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NCT02985879

A Study to Assess Efficacy, Safety, Tolerability, and Pharmacokinetics of ABBV-8E12 in Subjects With Progressive Supranuclear Palsy (PSP)

Terminated Phase 2 Results posted Last updated 3 February 2021
What this trial tests

Phase 2 trial testing Placebo in Progressive Supranuclear Palsy in 378 participants. Terminated before completion.

Timeline
12 December 2016
Primary endpoint
20 November 2019
20 November 2019

Quick facts

Lead sponsorAbbVie
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment378
Start date12 December 2016
Primary completion20 November 2019
Estimated completion20 November 2019
Sites66 locations across France, Italy, Japan, Germany, Canada, Australia, United States, Spain

Drugs / interventions tested

Conditions studied

Sponsor

AbbVie — full company profile →

Who can join

40 and older, any sex, with Progressive Supranuclear Palsy. 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 to Week 52 in Progressive Supranuclear Palsy Rating Scale (PSPRS) Total Score Primary · Baseline, Week 52

The PSPRS consists of 28 items grouped in six domains: daily activities (by history); behavior; bulbar; ocular motor; limb motor; and gait/midline. Items are scored on a 0 to 4 scale, except for six items that are scored on a 0 to 2 scale, with the total score ranging from 0 to 100. Higher scores indicate more severe disability or movement abnormality. Positive changes in score indicate worsening from baseline.

GroupValue95% CI
Placebo10.5± 0.94
ABBV-8E12 2000mg10.5± 0.96
ABBV-8E12 4000mg11.4± 0.94
Number of Participants With Adverse Events Primary · From the first dose of study drug until 20 weeks following discontinuation of study drug administration have elapsed (approximately 5 half-lives), up to 80 weeks

An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either reasonable possibility or no reasonable possibility. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important

GroupValue95% CI
Placebo108
ABBV-8E12 2000mg111
ABBV-8E12 4000mg111
Mean Change From Baseline to Week 52 in Unified Parkinson's Disease Rating Scale (UPDRS) Part II (Activities of Daily Living) Secondary · Baseline, Week 52

The Unified Parkinson's Disease Rating Scale (UPDRS) is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The Part II score is the sum of the answers to the 13 questions related to Activities of Daily Living, and ranges from 0-52. Higher scores are associated with more disability. Positive changes in score indicate worsening from baseline.

GroupValue95% CI
Placebo5.6± 0.62
ABBV-8E12 2000mg5.8± 0.63
ABBV-8E12 4000mg7.0± 0.63
Clinical Global Impression of Change (CGI-C) Score at Week 52 Secondary · Week 52

The Clinical Global Impression of Change (CGI-C) score is a clinician's rating scale for assessing Global Improvement of Change. The CGI-C rates improvement by 7 categories: very much improved (1), much improved (2), minimally improved (3), no change (4), minimally worse (5), much worse (6), very much worse (7). The CGI-C score ranges from 1 to 7, with lower scores indicating improvement.

GroupValue95% CI
Placebo5.1± 0.11
ABBV-8E12 2000mg5.1± 0.11
ABBV-8E12 4000mg5.0± 0.11
Mean Change From Baseline to Week 52 in Midbrain Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI) Secondary · Baseline, Week 52

Magnetic resonance imaging (MRI) of several different brain regions was performed and volumetric analysis was conducted to quantify midbrain atrophy. Negative changes in values indicate a reduction in volume.

GroupValue95% CI
Placebo-122.0± 9.64
ABBV-8E12 2000mg-129.1± 9.69
ABBV-8E12 4000mg-128.3± 9.69
Mean Change From Baseline to Week 52 in Schwab and England Activities of Daily Living Scale (SEADL) Secondary · Baseline, Week 52

The Schwab and England Activities of Daily Living (SEADL) consists of ten items intended to evaluate the daily life activities of a participant. The SEADL is composed of two sections: the first is a self-reported questionnaire in which participants grade their own daily life activities, such as dressing, using the toilet, resting, eating, and social activities (subjective assessment), and the second is an assessment of motor functions, such as postural balance, speaking, rigidity, and tremors, conducted by a clinician (objective assessment). It is a percentage scale divided into deciles, and t

GroupValue95% CI
Placebo-20.6± 1.79
ABBV-8E12 2000mg-18.0± 1.82
ABBV-8E12 4000mg-20.5± 1.77
Maximum Observed Serum Concentration (Cmax) for ABBV-8E12 Secondary · First Dosing Interval, 2 weeks, Day 1-14; Fifth Dosing Interval, 4 weeks, Day 85-113

The maximum observed serum concentration after the first and the fifth doses in Cohort 1 and Cohort J1 was determined.

First Dosing Interval, 2 weeks, Day 1-14
GroupValue95% CI
Cohort 1, ABBV-8E12 2000 mg714± 32
Cohort 1, ABBV-8E12 4000 mg1450± 20
Cohort J1, ABBV-8E12 2000 mg853± 6
Cohort J1, ABBV-8E12 4000 mg1580± 13
Fifth Dosing Interval, 4 weeks, Day 85-113
GroupValue95% CI
Cohort 1, ABBV-8E12 2000 mg1070± 56
Cohort 1, ABBV-8E12 4000 mg2350± 23
Cohort J1, ABBV-8E12 2000 mg1010± 21
Cohort J1, ABBV-8E12 4000 mg1960± 15
Time to Maximum Observed Serum Concentration (Tmax) for ABBV-8E12 Secondary · First Dosing Interval, 2 weeks, Day 1-14; Fifth Dosing Interval, 4 weeks, Day 85-113

The time to maximum plasma concentration (Tmax; measured in hours) is the time it takes for a drug to achieve Cmax, the maximum plasma concentration. Tmax was measured after the first and the fifth doses in Cohort 1 and Cohort J1.

First Dosing Interval, 2 weeks, Day 1-14
GroupValue95% CI
Cohort 1, ABBV-8E12 2000 mg4.03.2 – 6.1
Cohort 1, ABBV-8E12 4000 mg4.13.2 – 5.6
Cohort J1, ABBV-8E12 2000 mg5.04.0 – 5.2
Cohort J1, ABBV-8E12 4000 mg4.84.3 – 4.9
Fifth Dosing Interval, 4 weeks, Day 85-113
GroupValue95% CI
Cohort 1, ABBV-8E12 2000 mg3.62.9 – 5.5
Cohort 1, ABBV-8E12 4000 mg4.03.3 – 46.2
Cohort J1, ABBV-8E12 2000 mg5.04.4 – 5.7
Cohort J1, ABBV-8E12 4000 mg3.43.2 – 3.5
Area Under the Concentration Time Curve (AUC) for ABBV-8E12 Secondary · First Dosing Interval, 2 weeks, Day 1-14; Fifth Dosing Interval, 4 weeks, Day 85-113

The area under the plasma concentration-time curve (AUC; measured in µg•day/mL) is a method of measurement to determine the total exposure of a drug in blood plasma. The AUC24 of ABBV-8E12 was estimated using non-compartmental methods after the first and the fifth doses in Cohort 1 and Cohort J1.

First Dosing Interval, 2 weeks, Day 1-14
GroupValue95% CI
Cohort 1, ABBV-8E12 2000 mg5070± 25
Cohort 1, ABBV-8E12 4000 mg10400± 21
Cohort J1, ABBV-8E12 2000 mg5950± 12
Cohort J1, ABBV-8E12 4000 mg10400± 11
Fifth Dosing Interval, 4 weeks, Day 85-113
GroupValue95% CI
Cohort 1, ABBV-8E12 2000 mg13900± 28
Cohort 1, ABBV-8E12 4000 mg31600± 36
Cohort J1, ABBV-8E12 2000 mg15200± 21
Cohort J1, ABBV-8E12 4000 mg23900± 15
Serum Concentration of ABBV-8E12 Prior to Infusion of a Day of Dosing (Ctrough) Secondary · First day of the Fifth Dosing Interval, Day 85

The concentration of ABBV-8E12 immediately prior to infusion of the fifth dose (Ctrough; measured in µg/mL) was estimated using non-compartmental methods in Cohort 1 and Cohort J1.

GroupValue95% CI
Cohort 1, ABBV-8E12 2000 mg353± 27
Cohort 1, ABBV-8E12 4000 mg657± 45
Cohort J1, ABBV-8E12 2000 mg345± 32
Cohort J1, ABBV-8E12 4000 mg595± 16
Mean Change From Baseline to Week 52 in Clinical Global Impression of Severity (CGI-S) Score Secondary · Baseline, Week 52

The CGI-S is a clinician's rating of disease severity. The CGI-S rates severity of illness on a 7-point scale, using a range of responses from 1 (normal) through 7 (the most severely ill). This rating is based upon observed and reported symptoms, behavior, and function in the past 7 days. Positive changes in score indicate worsening from baseline.

GroupValue95% CI
Placebo0.6± 0.10
ABBV-8E12 2000mg0.6± 0.10
ABBV-8E12 4000mg0.6± 0.10
Mean Change From Baseline to Week 52 in Progressive Supranuclear Palsy Health Related Quality of Life Scale (PSP-QoL) Total Score Secondary · Baseline, Week 52

The PSP-QoL is a validated patient-reported outcome measure, specifically designed to assess the quality of life of participants with PSP. There are 45 items and two subscales: physical and mental impact. Items are scored from 0 (no problem) to 4 (extreme problems). The total subscale sum scores are linearly converted into a 0 to 100 scale, and higher scores indicate a lower quality of life. Positive changes in score indicate a decline in quality of life.

GroupValue95% CI
Placebo9.2± 1.63
ABBV-8E12 2000mg10.3± 1.65
ABBV-8E12 4000mg10.0± 1.64

Adverse events — posted to ClinicalTrials.gov

Time frame: Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the first dose of study drug until 20 weeks following discontinuation of study drug administration have elapsed (approximately 5 half-lives), up to 80 weeks. In addition, serious adverse events and protocol-related nonserious adverse events were collected from the time the participant signed the study-specific informed consent.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 33/126 (26%)
Deaths: 8/126
ABBV-8E12 2000mg
Serious: 29/126 (23%)
Deaths: 9/126
ABBV-8E12 4000mg
Serious: 34/125 (27%)
Deaths: 9/125

Serious adverse events (112 terms)

ReactionSystemPlaceboABBV-8E12 2000mgABBV-8E12 4000mg
FALLInjury, poisoning and procedural complications
PNEUMONIAInfections and infestations
PROGRESSIVE SUPRANUCLEAR PALSYNervous system disorders
URINARY TRACT INFECTIONInfections and infestations
HIP FRACTUREInjury, poisoning and procedural complications
RIB FRACTUREInjury, poisoning and procedural complications
SUBDURAL HAEMATOMAInjury, poisoning and procedural complications
LOSS OF CONSCIOUSNESSNervous system disorders
PNEUMONIA ASPIRATIONRespiratory, thoracic and mediastinal disorders
DYSPHAGIAGastrointestinal disorders
GASTROINTESTINAL HAEMORRHAGEGastrointestinal disorders
DEATHGeneral disorders
PYREXIAGeneral disorders
CELLULITISInfections and infestations
CERVICAL VERTEBRAL FRACTUREInjury, poisoning and procedural complications
FEMUR FRACTUREInjury, poisoning and procedural complications
HEAD INJURYInjury, poisoning and procedural complications
SKIN LACERATIONInjury, poisoning and procedural complications
SYNCOPENervous system disorders
LEUKOCYTOSISBlood and lymphatic system disorders
ACUTE MYOCARDIAL INFARCTIONCardiac disorders
ATRIAL FIBRILLATIONCardiac disorders
CARDIAC FAILURECardiac disorders
CARDIAC FAILURE CONGESTIVECardiac disorders
CARDIO-RESPIRATORY ARRESTCardiac disorders
Other adverse events (18 terms — click to expand)

ReactionSystemPlaceboABBV-8E12 2000mgABBV-8E12 4000mg
FALLInjury, poisoning and procedural complications
CONTUSIONInjury, poisoning and procedural complications
SKIN LACERATIONInjury, poisoning and procedural complications
URINARY TRACT INFECTIONInfections and infestations
SKIN ABRASIONInjury, poisoning and procedural complications
WEIGHT DECREASEDInvestigations
DIARRHOEAGastrointestinal disorders
DEPRESSIONPsychiatric disorders
CONSTIPATIONGastrointestinal disorders
FATIGUEGeneral disorders
HEADACHENervous system disorders
COUGHRespiratory, thoracic and mediastinal disorders
UPPER RESPIRATORY TRACT INFECTIONInfections and infestations
MUSCULOSKELETAL PAINMusculoskeletal and connective tissue disorders
DIZZINESSNervous system disorders
INSOMNIAPsychiatric disorders
RASHSkin and subcutaneous tissue disorders
ANXIETYPsychiatric disorders

Most-reported serious reactions: FALL, PNEUMONIA, PROGRESSIVE SUPRANUCLEAR PALSY, URINARY TRACT INFECTION, HIP FRACTURE, RIB FRACTURE, SUBDURAL HAEMATOMA, LOSS OF CONSCIOUSNESS.

Data from ClinicalTrials.gov NCT02985879 adverse events section.

Sponsor's own description

The purpose of this study was to assess efficacy, safety, tolerability, and pharmacokinetics of ABBV-8E12 in participants with progressive supranuclear palsy (PSP).

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. 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
  4. Tau-targeting therapies for Alzheimer disease: current status and future directions.
    Congdon EE, Ji C, Tetlow AM, Jiang Y, et al · · 2023 · cited 246× · PMID 37875627 · DOI 10.1038/s41582-023-00883-2
  5. From the prion-like propagation hypothesis to therapeutic strategies of anti-tau immunotherapy.
    Colin M, Dujardin S, Schraen-Maschke S, Meno-Tetang G, et al · · 2020 · cited 145× · PMID 31686182 · DOI 10.1007/s00401-019-02087-9
  6. Safety and efficacy of tilavonemab in progressive supranuclear palsy: a phase 2, randomised, placebo-controlled trial.
    Höglinger GU, Litvan I, Mendonca N, Wang D, et al · · 2021 · cited 111× · PMID 33609476 · DOI 10.1016/s1474-4422(20)30489-0
  7. An Overview on the Clinical Development of Tau-Based Therapeutics.
    Medina M. · · 2018 · cited 103× · PMID 29641484 · DOI 10.3390/ijms19041160
  8. New Insights Into Drug Discovery Targeting Tau Protein.
    Soeda Y, Takashima A. · · 2020 · cited 91× · PMID 33343298 · DOI 10.3389/fnmol.2020.590896

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