Trial Outcomes & Findings for A Study to Assess Efficacy, Safety, Tolerability, and Pharmacokinetics of ABBV-8E12 in Subjects With Progressive Supranuclear Palsy (PSP) (NCT NCT02985879)

NCT ID: NCT02985879

Last Updated: 2021-02-03

Results Overview

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

378 participants

Primary outcome timeframe

Baseline, Week 52

Results posted on

2021-02-03

Participant Flow

All randomized participants; one participant in the ABBV-8E12 2000 mg dose group never received study drug

Participant milestones

Participant milestones
Measure	Placebo 0.9% Sodium Chloride Injection/Solution for Infusion; intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks	ABBV-8E12 2000mg Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	ABBV-8E12 4000mg Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)
Overall Study STARTED	126	127	125
Overall Study COMPLETED	50	52	48
Overall Study NOT COMPLETED	76	75	77

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo 0.9% Sodium Chloride Injection/Solution for Infusion; intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks	ABBV-8E12 2000mg Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	ABBV-8E12 4000mg Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)
Overall Study Adverse Event	7	9	7
Overall Study Withdrew consent	6	8	10
Overall Study Lost to Follow-up	1	0	2
Overall Study Other, not specified	62	58	58

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=126 Participants 0.9% Sodium Chloride Injection/Solution for Infusion; intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks	ABBV-8E12 2000mg n=126 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	ABBV-8E12 4000mg n=125 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	Total n=377 Participants Total of all reporting groups
Age, Continuous	68.1 years STANDARD_DEVIATION 6.22 • n=99 Participants	68.3 years STANDARD_DEVIATION 7.25 • n=107 Participants	70.0 years STANDARD_DEVIATION 6.85 • n=206 Participants	68.8 years STANDARD_DEVIATION 6.82 • n=157 Participants
Sex: Female, Male Female	53 Participants n=99 Participants	49 Participants n=107 Participants	56 Participants n=206 Participants	158 Participants n=157 Participants
Sex: Female, Male Male	73 Participants n=99 Participants	77 Participants n=107 Participants	69 Participants n=206 Participants	219 Participants n=157 Participants
Race/Ethnicity, Customized White	109 Participants n=99 Participants	106 Participants n=107 Participants	109 Participants n=206 Participants	324 Participants n=157 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants	2 Participants n=157 Participants
Race/Ethnicity, Customized Asian	17 Participants n=99 Participants	17 Participants n=107 Participants	15 Participants n=206 Participants	49 Participants n=157 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=99 Participants	1 Participants n=107 Participants	0 Participants n=206 Participants	1 Participants n=157 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=157 Participants
Race/Ethnicity, Customized Multiple	0 Participants n=99 Participants	1 Participants n=107 Participants	0 Participants n=206 Participants	1 Participants n=157 Participants

PRIMARY outcome

Timeframe: Baseline, Week 52

Population: ITT dataset: all randomized participants who received at least one dose of study drug and those with available data at baseline and at Week 52

Outcome measures

Outcome measures
Measure	Placebo n=59 Participants 0.9% Sodium Chloride Injection/Solution for Infusion; intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks	ABBV-8E12 2000mg n=56 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	ABBV-8E12 4000mg n=59 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	Cohort J1, ABBV-8E12 4000 mg First 9 participants enrolled into the study from Japan who received augmented safety and PK assessments and ABBV-8E12 at a dose of 4000 mg
Change From Baseline to Week 52 in Progressive Supranuclear Palsy Rating Scale (PSPRS) Total Score	10.5 units on a scale Standard Error 0.94	10.5 units on a scale Standard Error 0.96	11.4 units on a scale Standard Error 0.94	—

PRIMARY outcome

Timeframe: 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

Population: Safety Dataset: all randomized participants who received at least one dose of study drug

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 medical event that, based on medical judgment, may jeopardize the subject and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent events (TEAEs) are defined as any event that began or worsened in severity from first dose of study drug until 20 weeks after the last dose. For more details on AEs please see the Adverse Event section.

Outcome measures

Outcome measures
Measure	Placebo n=126 Participants 0.9% Sodium Chloride Injection/Solution for Infusion; intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks	ABBV-8E12 2000mg n=126 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	ABBV-8E12 4000mg n=125 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	Cohort J1, ABBV-8E12 4000 mg First 9 participants enrolled into the study from Japan who received augmented safety and PK assessments and ABBV-8E12 at a dose of 4000 mg
Number of Participants With Adverse Events	108 Participants	111 Participants	111 Participants	—

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: ITT dataset: all randomized participants who received at least one dose of study drug and those with available data at baseline and at 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.

Outcome measures

Outcome measures
Measure	Placebo n=63 Participants 0.9% Sodium Chloride Injection/Solution for Infusion; intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks	ABBV-8E12 2000mg n=60 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	ABBV-8E12 4000mg n=60 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	Cohort J1, ABBV-8E12 4000 mg First 9 participants enrolled into the study from Japan who received augmented safety and PK assessments and ABBV-8E12 at a dose of 4000 mg
Mean Change From Baseline to Week 52 in Unified Parkinson's Disease Rating Scale (UPDRS) Part II (Activities of Daily Living)	5.6 units on a scale Standard Error 0.62	5.8 units on a scale Standard Error 0.63	7.0 units on a scale Standard Error 0.63	—

SECONDARY outcome

Timeframe: Week 52

Population: ITT dataset: all randomized participants who received at least one dose of study drug and those with available data at 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.

Outcome measures

Outcome measures
Measure	Placebo n=50 Participants 0.9% Sodium Chloride Injection/Solution for Infusion; intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks	ABBV-8E12 2000mg n=48 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	ABBV-8E12 4000mg n=51 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	Cohort J1, ABBV-8E12 4000 mg First 9 participants enrolled into the study from Japan who received augmented safety and PK assessments and ABBV-8E12 at a dose of 4000 mg
Clinical Global Impression of Change (CGI-C) Score at Week 52	5.1 units on a scale Standard Error 0.11	5.1 units on a scale Standard Error 0.11	5.0 units on a scale Standard Error 0.11	—

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: ITT dataset: all randomized participants who received at least one dose of study drug and those with available data at baseline and at 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.

Outcome measures

Outcome measures
Measure	Placebo n=53 Participants 0.9% Sodium Chloride Injection/Solution for Infusion; intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks	ABBV-8E12 2000mg n=55 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	ABBV-8E12 4000mg n=54 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	Cohort J1, ABBV-8E12 4000 mg First 9 participants enrolled into the study from Japan who received augmented safety and PK assessments and ABBV-8E12 at a dose of 4000 mg
Mean Change From Baseline to Week 52 in Midbrain Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI)	-122.0 mm^3 Standard Error 9.64	-129.1 mm^3 Standard Error 9.69	-128.3 mm^3 Standard Error 9.69	—

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: ITT dataset: all randomized participants who received at least one dose of study drug and those with available data at baseline and at 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 the results are reported between 0% (bedridden) and 100% (healthy). Negative changes in values indicate a decline in health.

Outcome measures

Outcome measures
Measure	Placebo n=58 Participants 0.9% Sodium Chloride Injection/Solution for Infusion; intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks	ABBV-8E12 2000mg n=56 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	ABBV-8E12 4000mg n=60 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	Cohort J1, ABBV-8E12 4000 mg First 9 participants enrolled into the study from Japan who received augmented safety and PK assessments and ABBV-8E12 at a dose of 4000 mg
Mean Change From Baseline to Week 52 in Schwab and England Activities of Daily Living Scale (SEADL)	-20.6 percentage of independence Standard Error 1.79	-18.0 percentage of independence Standard Error 1.82	-20.5 percentage of independence Standard Error 1.77	—

SECONDARY outcome

Timeframe: First Dosing Interval, 2 weeks, Day 1-14; Fifth Dosing Interval, 4 weeks, Day 85-113

Population: Participants in Cohort 1 and Cohort J1 with available data

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

Outcome measures

Outcome measures
Measure	Placebo n=11 Participants 0.9% Sodium Chloride Injection/Solution for Infusion; intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks	ABBV-8E12 2000mg n=9 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	ABBV-8E12 4000mg n=3 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	Cohort J1, ABBV-8E12 4000 mg n=3 Participants First 9 participants enrolled into the study from Japan who received augmented safety and PK assessments and ABBV-8E12 at a dose of 4000 mg
Maximum Observed Serum Concentration (Cmax) for ABBV-8E12 First Dosing Interval, 2 weeks, Day 1-14	714 µg/mL Geometric Coefficient of Variation 32	1450 µg/mL Geometric Coefficient of Variation 20	853 µg/mL Geometric Coefficient of Variation 6	1580 µg/mL Geometric Coefficient of Variation 13
Maximum Observed Serum Concentration (Cmax) for ABBV-8E12 Fifth Dosing Interval, 4 weeks, Day 85-113	1070 µg/mL Geometric Coefficient of Variation 56	2350 µg/mL Geometric Coefficient of Variation 23	1010 µg/mL Geometric Coefficient of Variation 21	1960 µg/mL Geometric Coefficient of Variation 15

SECONDARY outcome

Timeframe: First Dosing Interval, 2 weeks, Day 1-14; Fifth Dosing Interval, 4 weeks, Day 85-113

Population: Participants in Cohort 1 and Cohort J1 with available data

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.

Outcome measures

Outcome measures
Measure	Placebo n=11 Participants 0.9% Sodium Chloride Injection/Solution for Infusion; intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks	ABBV-8E12 2000mg n=9 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	ABBV-8E12 4000mg n=3 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	Cohort J1, ABBV-8E12 4000 mg n=3 Participants First 9 participants enrolled into the study from Japan who received augmented safety and PK assessments and ABBV-8E12 at a dose of 4000 mg
Time to Maximum Observed Serum Concentration (Tmax) for ABBV-8E12 Fifth Dosing Interval, 4 weeks, Day 85-113	3.6 hours Interval 2.9 to 5.5	4.0 hours Interval 3.3 to 46.2	5.0 hours Interval 4.4 to 5.7	3.4 hours Interval 3.2 to 3.5
Time to Maximum Observed Serum Concentration (Tmax) for ABBV-8E12 First Dosing Interval, 2 weeks, Day 1-14	4.0 hours Interval 3.2 to 6.1	4.1 hours Interval 3.2 to 5.6	5.0 hours Interval 4.0 to 5.2	4.8 hours Interval 4.3 to 4.9

SECONDARY outcome

Timeframe: First Dosing Interval, 2 weeks, Day 1-14; Fifth Dosing Interval, 4 weeks, Day 85-113

Population: Participants in Cohort 1 and Cohort J1 with available data

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.

Outcome measures

Outcome measures
Measure	Placebo n=11 Participants 0.9% Sodium Chloride Injection/Solution for Infusion; intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks	ABBV-8E12 2000mg n=9 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	ABBV-8E12 4000mg n=3 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	Cohort J1, ABBV-8E12 4000 mg n=3 Participants First 9 participants enrolled into the study from Japan who received augmented safety and PK assessments and ABBV-8E12 at a dose of 4000 mg
Area Under the Concentration Time Curve (AUC) for ABBV-8E12 First Dosing Interval, 2 weeks, Day 1-14	5070 µg•day/mL Geometric Coefficient of Variation 25	10400 µg•day/mL Geometric Coefficient of Variation 21	5950 µg•day/mL Geometric Coefficient of Variation 12	10400 µg•day/mL Geometric Coefficient of Variation 11
Area Under the Concentration Time Curve (AUC) for ABBV-8E12 Fifth Dosing Interval, 4 weeks, Day 85-113	13900 µg•day/mL Geometric Coefficient of Variation 28	31600 µg•day/mL Geometric Coefficient of Variation 36	15200 µg•day/mL Geometric Coefficient of Variation 21	23900 µg•day/mL Geometric Coefficient of Variation 15

SECONDARY outcome

Timeframe: First day of the Fifth Dosing Interval, Day 85

Population: Participants in Cohort 1 and Cohort J1 with available data

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.

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants 0.9% Sodium Chloride Injection/Solution for Infusion; intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks	ABBV-8E12 2000mg n=8 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	ABBV-8E12 4000mg n=3 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	Cohort J1, ABBV-8E12 4000 mg n=3 Participants First 9 participants enrolled into the study from Japan who received augmented safety and PK assessments and ABBV-8E12 at a dose of 4000 mg
Serum Concentration of ABBV-8E12 Prior to Infusion of a Day of Dosing (Ctrough)	353 µg/mL Geometric Coefficient of Variation 27	657 µg/mL Geometric Coefficient of Variation 45	345 µg/mL Geometric Coefficient of Variation 32	595 µg/mL Geometric Coefficient of Variation 16

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: ITT dataset: all randomized participants who received at least one dose of study drug and those with available data at baseline and at 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.

Outcome measures

Outcome measures
Measure	Placebo n=50 Participants 0.9% Sodium Chloride Injection/Solution for Infusion; intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks	ABBV-8E12 2000mg n=48 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	ABBV-8E12 4000mg n=51 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	Cohort J1, ABBV-8E12 4000 mg First 9 participants enrolled into the study from Japan who received augmented safety and PK assessments and ABBV-8E12 at a dose of 4000 mg
Mean Change From Baseline to Week 52 in Clinical Global Impression of Severity (CGI-S) Score	0.6 units on a scale Standard Error 0.10	0.6 units on a scale Standard Error 0.10	0.6 units on a scale Standard Error 0.10	—

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: ITT dataset: all randomized participants who received at least one dose of study drug and those with available data at baseline and at 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.

Outcome measures

Outcome measures
Measure	Placebo n=62 Participants 0.9% Sodium Chloride Injection/Solution for Infusion; intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks	ABBV-8E12 2000mg n=59 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	ABBV-8E12 4000mg n=60 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	Cohort J1, ABBV-8E12 4000 mg First 9 participants enrolled into the study from Japan who received augmented safety and PK assessments and ABBV-8E12 at a dose of 4000 mg
Mean Change From Baseline to Week 52 in Progressive Supranuclear Palsy Health Related Quality of Life Scale (PSP-QoL) Total Score	9.2 units on a scale Standard Error 1.63	10.3 units on a scale Standard Error 1.65	10.0 units on a scale Standard Error 1.64	—

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: ITT dataset: all randomized participants who received at least one dose of study drug and those with available data at baseline and at Week 52

The Progressive Supranuclear Palsy Rating Scale (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 four 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. The PSP-SS score is a composite of the dysphagia and gait items from the PSPRS. Positive changes in score indicate worsening from baseline.

Outcome measures

Outcome measures
Measure	Placebo n=59 Participants 0.9% Sodium Chloride Injection/Solution for Infusion; intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks	ABBV-8E12 2000mg n=57 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	ABBV-8E12 4000mg n=59 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	Cohort J1, ABBV-8E12 4000 mg First 9 participants enrolled into the study from Japan who received augmented safety and PK assessments and ABBV-8E12 at a dose of 4000 mg
Mean Change From Baseline to Week 52 in Progressive Supranuclear Palsy Staging System Score (PSP-SS) Score	0.8 units on a scale Standard Error 0.24	0.9 units on a scale Standard Error 0.24	1.0 units on a scale Standard Error 0.24	—

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: ITT dataset: all randomized participants who received at least one dose of study drug and those with available data at baseline and at Week 52

Magnetic resonance imaging (MRI) of several different brain regions was performed and volumetric analysis was conducted to quantify third ventricle atrophy. Positive changes in values indicate an increase in volume.

Outcome measures

Outcome measures
Measure	Placebo n=54 Participants 0.9% Sodium Chloride Injection/Solution for Infusion; intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks	ABBV-8E12 2000mg n=58 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	ABBV-8E12 4000mg n=53 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	Cohort J1, ABBV-8E12 4000 mg First 9 participants enrolled into the study from Japan who received augmented safety and PK assessments and ABBV-8E12 at a dose of 4000 mg
Mean Change From Baseline to Week 52 in Third Ventricle Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI)	157.9 mm^3 Standard Error 18.27	152.4 mm^3 Standard Error 18.04	125.0 mm^3 Standard Error 18.57	—

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: ITT dataset: all randomized participants who received at least one dose of study drug and those with available data at baseline and at Week 52

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

Outcome measures

Outcome measures
Measure	Placebo n=51 Participants 0.9% Sodium Chloride Injection/Solution for Infusion; intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks	ABBV-8E12 2000mg n=55 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	ABBV-8E12 4000mg n=54 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	Cohort J1, ABBV-8E12 4000 mg First 9 participants enrolled into the study from Japan who received augmented safety and PK assessments and ABBV-8E12 at a dose of 4000 mg
Mean Change From Baseline to Week 52 in Superior Cerebellar Peduncle Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI)	-8.3 mm^3 Standard Error 2.78	-4.3 mm^3 Standard Error 2.74	-3.7 mm^3 Standard Error 2.74	—

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: ITT dataset: all randomized participants who received at least one dose of study drug and those with available data at baseline and at Week 52

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

Outcome measures

Outcome measures
Measure	Placebo n=48 Participants 0.9% Sodium Chloride Injection/Solution for Infusion; intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks	ABBV-8E12 2000mg n=49 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	ABBV-8E12 4000mg n=43 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	Cohort J1, ABBV-8E12 4000 mg First 9 participants enrolled into the study from Japan who received augmented safety and PK assessments and ABBV-8E12 at a dose of 4000 mg
Mean Change From Baseline to Week 52 in Brainstem Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI)	-374.5 mm^3 Standard Error 38.42	-400.9 mm^3 Standard Error 38.60	-341.3 mm^3 Standard Error 40.61	—

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: ITT dataset: all randomized participants who received at least one dose of study drug and those with available data at baseline and at Week 52

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

Outcome measures

Outcome measures
Measure	Placebo n=45 Participants 0.9% Sodium Chloride Injection/Solution for Infusion; intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks	ABBV-8E12 2000mg n=46 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	ABBV-8E12 4000mg n=49 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	Cohort J1, ABBV-8E12 4000 mg First 9 participants enrolled into the study from Japan who received augmented safety and PK assessments and ABBV-8E12 at a dose of 4000 mg
Mean Change From Baseline to Week 52 in Whole Brain Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI)	-22496.2 mm^3 Standard Error 1793.36	-20757.1 mm^3 Standard Error 1783.00	-18811.3 mm^3 Standard Error 1740.72	—

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: ITT dataset: all randomized participants who received at least one dose of study drug and those with available data at baseline and at Week 52

Magnetic resonance imaging (MRI) of several different brain regions was performed and volumetric analysis was conducted to quantify frontal lobe atrophy. Positive changes in values indicate an increase in volume.

Outcome measures

Outcome measures
Measure	Placebo n=48 Participants 0.9% Sodium Chloride Injection/Solution for Infusion; intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks	ABBV-8E12 2000mg n=49 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	ABBV-8E12 4000mg n=43 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	Cohort J1, ABBV-8E12 4000 mg First 9 participants enrolled into the study from Japan who received augmented safety and PK assessments and ABBV-8E12 at a dose of 4000 mg
Mean Change From Baseline to Week 52 in Frontal Lobe Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI)	1052.6 mm^3 Standard Error 425.55	1260.5 mm^3 Standard Error 423.96	1186.1 mm^3 Standard Error 445.18	—

SECONDARY outcome

Timeframe: From Baseline to Week 52

Population: ITT dataset: all randomized participants who received at least one dose of study drug with available data

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. Item 26 pertains to gait, scored as either 0 (normal); 1 (slightly wide-based or irregular or slight pulsion on turns); 2 (must walk slowly or occasionally use walls or helper to avoid falling, especially on turns); 3 (must use assistance all or almost all the time); or 4 (unable to walk, even with walker; may be able to transfer).

Outcome measures

Outcome measures
Measure	Placebo n=126 Participants 0.9% Sodium Chloride Injection/Solution for Infusion; intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks	ABBV-8E12 2000mg n=126 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	ABBV-8E12 4000mg n=125 Participants Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)	Cohort J1, ABBV-8E12 4000 mg First 9 participants enrolled into the study from Japan who received augmented safety and PK assessments and ABBV-8E12 at a dose of 4000 mg
Time to Loss of Ability to Walk Independently as Measured by Progressive Supranuclear Palsy Rating Scale (PSPRS) Item 26	169.0 days Interval 89.0 to 255.0	170.0 days Interval 87.0 to 253.0	203.0 days Interval 169.0 to 255.0	—

Adverse Events

Placebo

Serious events: 33 serious events

Other events: 83 other events

Deaths: 8 deaths

ABBV-8E12 2000mg

Serious events: 29 serious events

Other events: 75 other events

Deaths: 9 deaths

ABBV-8E12 4000mg

Serious events: 34 serious events

Other events: 80 other events

Deaths: 9 deaths

Serious adverse events

Other adverse events

Additional Information

Global Medical Services

AbbVie

Phone: 800-633-9110

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.
Publication restrictions are in place

Restriction type: OTHER