CREAD

TerminatedPhase 3Results posted

A Study Evaluating the Efficacy and Safety of Crenezumab Versus Placebo in Participants With Prodromal to Mild Alzheimer's Disease (AD).

A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy And Safety Study of Crenezumab in Patients With Prodromal to Mild Alzheimer's Disease.

Lead sponsor

Hoffmann-La Roche

Asset

Crenezumab

Listed sites

196

Recruiting sites

Enrollment

813

actual

Study population

Alzheimer’s disease

Key I/E criteria

•prodromal AD•Amyloid biomarker required (PET/CSF)•MMSE ≥22•MRI contraindications excluded

Primary endpoint

•Clinical Dementia Rating-Sum of Boxes (CDR-SB)

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Eudract number2015-003034-27

Org study IDBN29552

NCT IDNCT02670083

Timeline

Milestones

Study first posted2016-02-01estimated

Study start2016-03-22actual

Primary completion2019-05-31actual

Study completion2019-05-31actual

Last update posted2020-07-16actual

Results first posted2020-07-16actual

Assets

Drug assets

Crenezumab

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age50 Years

Maximum age85 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Weight between 40 and 120 kilograms (Kg) inclusive

•Availability of a person (referred to as the "caregiver") who in the investigator's judgment:

•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

•Fluency in the language of the tests used at the study site

•Adequate visual and auditory acuity, in the investigator's judgment, sufficient to perform the neuropsychological testing (eye glasses and hearing aids are permitted)

•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

•Demonstrated abnormal memory function at screening (up to 4 weeks before screening begins) or screening (FCSRT cueing index =<0.67 AND free recall =<27)

•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

•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)

•If receiving symptomatic AD medications, the dosing regimen must have been stable for 3 months prior to screening

•Participant must have completed at least 6 years of formal education after the age of 5 years

Exclusion criteria

•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.

•History of major psychiatric illness such as schizophrenia or major depression (if not considered in remission)

•At risk of suicide in the opinion of the investigator

•Any abnormal MRI findings, such as presence of cerebral vascular pathology, cortical stroke, etc or inability to tolerate MRI procedures or contraindication to MRI

•Unstable or clinically significant cardiovascular (e.g., myocardial infarction), kidney or liver disease

•Uncontrolled hypertension

•Screening hemoglobin A1c (HbA1C) >8%

•Poor peripheral venous access

•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

Endpoints (42)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Global cognition

Behavior / neuropsychiatric

Function / daily living

Neuroimaging

Amyloid biomarkers

Other (unclassified)

Memory

Caregiver / quality of life

Safety / tolerability / PK

Global cognition

8 endpoints

Primary/protocol endpoint

Change From Baseline to Week 105 in Clinical Dementia Rating-Sum of Boxes (CDR-SB) Score

Time frame:Baseline, Week 105

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Primary/registry result

Change From Baseline to Week 105 in Clinical Dementia Rating-Sum of Boxes (CDR-SB) Score

Time frame:Baseline, Week 105

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Units on a Scale	Standard error
Placebon=88 Participants	3.42	0.263
Crenezumabn=86 Participants	3.59	0.264

Least Squares Mean Difference-0.1795% CI-0.86 - 0.53

Secondary/protocol endpoint

Change From Baseline to Week 105 on Cognition, as Assessed by Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog) (Subscale) 13 (ADAS-Cog-13)

Time frame:Baseline, Week 105

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline to Week 105 on Cognition, as Assessed by Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog) (Subscale) 11 (ADAS-Cog-11)

Time frame:Baseline, Week 105

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline to Week 105 on Severity of Dementia, Assessed Using the Mini Mental State Evaluation (MMSE)

Time frame:Baseline, Week 105

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Secondary/registry result

Change From Baseline to Week 105 on Cognition, as Assessed by Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog) (Subscale) 13 (ADAS-Cog-13)

Time frame:Baseline, Week 105

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Units on a Scale	Standard error
Placebon=86 Participants	9.55	0.824
Crenezumabn=80 Participants	9.82	0.841

Least Squares Mean Difference-0.2695% CI-2.39 - 1.87

Secondary/registry result

Change From Baseline to Week 105 on Cognition, as Assessed by Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog) (Subscale) 11 (ADAS-Cog-11)

Time frame:Baseline, Week 105

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Units on a Scale	Standard error
Placebon=86 Participants	8.43	0.758
Crenezumabn=80 Participants	8.53	0.773

Least Squares Mean Difference-0.1095% CI-2.08 - 1.88

Secondary/registry result

Change From Baseline to Week 105 on Severity of Dementia, Assessed Using the Mini Mental State Evaluation (MMSE)

Time frame:Baseline, Week 105

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Units on a Scale	Standard error
Placebon=90 Participants	-4.63	0.377
Crenezumabn=87 Participants	-4.96	0.383

Least Squares Mean Difference0.3395% CI-0.62 - 1.29

Memory

2 endpoints

Secondary/protocol endpoint

Change From Baseline to Week 105 on Severity of Dementia, Assessed Using the CDR-Global Score (CDR-GS)

Time frame:Baseline, Week 105

change from baseline, improvement

Secondary/registry result

Change From Baseline to Week 105 on Severity of Dementia, Assessed Using the CDR-Global Score (CDR-GS)

Time frame:Baseline, Week 105

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Units on a Scale	Standard error
Placebon=88 Participants	0.55	0.056
Crenezumabn=86 Participants	0.50	0.056

Least Squares Mean Difference0.0595% CI-0.10 - 0.20

Function / daily living

6 endpoints

Secondary/protocol endpoint

Change From Baseline to Week 105 on Function as Assessed by the ADCS-ADL Total Score

Time frame:Baseline, Week 105

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline to Week 105 on Function as Assessed by the ADCS-instrumental (ADCS-iADL) Subscore

Time frame:Baseline, Week 105

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline to Week 105 on a Measure of Dependence Derived From the ADCS-ADL Score

Time frame:Baseline, Week 105

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Secondary/registry result

Change From Baseline to Week 105 on Function as Assessed by the ADCS-ADL Total Score

Time frame:Baseline, Week 105

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Units on a Scale	Standard error
Placebon=90 Participants	-11.51	1.226
Crenezumabn=88 Participants	-13.39	1.242

Least Squares Mean Difference1.8895% CI-1.43 - 5.18

Secondary/registry result

Change From Baseline to Week 105 on Function as Assessed by the ADCS-instrumental (ADCS-iADL) Subscore

Time frame:Baseline, Week 105

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Units on a Scale	Standard error
Placebon=90 Participants	-9.22	0.967
Crenezumabn=88 Participants	-10.44	0.979

Least Squares Mean Difference1.2295% CI-1.35 - 3.79

Secondary/registry result

Change From Baseline to Week 105 on a Measure of Dependence Derived From the ADCS-ADL Score

Time frame:Baseline, Week 105

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Behavior / neuropsychiatric

8 endpoints

Secondary/protocol endpoint

Change From Baseline to Week 105 Assessed Using the Neuropsychiatric Inventory Questionnaire (NPI-Q)

Time frame:Baseline, Week 105

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/protocol endpoint

Quality of Life-Alzheimer's Disease (QoL-AD) Scale Score

Time frame:Baseline up to Week 105

change from baseline, improvement

Secondary/protocol endpoint

EQ-5D Questionnaire Domain Score for Participants

Time frame:Baseline up to Week 105

change from baseline, improvement

Secondary/protocol endpoint

EQ-5D Questionnaire Domain Score for Caregivers

Time frame:Baseline up to Week 105

change from baseline, improvement

Secondary/registry result

Change From Baseline to Week 105 Assessed Using the Neuropsychiatric Inventory Questionnaire (NPI-Q)

Time frame:Baseline, Week 105

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Units on a Scale	Standard error
Placebon=84 Participants	1.02	0.562
Crenezumabn=87 Participants	1.55	0.556

Least Squares Mean Difference-0.5395% CI-1.95 - 0.90

Secondary/registry result

Quality of Life-Alzheimer's Disease (QoL-AD) Scale Score

Time frame:Baseline up to Week 105

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Units on a Scale	Standard error
Placebon=90 Participants	-1.69	0.501
Crenezumabn=86 Participants	-2.08	0.513

Least Squares Mean Difference0.4095% CI-0.81 - 1.60

Secondary/registry result

EQ-5D Questionnaire Domain Score for Participants

Time frame:Baseline up to Week 105

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Units on a Scale	Standard error
Placebon=89 Participants	-4.54	1.732
Crenezumabn=87 Participants	-6.35	1.761

Least Squares Mean Difference1.8295% CI-2.64 - 6.27

Secondary/registry result

EQ-5D Questionnaire Domain Score for Caregivers

Time frame:Baseline up to Week 105

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Units on a Scale	Standard error
Placebon=89 Participants	-3.16	1.713
Crenezumabn=88 Participants	-4.09	1.721

Least Squares Mean Difference0.9495% CI-3.45 - 5.32

Amyloid biomarkers

4 endpoints

Secondary/protocol endpoint

Plasma Amyloid Beta (Abeta) 40 Concentrations

Time frame:Week 1 Day 1; Weeks 13, 25, 53, 77 and 105

concentration, descriptive

Secondary/protocol endpoint

Plasma Amyloid Beta (Abeta) 42 Concentrations

Time frame:Week 1 Day 1; Weeks 13, 25, 53, 77 and 105

concentration, descriptive

Secondary/registry result

Plasma Amyloid Beta (Abeta) 40 Concentrations

Time frame:Week 1 Day 1; Weeks 13, 25, 53, 77 and 105

concentration, descriptive

Posted result

Group	Value (mean), ng/mL	Standard deviation
CrenezumabWeek 1 Day 1 Predosen=101 Participants	0.377	0.136
Week 13 Predosen=20 Participants	44.6	10.0
Week 13 Postdosen=21 Participants	44.3	9.5
Week 25 Predosen=46 Participants	46.4	10.1
Week 53 Predosen=94 Participants	48.8	10.7
Week 77 Predosen=40 Participants	47.5	12.2
Week 105 Predosen=38 Participants	48.6	14.0

Secondary/registry result

Plasma Amyloid Beta (Abeta) 42 Concentrations

Time frame:Week 1 Day 1; Weeks 13, 25, 53, 77 and 105

concentration, descriptive

Posted result

Group	Value (mean), ng/mL	Standard deviation
CrenezumabWeek 1 Day 1 Predosen=101 Participants	0.0335	0.00812
Week 13 Predosen=20 Participants	2.72	0.553
Week 13 Postdosen=21 Participants	2.71	0.602
Week 25 Predosen=46 Participants	2.73	0.55
Week 53 Predosen=94 Participants	2.87	0.589
Week 77 Predosen=40 Participants	2.79	0.68
Week 105 Predosen=38 Participants	2.87	0.818

Neuroimaging

6 endpoints

Secondary/protocol endpoint

Percentage Change From Baseline to Week 105 in Whole Brain Volume as Determined by Magnetic Resonance Imaging (MRI)

Time frame:Baseline, Week 105

percent change from baseline, improvement

Secondary/protocol endpoint

Percentage Change From Baseline to Week 105 in Ventricle Volume as Determined by Magnetic Resonance Imaging (MRI)

Time frame:Baseline, Week 105

percent change from baseline, improvement

Secondary/protocol endpoint

Percentage Change From Baseline to Week 105 in Hippocampal Volume as Determined by Magnetic Resonance Imaging (MRI)

Time frame:Baseline, Week 105

percent change from baseline, improvement

Secondary/registry result

Percentage Change From Baseline to Week 105 in Whole Brain Volume as Determined by Magnetic Resonance Imaging (MRI)

Time frame:Baseline, Week 105

percent change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Percentage	Standard error
Placebon=180 Participants	-2.66	0.091
Crenezumabn=172 Participants	-2.65	0.092

Least Squares Mean Difference-0.0195% CI-0.24 - 0.22

Secondary/registry result

Percentage Change From Baseline to Week 105 in Ventricle Volume as Determined by Magnetic Resonance Imaging (MRI)

Time frame:Baseline, Week 105

percent change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Percentage	Standard error
Placebon=189 Participants	22.29	0.907
Crenezumabn=181 Participants	23.57	0.912

Least Squares Mean Difference-1.2895% CI-3.72 - 1.17

Secondary/registry result

Percentage Change From Baseline to Week 105 in Hippocampal Volume as Determined by Magnetic Resonance Imaging (MRI)

Time frame:Baseline, Week 105

percent change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Percentage	Standard error
Placebon=169 Participants	-6.57	0.200
Crenezumabn=160 Participants	-6.97	0.203

Least Squares Mean Difference0.3995% CI-0.10 - 0.89

Caregiver / quality of life

2 endpoints

Secondary/protocol endpoint

Zarit Caregiver Interview for Alzheimer's Disease (ZCI-AD) Scale Score

Time frame:Baseline up to Week 105

change from baseline, improvement

Secondary/registry result

Zarit Caregiver Interview for Alzheimer's Disease (ZCI-AD) Scale Score

Time frame:Baseline up to Week 105

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Units on a Scale	Standard error
Placebon=86 Participants	22.72	5.135
Crenezumabn=87 Participants	24.11	5.106

Least Squares Mean Difference-1.3995% CI-13.64 - 10.86

Safety / tolerability / PK

2 endpoints

Secondary/protocol endpoint

Percentage of Participants With Adverse Event (AEs) and Serious Adverse Event (SAEs)

Time frame:Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).

threshold achievement, event

Secondary/registry result

Percentage of Participants With Adverse Event (AEs) and Serious Adverse Event (SAEs)

Time frame:Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks).

threshold achievement, event

Posted result

Group	Value (number), Percentage	Reported bounds
PlaceboAEsn=405 Participants	83.2	-
SAEsn=405 Participants	15.6	-
CrenezumabAEsn=404 Participants	85.9	-
SAEsn=404 Participants	16.6	-

Other (unclassified)

4 endpoints

Secondary/protocol endpoint/low confidence

Percentage of Participants With Anti-Crenezumab Antibodies

Time frame:Baseline up to Week 105

threshold achievement, improvement

Secondary/protocol endpoint/low confidence

Serum Concentration of Crenezumab

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)

concentration, descriptive

Secondary/registry result/low confidence

Percentage of Participants With Anti-Crenezumab Antibodies

Time frame:Baseline up to Week 105

threshold achievement, improvement

Posted result

Group	Value (number), Percentage	Reported bounds
PlaceboBaseline ADAsn=385 Participants	0.3	-
Treatment Emergent ADAsn=382 Participants	0.5	-
CrenezumabBaseline ADAsn=404 Participants	0.2	-
Treatment Emergent ADAsn=397 Participants	0.5	-

Secondary/registry result/low confidence

Serum Concentration of Crenezumab

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)

concentration, descriptive

Posted result

Group	Value (mean), ug/mL	Standard deviation
CrenezumabWeek 1 Day 1 Predosen=392 Participants	NA	NA
Week 1 Day 1 Postdosen=74 Participants	1350	319
Week 13 Predosen=388 Participants	345	146
Week 13 Postdosen=384 Participants	1580	487
Week 25 Predosen=378 Participants	369	130
Week 25 Postdosen=54 Participants	1700	443
Week 37 Predosen=366 Participants	368	152
Week 53 Predosen=363 Participants	393	164
Week 53 Postdosen=60 Participants	1800	420
Week 77 Predosen=263 Participants	410	261
Week 77 Postdosen=50 Participants	1790	496
Week 105n=89 Participants	408	186

Publications (4)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.