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NCT02880956

A Study to Evaluate the Efficacy and Safety of ABBV-8E12 in Participants With Early Alzheimer's Disease

Completed Phase 2 Results posted Last updated 26 August 2022
What this trial tests

Phase 2 trial testing ABBV-8E12 in Alzheimer's Disease in 453 participants. Completed in 28 July 2021.

Timeline
26 January 2017
Primary endpoint
30 March 2021
28 July 2021

Quick facts

Lead sponsorAbbVie
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment453
Start date26 January 2017
Primary completion30 March 2021
Estimated completion28 July 2021
Sites68 locations across Denmark, Italy, Finland, Netherlands, New Zealand, Belgium, Sweden, Canada

Drugs / interventions tested

Conditions studied

Sponsor

AbbVie — full company profile →

Who can join

Adults 55 to 85, any sex, with Alzheimer's Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline Over Time in CDR-SB Score Primary · Baseline, Week 24, Week 48, Week 72, Week 96

The CDR-SB is a numeric scale used to quantify the severity of symptoms of dementia. A qualified health professional assesses a participant's cognitive and functional performance in 6 areas: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. The CDR scale gives a score from 0 to 3 for each of the 6 areas, with a lower value being desirable. The sum of these 6 areas, the CDR-SB score, can range from 0 to 18, with a lower value being desirable.

Change to Week 24
GroupValue95% CI
Placebo0.60± 0.125
ABBV-8E12 300 mg0.66± 0.129
ABBV-8E12 1000 mg0.44± 0.125
ABBV-8E12 2000 mg0.63± 0.130
Change to Week 48
GroupValue95% CI
Placebo1.06± 0.155
ABBV-8E12 300 mg1.15± 0.161
ABBV-8E12 1000 mg1.05± 0.154
ABBV-8E12 2000 mg0.99± 0.161
Change to Week 72
GroupValue95% CI
Placebo1.90± 0.213
ABBV-8E12 300 mg1.88± 0.220
ABBV-8E12 1000 mg1.85± 0.212
ABBV-8E12 2000 mg1.81± 0.219
Change to Week 96
GroupValue95% CI
Placebo2.54± 0.271
ABBV-8E12 300 mg2.47± 0.277
ABBV-8E12 1000 mg2.48± 0.267
ABBV-8E12 2000 mg2.70± 0.279
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Primary · From first dose of study drug up to last dose of study drug plus 20 weeks (up to Week 112)

A TEAE was defined as an adverse event (AE) that began on or after the first study drug dose date and no more than 20 weeks after the last dose of study drug. An adverse event (AE) was defined as any untoward medical occurrence which does not necessarily have a causal relationship with this treatment. Serious AEs (SAEs) were defined as an event that results in death, is life-threatening, results in hospitalization or prolongs hospitalization, is a congenital abnormality, results in persistent or significant disability/incapacity, or is an important medical event. Events were rated in severity

Any TEAE
GroupValue95% CI
Placebo108
ABBV-8E12 300 mg94
ABBV-8E12 1000 mg108
ABBV-8E12 2000 mg104
Severe TEAE
GroupValue95% CI
Placebo12
ABBV-8E12 300 mg13
ABBV-8E12 1000 mg14
ABBV-8E12 2000 mg11
TEAE With a Reasonable Possibility to Study Drug
GroupValue95% CI
Placebo28
ABBV-8E12 300 mg32
ABBV-8E12 1000 mg31
ABBV-8E12 2000 mg33
SAE
GroupValue95% CI
Placebo26
ABBV-8E12 300 mg19
ABBV-8E12 1000 mg22
ABBV-8E12 2000 mg17
TEAE Leading to Discontinuation of Study Drug
GroupValue95% CI
Placebo4
ABBV-8E12 300 mg6
ABBV-8E12 1000 mg6
ABBV-8E12 2000 mg4
Fatal TEAE
GroupValue95% CI
Placebo1
ABBV-8E12 300 mg2
ABBV-8E12 1000 mg2
ABBV-8E12 2000 mg1
All Deaths
GroupValue95% CI
Placebo1
ABBV-8E12 300 mg2
ABBV-8E12 1000 mg2
ABBV-8E12 2000 mg1
Maximum Observed Serum Concentration (Cmax) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses Secondary · Day 1 (Dose 1): Pre-infusion, post-infusion (within 15 minutes), 1 and 2 hours post-infusion; Days 5 and 15. Day 85 (Dose 4): Pre-infusion (0 hour), post-infusion (within 15 minutes) and 1 and 2 hours post-infusion; Days 89 and 99.
First Dosing Interval
GroupValue95% CI
ABBV-8E12 300 mg108± 28
ABBV-8E12 1000 mg284± 21
ABBV-8E12 2000 mg528± 27
Fourth Dosing Interval
GroupValue95% CI
ABBV-8E12 300 mg168± 23
ABBV-8E12 1000 mg426± 20
ABBV-8E12 2000 mg806± 37
Time to Cmax (Tmax) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses Secondary · Day 1 (Dose 1): Pre-infusion, post-infusion (within 15 minutes), 1 and 2 hours post-infusion; Days 5 and 15. Day 85 (Dose 4): Pre-infusion (0 hour), post-infusion (within 15 minutes) and 1 and 2 hours post-infusion; Days 89 and 99.
First Dosing Interval
GroupValue95% CI
ABBV-8E12 300 mg31.8 – 4.2
ABBV-8E12 1000 mg2.51.3 – 4.2
ABBV-8E12 2000 mg2.71.7 – 3.6
Fourth Dosing Interval
GroupValue95% CI
ABBV-8E12 300 mg2.41.1 – 4.1
ABBV-8E12 1000 mg2.51.7 – 4.3
ABBV-8E12 2000 mg2.31.7 – 3.6
Serum Concentration at the End of a Dose Interval (Ctrough) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses Secondary · Day 1 (Dose 1): Pre-infusion, post-infusion (within 15 minutes), 1 and 2 hours post-infusion; Days 5 and 15. Day 85 (Dose 4): Pre-infusion (0 hour), post-infusion (within 15 minutes) and 1 and 2 hours post-infusion; Days 89 and 99.
First Dosing Interval
GroupValue95% CI
ABBV-8E12 300 mg28.6± 22
ABBV-8E12 1000 mg75.1± 33
ABBV-8E12 2000 mg163± 26
Fourth Dosing Interval
GroupValue95% CI
ABBV-8E12 300 mg56.4± 25
ABBV-8E12 1000 mg182± 29
ABBV-8E12 2000 mg320± 36
Half-Life (T1/2) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses Secondary · Day 1 (Dose 1): Pre-infusion, post-infusion (within 15 minutes), 1 and 2 hours post-infusion; Days 5 and 15. Day 85 (Dose 4): Pre-infusion (0 hour), post-infusion (within 15 minutes) and 1 and 2 hours post-infusion; Days 89 and 99.

Harmonic mean is presented in the data table.

First Dosing Interval
GroupValue95% CI
ABBV-8E12 300 mg22.0± 17.2
ABBV-8E12 1000 mg19.4± 8.87
ABBV-8E12 2000 mg33.2± 10.5
Fourth Dosing Interval
GroupValue95% CI
ABBV-8E12 300 mg19.6± 6.09
ABBV-8E12 1000 mg24.0± 16.6
ABBV-8E12 2000 mg37.5± 13.5
Area Under the Concentration-Time Curve From Dosing (Time 0) to Day 28 (AUC0-28) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses Secondary · Day 1 (Dose 1): pre-infusion, up to Day 29 (trough level before Dose 2). Day 85 (Dose 4): pre-infusion, up to Day 113 (trough level before Dose 5). See Outcome Measure description above for complete time point details.

* The AUC0-28 for Dose 1 included the following timepoints: pre-infusion, post-infusion (within 15 min), 1 and 2 hours post-infusion, Day 5, Day 15 and Day 29 (trough level before Dose 2). * The AUC0-28 for Dose 4 included the following timepoints: Day 85 pre-infusion, post-infusion (within 15 min), 1 and 2 hours post-infusion, Day 89, Day 99 and Day 113 (trough level before Dose 5).

First Dosing Interval
GroupValue95% CI
ABBV-8E12 300 mg2520± 28
ABBV-8E12 1000 mg6090± 37
ABBV-8E12 2000 mg14800± 25
Fourth Dosing Interval
GroupValue95% CI
ABBV-8E12 300 mg4230± 33
ABBV-8E12 1000 mg13100± 36
ABBV-8E12 2000 mg30200± 36
Cmax/Dose for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses Secondary · Day 1 (Dose 1): Pre-infusion, post-infusion (within 15 minutes), 1 and 2 hours post-infusion; Days 5 and 15. Day 85 (Dose 4): Pre-infusion (0 hour), post-infusion (within 15 minutes) and 1 and 2 hours post-infusion; Days 89 and 99.
First Dosing Interval
GroupValue95% CI
ABBV-8E12 300 mg0.359± 28
ABBV-8E12 1000 mg0.284± 21
ABBV-8E12 2000 mg0.264± 27
Fourth Dosing Interval
GroupValue95% CI
ABBV-8E12 300 mg0.561± 23
ABBV-8E12 1000 mg0.426± 20
ABBV-8E12 2000 mg0.403± 37
AUC0-28/Dose for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses Secondary · Day 1 (Dose 1): pre-infusion, up to Day 29 (trough level before Dose 2). Day 85 (Dose 4): pre-infusion, up to Day 113 (trough level before Dose 5). See Outcome Measure description above for complete time point details.

* The AUC0-28/dose for Dose 1 included the following timepoints: pre-infusion, post-infusion (within 15 min), 1 and 2 hours post-infusion, Day 5, Day 15 and Day 29 (trough level before Dose 2). * The AUC0-28/dose for Dose 4 included the following timepoints: Day 85 pre-infusion, post-infusion (within 15 min), 1 and 2 hours post-infusion, Day 89, Day 99 and Day 113 (trough level before Dose 5).

First Dosing Interval
GroupValue95% CI
ABBV-8E12 300 mg8.40± 28
ABBV-8E12 1000 mg6.09± 37
ABBV-8E12 2000 mg7.41± 25
Fourth Dosing Interval
GroupValue95% CI
ABBV-8E12 300 mg14.1± 33
ABBV-8E12 1000 mg13.1± 36
ABBV-8E12 2000 mg15.1± 36
Change From Baseline Over Time in Alzheimer's Disease Assessment Scale (14-Item) Cognition Portion (ADAS-Cog-14) Total Score Secondary · Baseline, Week 24, Week 48, Week 72, Week 96

The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 \[1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task\] and includes 3 additional tasks \[12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning\], for increa

Change at Week 24
GroupValue95% CI
Placebo1.82± 0.492
ABBV-8E12 300 mg1.42± 0.498
ABBV-8E12 1000 mg0.56± 0.480
ABBV-8E12 2000 mg1.86± 0.503
Change at Week 48
GroupValue95% CI
Placebo4.50± 0.621
ABBV-8E12 300 mg3.51± 0.642
ABBV-8E12 1000 mg3.42± 0.605
ABBV-8E12 2000 mg4.03± 0.647
Change at Week 72
GroupValue95% CI
Placebo5.26± 0.718
ABBV-8E12 300 mg4.78± 0.730
ABBV-8E12 1000 mg5.00± 0.706
ABBV-8E12 2000 mg6.37± 0.738
Change at Week 96
GroupValue95% CI
Placebo8.43± 0.898
ABBV-8E12 300 mg7.99± 0.891
ABBV-8E12 1000 mg7.84± 0.872
ABBV-8E12 2000 mg9.46± 0.935
Change From Baseline Over Time in ADAS-Cog-14 Comprehension of Spoken Language Score Secondary · Baseline, Week 24, Week 48, Week 72, Week 96

The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 \[1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task\] and includes 3 additional tasks \[12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning\], for increa

Change at Week 24
GroupValue95% CI
Placebo0.01± 0.038
ABBV-8E12 300 mg0.03± 0.038
ABBV-8E12 1000 mg0.04± 0.037
ABBV-8E12 2000 mg0.08± 0.039
Change at Week 48
GroupValue95% CI
Placebo0.03± 0.044
ABBV-8E12 300 mg0.09± 0.046
ABBV-8E12 1000 mg0.07± 0.044
ABBV-8E12 2000 mg0.12± 0.046
Change at Week 72
GroupValue95% CI
Placebo0.17± 0.064
ABBV-8E12 300 mg0.11± 0.066
ABBV-8E12 1000 mg0.14± 0.064
ABBV-8E12 2000 mg0.31± 0.066
Change at Week 96
GroupValue95% CI
Placebo0.30± 0.083
ABBV-8E12 300 mg0.26± 0.083
ABBV-8E12 1000 mg0.19± 0.080
ABBV-8E12 2000 mg0.29± 0.085
Change From Baseline Over Time in ADAS-Cog-14 Constructional Praxis Score Secondary · Baseline, Week 24, Week 48, Week 72, Week 96

The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 \[1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task\] and includes 3 additional tasks \[12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning\], for increa

Change at Week 24
GroupValue95% CI
Placebo0.11± 0.057
ABBV-8E12 300 mg0.05± 0.058
ABBV-8E12 1000 mg-0.02± 0.056
ABBV-8E12 2000 mg0.09± 0.059
Change at Week 48
GroupValue95% CI
Placebo0.07± 0.073
ABBV-8E12 300 mg0.23± 0.077
ABBV-8E12 1000 mg0.17± 0.072
ABBV-8E12 2000 mg0.20± 0.077
Change at Week 72
GroupValue95% CI
Placebo0.25± 0.069
ABBV-8E12 300 mg0.22± 0.072
ABBV-8E12 1000 mg0.16± 0.070
ABBV-8E12 2000 mg0.16± 0.071
Change at Week 96
GroupValue95% CI
Placebo0.41± 0.089
ABBV-8E12 300 mg0.25± 0.089
ABBV-8E12 1000 mg0.026± 0.086
ABBV-8E12 2000 mg0.33± 0.092

Adverse events — posted to ClinicalTrials.gov

Time frame: From the time of study drug administration until 20 weeks following discontinuation of study drug administration. Overall median time on study was 680.0 days.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 26/116 (22%)
Deaths: 1/116
ABBV-8E12 300 mg
Serious: 19/108 (18%)
Deaths: 2/108
ABBV-8E12 1000 mg
Serious: 22/116 (19%)
Deaths: 2/116
ABBV-8E12 2000 mg
Serious: 17/113 (15%)
Deaths: 1/113

Serious adverse events (95 terms)

ReactionSystemPlaceboABBV-8E12 300 mgABBV-8E12 1000 mgABBV-8E12 2000 mg
URINARY TRACT INFECTIONInfections and infestations
FALLInjury, poisoning and procedural complications
SYNCOPENervous system disorders
MYOCARDIAL INFARCTIONCardiac disorders
DIVERTICULITISInfections and infestations
PNEUMONIAInfections and infestations
RIB FRACTUREInjury, poisoning and procedural complications
HYPONATRAEMIAMetabolism and nutrition disorders
OSTEOARTHRITISMusculoskeletal and connective tissue disorders
CEREBROVASCULAR ACCIDENTNervous system disorders
PULMONARY EMBOLISMRespiratory, thoracic and mediastinal disorders
ARTERIOSCLEROSIS CORONARY ARTERYCardiac disorders
ATRIAL FIBRILLATIONCardiac disorders
ATRIAL FLUTTERCardiac disorders
BRADYCARDIACardiac disorders
MYOCARDITISCardiac disorders
RIGHT VENTRICULAR FAILURECardiac disorders
SINUS NODE DYSFUNCTIONCardiac disorders
ABDOMINAL PAINGastrointestinal disorders
CONSTIPATIONGastrointestinal disorders
DYSPHAGIAGastrointestinal disorders
GASTRIC ULCER HAEMORRHAGEGastrointestinal disorders
GASTROINTESTINAL HAEMORRHAGEGastrointestinal disorders
NAUSEAGastrointestinal disorders
PANCREATITIS ACUTEGastrointestinal disorders
Other adverse events (26 terms — click to expand)

ReactionSystemPlaceboABBV-8E12 300 mgABBV-8E12 1000 mgABBV-8E12 2000 mg
FALLInjury, poisoning and procedural complications
HEADACHENervous system disorders
UPPER RESPIRATORY TRACT INFECTIONInfections and infestations
ANXIETYPsychiatric disorders
DIZZINESSNervous system disorders
URINARY TRACT INFECTIONInfections and infestations
DIARRHOEAGastrointestinal disorders
NASOPHARYNGITISInfections and infestations
ARTHRALGIAMusculoskeletal and connective tissue disorders
DEPRESSIONPsychiatric disorders
VOMITINGGastrointestinal disorders
FATIGUEGeneral disorders
BACK PAINMusculoskeletal and connective tissue disorders
NAUSEAGastrointestinal disorders
COUGHRespiratory, thoracic and mediastinal disorders
SINUSITISInfections and infestations
CONTUSIONInjury, poisoning and procedural complications
SKIN ABRASIONInjury, poisoning and procedural complications
SKIN LACERATIONInjury, poisoning and procedural complications
INSOMNIAPsychiatric disorders
SEASONAL ALLERGYImmune system disorders
BRONCHITISInfections and infestations
INFLUENZAInfections and infestations
MUSCULOSKELETAL CHEST PAINMusculoskeletal and connective tissue disorders
CEREBRAL MICROHAEMORRHAGENervous system disorders
HYPERTENSIONVascular disorders

Most-reported serious reactions: URINARY TRACT INFECTION, FALL, SYNCOPE, MYOCARDIAL INFARCTION, DIVERTICULITIS, PNEUMONIA, RIB FRACTURE, HYPONATRAEMIA.

Data from ClinicalTrials.gov NCT02880956 adverse events section.

Sponsor's own description

This study seeks to evaluate the efficacy and safety of ABBV-8E12 in participants with early Alzheimer's disease (AD).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Tau-targeting therapies for Alzheimer disease.
    Congdon EE, Sigurdsson EM. · · 2018 · cited 838× · PMID 29895964 · DOI 10.1038/s41582-018-0013-z
  2. Roles of tau protein in health and disease.
    Guo T, Noble W, Hanger DP. · · 2017 · cited 710× · PMID 28386764 · DOI 10.1007/s00401-017-1707-9
  3. Current and Future Treatments in Alzheimer Disease: An Update.
    Yiannopoulou KG, Papageorgiou SG. · · 2020 · cited 553× · PMID 32165850 · DOI 10.1177/1179573520907397
  4. Alzheimer's disease drug development pipeline: 2019.
    Cummings J, Lee G, Ritter A, Sabbagh M, et al · · 2019 · cited 485× · PMID 31334330 · DOI 10.1016/j.trci.2019.05.008
  5. Promoting the clearance of neurotoxic proteins in neurodegenerative disorders of ageing.
    Boland B, Yu WH, Corti O, Mollereau B, et al · · 2018 · cited 422× · PMID 30116051 · DOI 10.1038/nrd.2018.109
  6. Alzheimer's disease drug development pipeline: 2018.
    Cummings J, Lee G, Ritter A, Zhong K. · · 2018 · cited 402× · PMID 29955663 · DOI 10.1016/j.trci.2018.03.009
  7. Treatment Combinations for Alzheimer's Disease: Current and Future Pharmacotherapy Options.
    Cummings JL, Tong G, Ballard C. · · 2019 · cited 371× · PMID 30689575 · DOI 10.3233/jad-180766
  8. Alzheimer's disease drug development pipeline: 2020.
    Cummings J, Lee G, Ritter A, Sabbagh M, et al · · 2020 · cited 350× · PMID 32695874 · DOI 10.1002/trc2.12050

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing