares Mean (Standard Error) [Units on a Scale] |
1.02
(0.562)
|
1.55
(0.556)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Crenezumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference |
| Estimated Value | -0.53 | |
| Confidence Interval |
(2-Sided) 95% -1.95 to 0.90 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.723 |
|
| Estimation Comments | ||
| Title | Quality of Life-Alzheimer's Disease (QoL-AD) Scale Score |
|---|---|
| Description | The QoL-AD (Quality of Life - Alzheimer's Disease) scale assesses QoL in participants who have dementia. The QoL-AD consists of 13 items covering aspects of participants' relationships with friends and family, physical condition, mood, concerns about finances and overall assessment of QoL. Items are rated on 4-point Likert-type scales ranging from 1 [poor] to 4 [excellent]. The score range is from 13 to 52, with higher scores indicating a better QoL. The difference in mean change from Baseline to Week 105 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline. |
| Time Frame | Baseline up to Week 105 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent-To-Treat population (Placebo (n = 407); Cren (n = 402)) was defined as all randomized participants who received at least 1 dose of study drug, with participants grouped according to the treatment assigned at randomization. Data presented below is only for participants that were included in the actual analysis. |
| Arm/Group Title | Placebo | Crenezumab |
|---|---|---|
| Arm/Group Description | Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks. | Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks. |
| Measure Participants | 90 | 86 |
| Least Squares Mean (Standard Error) [Units on a Scale] |
-1.69
(0.501)
|
-2.08
(0.513)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Crenezumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference |
| Estimated Value | 0.40 | |
| Confidence Interval |
(2-Sided) 95% -0.81 to 1.60 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.609 |
|
| Estimation Comments | ||
| Title | Zarit Caregiver Interview for Alzheimer's Disease (ZCI-AD) Scale Score |
|---|---|
| Description | The ZCI-AD is a modified version of the Zarit Burden Interview, which was originally designed to reflect the stresses experienced by caregivers of people with dementia. This modified version includes slight modifications in item and title wording (e.g., removal of "your relative" to refer directly to the patient, removal of "burden" from title) and the use of 11-point numerical rating scales. The ZCI-AD scale consists of a total of 30 items. Total scores will be calculated with a total score range from 0 to 300 (higher scores indicate a higher burden on the caregiver). The difference in mean change from Baseline to Week 105 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline. |
| Time Frame | Baseline up to Week 105 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent-To-Treat population (Placebo (n = 407); Cren (n = 402)) was defined as all randomized participants who received at least 1 dose of study drug, with participants grouped according to the treatment assigned at randomization. Data presented below is only for participants that were included in the actual analysis. |
| Arm/Group Title | Placebo | Crenezumab |
|---|---|---|
| Arm/Group Description | Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks. | Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks. |
| Measure Participants | 86 | 87 |
| Least Squares Mean (Standard Error) [Units on a Scale] |
22.72
(5.135)
|
24.11
(5.106)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Crenezumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference |
| Estimated Value | -1.39 | |
| Confidence Interval |
(2-Sided) 95% -13.64 to 10.86 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 6.214 |
|
| Estimation Comments | ||
| Title | EQ-5D Questionnaire Domain Score for Participants |
|---|---|
| Description | The EQ-5D is a standardized measure of health status designed to provide a simple generic measure of health for clinical and economic appraisal. It is broadly applicable across a wide range of health conditions and treatment. The EQ-5D assesses five domains to provide a health state index. These are anxiety/depression, pain/discomfort, usual activities, mobility, and self-care. The scores on the EQ-5D ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). The difference in mean change from Baseline to Week 105 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline. |
| Time Frame | Baseline up to Week 105 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent-To-Treat population (Placebo (n = 407); Cren (n = 402)) was defined as all randomized participants who received at least 1 dose of study drug, with participants grouped according to the treatment assigned at randomization. Data presented below is only for participants that were included in the actual analysis. |
| Arm/Group Title | Placebo | Crenezumab |
|---|---|---|
| Arm/Group Description | Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks. | Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks. |
| Measure Participants | 89 | 87 |
| Least Squares Mean (Standard Error) [Units on a Scale] |
-4.54
(1.732)
|
-6.35
(1.761)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Crenezumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference |
| Estimated Value | 1.82 | |
| Confidence Interval |
(2-Sided) 95% -2.64 to 6.27 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.260 |
|
| Estimation Comments | ||
| Title | EQ-5D Questionnaire Domain Score for Caregivers |
|---|---|
| Description | The EQ-5D is a standardized measure of health status designed to provide a simple generic measure of health for clinical and economic appraisal. It is broadly applicable across a wide range of health conditions and treatment. The EQ-5D assesses five domains to provide a health state index. These are anxiety/depression, pain/discomfort, usual activities, mobility, and self-care. The scores on the EQ-5D ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). The difference in mean change from Baseline to Week 105 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline. |
| Time Frame | Baseline up to Week 105 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent-To-Treat population (Placebo (n = 407); Cren (n = 402)) was defined as all randomized participants who received at least 1 dose of study drug, with participants grouped according to the treatment assigned at randomization. Data presented below is only for participants that were included in the actual analysis. |
| Arm/Group Title | Placebo | Crenezumab |
|---|---|---|
| Arm/Group Description | Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks. | Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks. |
| Measure Participants | 89 | 88 |
| Least Squares Mean (Standard Error) [Units on a Scale] |
-3.16
(1.713)
|
-4.09
(1.721)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Crenezumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference |
| Estimated Value | 0.94 | |
| Confidence Interval |
(2-Sided) 95% -3.45 to 5.32 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.222 |
|
| Estimation Comments | ||
| Title | Percentage of Participants With Adverse Event (AEs) and Serious Adverse Event (SAEs) |
|---|---|
| Description | An Adverse Event is any untoward medical occurrence in a participant 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. |
| Time Frame | Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks). |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety analysis population included all randomized participants who received at least 1 dose of study drug with participants grouped according to actual treatment received. If a participant received at least 2 vials of crenezumab, then they were placed in the crenezumab arm. |
| Arm/Group Title | Placebo | Crenezumab |
|---|---|---|
| Arm/Group Description | Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks. | Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks. |
| Measure Participants | 405 | 404 |
| AEs |
83.2
|
85.9
|
| SAEs |
15.6
|
16.6
|
| Title | Percentage of Participants With Anti-Crenezumab Antibodies |
|---|---|
| Description | Participants were considered positive or negative for ADA based on their baseline and post-baseline sample results. The number and percentage of participants with confirmed positive ADA levels were determined for Crenezumab and Placebo groups. The prevalence of ADA at baseline was calculated as the proportion of participants with confirmed positive ADA levels at baseline relative to the total number of participants with a sample available at baseline. The incidence of treatment-emergent ADAs was determined as the proportion of participants with confirmed post-baseline positive ADAs relative to the total number of participants that had at least one post-baseline sample available for ADA analysis. |
| Time Frame | Baseline up to Week 105 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety analysis population included all randomized participants who received at least 1 dose of study drug with participants grouped according to actual treatment received. If a participant received at least 2 vials of crenezumab, then they were placed in the crenezumab arm. Data below is only for participants included in the actual analysis. |
| Arm/Group Title | Placebo | Crenezumab |
|---|---|---|
| Arm/Group Description | Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks. | Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks. |
| Measure Participants | 385 | 404 |
| Baseline ADAs |
0.3
|
0.2
|
| Treatment Emergent ADAs |
0.5
|
0.5
|
| Title | Serum Concentration of Crenezumab |
|---|---|
| Description | Serum concentration data for Crenezumab will be tabulated and summarized. Descriptive summary statistics will include the arithmetic mean and SD. Since a sparse PK sampling design is being used, population (non-linear mixed-effects) modeling will be used to analyze the dose concentration-time data of crenezumab. Information from other clinical studies may be incorporated to establish the PK model. Please note that Post-dose samples were not collected at Weeks 37 and 105. |
| Time Frame | Pre-infusion (0 hour), 60-90 minutes post-infusion on Day 1 Week 1 and on Week 25; Weeks 13, 37 (Pre-dose), 53, 77 and 105 (infusion length = as per the Pharmacy Manual) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK Analysis population was defined as all participants who have received at least one dose of crenezumab and with at least one evaluable post-dose PK sample. Data presented below is only for participants that were included in the actual analysis. |
| Arm/Group Title | Crenezumab |
|---|---|
| Arm/Group Description | Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks. |
| Measure Participants | 392 |
| Week 1 Day 1 Predose |
NA
(NA)
|
| Week 1 Day 1 Postdose |
1350
(319)
|
| Week 13 Predose |
345
(146)
|
| Week 13 Postdose |
1580
(487)
|
| Week 25 Predose |
369
(130)
|
| Week 25 Postdose |
1700
(443)
|
| Week 37 Predose |
368
(152)
|
| Week 53 Predose |
393
(164)
|
| Week 53 Postdose |
1800
(420)
|
| Week 77 Predose |
410
(261)
|
| Week 77 Postdose |
1790
(496)
|
| Week 105 |
408
(186)
|
| Title | Plasma Amyloid Beta (Abeta) 40 Concentrations |
|---|---|
| Description | Plasma Abeta 40 concentrations will be measured over time and descriptive summary statistics will include the arithmetic mean and SD. Please note that a Post-dose sample was only collected at Week 13. |
| Time Frame | Week 1 Day 1; Weeks 13, 25, 53, 77 and 105 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PD Analysis population was defined as all participants who have received at least one dose of crenezumab and with at least one evaluable post-dose PK sample. Data presented below is only for participants that were included in the actual analysis. |
| Arm/Group Title | Crenezumab |
|---|---|
| Arm/Group Description | Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks. |
| Measure Participants | 101 |
| Week 1 Day 1 Predose |
0.377
(0.136)
|
| Week 13 Predose |
44.6
(10.0)
|
| Week 13 Postdose |
44.3
(9.5)
|
| Week 25 Predose |
46.4
(10.1)
|
| Week 53 Predose |
48.8
(10.7)
|
| Week 77 Predose |
47.5
(12.2)
|
| Week 105 Predose |
48.6
(14.0)
|
| Title | Plasma Amyloid Beta (Abeta) 42 Concentrations |
|---|---|
| Description | Plasma Abeta 42 concentrations will be measured over time and descriptive summary statistics will include the arithmetic mean and SD. Please note that a Post-dose sample was only collected at Week 13. |
| Time Frame | Week 1 Day 1; Weeks 13, 25, 53, 77 and 105 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PD Analysis population was defined as all participants who have received at least one dose of crenezumab and with at least one evaluable post-dose PK sample. Data presented below is only for participants that were included in the actual analysis. |
| Arm/Group Title | Crenezumab |
|---|---|
| Arm/Group Description | Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks. |
| Measure Participants | 101 |
| Week 1 Day 1 Predose |
0.0335
(0.00812)
|
| Week 13 Predose |
2.72
(0.553)
|
| Week 13 Postdose |
2.71
(0.602)
|
| Week 25 Predose |
2.73
(0.55)
|
| Week 53 Predose |
2.87
(0.589)
|
| Week 77 Predose |
2.79
(0.68)
|
| Week 105 Predose |
2.87
(0.818)
|
| Title | Percentage Change From Baseline to Week 105 in Whole Brain Volume as Determined by Magnetic Resonance Imaging (MRI) |
|---|---|
| Description | Percentage Change in Whole Brain Volume will be measured over time and descriptive summary statistics will include the arithmetic mean, median, range, SD, and coefficient of variation, as appropriate. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline. |
| Time Frame | Baseline, Week 105 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent-To-Treat population (Placebo (n = 407); Cren (n = 402)) was defined as all randomized participants who received at least 1 dose of study drug, with participants grouped according to the treatment assigned at randomization. Data presented below is only for participants that were included in the actual analysis. |
| Arm/Group Title | Placebo | Crenezumab |
|---|---|---|
| Arm/Group Description | Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks. | Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks. |
| Measure Participants | 180 | 172 |
| Least Squares Mean (Standard Error) [Percentage] |
-2.66
(0.091)
|
-2.65
(0.092)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Crenezumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference |
| Estimated Value | -0.01 | |
| Confidence Interval |
(2-Sided) 95% -0.24 to 0.22 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.116 |
|
| Estimation Comments | ||
| Title | Percentage Change From Baseline to Week 105 in Ventricle Volume as Determined by Magnetic Resonance Imaging (MRI) |
|---|---|
| Description | Percentage Change in Ventricle Volume will be measured over time and descriptive summary statistics will include the arithmetic mean, median, range, SD, and coefficient of variation, as appropriate. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline. |
| Time Frame | Baseline, Week 105 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent-To-Treat population (Placebo (n = 407); Cren (n = 402)) was defined as all randomized participants who received at least 1 dose of study drug, with participants grouped according to the treatment assigned at randomization. Data presented below is only for participants that were included in the actual analysis. |
| Arm/Group Title | Placebo | Crenezumab |
|---|---|---|
| Arm/Group Description | Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks. | Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks. |
| Measure Participants | 189 | 181 |
| Least Squares Mean (Standard Error) [Percentage] |
22.29
(0.907)
|
23.57
(0.912)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Crenezumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference |
| Estimated Value | -1.28 | |
| Confidence Interval |
(2-Sided) 95% -3.72 to 1.17 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.245 |
|
| Estimation Comments | ||
| Title | Percentage Change From Baseline to Week 105 in Hippocampal Volume as Determined by Magnetic Resonance Imaging (MRI) |
|---|---|
| Description | Percentage Change in Hippocampal Volume will be measured over time and descriptive summary statistics will include the arithmetic mean, median, range, SD, and coefficient of variation, as appropriate. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline. |
| Time Frame | Baseline, Week 105 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent-To-Treat population (Placebo (n = 407); Cren (n = 402)) was defined as all randomized participants who received at least 1 dose of study drug, with participants grouped according to the treatment assigned at randomization. Data presented below is only for participants that were included in the actual analysis. |
| Arm/Group Title | Placebo | Crenezumab |
|---|---|---|
| Arm/Group Description | Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks. | Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks. |
| Measure Participants | 169 | 160 |
| Least Squares Mean (Standard Error) [Percentage] |
-6.57
(0.200)
|
-6.97
(0.203)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Crenezumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference |
| Estimated Value | 0.39 | |
| Confidence Interval |
(2-Sided) 95% -0.10 to 0.89 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.253 |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks). | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Placebo | Crenezumab | ||
| Arm/Group Description | Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks. | Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks. | ||
All Cause Mortality |
||||
| Placebo | Crenezumab | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/405 (1.2%) | 8/404 (2%) | ||
Serious Adverse Events |
||||
| Placebo | Crenezumab | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 63/405 (15.6%) | 67/404 (16.6%) | ||
| Cardiac disorders | ||||
| ACUTE CORONARY SYNDROME | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| ANGINA UNSTABLE | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| ATRIAL FLUTTER | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| ATRIOVENTRICULAR BLOCK COMPLETE | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| BRADYCARDIA | 2/405 (0.5%) | 2 | 1/404 (0.2%) | 1 |
| CARDIAC ARREST | 1/405 (0.2%) | 1 | 1/404 (0.2%) | 1 |
| CARDIAC FAILURE ACUTE | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| CORONARY ARTERY DISEASE | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| MYOCARDIAL INFARCTION | 2/405 (0.5%) | 2 | 2/404 (0.5%) | 2 |
| MYOCARDIAL ISCHAEMIA | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| Ear and labyrinth disorders | ||||
| VERTIGO | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| Endocrine disorders | ||||
| AUTOIMMUNE THYROIDITIS | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| HYPERPARATHYROIDISM PRIMARY | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| Gastrointestinal disorders | ||||
| ABDOMINAL DISCOMFORT | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| ABDOMINAL PAIN UPPER | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| CHRONIC GASTRITIS | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| COLITIS | 1/405 (0.2%) | 1 | 1/404 (0.2%) | 1 |
| COLITIS ISCHAEMIC | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| CONSTIPATION | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| DIVERTICULUM | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| GASTROINTESTINAL HAEMORRHAGE | 0/405 (0%) | 0 | 2/404 (0.5%) | 3 |
| GASTROINTESTINAL PERFORATION | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| GASTROINTESTINAL ULCER HAEMORRHAGE | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| GASTROINTESTINAL VASCULAR MALFORMATION | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| GASTROOESOPHAGEAL REFLUX DISEASE | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| INGUINAL HERNIA | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| LOWER GASTROINTESTINAL HAEMORRHAGE | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| RECTAL HAEMORRHAGE | 0/405 (0%) | 0 | 2/404 (0.5%) | 2 |
| General disorders | ||||
| CHEST PAIN | 0/405 (0%) | 0 | 2/404 (0.5%) | 3 |
| DEATH | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| NON-CARDIAC CHEST PAIN | 2/405 (0.5%) | 2 | 0/404 (0%) | 0 |
| Hepatobiliary disorders | ||||
| CHOLECYSTITIS ACUTE | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| CHOLELITHIASIS | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| Immune system disorders | ||||
| ANAPHYLACTIC REACTION | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| Infections and infestations | ||||
| APPENDICITIS | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| CELLULITIS | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| DIVERTICULITIS | 3/405 (0.7%) | 3 | 0/404 (0%) | 0 |
| ERYSIPELAS | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| HERPES ZOSTER | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| PERITONITIS | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| PERITONSILLAR ABSCESS | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| PNEUMONIA | 3/405 (0.7%) | 3 | 5/404 (1.2%) | 5 |
| PNEUMONIA BACTERIAL | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| PYELONEPHRITIS | 0/405 (0%) | 0 | 2/404 (0.5%) | 2 |
| SKIN INFECTION | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| TUBERCULOSIS OF CENTRAL NERVOUS SYSTEM | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| URINARY TRACT INFECTION | 0/405 (0%) | 0 | 2/404 (0.5%) | 2 |
| UROSEPSIS | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| VIRAL INFECTION | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||
| CLAVICLE FRACTURE | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| CONCUSSION | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| FACIAL BONES FRACTURE | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| FALL | 1/405 (0.2%) | 1 | 4/404 (1%) | 4 |
| FEMUR FRACTURE | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| HIP FRACTURE | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| RADIUS FRACTURE | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| RIB FRACTURE | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| ROAD TRAFFIC ACCIDENT | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| SKIN LACERATION | 0/405 (0%) | 0 | 2/404 (0.5%) | 2 |
| SKULL FRACTURED BASE | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| SOFT TISSUE INJURY | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| SUBDURAL HAEMATOMA | 3/405 (0.7%) | 4 | 4/404 (1%) | 5 |
| SUBDURAL HAEMORRHAGE | 1/405 (0.2%) | 2 | 0/404 (0%) | 0 |
| TRAUMATIC INTRACRANIAL HAEMORRHAGE | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| ULNA FRACTURE | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| UPPER LIMB FRACTURE | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| WRIST FRACTURE | 2/405 (0.5%) | 2 | 1/404 (0.2%) | 1 |
| Metabolism and nutrition disorders | ||||
| DEHYDRATION | 0/405 (0%) | 0 | 3/404 (0.7%) | 5 |
| DIABETIC KETOACIDOSIS | 2/405 (0.5%) | 3 | 0/404 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| ARTHRALGIA | 0/405 (0%) | 0 | 1/404 (0.2%) | 2 |
| ARTHRITIS | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| INTERVERTEBRAL DISC PROTRUSION | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| LUMBAR SPINAL STENOSIS | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| OSTEOARTHRITIS | 2/405 (0.5%) | 2 | 1/404 (0.2%) | 1 |
| SYSTEMIC SCLERODERMA | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| ADENOCARCINOMA | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| ADENOCARCINOMA GASTRIC | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| BREAST CANCER | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| DIFFUSE LARGE B-CELL LYMPHOMA | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| INVASIVE DUCTAL BREAST CARCINOMA | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| LUNG ADENOCARCINOMA | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| LUNG NEOPLASM MALIGNANT | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| LYMPHOPROLIFERATIVE DISORDER | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| PROSTATE CANCER | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| Nervous system disorders | ||||
| CAROTID ARTERY STENOSIS | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| CENTRAL NERVOUS SYSTEM LESION | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| CEREBRAL HAEMORRHAGE | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| CEREBRAL ISCHAEMIA | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| CEREBROVASCULAR ACCIDENT | 1/405 (0.2%) | 1 | 2/404 (0.5%) | 2 |
| CEREBROVASCULAR DISORDER | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| DEMENTIA ALZHEIMER'S TYPE | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| DEPRESSED LEVEL OF CONSCIOUSNESS | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| HYDROCEPHALUS | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| ISCHAEMIC STROKE | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| LOSS OF CONSCIOUSNESS | 2/405 (0.5%) | 3 | 0/404 (0%) | 0 |
| PARAESTHESIA | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| SEIZURE | 0/405 (0%) | 0 | 2/404 (0.5%) | 2 |
| SUBARACHNOID HAEMORRHAGE | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| SYNCOPE | 4/405 (1%) | 4 | 3/404 (0.7%) | 3 |
| Product Issues | ||||
| DEVICE FAILURE | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| Psychiatric disorders | ||||
| ACUTE PSYCHOSIS | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| AGITATION | 1/405 (0.2%) | 1 | 2/404 (0.5%) | 2 |
| DELIRIUM | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| DELUSION | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| HALLUCINATION, VISUAL | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| PERSONALITY CHANGE | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| SCHIZOPHRENIA | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| Renal and urinary disorders | ||||
| ACUTE KIDNEY INJURY | 0/405 (0%) | 0 | 1/404 (0.2%) | 3 |
| NEPHROLITHIASIS | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| Reproductive system and breast disorders | ||||
| OVARIAN CYST | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| ACUTE INTERSTITIAL PNEUMONITIS | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| PNEUMONIA ASPIRATION | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| PULMONARY EMBOLISM | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| ANGIOEDEMA | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| Surgical and medical procedures | ||||
| CORONARY ARTERY BYPASS | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| SKIN NEOPLASM EXCISION | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| URETHRAL STENT INSERTION | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
| Vascular disorders | ||||
| HYPOTENSION | 0/405 (0%) | 0 | 1/404 (0.2%) | 1 |
| PERIPHERAL ARTERIAL OCCLUSIVE DISEASE | 1/405 (0.2%) | 1 | 0/404 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| Placebo | Crenezumab | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 214/405 (52.8%) | 225/404 (55.7%) | ||
| Gastrointestinal disorders | ||||
| DIARRHOEA | 26/405 (6.4%) | 42 | 25/404 (6.2%) | 27 |
| Infections and infestations | ||||
| BRONCHITIS | 13/405 (3.2%) | 13 | 21/404 (5.2%) | 21 |
| NASOPHARYNGITIS | 33/405 (8.1%) | 41 | 40/404 (9.9%) | 50 |
| UPPER RESPIRATORY TRACT INFECTION | 29/405 (7.2%) | 38 | 33/404 (8.2%) | 36 |
| URINARY TRACT INFECTION | 22/405 (5.4%) | 29 | 20/404 (5%) | 22 |
| Injury, poisoning and procedural complications | ||||
| FALL | 33/405 (8.1%) | 42 | 42/404 (10.4%) | 60 |
| Investigations | ||||
| WEIGHT DECREASED | 11/405 (2.7%) | 11 | 22/404 (5.4%) | 22 |
| Musculoskeletal and connective tissue disorders | ||||
| BACK PAIN | 31/405 (7.7%) | 36 | 26/404 (6.4%) | 38 |
| Nervous system disorders | ||||
| DIZZINESS | 27/405 (6.7%) | 34 | 23/404 (5.7%) | 28 |
| HEADACHE | 45/405 (11.1%) | 60 | 39/404 (9.7%) | 48 |
| Psychiatric disorders | ||||
| ANXIETY | 21/405 (5.2%) | 24 | 28/404 (6.9%) | 31 |
| DEPRESSION | 27/405 (6.7%) | 27 | 28/404 (6.9%) | 28 |
| Skin and subcutaneous tissue disorders | ||||
| RASH | 22/405 (5.4%) | 26 | 7/404 (1.7%) | 8 |
| Vascular disorders | ||||
| HYPERTENSION | 22/405 (5.4%) | 22 | 27/404 (6.7%) | 29 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
| Name/Title | Medical Communications |
|---|---|
| Organization | Hoffmann-La Roche |
| Phone | 800 821-8590 |
| genentech@druginfo.com |
- BN29552
- 2015-003034-27