← Trials/Trial dossier/NCT01998841

CompletedPhase 2Results posted

A Study of Crenezumab Versus Placebo in Preclinical Presenilin1 (PSEN1) E280A Mutation Carriers to Evaluate Efficacy and Safety in the Treatment of Autosomal-Dominant Alzheimer's Disease (AD), Including a Placebo-Treated Non-Carrier Cohort

A Double-Blind, Placebo-Controlled Parallel-Group Study in Preclinical PSEN1 E280A Mutation Carriers Randomized to Crenezumab or Placebo, and in Non-Randomized, Placebo-Treated Non-Carriers From the Same Kindred, to Evaluate the Efficacy and Safety of Crenezumab in the Treatment of Autosomal-Dominant Alzheimer's Disease

Lead sponsor

Genentech, Inc.

Asset

Crenezumab

Listed sites

Recruiting sites

Enrollment

252

actual

Study population

Alzheimer’s disease

Key I/E criteria

•PSEN1 mutation required•Study partner/caregiver required•MRI contraindications excluded

Primary endpoints

•Mini-Mental State Examination (MMSE)•Period

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

Org study IDGN28352

NCT IDNCT01998841

Timeline

Milestones

Study first posted2013-12-02estimated

Study start2013-12-20actual

Primary completion2022-03-22actual

Study completion2023-08-08actual

Results first posted2023-09-22actual

Last update posted2024-07-30actual

Assets

Drug assets

Crenezumab

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age30 Years

Maximum age60 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Membership in PSEN1 E280A mutation carrier kindred

•Agrees to conditions of, and is willing to undergo, genetic testing (for example [e.g.], apolipoprotein E [APOE], PSEN1 E280A, and other genetic testing)

•PSEN1 E280A mutation carrier or non-carrier status has been confirmed prior to or during the screening period

•Mini-Mental Stage Examination (MMSE) greater than or equal to (>=) 24 for participants with less than (<) 9 years of education or MMSE >=26 for participants with 9 or more years of education

•Does not meet criteria for dementia due to AD per the National Institute on Aging and the Alzheimer's Association Workgroup (McKhann et al. 2011) criteria

•Does not meet criteria for mild cognitive impairment (MCI) due to AD per the National Institute on Aging and the Alzheimer's Association Workgroup (Albert et al. 2011) criteria

•Adequate vision and hearing in the investigator's judgment to be able to complete testing

•If female, and not documented (by medical records or physician's note) to be surgically sterile (absence of ovaries and/or uterus) or postmenopausal, willing to undergo pregnancy tests at protocol-specific timepoints

•For women who are not documented (by medical records or physician's note) to be surgically sterile (absence of ovaries and/or uterus) or postmenopausal, agreement to remain abstinent or use two adequate methods of contraception, including at least one method with a failure rate of <1 percent (%) per year (e.g., hormonal implants, combined oral contraceptives, vasectomized partner, tubal ligation) during the treatment period and for at least 16 weeks after the last dose of study drug

•For men with partners of childbearing potential (that is [i.e.], women who are not surgically sterile and are not postmenopausal), agreement to remain abstinent or use a condom as a method of contraception during the treatment period and for at least 8 weeks after the last dose of study drug

•Study partner who agrees to participate in the study and is capable of and willing to: accompany the participant to all required visits; provide information for required telephone assessments; spend sufficient time with the participant to be familiar with his/her overall function and behavior and be able to provide adequate information about the participant including knowledge about domestic activities, hobbies, routines, social skills and basic activities of daily life; work and educational history; cognitive performance including memory abilities, language abilities, temporal and spatial orientation, judgment and problem solving; emotional and psychological state; and general health status

•Participant and study partner have evidence of adequate premorbid functioning (e.g., intellectual, visual, and auditory) and are fluent in, and able to read, the language in which study assessments are administered

•Willing and able to undergo neuroimaging (PET and MRI)

•Serum thyroid stimulating hormone (TSH) and B12 levels within normal or expected ranges for the testing laboratory or if TSH and B12 values are out of range they are judged by the investigator not to be clinically significant. If participant is undergoing thyroid replacement therapy, TSH levels must be within normal or expected ranges for the testing laboratory or, if TSH values are out of range, they do not require any therapeutic actions (treatment or surveillance). If participant is receiving vitamin B12 injections or oral vitamin B12 therapy, B12 levels must be at or above the lower limit of normal for the testing laboratory or, if B12 values are out of range, they do not require any therapeutic actions (treatment or surveillance)

•In good general health with no known co-morbidities expected to interfere with participation in the study

Exclusion criteria

•Significant medical, psychiatric, or neurological condition or disorder documented by history, physical, neurological, laboratory, or electrocardiogram (ECG) examination that would place the participant at undue risk in the investigator's judgment or impact the interpretation of efficacy

•History of stroke. Participants with a history of transient ischemic attack may be enrolled if the event occurred >=2 years prior to screening

•History of severe, clinically significant (persistent neurological deficit or structural brain damage) central nervous system trauma (e.g. cerebral contusion)

•Body weight <45 or >120 kilograms (kg)

•History or presence of atrial fibrillation that poses a risk for future stroke in the investigator's judgment

•Clinically significant laboratory or ECG abnormalities (e.g., abnormally prolonged or shortened QTc interval) in the investigator's judgment

•Current presence of bipolar disorder or other clinically significant major psychiatric disorder according to Diagnostic and Statistical Manual of Mental Disorders 4th Edition Text Revision (DSM-IV-TR) or symptom (e.g., hallucinations, agitation, paranoia) that could affect the participant's ability to complete evaluations

•Clinically significant depression, based in part by a Geriatric Depression Scale (short form) (15-point scale) score >9 at screening

•History of seizures (excluding febrile seizures of childhood, or other isolated seizure episodes that were not due to epilepsy in the judgment of the investigator, and required at most time-limited anticonvulsant treatment, and which occurred more than 7 years prior to the screening visit)

•Myocardial infarction within 2 years, congestive heart failure, atrial fibrillation, or uncontrolled hypertension

•Pregnant or nursing women, or women who intend to become pregnant or to nurse infants during the conduct of this trial

•Clinically significant infection within the last 30 days prior to screening

•Positive urine test for drugs of abuse at screening

•History of alcohol or substance dependence within the previous two years

•Use of any other medications with the potential to significantly affect cognition; intermittent or short-term use of these medications may be allowed if deemed medically necessary for the treatment of a non-excluded medical condition with approval from the Medical Monitor. In addition, use of tricyclic antidepressants or benzodiazepines will be permitted if used in stable, low doses for the treatment of a non-excluded medical condition with approval from the Medical Monitor

•Use of typical anti-psychotics or barbiturates

•Use of non-anti-cholinergic antidepressant medications or atypical anti-psychotics unless maintained on a stable dose regimen for at least 6 weeks prior to screening

•Use of any Food and Drug Administration (FDA)/Instituto Nacional de Vigilancia de Medicamentos y Alimentos (INVIMA)-approved medications for treatment of late onset Alzheimer's disease (LOAD) at screening/baseline. Cholinesterase inhibitors and/or memantine are prohibited during the study except in participants enrolled in the study that develop AD dementia

•Use of anti-coagulant medication (heparinoids, heparin, warfarin, thrombin inhibitors, Factor Xa inhibitors), or known coagulopathy or platelet count <100,000 cells/microliter, within 4 weeks of the screening visit; Anti-platelet medications (e.g., aspirin, clopidigrel, dipyridamole) are permitted if on a stable dose for 4 or more weeks prior to screening. Short-term, peri-operative use of anti-coagulants may not result in discontinuation from the study; however, any such use must be discussed with the Medical Monitor

•Treatment with any biologic therapy within five half-lives or 3 months prior to screening, whichever is longer, with the exception of routinely recommended vaccinations, which are allowed

•Use of anti-seizure medication (except in childhood for febrile seizures or if used for non-seizure indications), anti-parkinsonian, or stimulant (e.g., methylphenidate) medications

•Use of investigational drug, device, or experimental medication within 60 days (or five half-lives, whichever is longer) of the screening visit

•Previous treatment with crenezumab or any other therapeutic that targets A-beta

•History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins

•Contraindication to MRI scan procedures or clinically significant claustrophobia that would contraindicate a brain MRI scan

•Contraindication to PET scan procedures

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

Other (unclassified)

Global cognition

Amyloid biomarkers

Memory

Neuroimaging

Safety / tolerability / PK

Tau biomarkers

Fluid / digital biomarkers

Global cognition

8 endpoints

Primary/protocol endpoint

Period A: Annualized Rate of Change in the Autosomal-Dominant Alzheimer's Disease (API ADAD) Composite Cognitive Test Total Score

Time frame:Baseline up to approximately Week 416

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Primary/registry result

Period A: Annualized Rate of Change in the Autosomal-Dominant Alzheimer's Disease (API ADAD) Composite Cognitive Test Total Score

Time frame:Baseline up to approximately Week 416

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Posted result

Group	Value (mean), points on scale per year	Standard error
Study Period A: Crenezumab - Mutation Carriern=84 Participants	-1.10	0.29
Study Period A: Placebo - Mutation Carriersn=84 Participants	-1.42	0.29

Difference in Annualized Rate of Change0.3395% CI-0.48 - 1.13p0.43RCRM

Secondary/protocol endpoint

Period A: Annualized Rate of Change in the CDR Scale - Sum of Boxes (SOB)

Time frame:Baseline up to approximately Week 416

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

change from baseline, improvement

Secondary/protocol endpoint

Period A: Annualized Rate of Change in a Measure of Overall Neurocognitive Functioning: RBANS

Time frame:Baseline up to approximately Week 416

change from baseline, improvement

Secondary/protocol endpoint

Period A: Annualized Rate of Change in Brain Atrophy Measured by Volumetric Measurements Using Magnetic Resonance Imaging (MRI)

Time frame:Baseline up to approximately Week 416

change from baseline, improvement

Secondary/registry result

Period A: Annualized Rate of Change in the CDR Scale - Sum of Boxes (SOB)

Time frame:Baseline up to approximately Week 416

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

change from baseline, improvement

Posted result

Group	Value (mean), points on scale per year	Standard error
Study Period A: Crenezumab - Mutation Carriern=84 Participants	0.30	0.06
Study Period A: Placebo - Mutation Carriersn=84 Participants	0.33	0.06

Difference in Annualized Rate of Change-0.0395% CI-0.15 - 0.09p0.64RCRM

Secondary/registry result

Period A: Annualized Rate of Change in a Measure of Overall Neurocognitive Functioning: RBANS

Time frame:Baseline up to approximately Week 416

change from baseline, improvement

Posted result

Group	Value (mean), points on scale per year	Standard error
Study Period A: Crenezumab - Mutation Carriern=84 Participants	-0.23	0.21
Study Period A: Placebo - Mutation Carriersn=84 Participants	-0.40	0.21

Difference in Annualized Rate of Change0.1895% CI-0.40 - 0.75p0.55RCRM

Secondary/registry result

Period A: Annualized Rate of Change in Brain Atrophy Measured by Volumetric Measurements Using Magnetic Resonance Imaging (MRI)

Time frame:Baseline up to approximately Week 416

change from baseline, improvement

Posted result

Group	Value (mean), cubic millimeter (mm^3)/year	Standard error
Study Period A: Crenezumab - Mutation CarrierWhole Brainn=84 Participants	-721.91	65.33
Bilateral Hippocampusn=84 Participants	-92.62	12.25
Bilateral Ventriclesn=84 Participants	808.16	150.14
Study Period A: Placebo - Mutation CarriersWhole Brainn=84 Participants	-829.69	65.42
Bilateral Hippocampusn=84 Participants	-102.22	12.27
Bilateral Ventriclesn=84 Participants	788.25	150.29

Difference in Annualized Rate of Change107.7895% CI-74.5 - 290.05p0.25RCRM

Difference in Annualized Rate of Change9.6095% CI-24.74 - 43.94p0.58RCRM

Difference in Annualized Rate of Change19.9295% CI-400.78 - 440.62p0.93RCRM

Memory

4 endpoints

Primary/protocol endpoint

Period A: Annualized Rate of Change in an Episodic Memory Measure: Free and Cued Selective Reminding Task (FCSRT) Cueing Index

Time frame:Baseline up to approximately Week 416

change from baseline, improvement

Primary/registry result

Period A: Annualized Rate of Change in an Episodic Memory Measure: Free and Cued Selective Reminding Task (FCSRT) Cueing Index

Time frame:Baseline up to approximately Week 416

change from baseline, improvement

Posted result

Group	Value (mean), points on scale per year	Standard error
Study Period A: Crenezumab - Mutation Carriern=84 Participants	-0.03	0.004
Study Period A: Placebo - Mutation Carriersn=84 Participants	-0.04	0.004

Difference in Annualized Rate of Change0.00895% CI-0.003 - 0.02p0.16RCRM

Secondary/protocol endpoint

Period A: Time to Progression to Non-zero in CDR Scale Global Score

Time frame:Baseline up to approximately Week 416

time to event, event

Secondary/registry result

Period A: Time to Progression to Non-zero in CDR Scale Global Score

Time frame:Baseline up to approximately Week 416

time to event, event

Posted result

Group	Value (median), days	Reported bounds
Study Period A: Crenezumab - Mutation Carriern=84 Participants	2759.0	-2391.0 - NA
Study Period A: Placebo - Mutation Carriersn=84 Participants	NA	-2395.0 - NA

Hazard Ratio (HR)0.9295% CI0.53 - 1.59p0.76Stratified Log Rank

Stratification factors used: Age Group, Education History, APOE4 Carrier Status.

Amyloid biomarkers

6 endpoints

Secondary/protocol endpoint

Period A: Annualized Rate of Change in Mean Cerebral Fibrillar Amyloid Accumulation Using Florbetapir Positron Emission Tomography (PET)

Time frame:Baseline up to approximately Week 416

change from baseline, improvement

Secondary/protocol endpoint

Period A: Number of Participants With Adverse Events of Special Interest (AESIs)

Time frame:From Baseline up to approximately Week 416

event count, event

Secondary/protocol endpoint

Period A: Annualized Rate of Change in Plasma Concentrations of Amyloid Beta 1(Aβ1)-40 and Amyloid Peptide Beta 42 (Aβ1-42)

Time frame:Baseline up to approximately Week 416

change from baseline, improvement

Secondary/registry result

Period A: Annualized Rate of Change in Mean Cerebral Fibrillar Amyloid Accumulation Using Florbetapir Positron Emission Tomography (PET)

Time frame:Baseline up to approximately Week 416

change from baseline, improvement

Posted result

Group	Value (mean), SUVR per year	Standard error
Study Period A: Crenezumab - Mutation Carriern=84 Participants	0.017	0.001
Study Period A: Placebo - Mutation Carriersn=84 Participants	0.017	0.001

Difference in Annualized Rate of Change-0.000695% CI-0.0037 - 0.0024p0.69RCRM

Secondary/registry result

Period A: Number of Participants With Adverse Events of Special Interest (AESIs)

Time frame:From Baseline up to approximately Week 416

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Study Period A: Combined BlindedARIA-Hn=251 Participants	6	-
ARIA-En=251 Participants	1	-
Cerebral Macrohemorrhagen=251 Participants	0	-
Drug Induced Liver Injuryn=251 Participants	1	-
Suspected Transmission of Infectious Agents via a Medicinal Productn=251 Participants	0	-
Pneumonian=251 Participants	0	-

Secondary/registry result

Period A: Annualized Rate of Change in Plasma Concentrations of Amyloid Beta 1(Aβ1)-40 and Amyloid Peptide Beta 42 (Aβ1-42)

Time frame:Baseline up to approximately Week 416

change from baseline, improvement

Posted result

Group	Value (mean), (pg/mL)/year	Standard error
Study Period A: Crenezumab - Mutation CarrierAβ1-40n=84 Participants	6836.37	236.49
Aβ1-42n=84 Participants	509.44	17.74
Study Period A: Placebo - Mutation CarriersAβ1-40n=84 Participants	-686.18	234.84
Aβ1-42n=84 Participants	-46.59	17.61

Difference in Annualized Rate of Change7522.5595% CI6903.44 - 8141.65p<0.0001RCRM

Difference in Annualized Rate of Change556.0395% CI508.63 - 603.44p<0.0001RCRM

Tau biomarkers

2 endpoints

Secondary/protocol endpoint

Period A: Annualized Rate of Change in Tau-Based Cerebral Spinal Fluid (CSF) Biomarkers (Total Tau (tTau) and Phospho-tau (pTau)

Time frame:Baseline up to approximately Week 416

change from baseline, improvement

Secondary/registry result

Period A: Annualized Rate of Change in Tau-Based Cerebral Spinal Fluid (CSF) Biomarkers (Total Tau (tTau) and Phospho-tau (pTau)

Time frame:Baseline up to approximately Week 416

change from baseline, improvement

Posted result

Group	Value (mean), picograms per milliliters (pg/mL)/year	Standard error
Study Period A: Crenezumab - Mutation CarriertTaun=48 Participants	4.91	2.16
pTaun=44 Participants	0.84	0.32
Study Period A: Placebo - Mutation CarrierstTaun=42 Participants	6.88	2.19
pTaun=40 Participants	1.34	0.33

Difference in Annualized Rate of Change-1.9795% CI-8.17 - 4.23p0.53RCRM

Difference in Annualized Rate of Change-0.5095% CI-1.43 - 0.43p0.28RCRM

Neuroimaging

4 endpoints

Secondary/protocol endpoint

Period A: Annualized Rate of Change in Regional Cerebral Metabolic Rate of Glucose (CMRgI) Using Fluorine-18-Labeled 2-Deoxyglucose (FDG)-PET in a Predefined ROI

Time frame:Baseline up to approximately Week 416

change from baseline, improvement

Secondary/protocol endpoint

Period B: Number of Participants With AESIs: ARIA-E, ARIA-H, Cerebral Macrohemorrhages, and Pneumonia

Time frame:From Day 1 (Period B) up to 67 weeks

event count, event

Secondary/registry result

Period A: Annualized Rate of Change in Regional Cerebral Metabolic Rate of Glucose (CMRgI) Using Fluorine-18-Labeled 2-Deoxyglucose (FDG)-PET in a Predefined ROI

Time frame:Baseline up to approximately Week 416

change from baseline, improvement

Posted result

Group	Value (mean), SUVR per year	Standard error
Study Period A: Crenezumab - Mutation Carriern=84 Participants	-0.012	0.002
Study Period A: Placebo - Mutation Carriersn=84 Participants	-0.015	0.002

Difference in Annualized Rate of Change0.00395% CI-0.002 - 0.007p0.25RCRM

Secondary/registry result

Period B: Number of Participants With AESIs: ARIA-E, ARIA-H, Cerebral Macrohemorrhages, and Pneumonia

Time frame:From Day 1 (Period B) up to 67 weeks

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Study Period B: Combined BlindedPneumonian=219 Participants	1	-
ARIA-Hn=219 Participants	0	-
ARIA-En=219 Participants	0	-
Cerebral Macrohemorrhagen=219 Participants	0	-
Drug Induced Liver Injuryn=219 Participants	0	-
Suspected Transmission of Infectious Agents via a Medicinal Productn=219 Participants	0	-

Fluid / digital biomarkers

2 endpoints

Secondary/protocol endpoint

Period A: Cerebrospinal Fluid (CSF) Crenezumab Concentration

Time frame:Predose: Baseline (Day 1), Weeks 104 and 260; early termination visit and unscheduled visit (up to approximately Week 416)

concentration, descriptive

Secondary/registry result

Period A: Cerebrospinal Fluid (CSF) Crenezumab Concentration

Time frame:Predose: Baseline (Day 1), Weeks 104 and 260; early termination visit and unscheduled visit (up to approximately Week 416)

concentration, descriptive

Posted result

Group	Value (geometric_mean), micrograms per milliliters (µg/ml)	Geometric coefficient of variation
Study Period A: Crenezumab - Mutation CarrierBaseline (Day 1)n=25 Participants	NA	NA
Week 104n=36 Participants	0.198	81.6
Week 260n=27 Participants	0.311	214.6
Early Termination Visitn=22 Participants	0.238	190.4
Unscheduled Visitn=1 Participants	2.23	NA

Safety / tolerability / PK

4 endpoints

Secondary/protocol endpoint

Period A: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Time frame:From Baseline up to approximately Week 416

event count, event

Secondary/protocol endpoint

Period B: Number of Participants With AEs and SAEs

Time frame:From Day 1 (Period B) up to 67 weeks

event count, event

Secondary/registry result

Period A: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Time frame:From Baseline up to approximately Week 416

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Study Period A: Combined BlindedParticipants with AEsn=251 Participants	251	-
Participants with SAEsn=251 Participants	56	-

Secondary/registry result

Period B: Number of Participants With AEs and SAEs

Time frame:From Day 1 (Period B) up to 67 weeks

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Study Period B: Combined BlindedParticipants with AEsn=219 Participants	219	-
Participants with SAEsn=219 Participants	12	-

Other (unclassified)

14 endpoints

Secondary/protocol endpoint/low confidence

Period A: Time to Progression From Preclinical AD to Mild Cognitive Impairment (MCI) Due to AD or From Preclinical AD to Dementia Due to AD

Time frame:Baseline up to approximately Week 416

time to event, event

Secondary/protocol endpoint/low confidence

Period A: Number of Participants Who Withdrew From the Study Treatment Due to AEs

Time frame:From Baseline up to approximately Week 416

event count, event

Secondary/protocol endpoint/low confidence

Period A: Number of Participants Injection Reactions and Infusion-related Reaction (IRRs)

Time frame:Baseline (Day 1) up to approximately Week 416

event count, event

Secondary/protocol endpoint/low confidence

Period A: Number of Participants With Anti-Crenezumab Antibodies

Time frame:Baseline up to approximately Week 260

event count, event

Secondary/protocol endpoint/low confidence

Period A: Serum Crenezumab Concentration

Time frame:Baseline (Day 1), Weeks 4, 12, 16, 17, 26, 38, 52, 78, 104, 128, 130, 156, 180, 182, 208, 232, 234, 260, 284, 312, 336, 364, 388, early termination visit and unscheduled visit (up to approximately Week 416)

concentration, descriptive

Secondary/protocol endpoint/low confidence

Period B: Number of Participants Who Withdraw From the Study Treatment Due to AEs

Time frame:From Day 1 (Period B) up to 67 weeks

event count, event

Secondary/protocol endpoint/low confidence

Period B: Number of Participants With Injection Reactions and IRRs

Time frame:From Day 1 (Period B) up to 67 weeks

event count, event

Secondary/registry result/low confidence

Period A: Time to Progression From Preclinical AD to Mild Cognitive Impairment (MCI) Due to AD or From Preclinical AD to Dementia Due to AD

Time frame:Baseline up to approximately Week 416

time to event, event

Posted result

Group	Value (median), days	Reported bounds
Study Period A: Crenezumab - Mutation Carriern=84 Participants	NA	-NA - NA
Study Period A: Placebo - Mutation Carriersn=84 Participants	NA	-2622.0 - NA

Hazard Ratio (HR)0.7995% CI0.41 - 1.52p0.48Stratified Log Rank

Stratification factors used: Age Group, Education History, APOE4 Carrier Status, Clinical Dementia Rating (CDR) Global Score.

Secondary/registry result/low confidence

Period A: Number of Participants Who Withdrew From the Study Treatment Due to AEs

Time frame:From Baseline up to approximately Week 416

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Study Period A: Combined Blindedn=251 Participants	1	-

Secondary/registry result/low confidence

Period A: Number of Participants Injection Reactions and Infusion-related Reaction (IRRs)

Time frame:Baseline (Day 1) up to approximately Week 416

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Study Period A: Combined BlindedInjection Reactionn=251 Participants	92	-
Infusion Related Reactionn=200 Participants	70	-

Secondary/registry result/low confidence

Period A: Number of Participants With Anti-Crenezumab Antibodies

Time frame:Baseline up to approximately Week 260

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Study Period A: Crenezumab - Mutation Carriern=84 Participants	5	-

Secondary/registry result/low confidence

Period A: Serum Crenezumab Concentration

concentration, descriptive

Posted result

Group	Value (geometric_mean), µg/ml	Geometric coefficient of variation
Study Period A: Crenezumab - Mutation CarrierBaseline (Day 1)n=80 Participants	NA	NA
Week 4n=84 Participants	69.2	39.1
Week 12n=84 Participants	93.9	51.8
Week 16n=47 Participants	85.8	37.2
Week 17n=46 Participants	114	37.3
Week 26n=82 Participants	96.5	86.3
Week 38n=81 Participants	98.0	121.6
Week 52n=82 Participants	82.9	285.3
Week 78n=82 Participants	75.9	777.0
Week 104n=83 Participants	86.2	680.2
Week 128n=5 Participants	124	28.6
Week 130n=78 Participants	72.3	1514.9
Week 156n=82 Participants	80.7	1445.4
Week 180n=26 Participants	56.1	3140.6
Week 182n=55 Participants	85.5	1135.4
Week 208n=80 Participants	94.3	983.0
Week 232n=60 Participants	69.4	3990.1
Week 234n=21 Participants	62.3	2724.2
Week 260n=79 Participants	101	1417.7
Week 284n=66 Participants	131	690.6
Week 312n=53 Participants	116	645.0
Week 336n=30 Participants	117	544.7
Week 364n=16 Participants	227	38.2
Week 388n=11 Participants	162	79.8
Early Termination Visitn=77 Participants	223	135.5
Unscheduledn=1 Participants	98.4	NA

Secondary/registry result/low confidence

Period B: Number of Participants Who Withdraw From the Study Treatment Due to AEs

Time frame:From Day 1 (Period B) up to 67 weeks

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Study Period B: Combined Blindedn=219 Participants	0	-

Secondary/registry result/low confidence

Period B: Number of Participants With Injection Reactions and IRRs

Time frame:From Day 1 (Period B) up to 67 weeks

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Study Period B: Combined BlindedInjection Reactionn=219 Participants	1	-
Infusion Related Reactionn=219 Participants	12	-

Publications (3)

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.