Trial Outcomes & Findings for A Study of Crenezumab Versus Placebo to Evaluate the Efficacy and Safety in Participants With Prodromal to Mild Alzheimer's Disease (AD) (NCT NCT03114657)
NCT ID: NCT03114657
Last Updated: 2020-07-16
Results Overview
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 77 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.
TERMINATED
PHASE3
806 participants
Baseline, Week 77
2020-07-16
Participant Flow
The study was conducted at 209 centers in 27 countries.
A total of 806 participants were enrolled at 209 centers. 4 participants did not receive any study treatment meaning that the modified intent-to-treat and safety populations consisted of 802 participants.
Participant milestones
| Measure |
Placebo
Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks.
|
Crenezumab
Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
399
|
407
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
399
|
407
|
Reasons for withdrawal
| Measure |
Placebo
Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks.
|
Crenezumab
Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks.
|
|---|---|---|
|
Overall Study
Adverse Event
|
9
|
6
|
|
Overall Study
Death
|
4
|
0
|
|
Overall Study
Multiple Reasons
|
1
|
2
|
|
Overall Study
Physician Decision
|
2
|
2
|
|
Overall Study
Study Terminated By Sponsor
|
355
|
374
|
|
Overall Study
Symptomatic Deterioration
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
28
|
22
|
Baseline Characteristics
A Study of Crenezumab Versus Placebo to Evaluate the Efficacy and Safety in Participants With Prodromal to Mild Alzheimer's Disease (AD)
Baseline characteristics by cohort
| Measure |
Placebo
n=399 Participants
Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks.
|
Crenezumab
n=407 Participants
Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks.
|
Total
n=806 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
70.7 Years
STANDARD_DEVIATION 7.9 • n=5 Participants
|
71.1 Years
STANDARD_DEVIATION 7.5 • n=7 Participants
|
70.9 Years
STANDARD_DEVIATION 7.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
225 Participants
n=5 Participants
|
231 Participants
n=7 Participants
|
456 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
174 Participants
n=5 Participants
|
176 Participants
n=7 Participants
|
350 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
42 Participants
n=5 Participants
|
35 Participants
n=7 Participants
|
77 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
334 Participants
n=5 Participants
|
348 Participants
n=7 Participants
|
682 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not Stated
|
15 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Unknown
|
5 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
8 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
45 Participants
n=5 Participants
|
47 Participants
n=7 Participants
|
92 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Multiple
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
333 Participants
n=5 Participants
|
342 Participants
n=7 Participants
|
675 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 77Population: The Modified Intent-To-Treat population (Placebo (n = 398); Cren (n = 404)) 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.
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 77 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.
Outcome measures
| Measure |
Placebo
n=15 Participants
Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks.
|
Crenezumab
n=12 Participants
Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks.
|
|---|---|---|
|
Change From Baseline to Week 77 in Clinical Dementia Rating-Sum of Boxes (CDR-SB) Scale Score
|
3.19 Units on a Scale
Standard Error 0.434
|
1.89 Units on a Scale
Standard Error 0.471
|
SECONDARY outcome
Timeframe: Baseline, Week 77Population: The Modified Intent-To-Treat population (Placebo (n = 398); Cren (n = 404)) 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.
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 77 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.
Outcome measures
| Measure |
Placebo
n=15 Participants
Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks.
|
Crenezumab
n=12 Participants
Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks.
|
|---|---|---|
|
Change From Baseline to Week 77 in Alzheimer's Disease Assessment Scale-Cognition 13 (ADAS-Cog-13) Subscale Score
|
8.90 Units on a Scale
Standard Error 1.382
|
7.16 Units on a Scale
Standard Error 1.526
|
SECONDARY outcome
Timeframe: Baseline, Week 77Population: The Modified Intent-To-Treat population (Placebo (n = 398); Cren (n = 404)) 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.
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 77 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.
Outcome measures
| Measure |
Placebo
n=15 Participants
Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks.
|
Crenezumab
n=12 Participants
Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks.
|
|---|---|---|
|
Change From Baseline to Week 77 in Alzheimer's Disease Assessment Scale-Cognition 11 (ADAS-Cog-11) Subscale Score
|
7.16 Units on a Scale
Standard Error 1.452
|
6.84 Units on a Scale
Standard Error 1.592
|
SECONDARY outcome
Timeframe: Baseline, Week 77Population: The Modified Intent-To-Treat population (Placebo (n = 398); Cren (n = 404)) 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.
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 77 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.
Outcome measures
| Measure |
Placebo
n=15 Participants
Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks.
|
Crenezumab
n=12 Participants
Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks.
|
|---|---|---|
|
Change From Baseline to Week 77 on Severity of Dementia, Assessed Using the CDR-Global Score (CDR-GS)
|
0.39 Units on a Scale
Standard Error 0.096
|
0.29 Units on a Scale
Standard Error 0.102
|
SECONDARY outcome
Timeframe: Baseline, Week 77Population: The Modified Intent-To-Treat population (Placebo (n = 398); Cren (n = 404)) 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.
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 77 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.
Outcome measures
| Measure |
Placebo
n=15 Participants
Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks.
|
Crenezumab
n=12 Participants
Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks.
|
|---|---|---|
|
Change From Baseline to Week 77 on Severity of Dementia, Assessed Using the Mini Mental State Evaluation (MMSE)
|
-3.63 Units on a Scale
Standard Error 0.672
|
-3.21 Units on a Scale
Standard Error 0.740
|
SECONDARY outcome
Timeframe: Baseline, Week 77Population: The Modified Intent-To-Treat population (Placebo (n = 398); Cren (n = 404)) 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.
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 77 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.
Outcome measures
| Measure |
Placebo
n=15 Participants
Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks.
|
Crenezumab
n=12 Participants
Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks.
|
|---|---|---|
|
Change From Baseline to Week 77 on Function as Assessed by (ADCS-ADL) Total Score
|
-8.83 Units on a Scale
Standard Error 2.064
|
-6.31 Units on a Scale
Standard Error 2.278
|
SECONDARY outcome
Timeframe: Baseline, Week 77Population: The Modified Intent-To-Treat population (Placebo (n = 398); Cren (n = 404)) 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.
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 77 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.
Outcome measures
| Measure |
Placebo
n=15 Participants
Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks.
|
Crenezumab
n=12 Participants
Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks.
|
|---|---|---|
|
Change From Baseline to Week 77 on Function as Assessed by (ADCS-iADL) Instrumental Score
|
-6.69 Units on a Scale
Standard Error 1.692
|
-5.51 Units on a Scale
Standard Error 1.872
|
SECONDARY outcome
Timeframe: Baseline, Week 77Population: The Modified Intent-To-Treat population (Placebo (n = 398); Cren (n = 404)) 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.
The Functional Activities Questionnaire (FAQ) is an instrument consisting of 10 items and assesses instrumental, social and cognitive functioning. The score range is from 0 to 30 with higher scores representing higher impairment. The difference in mean change from Baseline to Week 77 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.
Outcome measures
| Measure |
Placebo
n=15 Participants
Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks.
|
Crenezumab
n=12 Participants
Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks.
|
|---|---|---|
|
Change From Baseline to Week 77 on Function as Assessed by the Functional Activities Questionnaire (FAQ) Total Score
|
5.00 Units on a Scale
Standard Error 0.991
|
4.37 Units on a Scale
Standard Error 1.059
|
SECONDARY outcome
Timeframe: Baseline, Week 77Population: 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.
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 77 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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, Week 53Population: The Modified Intent-To-Treat population (Placebo (n = 398); Cren (n = 404)) 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.
The NPI-Q 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/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. Difference in mean change from Baseline to Week 53 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures adjusting for disease severity, APOEe4 status, geographic region and the use/non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.
Outcome measures
| Measure |
Placebo
n=102 Participants
Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks.
|
Crenezumab
n=110 Participants
Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks.
|
|---|---|---|
|
Change From Baseline to Week 53 on Behavior in Neuropsychiatric Inventory Questionnaire (NPI-Q) Total Score
|
-0.00 Units on a Scale
Standard Error 0.852
|
0.76 Units on a Scale
Standard Error 0.886
|
SECONDARY outcome
Timeframe: Baseline, Week 77Population: The Modified Intent-To-Treat population (Placebo (n = 398); Cren (n = 404)) 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.
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 77 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.
Outcome measures
| Measure |
Placebo
n=15 Participants
Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks.
|
Crenezumab
n=11 Participants
Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks.
|
|---|---|---|
|
Quality of Life-Alzheimer's Disease (QoL-AD) Scale Score
|
-1.61 Units on a Scale
Standard Error 1.310
|
-1.16 Units on a Scale
Standard Error 1.432
|
SECONDARY outcome
Timeframe: Baseline, Week 53Population: The Modified Intent-To-Treat population (Placebo (n = 398); Cren (n = 404)) 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.
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 53 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.
Outcome measures
| Measure |
Placebo
n=101 Participants
Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks.
|
Crenezumab
n=108 Participants
Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks.
|
|---|---|---|
|
Zarit Caregiver Interview for Alzheimer's Disease (ZCI-AD) Scale Score
|
9.20 Units on a Scale
Standard Error 9.292
|
2.65 Units on a Scale
Standard Error 9.643
|
SECONDARY outcome
Timeframe: Baseline, Week 77Population: The Modified Intent-To-Treat population (Placebo (n = 398); Cren (n = 404)) 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.
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 77 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.
Outcome measures
| Measure |
Placebo
n=15 Participants
Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks.
|
Crenezumab
n=12 Participants
Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks.
|
|---|---|---|
|
European Quality of Life-5 Dimensions (EQ-5D) Questionnaire Domain Scores for Participants
|
-3.69 Units on a Scale
Standard Error 3.961
|
-3.39 Units on a Scale
Standard Error 4.392
|
SECONDARY outcome
Timeframe: Baseline, Week 77Population: The Modified Intent-To-Treat population (Placebo (n = 398); Cren (n = 404)) 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.
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 77 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.
Outcome measures
| Measure |
Placebo
n=15 Participants
Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks.
|
Crenezumab
n=12 Participants
Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks.
|
|---|---|---|
|
European Quality of Life-5 Dimensions (EQ-5D) Questionnaire Domain Scores for Caregivers
|
-4.07 Units on a Scale
Standard Error 2.724
|
-0.68 Units on a Scale
Standard Error 3.031
|
SECONDARY outcome
Timeframe: Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=398 Participants
Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks.
|
Crenezumab
n=404 Participants
Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks.
|
|---|---|---|
|
Percentage of Participants With Adverse Event (AEs) and Serious Adverse Event (SAEs)
AEs
|
73.1 Percentage
|
73.5 Percentage
|
|
Percentage of Participants With Adverse Event (AEs) and Serious Adverse Event (SAEs)
SAEs
|
10.6 Percentage
|
8.2 Percentage
|
SECONDARY outcome
Timeframe: Baseline up to Week 105Population: Please note that for this Outcome Measure, no Participants were evaluated at all as the existing immunogenicity data from an identical study (Study BN29552) showed a low potential of Crenezumab to induce Anti-Drug Antibodies (ADAs).
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Pre-infusion (0 hour), 60-90 minutes post-infusion on Day 1 Week 1 and on Week 25; Weeks 13 (Pre-dose), 37 (Pre-dose), 53 (Pre-dose) and 77 (Pre-dose) (infusion length = as per the Pharmacy Manual)Population: 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.
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 5, 13, 37, 53 and 77.
Outcome measures
| Measure |
Placebo
n=138 Participants
Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks.
|
Crenezumab
Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks.
|
|---|---|---|
|
Serum Concentration of Crenezumab
Week 1 Day 1 Predose
|
NA ug/mL
Standard Deviation NA
No Drug was administered at this point so no concentrations detected.
|
—
|
|
Serum Concentration of Crenezumab
Week 1 Day 1 Postdose
|
1260 ug/mL
Standard Deviation 437
|
—
|
|
Serum Concentration of Crenezumab
Week 5 Predose
|
246 ug/mL
Standard Deviation 128
|
—
|
|
Serum Concentration of Crenezumab
Week 13 Predose
|
360 ug/mL
Standard Deviation 162
|
—
|
|
Serum Concentration of Crenezumab
Week 25 Predose
|
401 ug/mL
Standard Deviation 196
|
—
|
|
Serum Concentration of Crenezumab
Week 25 Postdose
|
1650 ug/mL
Standard Deviation 443
|
—
|
|
Serum Concentration of Crenezumab
Week 37 Predose
|
456 ug/mL
Standard Deviation 351
|
—
|
|
Serum Concentration of Crenezumab
Week 53 Predose
|
401 ug/mL
Standard Deviation 130
|
—
|
|
Serum Concentration of Crenezumab
Week 77 Predose
|
357 ug/mL
Standard Deviation 94.2
|
—
|
SECONDARY outcome
Timeframe: Week 1 Day 1; Weeks 53Population: 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.
Plasma Abeta 40 concentrations will be measured over time and descriptive summary statistics will include the arithmetic mean and SD. Please note that Pre-dose samples were only collected at Weeks 1 and 53.
Outcome measures
| Measure |
Placebo
n=36 Participants
Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks.
|
Crenezumab
Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks.
|
|---|---|---|
|
Plasma Amyloid Beta (Abeta) 40 Concentrations
Week 1 Day 1 Predose
|
0.415 ng/mL
Standard Deviation 0.0687
|
—
|
|
Plasma Amyloid Beta (Abeta) 40 Concentrations
Week 53 Predose
|
46.6 ng/mL
Standard Deviation 6.91
|
—
|
SECONDARY outcome
Timeframe: Week 1 Day 1; Weeks 53Population: 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.
Plasma Abeta 42 concentrations will be measured over time and descriptive summary statistics will include the arithmetic mean and SD. Please note that Pre-dose samples were only collected at Weeks 1 and 53.
Outcome measures
| Measure |
Placebo
n=36 Participants
Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks.
|
Crenezumab
Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks.
|
|---|---|---|
|
Plasma Amyloid Beta (Abeta) 42 Concentrations
Week 1 Day 1 Predose
|
0.0331 ng/mL
Standard Deviation 0.00463
|
—
|
|
Plasma Amyloid Beta (Abeta) 42 Concentrations
Week 53 Predose
|
2.94 ng/mL
Standard Deviation 0.473
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 105Population: The Modified Intent-To-Treat population (Placebo (n = 398); Cren (n = 404)) 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.
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.
Outcome measures
| Measure |
Placebo
n=4 Participants
Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks.
|
Crenezumab
n=4 Participants
Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks.
|
|---|---|---|
|
Percentage Change From Baseline to Week 105 in Whole Brain Volume as Determined by Magnetic Resonance Imaging (MRI)
|
-2.71 Percentage
Standard Error 0.444
|
-2.15 Percentage
Standard Error 0.345
|
SECONDARY outcome
Timeframe: Baseline, Week 105Population: The Modified Intent-To-Treat population (Placebo (n = 398); Cren (n = 404)) 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.
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.
Outcome measures
| Measure |
Placebo
n=4 Participants
Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks.
|
Crenezumab
n=4 Participants
Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks.
|
|---|---|---|
|
Percentage Change From Baseline to Week 105 in Ventricle Volume as Determined by Magnetic Resonance Imaging (MRI)
|
18.78 Percentage
Standard Error 1.343
|
17.18 Percentage
Standard Error 1.145
|
SECONDARY outcome
Timeframe: Baseline, Week 105Population: The Modified Intent-To-Treat population (Placebo (n = 398); Cren (n = 404)) 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.
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.
Outcome measures
| Measure |
Placebo
n=2 Participants
Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks.
|
Crenezumab
n=2 Participants
Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks.
|
|---|---|---|
|
Percentage Change From Baseline to Week 105 in Hippocampal Volume as Determined by Magnetic Resonance Imaging (MRI)
|
-6.34 Percentage
Standard Error 0.338
|
-5.98 Percentage
Standard Error 0.290
|
Adverse Events
Placebo
Crenezumab
Serious adverse events
| Measure |
Placebo
n=398 participants at risk
Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks.
|
Crenezumab
n=404 participants at risk
Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks.
|
|---|---|---|
|
Blood and lymphatic system disorders
ANAEMIA
|
0.25%
1/398 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.50%
2/404 • Number of events 2 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Cardiac disorders
ATRIAL FIBRILLATION
|
0.50%
2/398 • Number of events 2 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Cardiac disorders
CORONARY ARTERY DISEASE
|
0.25%
1/398 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Cardiac disorders
PALPITATIONS
|
0.00%
0/398 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.25%
1/404 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Cardiac disorders
TACHYCARDIA
|
0.00%
0/398 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.25%
1/404 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Cardiac disorders
TRIFASCICULAR BLOCK
|
0.00%
0/398 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.25%
1/404 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Ear and labyrinth disorders
TINNITUS
|
0.25%
1/398 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Ear and labyrinth disorders
VERTIGO
|
0.50%
2/398 • Number of events 2 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Gastrointestinal disorders
COLITIS ISCHAEMIC
|
0.25%
1/398 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Gastrointestinal disorders
CONSTIPATION
|
0.25%
1/398 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Gastrointestinal disorders
GASTROINTESTINAL HAEMORRHAGE
|
0.25%
1/398 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Gastrointestinal disorders
UPPER GASTROINTESTINAL HAEMORRHAGE
|
0.25%
1/398 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
General disorders
ASTHENIA
|
0.25%
1/398 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
General disorders
CHEST DISCOMFORT
|
0.00%
0/398 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.25%
1/404 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
General disorders
CHEST PAIN
|
0.00%
0/398 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.25%
1/404 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
General disorders
NON-CARDIAC CHEST PAIN
|
0.00%
0/398 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.25%
1/404 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
General disorders
PYREXIA
|
0.25%
1/398 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
General disorders
SUDDEN DEATH
|
0.50%
2/398 • Number of events 2 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Infections and infestations
BACTERAEMIA
|
0.25%
1/398 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Infections and infestations
BRONCHITIS
|
0.00%
0/398 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.25%
1/404 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Infections and infestations
CELLULITIS STAPHYLOCOCCAL
|
0.25%
1/398 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Infections and infestations
CLOSTRIDIUM DIFFICILE INFECTION
|
0.25%
1/398 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Infections and infestations
ENDOCARDITIS
|
0.00%
0/398 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.25%
1/404 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Infections and infestations
ENTEROBACTER PNEUMONIA
|
0.25%
1/398 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Infections and infestations
GASTROENTERITIS
|
0.50%
2/398 • Number of events 2 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Infections and infestations
LIVER ABSCESS
|
0.00%
0/398 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.25%
1/404 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Infections and infestations
NEUROSYPHILIS
|
0.00%
0/398 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.25%
1/404 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Infections and infestations
PHARYNGITIS STREPTOCOCCAL
|
0.00%
0/398 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.25%
1/404 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Infections and infestations
PNEUMONIA
|
0.50%
2/398 • Number of events 2 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.25%
1/404 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Infections and infestations
PNEUMONIA INFLUENZAL
|
0.00%
0/398 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.25%
1/404 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Infections and infestations
STAPHYLOCOCCAL BACTERAEMIA
|
0.25%
1/398 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Infections and infestations
URINARY TRACT INFECTION
|
0.25%
1/398 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Injury, poisoning and procedural complications
ANKLE FRACTURE
|
0.00%
0/398 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.25%
1/404 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Injury, poisoning and procedural complications
CLAVICLE FRACTURE
|
0.25%
1/398 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Injury, poisoning and procedural complications
CRANIOCEREBRAL INJURY
|
0.25%
1/398 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Injury, poisoning and procedural complications
FALL
|
1.5%
6/398 • Number of events 6 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.50%
2/404 • Number of events 2 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Injury, poisoning and procedural complications
HIP FRACTURE
|
0.75%
3/398 • Number of events 3 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Injury, poisoning and procedural complications
HUMERUS FRACTURE
|
0.00%
0/398 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.25%
1/404 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Injury, poisoning and procedural complications
LOWER LIMB FRACTURE
|
0.00%
0/398 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.25%
1/404 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Injury, poisoning and procedural complications
MENISCUS INJURY
|
0.25%
1/398 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Injury, poisoning and procedural complications
PUBIS FRACTURE
|
0.25%
1/398 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Injury, poisoning and procedural complications
RIB FRACTURE
|
0.25%
1/398 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.25%
1/404 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Injury, poisoning and procedural complications
SUBDURAL HAEMATOMA
|
0.00%
0/398 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.74%
3/404 • Number of events 3 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Investigations
ARTHROSCOPY
|
0.00%
0/398 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.25%
1/404 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Metabolism and nutrition disorders
DEHYDRATION
|
0.00%
0/398 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.25%
1/404 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Musculoskeletal and connective tissue disorders
ARTHRITIS
|
0.00%
0/398 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.25%
1/404 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Musculoskeletal and connective tissue disorders
INTERVERTEBRAL DISC PROTRUSION
|
0.00%
0/398 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.25%
1/404 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL PAIN
|
0.25%
1/398 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BONE GIANT CELL TUMOUR MALIGNANT
|
0.25%
1/398 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
CLEAR CELL ENDOMETRIAL CARCINOMA
|
0.25%
1/398 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LUNG ADENOCARCINOMA
|
0.00%
0/398 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.25%
1/404 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LUNG NEOPLASM MALIGNANT
|
0.00%
0/398 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.25%
1/404 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
PROSTATE CANCER
|
0.25%
1/398 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Nervous system disorders
AMYOTROPHIC LATERAL SCLEROSIS
|
0.25%
1/398 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Nervous system disorders
CEREBRAL ARTERIOSCLEROSIS
|
0.25%
1/398 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Nervous system disorders
ISCHAEMIC CEREBRAL INFARCTION
|
0.00%
0/398 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.25%
1/404 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Nervous system disorders
SPEECH DISORDER
|
0.00%
0/398 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.25%
1/404 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Nervous system disorders
SUBARACHNOID HAEMORRHAGE
|
0.00%
0/398 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.25%
1/404 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Nervous system disorders
SUPERIOR SAGITTAL SINUS THROMBOSIS
|
0.25%
1/398 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Nervous system disorders
SYNCOPE
|
0.50%
2/398 • Number of events 2 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Psychiatric disorders
AGGRESSION
|
0.25%
1/398 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Psychiatric disorders
DELUSION
|
0.25%
1/398 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Psychiatric disorders
DEPRESSIVE SYMPTOM
|
0.00%
0/398 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.25%
1/404 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Psychiatric disorders
SUICIDE THREAT
|
0.00%
0/398 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.25%
1/404 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Respiratory, thoracic and mediastinal disorders
ASTHMA
|
0.25%
1/398 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Respiratory, thoracic and mediastinal disorders
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
|
0.00%
0/398 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.25%
1/404 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
0.25%
1/398 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
0.50%
2/398 • Number of events 3 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Respiratory, thoracic and mediastinal disorders
INTERSTITIAL LUNG DISEASE
|
0.25%
1/398 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY EMBOLISM
|
0.25%
1/398 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.25%
1/404 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Skin and subcutaneous tissue disorders
SKIN ULCER
|
0.00%
0/398 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.25%
1/404 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Surgical and medical procedures
CARDIAC ABLATION
|
0.00%
0/398 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.25%
1/404 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Surgical and medical procedures
KNEE ARTHROPLASTY
|
0.00%
0/398 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.25%
1/404 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Vascular disorders
ARTERIOVENOUS FISTULA
|
0.25%
1/398 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Vascular disorders
HYPERTENSIVE CRISIS
|
0.25%
1/398 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Vascular disorders
HYPOTENSION
|
0.25%
1/398 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.25%
1/404 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Vascular disorders
PERIPHERAL VASCULAR DISORDER
|
0.00%
0/398 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.25%
1/404 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Vascular disorders
SHOCK HAEMORRHAGIC
|
0.25%
1/398 • Number of events 1 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
0.00%
0/404 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
Other adverse events
| Measure |
Placebo
n=398 participants at risk
Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks.
|
Crenezumab
n=404 participants at risk
Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks.
|
|---|---|---|
|
Infections and infestations
NASOPHARYNGITIS
|
6.3%
25/398 • Number of events 32 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
5.9%
24/404 • Number of events 28 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Injury, poisoning and procedural complications
FALL
|
5.0%
20/398 • Number of events 34 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
4.7%
19/404 • Number of events 26 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Nervous system disorders
HEADACHE
|
5.5%
22/398 • Number of events 28 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
6.2%
25/404 • Number of events 30 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
|
Vascular disorders
HYPERTENSION
|
3.8%
15/398 • Number of events 18 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
6.7%
27/404 • Number of events 29 • Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER