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

• Sponsor: AbbVie (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02985879
• Collaborator: (none)
• Enrollment: 378
• Locations: 66
• Arms: 3
• Actual Duration (Months): 35.3
• Patients Per Site: 5.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Progressive Supranuclear Palsy	Drug: Placebo; Drug: ABBV-8E12	Phase 2

Detailed Description

This was a Phase 2, randomized, double-blind, placebo-controlled, multiple dose, multicenter study consisting of a screening period of up to 8 weeks (56 days), a 52-week double-blind treatment period, and a post-treatment follow-up period of approximately 20 weeks following last study drug administration (for those participants who prematurely discontinued from treatment, declined to participate in or did not qualify for participation in a long term extension [LTE] study). At the end of the treatment period, extended treatment was available for eligible participants who completed the 52-week treatment period and entered the separate long-term extension study (NCT03391765; Study M15-563). There were 3 cohorts in the study (Cohort 1, Cohort J1, and Cohort 2). Cohort 1 had augmented safety and pharmacokinetic (PK) assessments in the first 30 participants enrolled into the global study from countries other than Japan. Cohort J1 had augmented safety and PK assessments in the first 9 participants enrolled into the study from Japan. Cohort 2 consisted of all other participants enrolled in the global study not participating in Cohort 1 or Cohort J1.

This study was prematurely discontinued because the program for progressive supranuclear palsy was discontinued due to lack of efficacy of study drug.

Study Design

• Study Type: Interventional
• Actual Enrollment: 378 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled Multiple Dose Study to Assess Efficacy, Safety, Tolerability, and Pharmacokinetics of ABBV-8E12 in Progressive Supranuclear Palsy
• Actual Study Start Date: Dec 12, 2016
• Actual Primary Completion Date: Nov 20, 2019
• Actual Study Completion Date: Nov 20, 2019

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: 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	Drug: Placebo; Participants with 44-49 kg body weight (BW) had an intravenous infusion rate of 3.5 mL/min or 210 mL/hr; those with 50-58 kg BW, 4.0 mL/min or 240 mL/hr; and those with a BW >59 kg, 4.7 mL/min or 282 mL/hr.
Experimental: ABBV-8E12 2000 mg 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)	Drug: ABBV-8E12; Participants with 44-49 kg body weight (BW) had an intravenous infusion rate of 3.5 mL/min or 210 mL/hr; those with 50-58 kg BW, 4.0 mL/min or 240 mL/hr; and those with a BW >59 kg, 4.7 mL/min or 282 mL/hr. For participants in Cohort 2, ABBV-8E12 doses may have been decreased after the evaluation by the Data Monitoring Committee of available safety, tolerability and pharmacokinetic data.; Other Names: Tilavonemab
Experimental: ABBV-8E12 4000 mg 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)	Drug: ABBV-8E12; Participants with 44-49 kg body weight (BW) had an intravenous infusion rate of 3.5 mL/min or 210 mL/hr; those with 50-58 kg BW, 4.0 mL/min or 240 mL/hr; and those with a BW >59 kg, 4.7 mL/min or 282 mL/hr. For participants in Cohort 2, ABBV-8E12 doses may have been decreased after the evaluation by the Data Monitoring Committee of available safety, tolerability and pharmacokinetic data.; Other Names: Tilavonemab

Outcome Measures

Primary Outcome Measures

1. Change From Baseline to Week 52 in Progressive Supranuclear Palsy Rating Scale (PSPRS) Total Score [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.

2. Number of Participants With Adverse Events [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 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.

Secondary Outcome Measures

1. Mean Change From Baseline to Week 52 in Unified Parkinson's Disease Rating Scale (UPDRS) Part II (Activities of Daily Living) [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.

2. Clinical Global Impression of Change (CGI-C) Score at Week 52 [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.

3. Mean Change From Baseline to Week 52 in Midbrain Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI) [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.

4. Mean Change From Baseline to Week 52 in Schwab and England Activities of Daily Living Scale (SEADL) [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 the results are reported between 0% (bedridden) and 100% (healthy). Negative changes in values indicate a decline in health.

5. Maximum Observed Serum Concentration (Cmax) for ABBV-8E12 [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.

6. Time to Maximum Observed Serum Concentration (Tmax) for ABBV-8E12 [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.

7. Area Under the Concentration Time Curve (AUC) for ABBV-8E12 [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.

8. Serum Concentration of ABBV-8E12 Prior to Infusion of a Day of Dosing (Ctrough) [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.

9. Mean Change From Baseline to Week 52 in Clinical Global Impression of Severity (CGI-S) Score [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.

10. Mean Change From Baseline to Week 52 in Progressive Supranuclear Palsy Health Related Quality of Life Scale (PSP-QoL) Total Score [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.

11. Mean Change From Baseline to Week 52 in Progressive Supranuclear Palsy Staging System Score (PSP-SS) Score [Baseline, 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.

12. Mean Change From Baseline to Week 52 in Third Ventricle Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI) [Baseline, 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.

13. Mean Change From Baseline to Week 52 in Superior Cerebellar Peduncle Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI) [Baseline, 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.

14. Mean Change From Baseline to Week 52 in Brainstem Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI) [Baseline, 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.

15. Mean Change From Baseline to Week 52 in Whole Brain Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI) [Baseline, 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.

16. Mean Change From Baseline to Week 52 in Frontal Lobe Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI) [Baseline, 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.

17. Time to Loss of Ability to Walk Independently as Measured by Progressive Supranuclear Palsy Rating Scale (PSPRS) Item 26 [From Baseline to 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. 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Male or female participant with age 40 years or greater at the time of signed consent

• Meets the criteria for possible or probable progressive supranuclear palsy (PSP; Steele-Richardson-Olszewski Syndrome)

• Presence of PSP symptoms for less than 5 years

• Participant is able to walk 5 steps with minimal assistance (stabilization of one arm or use of cane/walker)

• Participant has an identified, reliable, study partner (e.g., caregiver, family member, social worker, or friend)

Key Exclusion Criteria:

• Participants who weigh less than 44 kg (97 lbs) at screening

• Mini-Mental State Examination (MMSE) score less than 15 at screening

• Any contraindication or inability to tolerate brain magnetic resonance imaging (MRI)

• Participant resides at a skilled nursing or dementia care facility, or admission to such a facility is planned during the study period

• Evidence of any clinically significant neurological disorder other than PSP

• The participant has a history of or currently has schizophrenia, schizoaffective disorder or bipolar disorder according to Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V) or International Classification of Diseases (ICD-10) criteria

• Participant has had a significant illness or infection requiring medical intervention in the past 30 days

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham - Main /ID# 144892	Birmingham	Alabama	United States	35233
2	Mayo Clinic - Scottsdale /ID# 144893	Scottsdale	Arizona	United States	85259
3	Cedars-Sinai Medical Center /ID# 149775	Beverly Hills	California	United States	90211
4	Ucsd /Id# 144905	La Jolla	California	United States	92093
5	Usc /Id# 149773	Los Angeles	California	United States	90033
6	University of California, Los Angeles /ID# 144896	Los Angeles	California	United States	90095
7	Univ California, San Francisco /ID# 144897	San Francisco	California	United States	94143-2204
8	Rocky Mountain Movement Disorders Center /ID# 153397	Englewood	Colorado	United States	80113-2736
9	University of Florida - Archer /ID# 144906	Gainesville	Florida	United States	32610
10	Mayo Clinic /ID# 144911	Jacksonville	Florida	United States	32224
11	University of South Florida /ID# 144912	Tampa	Florida	United States	33612
12	Georgia Regents University /ID# 144908	Augusta	Georgia	United States	30912
13	Rush University Medical Center /ID# 144894	Chicago	Illinois	United States	60612
14	University of Chicago /ID# 148672	Chicago	Illinois	United States	60637-1443
15	Indiana University /ID# 149036	Indianapolis	Indiana	United States	46202
16	University of Kentucky Chandler Medical Center /ID# 144891	Lexington	Kentucky	United States	40536
17	Mayo Clinic - Rochester /ID# 144895	Rochester	Minnesota	United States	55905-0001
18	St. Luke's Hosp. of Kansas Cit /ID# 168629	Kansas City	Missouri	United States	64111
19	Cleveland Clinic Lou Ruvo Cent /ID# 148919	Las Vegas	Nevada	United States	89106
20	Rutgers Robert Wood Johnson /ID# 144901	New Brunswick	New Jersey	United States	08901
21	COLUMBIA University Medical Center /ID# 149037	New York	New York	United States	10032-3725
22	Cleveland Clinic Main Campus /ID# 144885	Cleveland	Ohio	United States	44195
23	Oregon Health and Science University /ID# 149774	Portland	Oregon	United States	97239
24	Vanderbilt Univ Med Ctr /ID# 144898	Nashville	Tennessee	United States	37232-0011
25	Kerwin Research Center /ID# 144904	Dallas	Texas	United States	75231-4316
26	McGovern Medical School /ID# 149236	Houston	Texas	United States	77054
27	Central Texas Neurology Consul /ID# 167417	Round Rock	Texas	United States	78681
28	Westmead Hospital /ID# 154403	Westmead	New South Wales	Australia	2145
29	Q-Pharm Pty Limited /ID# 154410	Herston	Queensland	Australia	4006
30	Royal Adelaide Hospital /ID# 153157	Adelaide	South Australia	Australia	5000
31	Alfred Hospital /ID# 153158	Melbourne	Victoria	Australia	3004
32	Neurodegenerative Disorders Re /ID# 153770	West Perth	Western Australia	Australia	6005
33	University of Calgary /ID# 154393	Calgary	Alberta	Canada	T2N 4Z6
34	OCT Research ULC /ID# 169688	Kelowna	British Columbia	Canada	V1Y 1Z9
35	Toronto Western Hospital /ID# 152818	Toronto	Ontario	Canada	M5T 2S8
36	Crchum /Id# 152819	Montreal	Quebec	Canada	H2X 0A9
37	Montreal Neurological Institut /ID# 156413	Montreal	Quebec	Canada	H3A 2B4
38	Hopital Universitaire Purpan /ID# 153152	Toulouse	Haute-Garonne	France	31059
39	Hopital de la Timone /ID# 153113	Marseille CEDEX 05	Provence-Alpes-Cote-d Azur	France	13385
40	Chu de Bordeaux Hopital /Id# 153151	Bordeaux		France	33076
41	Hopital B Roger Salengro /ID# 153943	Lille		France	59037
42	Hopital Pitie Salpetriere /ID# 153942	Paris		France	75651
43	CHU Strasbourg Hautepierre Hos /ID# 206942	Strasbourg		France	67200
44	St. Josef-Hospital /ID# 201984	Bochum	Nordrhein-Westfalen	Germany	44791
45	Universitaetsklinikum Leipzig /ID# 201761	Leipzig	Sachsen	Germany	04103
46	Universitaetsklinikum Ulm /ID# 153155	Ulm	Thueringen	Germany	89081
47	KH Agatharied /ID# 154166	Hausham		Germany	83734
48	TU Uniklinik Munchen /ID# 153154	Munich		Germany	80802
49	Universita di Catanzaro Magna Graecia /ID# 166322	Catanzaro	Calabria	Italy	88100
50	Policlinico Agostino Gemelli /ID# 153104	Rome	Lazio	Italy	00168
51	IBD Center - IRCCS Istituto Clinico Humanitas /ID# 155092	Rozzano	Milano	Italy	20089
52	Fondazione IRCCS Istituto Neurologico Carlo Besta /ID# 201982	Milan		Italy	20133
53	Istituto Neuro Mediterraneo IR /ID# 153106	Pozzilli		Italy	86077
54	A.O. Santa Maria /ID# 153102	Terni		Italy	05100
55	IRCCS Ospedale San Camillo /ID# 153101	Venezia LIDO		Italy	30126
56	National Hospital Organization Higashinagoya National Hospital /ID# 201514	Nagoya-shi	Aichi	Japan	4658620
57	National Hospital Organization Asahikawa Medical Center /ID# 201585	Asahikawa	Hokkaido	Japan	070-8644
58	National Hospital Organization Utano National Hospital /ID# 201979	Kyoto City	Kyoto	Japan	616-8255
59	Tohoku University Hospital /ID# 202307	Sendai-shi	Miyagi	Japan	980-8574
60	NHO Sendai Nishitaga National Hospital /ID# 202132	Sendai	Miyagi	Japan	982-8555
61	Niigata University Medical & Dental Hospital /ID# 201680	Niigata-shi	Niigata	Japan	951-8520
62	Osaka University Hospital /ID# 201980	Suita-shi	Osaka	Japan	565-0871
63	Juntendo University Hospital /ID# 200870	Bunkyo-ku	Tokyo	Japan	113-8431
64	National Center of Neurology and Psychiatry /ID# 202037	Kodaira	Tokyo	Japan	187-8551
65	Hospital General Universitario Gregorio Maranon /ID# 200876	Madrid		Spain	28007
66	Hosp Univ Virgen del Rocio /ID# 201039	Sevilla		Spain	41001

Sponsors and Collaborators

• AbbVie

Investigators

• Study Director: AbbVie Inc., AbbVie

Study Documents (Full-Text)

• Study Protocol - Dec 13, 2018
• Statistical Analysis Plan - Oct 23, 2018

More Information

Publications

None provided.

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT02985879
• Other Study ID Numbers: M15-562; 2016-001635-12
• First Posted: Dec 7, 2016
• Last Update Posted: Feb 3, 2021
• Last Verified: Feb 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by AbbVie: PSP; Steele-Richardson-Olszewski syndrome; Tauopathy
• Additional relevant MeSH terms: Supranuclear Palsy, Progressive; Tilavonemab

Study Results

Participant Flow

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

Arm/Group Title	Placebo	ABBV-8E12 2000mg	ABBV-8E12 4000mg
Arm/Group Description	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	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)	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)
Period Title: Overall Study
STARTED	126	127	125
COMPLETED	50	52	48
NOT COMPLETED	76	75	77

Baseline Characteristics

Arm/Group Title	Placebo	ABBV-8E12 2000mg	ABBV-8E12 4000mg	Total
Arm/Group Description	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	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)	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 of all reporting groups
Overall Participants	126	126	125	377
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.1 (6.22)	68.3 (7.25)	70.0 (6.85)	68.8 (6.82)
Sex: Female, Male (Count of Participants)
Female	53 42.1%	49 38.9%	56 44.8%	158 41.9%
Male	73 57.9%	77 61.1%	69 55.2%	219 58.1%
Race/Ethnicity, Customized (Count of Participants)
White	109 86.5%	106 84.1%	109 87.2%	324 85.9%
Black or African American	0 0%	1 0.8%	1 0.8%	2 0.5%
Asian	17 13.5%	17 13.5%	15 12%	49 13%
American Indian or Alaska Native	0 0%	1 0.8%	0 0%	1 0.3%
Native Hawaiian or other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Multiple	0 0%	1 0.8%	0 0%	1 0.3%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to Week 52 in Progressive Supranuclear Palsy Rating Scale (PSPRS) Total Score
Description	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.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	ABBV-8E12 2000mg	ABBV-8E12 4000mg
Arm/Group Description	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	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)	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)
Measure Participants	59	56	59
Least Squares Mean (Standard Error) [units on a scale]	10.5 (0.94)	10.5 (0.96)	11.4 (0.94)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABBV-8E12 2000mg
	Comments	ABBV-8E12 2000 mg vs Placebo
	Type of Statistical Test	Superiority
	Comments	The primary efficacy analysis utilized a likelihood-based, mixed-effects model, repeated measures (MMRM) analysis of the change from baseline for each postbaseline value and compared each ABBV-8E12 dose group with the placebo group. The model, which used all observed data, included fixed, categorical effects for treatment, site, visit, baseline score-by-visit interaction and treatment-by-visit interaction, with continuous fixed covariates for the corresponding baseline score.
Statistical Test of Hypothesis	p-Value	=0.998
	Comments
	Method	Mixed-effects model, repeated measures
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -2.63 to 2.63
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.34
	Estimation Comments	ABBV-8E12 2000 mg - Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABBV-8E12 4000mg
	Comments	ABBV-8E12 4000 mg vs Placebo
	Type of Statistical Test	Superiority
	Comments	The primary efficacy analysis utilized a likelihood-based, mixed-effects model, repeated measures (MMRM) analysis of the change from baseline for each postbaseline value and compared each ABBV-8E12 dose group with the placebo group. The model, which used all observed data, included fixed, categorical effects for treatment, site, visit, baseline score-by-visit interaction and treatment-by-visit interaction, with continuous fixed covariates for the corresponding baseline score.
Statistical Test of Hypothesis	p-Value	=0.464
	Comments
	Method	Mixed-effects model, repeated measures
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95%; -1.63 to 3.58
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.32
	Estimation Comments	ABBV-8E12 4000 mg - Placebo

2. Primary Outcome

Title	Number of Participants With Adverse Events
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	ABBV-8E12 2000mg	ABBV-8E12 4000mg
Arm/Group Description	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	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)	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)
Measure Participants	126	126	125
Count of Participants [Participants]	108 85.7%	111 88.1%	111 88.8%

3. Secondary Outcome

Title	Mean Change From Baseline to Week 52 in Unified Parkinson's Disease Rating Scale (UPDRS) Part II (Activities of Daily Living)
Description	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.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	ABBV-8E12 2000mg	ABBV-8E12 4000mg
Arm/Group Description	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	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)	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)
Measure Participants	63	60	60
Least Squares Mean (Standard Error) [units on a scale]	5.6 (0.62)	5.8 (0.63)	7.0 (0.63)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABBV-8E12 2000mg
	Comments	ABBV-8E12 2000 mg vs Placebo
	Type of Statistical Test	Superiority
	Comments	The analysis utilized a likelihood-based, mixed-effects model, repeated measures (MMRM) analysis of the change from baseline for each postbaseline value and compared each ABBV-8E12 dose group with the placebo group. The model, which used all observed data, included fixed, categorical effects for treatment, site, visit, baseline score-by-visit interaction and treatment-by-visit interaction, with continuous fixed covariates for the corresponding baseline score.
Statistical Test of Hypothesis	p-Value	=0.812
	Comments
	Method	Mixed-effects model, repeated measures
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -1.52 to 1.93
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.88
	Estimation Comments	ABBV-8E12 2000 mg - Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABBV-8E12 4000mg
	Comments	ABBV-8E12 4000 mg vs Placebo
	Type of Statistical Test	Superiority
	Comments	The analysis utilized a likelihood-based, mixed-effects model, repeated measures (MMRM) analysis of the change from baseline for each postbaseline value and compared each ABBV-8E12 dose group with the placebo group. The model, which used all observed data, included fixed, categorical effects for treatment, site, visit, baseline score-by-visit interaction and treatment-by-visit interaction, with continuous fixed covariates for the corresponding baseline score.
Statistical Test of Hypothesis	p-Value	=0.104
	Comments
	Method	Mixed-effects model, repeated measures
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.4
	Confidence Interval	(2-Sided) 95%; -0.30 to 3.16
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.88
	Estimation Comments	ABBV-8E12 4000 mg - Placebo

4. Secondary Outcome

Title	Clinical Global Impression of Change (CGI-C) Score at Week 52
Description	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.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	ABBV-8E12 2000mg	ABBV-8E12 4000mg
Arm/Group Description	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	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)	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)
Measure Participants	50	48	51
Least Squares Mean (Standard Error) [units on a scale]	5.1 (0.11)	5.1 (0.11)	5.0 (0.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABBV-8E12 2000mg
	Comments	ABBV-8E12 2000 mg vs Placebo
	Type of Statistical Test	Superiority
	Comments	The analysis utilized a likelihood-based, mixed-effects model, repeated measures (MMRM) analysis of the change from baseline for each postbaseline value and compared each ABBV-8E12 dose group with the placebo group. The model, which used all observed data, included fixed, categorical effects for treatment, site, visit, baseline score-by-visit interaction and treatment-by-visit interaction, with continuous fixed covariates for the corresponding baseline score.
Statistical Test of Hypothesis	p-Value	=0.756
	Comments
	Method	Mixed-effects model, repeated measures
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.0
	Confidence Interval	(2-Sided) 95%; -0.36 to 0.26
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.16
	Estimation Comments	ABBV-8E12 2000 mg - Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABBV-8E12 4000mg
	Comments	ABBV-8E12 4000 mg vs Placebo
	Type of Statistical Test	Superiority
	Comments	The analysis utilized a likelihood-based, mixed-effects model, repeated measures (MMRM) analysis of the change from baseline for each postbaseline value and compared each ABBV-8E12 dose group with the placebo group. The model, which used all observed data, included fixed, categorical effects for treatment, site, visit, baseline score-by-visit interaction and treatment-by-visit interaction, with continuous fixed covariates for the corresponding baseline score.
Statistical Test of Hypothesis	p-Value	=0.409
	Comments
	Method	Mixed-effects model, repeated measures
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.44 to 0.18
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.16
	Estimation Comments	ABBV-8E12 4000 mg - Placebo

5. Secondary Outcome

Title	Mean Change From Baseline to Week 52 in Midbrain Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI)
Description	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.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	ABBV-8E12 2000mg	ABBV-8E12 4000mg
Arm/Group Description	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	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)	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)
Measure Participants	53	55	54
Least Squares Mean (Standard Error) [mm^3]	-122.0 (9.64)	-129.1 (9.69)	-128.3 (9.69)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABBV-8E12 2000mg
	Comments	ABBV-8E12 2000 mg vs Placebo
	Type of Statistical Test	Superiority
	Comments	The analysis utilized a likelihood-based, mixed-effects model, repeated measures (MMRM) analysis of the change from baseline for each postbaseline value and compared each ABBV-8E12 dose group with the placebo group. The model, which used all observed data, included fixed, categorical effects for treatment, site, visit, baseline score-by-visit interaction and treatment-by-visit interaction, with continuous fixed covariates for the corresponding baseline score.
Statistical Test of Hypothesis	p-Value	=0.597
	Comments
	Method	Mixed-effects model, repeated measures
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-7.2
	Confidence Interval	(2-Sided) 95%; -33.86 to 19.53
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 13.54
	Estimation Comments	ABBV-8E12 2000 mg - Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABBV-8E12 4000mg
	Comments	ABBV-8E12 4000 mg vs Placebo
	Type of Statistical Test	Superiority
	Comments	The analysis utilized a likelihood-based, mixed-effects model, repeated measures (MMRM) analysis of the change from baseline for each postbaseline value and compared each ABBV-8E12 dose group with the placebo group. The model, which used all observed data, included fixed, categorical effects for treatment, site, visit, baseline score-by-visit interaction and treatment-by-visit interaction, with continuous fixed covariates for the corresponding baseline score.
Statistical Test of Hypothesis	p-Value	=0.642
	Comments
	Method	Mixed-effects model, repeated measures
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-6.3
	Confidence Interval	(2-Sided) 95%; -33.04 to 20.42
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 13.56
	Estimation Comments	ABBV-8E12 4000 mg - Placebo

6. Secondary Outcome

Title	Mean Change From Baseline to Week 52 in Schwab and England Activities of Daily Living Scale (SEADL)
Description	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.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	ABBV-8E12 2000mg	ABBV-8E12 4000mg
Arm/Group Description	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	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)	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)
Measure Participants	58	56	60
Least Squares Mean (Standard Error) [percentage of independence]	-20.6 (1.79)	-18.0 (1.82)	-20.5 (1.77)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABBV-8E12 2000mg
	Comments	ABBV-8E12 2000 mg vs Placebo
	Type of Statistical Test	Superiority
	Comments	The analysis utilized a likelihood-based, mixed-effects model, repeated measures (MMRM) analysis of the change from baseline for each postbaseline value and compared each ABBV-8E12 dose group with the placebo group. The model, which used all observed data, included fixed, categorical effects for treatment, site, visit, baseline score-by-visit interaction and treatment-by-visit interaction, with continuous fixed covariates for the corresponding baseline score.
Statistical Test of Hypothesis	p-Value	=0.323
	Comments
	Method	Mixed-effects model, repeated measures
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.5
	Confidence Interval	(2-Sided) 95%; -2.48 to 7.51
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.53
	Estimation Comments	ABBV-8E12 2000 mg - Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABBV-8E12 4000mg
	Comments	ABBV-8E12 4000 mg vs Placebo
	Type of Statistical Test	Superiority
	Comments	The analysis utilized a likelihood-based, mixed-effects model, repeated measures (MMRM) analysis of the change from baseline for each postbaseline value and compared each ABBV-8E12 dose group with the placebo group. The model, which used all observed data, included fixed, categorical effects for treatment, site, visit, baseline score-by-visit interaction and treatment-by-visit interaction, with continuous fixed covariates for the corresponding baseline score.
Statistical Test of Hypothesis	p-Value	=0.974
	Comments
	Method	Mixed-effects model, repeated measures
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -4.86 to 5.02
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.51
	Estimation Comments	ABBV-8E12 4000 mg - Placebo

7. Secondary Outcome

Title	Maximum Observed Serum Concentration (Cmax) for ABBV-8E12
Description	The maximum observed serum concentration after the first and the fifth doses in Cohort 1 and Cohort J1 was determined.
Time Frame	First Dosing Interval, 2 weeks, Day 1-14; Fifth Dosing Interval, 4 weeks, Day 85-113

Outcome Measure Data

Analysis Population Description

Participants in Cohort 1 and Cohort J1 with available data

Arm/Group Title	Cohort 1, ABBV-8E12 2000 mg	Cohort 1, ABBV-8E12 4000 mg	Cohort J1, ABBV-8E12 2000 mg	Cohort J1, ABBV-8E12 4000 mg
Arm/Group Description	First 30 participants enrolled into the global study from countries other than Japan who received augmented safety and PK assessments and ABBV-8E12 at a dose of 2000 mg	First 30 participants enrolled into the global study from countries other than Japan who received augmented safety and PK assessments and ABBV-8E12 at a dose of 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 2000 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
Measure Participants	11	9	3	3
First Dosing Interval, 2 weeks, Day 1-14	714 (32)	1450 (20)	853 (6)	1580 (13)
Fifth Dosing Interval, 4 weeks, Day 85-113	1070 (56)	2350 (23)	1010 (21)	1960 (15)

8. Secondary Outcome

Title	Time to Maximum Observed Serum Concentration (Tmax) for ABBV-8E12
Description	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.
Time Frame	First Dosing Interval, 2 weeks, Day 1-14; Fifth Dosing Interval, 4 weeks, Day 85-113

Outcome Measure Data

Analysis Population Description

Participants in Cohort 1 and Cohort J1 with available data

Arm/Group Title	Cohort 1, ABBV-8E12 2000 mg	Cohort 1, ABBV-8E12 4000 mg	Cohort J1, ABBV-8E12 2000 mg	Cohort J1, ABBV-8E12 4000 mg
Arm/Group Description	First 30 participants enrolled into the global study from countries other than Japan who received augmented safety and PK assessments and ABBV-8E12 at a dose of 2000 mg	First 30 participants enrolled into the global study from countries other than Japan who received augmented safety and PK assessments and ABBV-8E12 at a dose of 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 2000 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
Measure Participants	11	9	3	3
First Dosing Interval, 2 weeks, Day 1-14	4.0	4.1	5.0	4.8
Fifth Dosing Interval, 4 weeks, Day 85-113	3.6	4.0	5.0	3.4

9. Secondary Outcome

Title	Area Under the Concentration Time Curve (AUC) for ABBV-8E12
Description	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.
Time Frame	First Dosing Interval, 2 weeks, Day 1-14; Fifth Dosing Interval, 4 weeks, Day 85-113

Outcome Measure Data

Analysis Population Description

Participants in Cohort 1 and Cohort J1 with available data

Arm/Group Title	Cohort 1, ABBV-8E12 2000 mg	Cohort 1, ABBV-8E12 4000 mg	Cohort J1, ABBV-8E12 2000 mg	Cohort J1, ABBV-8E12 4000 mg
Arm/Group Description	First 30 participants enrolled into the global study from countries other than Japan who received augmented safety and PK assessments and ABBV-8E12 at a dose of 2000 mg	First 30 participants enrolled into the global study from countries other than Japan who received augmented safety and PK assessments and ABBV-8E12 at a dose of 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 2000 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
Measure Participants	11	9	3	3
First Dosing Interval, 2 weeks, Day 1-14	5070 (25)	10400 (21)	5950 (12)	10400 (11)
Fifth Dosing Interval, 4 weeks, Day 85-113	13900 (28)	31600 (36)	15200 (21)	23900 (15)

10. Secondary Outcome

Title	Serum Concentration of ABBV-8E12 Prior to Infusion of a Day of Dosing (Ctrough)
Description	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.
Time Frame	First day of the Fifth Dosing Interval, Day 85

Outcome Measure Data

Analysis Population Description

Participants in Cohort 1 and Cohort J1 with available data

Arm/Group Title	Cohort 1, ABBV-8E12 2000 mg	Cohort 1, ABBV-8E12 4000 mg	Cohort J1, ABBV-8E12 2000 mg	Cohort J1, ABBV-8E12 4000 mg
Arm/Group Description	First 30 participants enrolled into the global study from countries other than Japan who received augmented safety and PK assessments and ABBV-8E12 at a dose of 2000 mg	First 30 participants enrolled into the global study from countries other than Japan who received augmented safety and PK assessments and ABBV-8E12 at a dose of 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 2000 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
Measure Participants	10	8	3	3
Geometric Mean (Geometric Coefficient of Variation) [µg/mL]	353 (27)	657 (45)	345 (32)	595 (16)

11. Secondary Outcome

Title	Mean Change From Baseline to Week 52 in Clinical Global Impression of Severity (CGI-S) Score
Description	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.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	ABBV-8E12 2000mg	ABBV-8E12 4000mg
Arm/Group Description	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	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)	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)
Measure Participants	50	48	51
Least Squares Mean (Standard Error) [units on a scale]	0.6 (0.10)	0.6 (0.10)	0.6 (0.10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABBV-8E12 2000mg
	Comments	ABBV-8E12 2000 mg vs Placebo
	Type of Statistical Test	Superiority
	Comments	The analysis utilized a likelihood-based, mixed-effects model, repeated measures (MMRM) analysis of the change from baseline for each postbaseline value and compared each ABBV-8E12 dose group with the placebo group. The model, which used all observed data, included fixed, categorical effects for treatment, site, visit, baseline score-by-visit interaction and treatment-by-visit interaction, with continuous fixed covariates for the corresponding baseline score.
Statistical Test of Hypothesis	p-Value	=0.761
	Comments
	Method	Mixed-effects model, repeated measures
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.0
	Confidence Interval	(2-Sided) 95%; -0.31 to 0.23
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments	ABBV-8E12 2000 mg - Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABBV-8E12 4000mg
	Comments	ABBV-8E12 4000 mg vs Placebo
	Type of Statistical Test	Superiority
	Comments	The analysis utilized a likelihood-based, mixed-effects model, repeated measures (MMRM) analysis of the change from baseline for each postbaseline value and compared each ABBV-8E12 dose group with the placebo group. The model, which used all observed data, included fixed, categorical effects for treatment, site, visit, baseline score-by-visit interaction and treatment-by-visit interaction, with continuous fixed covariates for the corresponding baseline score.
Statistical Test of Hypothesis	p-Value	=0.678
	Comments
	Method	Mixed-effects model, repeated measures
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.32 to 0.21
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments	ABBV-8E12 4000 mg - Placebo

12. Secondary Outcome

Title	Mean Change From Baseline to Week 52 in Progressive Supranuclear Palsy Health Related Quality of Life Scale (PSP-QoL) Total Score
Description	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.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	ABBV-8E12 2000mg	ABBV-8E12 4000mg
Arm/Group Description	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	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)	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)
Measure Participants	62	59	60
Least Squares Mean (Standard Error) [units on a scale]	9.2 (1.63)	10.3 (1.65)	10.0 (1.64)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABBV-8E12 2000mg
	Comments	ABBV-8E12 2000 mg vs Placebo
	Type of Statistical Test	Superiority
	Comments	The analysis utilized a likelihood-based, mixed-effects model, repeated measures (MMRM) analysis of the change from baseline for each postbaseline value and compared each ABBV-8E12 dose group with the placebo group. The model, which used all observed data, included fixed, categorical effects for treatment, site, visit, baseline score-by-visit interaction and treatment-by-visit interaction, with continuous fixed covariates for the corresponding baseline score.
Statistical Test of Hypothesis	p-Value	=0.653
	Comments
	Method	Mixed-effects model, repeated measures
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95%; -3.50 to 5.57
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.30
	Estimation Comments	ABBV-8E12 2000 mg - Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABBV-8E12 4000mg
	Comments	ABBV-8E12 4000 mg vs Placebo
	Type of Statistical Test	Superiority
	Comments	The primary efficacy analysis utilized a likelihood-based, mixed-effects model, repeated measures (MMRM) analysis of the change from baseline for each postbaseline value and compared each ABBV-8E12 dose group with the placebo group. The model, which used all observed data, included fixed, categorical effects for treatment, site, visit, baseline score-by-visit interaction and treatment-by-visit interaction, with continuous fixed covariates for the corresponding baseline score.
Statistical Test of Hypothesis	p-Value	=0.748
	Comments
	Method	Mixed-effects model, repeated measures
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95%; -3.50 to 5.57
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.30
	Estimation Comments	ABBV-8E12 4000 mg - Placebo

13. Secondary Outcome

Title	Mean Change From Baseline to Week 52 in Progressive Supranuclear Palsy Staging System Score (PSP-SS) Score
Description	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.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	ABBV-8E12 2000mg	ABBV-8E12 4000mg
Arm/Group Description	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	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)	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)
Measure Participants	59	57	59
Least Squares Mean (Standard Error) [units on a scale]	0.8 (0.24)	0.9 (0.24)	1.0 (0.24)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABBV-8E12 2000mg
	Comments	ABBV-8E12 2000 mg vs Placebo
	Type of Statistical Test	Superiority
	Comments	The analysis utilized a likelihood-based, mixed-effects model, repeated measures (MMRM) analysis of the change from baseline for each postbaseline value and compared each ABBV-8E12 dose group with the placebo group. The model, which used all observed data, included fixed, categorical effects for treatment, site, visit, baseline score-by-visit interaction and treatment-by-visit interaction, with continuous fixed covariates for the corresponding baseline score.
Statistical Test of Hypothesis	p-Value	=0.828
	Comments
	Method	Mixed-effects model, repeated measures
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -0.60 to 0.74
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.34
	Estimation Comments	ABBV-8E12 2000 mg - Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABBV-8E12 4000mg
	Comments	ABBV-8E12 4000 mg vs Placebo
	Type of Statistical Test	Superiority
	Comments	The primary efficacy analysis utilized a likelihood-based, mixed-effects model, repeated measures (MMRM) analysis of the change from baseline for each postbaseline value and compared each ABBV-8E12 dose group with the placebo group. The model, which used all observed data, included fixed, categorical effects for treatment, site, visit, baseline score-by-visit interaction and treatment-by-visit interaction, with continuous fixed covariates for the corresponding baseline score.
Statistical Test of Hypothesis	p-Value	=0.543
	Comments
	Method	Mixed-effects model, repeated measures
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -0.46 to 0.87
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.34
	Estimation Comments	ABBV-8E12 4000 mg - Placebo

14. Secondary Outcome

Title	Mean Change From Baseline to Week 52 in Third Ventricle Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI)
Description	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.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	ABBV-8E12 2000mg	ABBV-8E12 4000mg
Arm/Group Description	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	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)	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)
Measure Participants	54	58	53
Least Squares Mean (Standard Error) [mm^3]	157.9 (18.27)	152.4 (18.04)	125.0 (18.57)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABBV-8E12 2000mg
	Comments	ABBV-8E12 2000 mg vs Placebo
	Type of Statistical Test	Superiority
	Comments	The analysis utilized a likelihood-based, mixed-effects model, repeated measures (MMRM) analysis of the change from baseline for each postbaseline value and compared each ABBV-8E12 dose group with the placebo group. The model, which used all observed data, included fixed, categorical effects for treatment, site, visit, baseline score-by-visit interaction and treatment-by-visit interaction, with continuous fixed covariates for the corresponding baseline score.
Statistical Test of Hypothesis	p-Value	=0.829
	Comments
	Method	Mixed-effects model, repeated measures
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-5.5
	Confidence Interval	(2-Sided) 95%; -55.66 to 44.63
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 25.44
	Estimation Comments	ABBV-8E12 2000 mg - Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABBV-8E12 4000mg
	Comments	ABBV-8E12 4000 mg vs Placebo
	Type of Statistical Test	Superiority
	Comments	The analysis utilized a likelihood-based, mixed-effects model, repeated measures (MMRM) analysis of the change from baseline for each postbaseline value and compared each ABBV-8E12 dose group with the placebo group. The model, which used all observed data, included fixed, categorical effects for treatment, site, visit, baseline score-by-visit interaction and treatment-by-visit interaction, with continuous fixed covariates for the corresponding baseline score.
Statistical Test of Hypothesis	p-Value	=0.206
	Comments
	Method	Mixed-effects model, repeated measures
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-32.9
	Confidence Interval	(2-Sided) 95%; -83.94 to 18.23
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 25.92
	Estimation Comments	ABBV-8E12 4000 mg - Placebo

15. Secondary Outcome

Title	Mean Change From Baseline to Week 52 in Superior Cerebellar Peduncle Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI)
Description	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.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	ABBV-8E12 2000mg	ABBV-8E12 4000mg
Arm/Group Description	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	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)	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)
Measure Participants	51	55	54
Least Squares Mean (Standard Error) [mm^3]	-8.3 (2.78)	-4.3 (2.74)	-3.7 (2.74)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABBV-8E12 2000mg
	Comments	ABBV-8E12 2000 mg vs Placebo
	Type of Statistical Test	Superiority
	Comments	The analysis utilized a likelihood-based, mixed-effects model, repeated measures (MMRM) analysis of the change from baseline for each postbaseline value and compared each ABBV-8E12 dose group with the placebo group. The model, which used all observed data, included fixed, categorical effects for treatment, site, visit, baseline score-by-visit interaction and treatment-by-visit interaction, with continuous fixed covariates for the corresponding baseline score.
Statistical Test of Hypothesis	p-Value	=0.304
	Comments
	Method	Mixed-effects model, repeated measures
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	4.0
	Confidence Interval	(2-Sided) 95%; -3.65 to 11.65
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.88
	Estimation Comments	ABBV-8E12 2000 mg - Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABBV-8E12 4000mg
	Comments	ABBV-8E12 4000 mg vs Placebo
	Type of Statistical Test	Superiority
	Comments	The analysis utilized a likelihood-based, mixed-effects model, repeated measures (MMRM) analysis of the change from baseline for each postbaseline value and compared each ABBV-8E12 dose group with the placebo group. The model, which used all observed data, included fixed, categorical effects for treatment, site, visit, baseline score-by-visit interaction and treatment-by-visit interaction, with continuous fixed covariates for the corresponding baseline score.
Statistical Test of Hypothesis	p-Value	=0.243
	Comments
	Method	Mixed-effects model, repeated measures
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	4.5
	Confidence Interval	(2-Sided) 95%; -3.11 to 12.19
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.88
	Estimation Comments	ABBV-8E12 4000 mg - Placebo

16. Secondary Outcome

Title	Mean Change From Baseline to Week 52 in Brainstem Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI)
Description	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.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	ABBV-8E12 2000mg	ABBV-8E12 4000mg
Arm/Group Description	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	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)	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)
Measure Participants	48	49	43
Least Squares Mean (Standard Error) [mm^3]	-374.5 (38.42)	-400.9 (38.60)	-341.3 (40.61)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABBV-8E12 2000mg
	Comments	ABBV-8E12 2000 mg vs Placebo
	Type of Statistical Test	Superiority
	Comments	The analysis utilized a likelihood-based, mixed-effects model, repeated measures (MMRM) analysis of the change from baseline for each postbaseline value and compared each ABBV-8E12 dose group with the placebo group. The model, which used all observed data, included fixed, categorical effects for treatment, site, visit, baseline score-by-visit interaction and treatment-by-visit interaction, with continuous fixed covariates for the corresponding baseline score.
Statistical Test of Hypothesis	p-Value	0.625
	Comments
	Method	Mixed-effects model, repeated measures
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-26.4
	Confidence Interval	(2-Sided) 95%; -132.76 to 79.94
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 53.86
	Estimation Comments	ABBV-8E12 2000 mg - Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABBV-8E12 4000mg
	Comments	ABBV-8E12 4000 mg vs Placebo
	Type of Statistical Test	Superiority
	Comments	The analysis utilized a likelihood-based, mixed-effects model, repeated measures (MMRM) analysis of the change from baseline for each postbaseline value and compared each ABBV-8E12 dose group with the placebo group. The model, which used all observed data, included fixed, categorical effects for treatment, site, visit, baseline score-by-visit interaction and treatment-by-visit interaction, with continuous fixed covariates for the corresponding baseline score.
Statistical Test of Hypothesis	p-Value	=0.550
	Comments
	Method	Mixed-effects model, repeated measures
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	33.2
	Confidence Interval	(2-Sided) 95%; -76.34 to 142.71
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 55.47
	Estimation Comments	ABBV-8E12 4000 mg - Placebo

17. Secondary Outcome

Title	Mean Change From Baseline to Week 52 in Whole Brain Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI)
Description	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.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	ABBV-8E12 2000mg	ABBV-8E12 4000mg
Arm/Group Description	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	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)	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)
Measure Participants	45	46	49
Least Squares Mean (Standard Error) [mm^3]	-22496.2 (1793.36)	-20757.1 (1783.00)	-18811.3 (1740.72)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABBV-8E12 2000mg
	Comments	ABBV-8E12 2000 mg vs Placebo
	Type of Statistical Test	Superiority
	Comments	The analysis utilized a likelihood-based, mixed-effects model, repeated measures (MMRM) analysis of the change from baseline for each postbaseline value and compared each ABBV-8E12 dose group with the placebo group. The model, which used all observed data, included fixed, categorical effects for treatment, site, visit, baseline score-by-visit interaction and treatment-by-visit interaction, with continuous fixed covariates for the corresponding baseline score.
Statistical Test of Hypothesis	p-Value	=0.488
	Comments
	Method	Mixed-effects model, repeated measures
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1739.1
	Confidence Interval	(2-Sided) 95%; -3201.75 to 6680.02
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2502.95
	Estimation Comments	ABBV-8E12 2000 mg - Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABBV-8E12 4000mg
	Comments	ABBV-8E12 4000 mg vs Placebo
	Type of Statistical Test	Superiority
	Comments	The analysis utilized a likelihood-based, mixed-effects model, repeated measures (MMRM) analysis of the change from baseline for each postbaseline value and compared each ABBV-8E12 dose group with the placebo group. The model, which used all observed data, included fixed, categorical effects for treatment, site, visit, baseline score-by-visit interaction and treatment-by-visit interaction, with continuous fixed covariates for the corresponding baseline score.
Statistical Test of Hypothesis	p-Value	=0.140
	Comments
	Method	Mixed-effects model, repeated measures
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3684.9
	Confidence Interval	(2-Sided) 95%; -1225.46 to 8595.29
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2487.32
	Estimation Comments	ABBV-8E12 4000 mg - Placebo

18. Secondary Outcome

Title	Mean Change From Baseline to Week 52 in Frontal Lobe Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI)
Description	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.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	ABBV-8E12 2000mg	ABBV-8E12 4000mg
Arm/Group Description	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	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)	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)
Measure Participants	48	49	43
Least Squares Mean (Standard Error) [mm^3]	1052.6 (425.55)	1260.5 (423.96)	1186.1 (445.18)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABBV-8E12 2000mg
	Comments	ABBV-8E12 2000 mg vs Placebo
	Type of Statistical Test	Superiority
	Comments	The analysis utilized a likelihood-based, mixed-effects model, repeated measures (MMRM) analysis of the change from baseline for each postbaseline value and compared each ABBV-8E12 dose group with the placebo group. The model, which used all observed data, included fixed, categorical effects for treatment, site, visit, baseline score-by-visit interaction and treatment-by-visit interaction, with continuous fixed covariates for the corresponding baseline score.
Statistical Test of Hypothesis	p-Value	=0.726
	Comments
	Method	Mixed-effects model, repeated measures
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	207.9
	Confidence Interval	(2-Sided) 95%; -962.98 to 1378.88
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 592.68
	Estimation Comments	ABBV-8E12 2000 mg - Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABBV-8E12 4000mg
	Comments	ABBV-8E12 4000 mg vs Placebo
	Type of Statistical Test	Superiority
	Comments	The analysis utilized a likelihood-based, mixed-effects model, repeated measures (MMRM) analysis of the change from baseline for each postbaseline value and compared each ABBV-8E12 dose group with the placebo group. The model, which used all observed data, included fixed, categorical effects for treatment, site, visit, baseline score-by-visit interaction and treatment-by-visit interaction, with continuous fixed covariates for the corresponding baseline score.
Statistical Test of Hypothesis	p-Value	=0.828
	Comments
	Method	Mixed-effects model, repeated measures
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	133.6
	Confidence Interval	(2-Sided) 95%; -1075.26 to 1342.40
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 611.91
	Estimation Comments	ABBV-8E12 4000 mg - Placebo

19. Secondary Outcome

Title	Time to Loss of Ability to Walk Independently as Measured by Progressive Supranuclear Palsy Rating Scale (PSPRS) Item 26
Description	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).
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	ABBV-8E12 2000 mg	ABBV-8E12 4000 mg
Arm/Group Description	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	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)	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)
Measure Participants	126	126	125
Median (95% Confidence Interval) [days]	169.0	170.0	203.0

Adverse Events

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.
Adverse Event Reporting Description	TEAEs and TESAEs are defined as any AE or TESAE with onset or worsening reported by a participant from the time that the first dose of study is administered until 20 weeks (approximately 5 half-lives) have elapsed following discontinuation of study drug. TEAEs were collected whether elicited or spontaneously reported by the participant.
Arm/Group Title	Placebo		ABBV-8E12 2000mg		ABBV-8E12 4000mg
Arm/Group Description	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		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)		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)
All Cause Mortality
	Placebo		ABBV-8E12 2000mg		ABBV-8E12 4000mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/126 (6.3%)		9/126 (7.1%)		9/125 (7.2%)
Serious Adverse Events
	Placebo		ABBV-8E12 2000mg		ABBV-8E12 4000mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	33/126 (26.2%)		29/126 (23%)		34/125 (27.2%)
Blood and lymphatic system disorders
LEUKOCYTOSIS	0/126 (0%)	0	0/126 (0%)	0	1/125 (0.8%)	1
Cardiac disorders
ACUTE MYOCARDIAL INFARCTION	0/126 (0%)	0	1/126 (0.8%)	1	0/125 (0%)	0
ATRIAL FIBRILLATION	1/126 (0.8%)	1	1/126 (0.8%)	1	0/125 (0%)	0
CARDIAC FAILURE	0/126 (0%)	0	1/126 (0.8%)	1	0/125 (0%)	0
CARDIAC FAILURE CONGESTIVE	0/126 (0%)	0	1/126 (0.8%)	1	0/125 (0%)	0
CARDIO-RESPIRATORY ARREST	0/126 (0%)	0	0/126 (0%)	0	1/125 (0.8%)	1
CARDIOPULMONARY FAILURE	1/126 (0.8%)	1	0/126 (0%)	0	0/125 (0%)	0
Eye disorders
CATARACT	1/126 (0.8%)	1	0/126 (0%)	0	1/125 (0.8%)	1
EYE SWELLING	0/126 (0%)	0	0/126 (0%)	0	1/125 (0.8%)	1
OCULAR HYPERAEMIA	0/126 (0%)	0	0/126 (0%)	0	1/125 (0.8%)	1
Gastrointestinal disorders
COLITIS ISCHAEMIC	0/126 (0%)	0	0/126 (0%)	0	1/125 (0.8%)	1
DYSPHAGIA	0/126 (0%)	0	0/126 (0%)	0	2/125 (1.6%)	2
ENTEROVESICAL FISTULA	0/126 (0%)	0	0/126 (0%)	0	1/125 (0.8%)	1
GASTRIC PERFORATION	1/126 (0.8%)	1	0/126 (0%)	0	0/125 (0%)	0
GASTROINTESTINAL HAEMORRHAGE	0/126 (0%)	0	2/126 (1.6%)	2	1/125 (0.8%)	1
GASTROINTESTINAL HYPERMOTILITY	1/126 (0.8%)	1	0/126 (0%)	0	0/125 (0%)	0
INTESTINAL OBSTRUCTION	1/126 (0.8%)	1	1/126 (0.8%)	1	0/125 (0%)	0
PANCREATITIS	0/126 (0%)	0	1/126 (0.8%)	1	0/125 (0%)	0
VOMITING	0/126 (0%)	0	0/126 (0%)	0	1/125 (0.8%)	1
General disorders
DEATH	1/126 (0.8%)	1	2/126 (1.6%)	2	1/125 (0.8%)	1
DISEASE PROGRESSION	0/126 (0%)	0	0/126 (0%)	0	1/125 (0.8%)	1
GAIT DISTURBANCE	0/126 (0%)	0	0/126 (0%)	0	1/125 (0.8%)	1
GENERAL PHYSICAL HEALTH DETERIORATION	0/126 (0%)	0	0/126 (0%)	0	1/125 (0.8%)	1
PYREXIA	0/126 (0%)	0	0/126 (0%)	0	2/125 (1.6%)	2
Hepatobiliary disorders
BILE DUCT STONE	0/126 (0%)	0	1/126 (0.8%)	1	0/125 (0%)	0
Immune system disorders
DRUG HYPERSENSITIVITY	0/126 (0%)	0	0/126 (0%)	0	1/125 (0.8%)	1
Infections and infestations
CELLULITIS	0/126 (0%)	0	2/126 (1.6%)	2	0/125 (0%)	0
CHOLECYSTITIS INFECTIVE	0/126 (0%)	0	0/126 (0%)	0	1/125 (0.8%)	1
CYSTITIS	0/126 (0%)	0	0/126 (0%)	0	1/125 (0.8%)	1
INFLUENZA	1/126 (0.8%)	1	0/126 (0%)	0	0/125 (0%)	0
NASOPHARYNGITIS	1/126 (0.8%)	1	0/126 (0%)	0	0/125 (0%)	0
ORCHITIS	0/126 (0%)	0	0/126 (0%)	0	1/125 (0.8%)	1
PNEUMONIA	4/126 (3.2%)	4	1/126 (0.8%)	1	3/125 (2.4%)	4
PNEUMONIA MYCOPLASMAL	0/126 (0%)	0	1/126 (0.8%)	1	0/125 (0%)	0
SEPSIS	1/126 (0.8%)	1	1/126 (0.8%)	1	0/125 (0%)	0
URINARY TRACT INFECTION	3/126 (2.4%)	3	0/126 (0%)	0	1/125 (0.8%)	2
Injury, poisoning and procedural complications
BRAIN CONTUSION	0/126 (0%)	0	1/126 (0.8%)	1	0/125 (0%)	0
CERVICAL VERTEBRAL FRACTURE	0/126 (0%)	0	2/126 (1.6%)	2	1/125 (0.8%)	1
CLAVICLE FRACTURE	0/126 (0%)	0	0/126 (0%)	0	1/125 (0.8%)	1
CONCUSSION	1/126 (0.8%)	1	1/126 (0.8%)	1	0/125 (0%)	0
CONTUSION	0/126 (0%)	0	0/126 (0%)	0	1/125 (0.8%)	1
FACIAL BONES FRACTURE	0/126 (0%)	0	1/126 (0.8%)	1	0/125 (0%)	0
FALL	6/126 (4.8%)	7	5/126 (4%)	7	6/125 (4.8%)	7
FEMORAL NECK FRACTURE	0/126 (0%)	0	1/126 (0.8%)	1	0/125 (0%)	0
FEMUR FRACTURE	2/126 (1.6%)	2	1/126 (0.8%)	1	2/125 (1.6%)	2
FIBULA FRACTURE	0/126 (0%)	0	0/126 (0%)	0	1/125 (0.8%)	1
FOREIGN BODY ASPIRATION	0/126 (0%)	0	0/126 (0%)	0	1/125 (0.8%)	1
GUN SHOT WOUND	0/126 (0%)	0	1/126 (0.8%)	1	0/125 (0%)	0
HEAD INJURY	2/126 (1.6%)	2	0/126 (0%)	0	0/125 (0%)	0
HIP FRACTURE	3/126 (2.4%)	3	1/126 (0.8%)	1	0/125 (0%)	0
HUMERUS FRACTURE	0/126 (0%)	0	1/126 (0.8%)	1	1/125 (0.8%)	1
JOINT DISLOCATION	0/126 (0%)	0	1/126 (0.8%)	1	0/125 (0%)	0
PERIPROSTHETIC FRACTURE	0/126 (0%)	0	1/126 (0.8%)	1	0/125 (0%)	0
RADIUS FRACTURE	1/126 (0.8%)	1	0/126 (0%)	0	0/125 (0%)	0
RIB FRACTURE	0/126 (0%)	0	2/126 (1.6%)	2	3/125 (2.4%)	3
SKIN LACERATION	0/126 (0%)	0	2/126 (1.6%)	2	0/125 (0%)	0
SKULL FRACTURE	0/126 (0%)	0	0/126 (0%)	0	1/125 (0.8%)	1
SPINAL FRACTURE	0/126 (0%)	0	0/126 (0%)	0	1/125 (0.8%)	1
SUBDURAL HAEMATOMA	3/126 (2.4%)	3	0/126 (0%)	0	2/125 (1.6%)	2
ULNA FRACTURE	1/126 (0.8%)	1	0/126 (0%)	0	0/125 (0%)	0
UPPER LIMB FRACTURE	0/126 (0%)	0	1/126 (0.8%)	1	0/125 (0%)	0
WRIST FRACTURE	0/126 (0%)	0	1/126 (0.8%)	1	1/125 (0.8%)	1
Investigations
RESIDUAL URINE VOLUME	0/126 (0%)	0	1/126 (0.8%)	1	0/125 (0%)	0
Metabolism and nutrition disorders
DEHYDRATION	1/126 (0.8%)	1	0/126 (0%)	0	0/125 (0%)	0
HYPOGLYCAEMIA	0/126 (0%)	0	1/126 (0.8%)	1	1/125 (0.8%)	1
MALNUTRITION	1/126 (0.8%)	1	0/126 (0%)	0	0/125 (0%)	0
Musculoskeletal and connective tissue disorders
MUSCLE RIGIDITY	0/126 (0%)	0	0/126 (0%)	0	1/125 (0.8%)	1
MUSCULOSKELETAL CHEST PAIN	1/126 (0.8%)	1	0/126 (0%)	0	0/125 (0%)	0
OSTEOARTHRITIS	0/126 (0%)	0	0/126 (0%)	0	1/125 (0.8%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BREAST CANCER	0/126 (0%)	0	0/126 (0%)	0	1/125 (0.8%)	1
PROSTATE CANCER	0/126 (0%)	0	1/126 (0.8%)	1	0/125 (0%)	0
PROSTATE CANCER METASTATIC	1/126 (0.8%)	1	0/126 (0%)	0	0/125 (0%)	0
Nervous system disorders
APHASIA	0/126 (0%)	0	0/126 (0%)	0	1/125 (0.8%)	1
BRAIN MIDLINE SHIFT	0/126 (0%)	0	0/126 (0%)	0	1/125 (0.8%)	1
CARPAL TUNNEL SYNDROME	1/126 (0.8%)	1	0/126 (0%)	0	0/125 (0%)	0
CEREBRAL HAEMORRHAGE	1/126 (0.8%)	1	0/126 (0%)	0	0/125 (0%)	0
HEMIPARESIS	0/126 (0%)	0	0/126 (0%)	0	1/125 (0.8%)	1
LOSS OF CONSCIOUSNESS	1/126 (0.8%)	1	0/126 (0%)	0	3/125 (2.4%)	3
PROGRESSIVE SUPRANUCLEAR PALSY	4/126 (3.2%)	4	1/126 (0.8%)	1	2/125 (1.6%)	2
SEIZURE	0/126 (0%)	0	1/126 (0.8%)	1	0/125 (0%)	0
SPINAL STROKE	0/126 (0%)	0	0/126 (0%)	0	1/125 (0.8%)	1
SUBDURAL HYGROMA	0/126 (0%)	0	0/126 (0%)	0	1/125 (0.8%)	1
SYNCOPE	0/126 (0%)	0	2/126 (1.6%)	2	0/125 (0%)	0
Psychiatric disorders
COMPLETED SUICIDE	0/126 (0%)	0	1/126 (0.8%)	1	0/125 (0%)	0
DELIRIUM	1/126 (0.8%)	1	0/126 (0%)	0	0/125 (0%)	0
MENTAL STATUS CHANGES	1/126 (0.8%)	1	0/126 (0%)	0	0/125 (0%)	0
PSYCHOTIC DISORDER	1/126 (0.8%)	1	0/126 (0%)	0	0/125 (0%)	0
SUICIDAL IDEATION	1/126 (0.8%)	1	0/126 (0%)	0	0/125 (0%)	0
SUICIDE ATTEMPT	0/126 (0%)	0	1/126 (0.8%)	3	0/125 (0%)	0
Renal and urinary disorders
ACUTE KIDNEY INJURY	1/126 (0.8%)	1	0/126 (0%)	0	0/125 (0%)	0
BLADDER OBSTRUCTION	0/126 (0%)	0	1/126 (0.8%)	1	0/125 (0%)	0
DYSURIA	0/126 (0%)	0	0/126 (0%)	0	1/125 (0.8%)	1
MICTURITION DISORDER	1/126 (0.8%)	1	0/126 (0%)	0	0/125 (0%)	0
NOCTURIA	0/126 (0%)	0	1/126 (0.8%)	1	0/125 (0%)	0
URETEROLITHIASIS	0/126 (0%)	0	1/126 (0.8%)	1	0/125 (0%)	0
URINARY RETENTION	0/126 (0%)	0	1/126 (0.8%)	1	0/125 (0%)	0
Respiratory, thoracic and mediastinal disorders
ACUTE RESPIRATORY DISTRESS SYNDROME	0/126 (0%)	0	1/126 (0.8%)	1	0/125 (0%)	0
ASPIRATION	0/126 (0%)	0	1/126 (0.8%)	1	0/125 (0%)	0
CHOKING	0/126 (0%)	0	0/126 (0%)	0	1/125 (0.8%)	1
COUGH	0/126 (0%)	0	1/126 (0.8%)	1	0/125 (0%)	0
DYSPNOEA	0/126 (0%)	0	0/126 (0%)	0	1/125 (0.8%)	1
HYPOXIA	0/126 (0%)	0	0/126 (0%)	0	1/125 (0.8%)	1
INTERSTITIAL LUNG DISEASE	1/126 (0.8%)	1	0/126 (0%)	0	0/125 (0%)	0
PNEUMONIA ASPIRATION	2/126 (1.6%)	2	3/126 (2.4%)	4	1/125 (0.8%)	1
PNEUMOTHORAX	0/126 (0%)	0	0/126 (0%)	0	1/125 (0.8%)	1
PULMONARY EMBOLISM	1/126 (0.8%)	1	1/126 (0.8%)	1	0/125 (0%)	0
RESPIRATORY ARREST	1/126 (0.8%)	1	0/126 (0%)	0	0/125 (0%)	0
RESPIRATORY DISTRESS	0/126 (0%)	0	0/126 (0%)	0	1/125 (0.8%)	1
RESPIRATORY FAILURE	0/126 (0%)	0	1/126 (0.8%)	1	1/125 (0.8%)	1
Vascular disorders
DEEP VEIN THROMBOSIS	1/126 (0.8%)	1	0/126 (0%)	0	0/125 (0%)	0
HAEMORRHAGE	0/126 (0%)	0	1/126 (0.8%)	1	0/125 (0%)	0
HYPERTENSION	0/126 (0%)	0	0/126 (0%)	0	1/125 (0.8%)	1
Other (Not Including Serious) Adverse Events
	Placebo		ABBV-8E12 2000mg		ABBV-8E12 4000mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	83/126 (65.9%)		75/126 (59.5%)		80/125 (64%)
Gastrointestinal disorders
CONSTIPATION	7/126 (5.6%)	7	9/126 (7.1%)	12	6/125 (4.8%)	6
DIARRHOEA	6/126 (4.8%)	6	10/126 (7.9%)	10	8/125 (6.4%)	10
General disorders
FATIGUE	2/126 (1.6%)	9	9/126 (7.1%)	19	4/125 (3.2%)	4
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION	8/126 (6.3%)	9	5/126 (4%)	5	6/125 (4.8%)	9
URINARY TRACT INFECTION	14/126 (11.1%)	19	13/126 (10.3%)	14	18/125 (14.4%)	28
Injury, poisoning and procedural complications
CONTUSION	17/126 (13.5%)	23	16/126 (12.7%)	20	23/125 (18.4%)	30
FALL	43/126 (34.1%)	96	37/126 (29.4%)	70	48/125 (38.4%)	85
SKIN ABRASION	15/126 (11.9%)	27	11/126 (8.7%)	16	8/125 (6.4%)	9
SKIN LACERATION	19/126 (15.1%)	29	17/126 (13.5%)	19	21/125 (16.8%)	26
Investigations
WEIGHT DECREASED	11/126 (8.7%)	12	10/126 (7.9%)	12	13/125 (10.4%)	15
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL PAIN	8/126 (6.3%)	8	3/126 (2.4%)	3	8/125 (6.4%)	8
Nervous system disorders
DIZZINESS	2/126 (1.6%)	2	8/126 (6.3%)	9	4/125 (3.2%)	4
HEADACHE	8/126 (6.3%)	13	9/126 (7.1%)	11	4/125 (3.2%)	4
Psychiatric disorders
ANXIETY	7/126 (5.6%)	8	2/126 (1.6%)	2	0/125 (0%)	0
DEPRESSION	8/126 (6.3%)	8	10/126 (7.9%)	12	3/125 (2.4%)	3
INSOMNIA	5/126 (4%)	6	6/126 (4.8%)	8	8/125 (6.4%)	8
Respiratory, thoracic and mediastinal disorders
COUGH	9/126 (7.1%)	10	5/126 (4%)	6	5/125 (4%)	5
Skin and subcutaneous tissue disorders
RASH	8/126 (6.3%)	8	4/126 (3.2%)	4	3/125 (2.4%)	3

Limitations/Caveats

[Not Specified]

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Principal Investigators are NOT employed by the organization sponsoring the study.

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.