CREAD 2

TerminatedPhase 3Results posted

A Study of Crenezumab Versus Placebo to Evaluate the Efficacy and Safety 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

211

Recruiting sites

Enrollment

806

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 number2016-003288-20

Org study IDBN29553

NCT IDNCT03114657

Timeline

Milestones

Study start2017-03-29actual

Study first posted2017-04-14actual

Primary completion2019-06-11actual

Study completion2019-06-11actual

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 (44)

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

Function / daily living

Behavior / neuropsychiatric

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 77 in Clinical Dementia Rating-Sum of Boxes (CDR-SB) Scale Score

Time frame:Baseline, Week 77

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

change from baseline, improvement

Primary/registry result

Change From Baseline to Week 77 in Clinical Dementia Rating-Sum of Boxes (CDR-SB) Scale Score

Time frame:Baseline, Week 77

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=15 Participants	3.19	0.434
Crenezumabn=12 Participants	1.89	0.471

Least Squares Mean Difference1.3095% CI0.00 - 2.60

Secondary/protocol endpoint

Change From Baseline to Week 77 in Alzheimer's Disease Assessment Scale-Cognition 13 (ADAS-Cog-13) Subscale Score

Time frame:Baseline, Week 77

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline to Week 77 in Alzheimer's Disease Assessment Scale-Cognition 11 (ADAS-Cog-11) Subscale Score

Time frame:Baseline, Week 77

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline to Week 77 on Severity of Dementia, Assessed Using the Mini Mental State Evaluation (MMSE)

Time frame:Baseline, Week 77

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Secondary/registry result

Change From Baseline to Week 77 in Alzheimer's Disease Assessment Scale-Cognition 13 (ADAS-Cog-13) Subscale Score

Time frame:Baseline, Week 77

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Units on a Scale	Standard error
Placebon=15 Participants	8.90	1.382
Crenezumabn=12 Participants	7.16	1.526

Least Squares Mean Difference1.7495% CI-2.40 - 5.89

Secondary/registry result

Change From Baseline to Week 77 in Alzheimer's Disease Assessment Scale-Cognition 11 (ADAS-Cog-11) Subscale Score

Time frame:Baseline, Week 77

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Units on a Scale	Standard error
Placebon=15 Participants	7.16	1.452
Crenezumabn=12 Participants	6.84	1.592

Least Squares Mean Difference0.3395% CI-4.03 - 4.68

Secondary/registry result

Change From Baseline to Week 77 on Severity of Dementia, Assessed Using the Mini Mental State Evaluation (MMSE)

Time frame:Baseline, Week 77

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Units on a Scale	Standard error
Placebon=15 Participants	-3.63	0.672
Crenezumabn=12 Participants	-3.21	0.740

Least Squares Mean Difference-0.4195% CI-2.42 - 1.60

Memory

2 endpoints

Secondary/protocol endpoint

Change From Baseline to Week 77 on Severity of Dementia, Assessed Using the CDR-Global Score (CDR-GS)

Time frame:Baseline, Week 77

change from baseline, improvement

Secondary/registry result

Change From Baseline to Week 77 on Severity of Dementia, Assessed Using the CDR-Global Score (CDR-GS)

Time frame:Baseline, Week 77

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Units on a Scale	Standard error
Placebon=15 Participants	0.39	0.096
Crenezumabn=12 Participants	0.29	0.102

Least Squares Mean Difference0.0995% CI-0.20 - 0.39

Function / daily living

8 endpoints

Secondary/protocol endpoint

Change From Baseline to Week 77 on Function as Assessed by (ADCS-ADL) Total Score

Time frame:Baseline, Week 77

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline to Week 77 on Function as Assessed by (ADCS-iADL) Instrumental Score

Time frame:Baseline, Week 77

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline to Week 77 on Function as Assessed by the Functional Activities Questionnaire (FAQ) Total Score

Time frame:Baseline, Week 77

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline to Week 77 on a Measure of Dependence Level Assessed From the ADCS-ADL Score

Time frame:Baseline, Week 77

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Secondary/registry result

Change From Baseline to Week 77 on Function as Assessed by (ADCS-ADL) Total Score

Time frame:Baseline, Week 77

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=15 Participants	-8.83	2.064
Crenezumabn=12 Participants	-6.31	2.278

Least Squares Mean Difference-2.5295% CI-8.74 - 3.70

Secondary/registry result

Change From Baseline to Week 77 on Function as Assessed by (ADCS-iADL) Instrumental Score

Time frame:Baseline, Week 77

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Units on a Scale	Standard error
Placebon=15 Participants	-6.69	1.692
Crenezumabn=12 Participants	-5.51	1.872

Least Squares Mean Difference-1.1995% CI-6.29 - 3.92

Secondary/registry result

Change From Baseline to Week 77 on Function as Assessed by the Functional Activities Questionnaire (FAQ) Total Score

Time frame:Baseline, Week 77

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Units on a Scale	Standard error
Placebon=15 Participants	5.00	0.991
Crenezumabn=12 Participants	4.37	1.059

Least Squares Mean Difference0.6395% CI-2.25 - 3.51

Secondary/registry result

Change From Baseline to Week 77 on a Measure of Dependence Level Assessed From the ADCS-ADL Score

Time frame:Baseline, Week 77

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Behavior / neuropsychiatric

8 endpoints

Secondary/protocol endpoint

Change From Baseline to Week 53 on Behavior in Neuropsychiatric Inventory Questionnaire (NPI-Q) Total Score

Time frame:Baseline, Week 53

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/protocol endpoint

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

Time frame:Baseline, Week 77

change from baseline, improvement

Secondary/protocol endpoint

European Quality of Life-5 Dimensions (EQ-5D) Questionnaire Domain Scores for Participants

Time frame:Baseline, Week 77

change from baseline, improvement

Secondary/protocol endpoint

European Quality of Life-5 Dimensions (EQ-5D) Questionnaire Domain Scores for Caregivers

Time frame:Baseline, Week 77

change from baseline, improvement

Secondary/registry result

Change From Baseline to Week 53 on Behavior in Neuropsychiatric Inventory Questionnaire (NPI-Q) Total Score

Time frame:Baseline, Week 53

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Units on a Scale	Standard error
Placebon=102 Participants	-0.00	0.852
Crenezumabn=110 Participants	0.76	0.886

Least Squares Mean Difference-0.7695% CI-1.75 - 0.23

Secondary/registry result

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

Time frame:Baseline, Week 77

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Units on a Scale	Standard error
Placebon=15 Participants	-1.61	1.310
Crenezumabn=11 Participants	-1.16	1.432

Least Squares Mean Difference-0.4695% CI-3.30 - 2.39

Secondary/registry result

European Quality of Life-5 Dimensions (EQ-5D) Questionnaire Domain Scores for Participants

Time frame:Baseline, Week 77

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Units on a Scale	Standard error
Placebon=15 Participants	-3.69	3.961
Crenezumabn=12 Participants	-3.39	4.392

Least Squares Mean Difference-0.3095% CI-12.31 - 11.71

Secondary/registry result

European Quality of Life-5 Dimensions (EQ-5D) Questionnaire Domain Scores for Caregivers

Time frame:Baseline, Week 77

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Units on a Scale	Standard error
Placebon=15 Participants	-4.07	2.724
Crenezumabn=12 Participants	-0.68	3.031

Least Squares Mean Difference-3.3895% CI-11.50 - 4.73

Amyloid biomarkers

4 endpoints

Secondary/protocol endpoint

Plasma Amyloid Beta (Abeta) 40 Concentrations

Time frame:Week 1 Day 1; Weeks 53

concentration, descriptive

Secondary/protocol endpoint

Plasma Amyloid Beta (Abeta) 42 Concentrations

Time frame:Week 1 Day 1; Weeks 53

concentration, descriptive

Secondary/registry result

Plasma Amyloid Beta (Abeta) 40 Concentrations

Time frame:Week 1 Day 1; Weeks 53

concentration, descriptive

Posted result

Group	Value (mean), ng/mL	Standard deviation
CrenezumabWeek 1 Day 1 Predosen=36 Participants	0.415	0.0687
Week 53 Predosen=13 Participants	46.6	6.91

Secondary/registry result

Plasma Amyloid Beta (Abeta) 42 Concentrations

Time frame:Week 1 Day 1; Weeks 53

concentration, descriptive

Posted result

Group	Value (mean), ng/mL	Standard deviation
CrenezumabWeek 1 Day 1 Predosen=36 Participants	0.0331	0.00463
Week 53 Predosen=13 Participants	2.94	0.473

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=4 Participants	-2.71	0.444
Crenezumabn=4 Participants	-2.15	0.345

Least Squares Mean Difference-0.5695% CI-2.01 - 0.89

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=4 Participants	18.78	1.343
Crenezumabn=4 Participants	17.18	1.145

Least Squares Mean Difference1.6095% CI-1.70 - 4.90

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=2 Participants	-6.34	0.338
Crenezumabn=2 Participants	-5.98	0.290

Least Squares Mean Difference-0.3695% CI-1.13 - 0.41

Caregiver / quality of life

2 endpoints

Secondary/protocol endpoint

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

Time frame:Baseline, Week 53

change from baseline, improvement

Secondary/registry result

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

Time frame:Baseline, Week 53

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Units on a Scale	Standard error
Placebon=101 Participants	9.20	9.292
Crenezumabn=108 Participants	2.65	9.643

Least Squares Mean Difference6.5595% CI-4.35 - 17.44

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=398 Participants	73.1	-
SAEsn=398 Participants	10.6	-
CrenezumabAEsn=404 Participants	73.5	-
SAEsn=404 Participants	8.2	-

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 (Pre-dose), 37 (Pre-dose), 53 (Pre-dose) and 77 (Pre-dose) (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

Secondary/registry result/low confidence

Serum Concentration of Crenezumab

concentration, descriptive

Posted result

Group	Value (mean), ug/mL	Standard deviation
CrenezumabWeek 1 Day 1 Predosen=138 Participants	NA	NA
Week 1 Day 1 Postdosen=110 Participants	1260	437
Week 5 Predosen=138 Participants	246	128
Week 13 Predosen=128 Participants	360	162
Week 25 Predosen=125 Participants	401	196
Week 25 Postdosen=106 Participants	1650	443
Week 37 Predosen=97 Participants	456	351
Week 53 Predosen=32 Participants	401	130
Week 77 Predosen=3 Participants	357	94.2

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.