Clinical trial NCT03391765
Conditions: Progressive Supranuclear Palsy (PSP)
Keywords: Tauopathy Steele-Richardson-Olszewski Syndrome PSP
Sponsor: AbbVie
Start date: 2018-01-24; Completion date: 2019-12-13
Enrollment: 142 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study was to assess the long-term safety and efficacy of ABBV-8E12 (tilavonemab) in participants with progressive supranuclear palsy (PSP).

Detailed description:
This study (M15-563) was a Phase 2, randomized, double-blind, multiple-dose, multicenter, long-term extension of NCT 02985879 (Study M15-562) in participants with progressive supranuclear palsy (PSP). Those who completed the 52-week Treatment Period in Study M15-562 and met all entry criteria were eligible for enrollment into this study. This study planned for a Treatment Period of up to 5 years and a post-treatment follow-up visit approximately 20 weeks after the last dose of study drug (including participants who prematurely discontinued treatment). All participants received ABBV-8E12 as follows: those who received placebo in Study M15-562 were randomized, in a 1:1 ratio, to either 2000 or 4000 mg; those who received ABBV-8E12 at a dose of either 2000 or 4000 mg in Study M15-562 continued on the same dose in this study.

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

Arms: arm 1: Intravenous (IV) infusions of 2000 mg ABBV-8E12 at Day 1 and Day 29, then every 28 days for up to 5 years; administered at 300 mg/15 mL and 1000 mg/10 mL strength. Placebo IV infusion was administered on Day 15 in Study M15-563 (to maintain the blind in Study M15-562). arm 2: Intravenous (IV) infusions of 4000 mg ABBV-8E12 at Day 1 and Day 29, then every 28 days for up to 5 years; administered at 300 mg/15 mL and 1000 mg/10 mL strength. Placebo IV infusion was administered on Day 15 in Study M15-563 (to maintain the blind in Study M15-562). arm 3: Intravenous (IV) infusions of 2000 mg ABBV-8E12 at Day 1, Day 15, and Day 29, then every 28 days for up to 5 years; administered at 300 mg/15 mL and 1000 mg/10 mL strength. arm 4: Intravenous (IV) infusions of 4000 mg ABBV-8E12 at Day 1, Day 15, and Day 29, then every 28 days for up to 5 years; administered at 300 mg/15 mL and 1000 mg/10 mL strength.
Interventions: intervention 1: ABBV-8E12 intervention 2: Placebo solution for IV infusion on Day 15
Intervention descriptions: intervention 1: 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. intervention 2: 0.9% NaCl injection/solution for infusion 500 mL; 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.

Protocol documents:
Prot_000.pdf: 
ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
1
1.0
Title Page
Clinical Study Protocol M15-563
An Extension Study of ABBV-8E12 in Progressive 
Supranuclear Palsy (PSP)
Incorporating Administrative Change 1, 
Amendment 1, and Amendment 2
AbbVie Investigational
Product:
ABBV-8E12
Date:
21 February 2019
EudraCT Number:
2017-001590-16
Development Phase:
2
Study Design:
Phase 2 extension of Study M15-562 to assess the long-term 
safety, tolerability, and efficacy of ABBV-8E12 in subjects 
with progressive supranuclear palsy (PSP)
Investigators:
Multicenter Trial:  Investigator Information is on file at 
AbbVie
Sponsor:
AbbVie
Sponsor/Emergency
Contact:
Medical Director
Neuroscience Development
1 North Waukegan Road
North Chicago, IL 60064
Phone:
Fax:
Cell:
The specific contact details of the AbbVie legal/regulatory entity (person) within the relevant country are 
provided within the clinical trial agreement with the Investigator/Institution and in the Clinical Trial 
Application with the Competent Authority
This study will be conducted in compliance with the protocol, Good Clinical Practice and all other 
applicable regulatory requirements, including the archiving of essential documents.
Confidential Information
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
NCT03391765


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
2
1.1
Protocol Amendment:  Summary of Changes
Previous Protocol Versions
Protocol
Date
Original
19 May 2017
Amendment 1
29 March 2018
The purpose of this amendment is to:
●
Update Section 5.2.1, Inclusion Criteria, to remove the need for subjects to 
sign an assent form.
Rationale:  To align with Study M15-562 and clarify that subject assent is not 
required.
●
Update Section 5.3.1.1.9, 12-Lead Electrocardiogram, to remove the 
requirement for postdose ECG on Day 1.
Rationale:  To align with Study M15-562.
●
Update Section 5.3.1.1.11, Magnetic Resonance Imaging, to remove the 
requirement that study entry MRI must be completed after other relevant 
procedures have been completed.
Rationale:  To align Study M15-563 as an extension study to Study M15-562.
●
Update Section 5.3.1.1.11, Magnetic Resonance Imaging, to add that if a 
subject cannot undergo MRI for clinical reasons, the AbbVie TA MD should 
be consulted for approval.
Rationale:  To reduce subject burden.
●
Update Section 5.3.1.1.12, Lumbar Puncture, to add that subjects who are 
unable to undergo an LP may be enrolled with permission of the AbbVie TA 
MD without the requirement of an LP during the study.
Rationale:  To align with Study M15-562 procedures.
●
Update Section 5.3.1.1.13, Diagnostic Tools and Rating Scales, to add a 
Treatment Satisfaction Questionnaire for Medication, PSP Caregiver 
Questionnaires, and the BioStamp nPoint device.


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
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Rationale:  To collect additional data related to the subject's caregiver.  To 
collect data related to subject's movement.
●
Update Section 5.5.1, Treatments Administered, to align the infusion rates in 
this extension study with those of the parent study (Study M15-562).
Rationale:  To maintain consistency and reduce subject burden.
●
Update Section 5.5.2.2, Storage and Disposition of Study Drug, to clarify the 
requirements for reporting temperature excursions.
Rationale:  To clarify temperature reporting procedures.
●
Update Section 6.2.2, Reporting, to correct the time frame for which product 
complaints must be reported.
Rationale:  To align with Sponsor updates.
●
Update Appendix C, Study Activities, to align with changes above as 
appropriate.
Rationale:  To be consistent with the study design throughout the protocol.
●
Update Section 5.1, Overall Study Design and Plan: Description, to add a 
digital BioStamp substudy.
Rationale:  To assess the utility of BioStamp digital sensor to monitor body 
position and gait.
An itemized list of all changes made to this protocol under this amendment is located in 
Appendix E.


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
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1.2
Synopsis
AbbVie Inc.
Protocol Number:  M15-563
Name of Study Drug:  ABBV-8E12
Phase of Development:  2
Name of Active Ingredient:  ABBV-8E12
Date of Protocol Synopsis:  21 February 2019
Protocol Title:  An Extension Study of ABBV-8E12 in Progressive Supranuclear Palsy (PSP)
Objectives:
The primary objectives of this study are:
•
To assess the long-term safety and tolerability of ABBV-8E12 in subjects with PSP.
•
To assess the long-term efficacy of ABBV-8E12 in slowing disease progression in subjects 
with PSP as measured by the PSP Rating Scale (PSPRS).
The secondary objectives of this study are:
•
To assess the long-term efficacy of ABBV-8E12 in slowing disease progression and functional 
impairment in subjects with PSP as measured by secondary endpoints.
•
To assess the pharmacokinetics of ABBV-8E12 in subjects with PSP.
•
To assess the long-term efficacy of ABBV-8E12 in slowing regional and/or whole brain 
atrophy in subjects with PSP as measured by volumetric magnetic resonance imaging (MRI).
The exploratory objectives of this study are:
•
To assess the long-term efficacy of ABBV-8E12 in slowing disease progression and functional 
impairment in subjects with PSP as measured by exploratory endpoints.
•
To assess the long-term effect of ABBV-8E12 on cerebrospinal fluid (CSF) and plasma tau 
protein levels.
•
To assess the long-term effect of ABBV-8E12 on other potential CSF and plasma biomarkers of 
disease progression.
•
To assess body position and gait in a subset of participating subjects using BioStamp digital 
sensors.
Investigators:  Multicenter
Study Sites:  Approximately 60 multinational sites.
Study Population:  Adult male and female subjects with possible or probable PSP who complete 
Study M15-562, meet all inclusion criteria, and do not meet any exclusion criteria.
Number of Subjects to be Enrolled:  Up to the number of subjects enrolled in Study M15-562.
Methodology:
Study M15-563 is a long-term extension of the Phase 2, double-blind study, Study M15-562.  Subjects 
who completed the 52-week Treatment Period in Study M15-562 will be eligible for enrollment into 
Study M15-563.  All subjects in Study M15-563 will receive ABBV-8E12 as follows:  1) subjects who 
received placebo in Study M15-562 will be randomized, in a 1:1 ratio, to 1 of 2 ABBV-8E12 doses 
(2000 or 4000 mg); and 2) subjects who received ABBV-8E12 2000 or 4000 mg in Study M15-562 will 
continue on the same dose.  Investigators and subjects will remain blinded to the treatment assignments 
in Study M15-562 and will be blinded to the dose level of ABBV-8E12 in Study M15-563.


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
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Methodology (Continued):
Subjects who enroll in Study M15-563 from Study M15-562 will complete baseline procedures and 
receive their first infusion of study drug on Day 1 of Study M15-563.  Subjects will receive 3 infusions 
of study drug during the first 4 weeks of Study M15-563, the first on Day 1, the second on Day 15 
(subjects who received placebo in Study M15-562 will receive ABBV-8E12 on Day 15 of 
Study M15-563, and subjects who received ABBV-8E12 in Study M15-562 will receive placebo on 
Day 15 of Study M15-563 to maintain the blind in Study M15-562), and the third on Day 29.  After 
Day 29, subjects will receive study drug infusions every 28 days and will continue to receive 
ABBV-8E12 until one of the discontinuation criteria is met, until the study is discontinued by the 
Sponsor, or until the study reaches completion.  Subjects will be observed on-site for at least 30 minutes 
after the end of study drug infusions.  Subjects will return to the site approximately 20 weeks after their 
last dose for a post-treatment Follow-up Visit.  
Safety and tolerability will be monitored throughout the study.  Blood samples will be collected for 
pharmacokinetic and anti-drug antibodies (ADAs) assessments every 3 months during the first 6 months 
and every 6 months thereafter.  Lumbar puncture will be performed every 6 months during the first year, 
then once a year thereafter; it is optional every 6 months in years 2 through 5.  Volumetric MRI will be 
performed every 3 months in the first 6 months, then every 6 months thereafter.  In a subset of subjects 
(up to 50) at participating sites, subjects will be assigned digital sensor BioStamp units to be worn for 
1-week epochs starting on Day 1, Day 29 (Week 4), Day 57 (Week 8), and Day 85 (Week 12).
A Data Monitoring Committee (DMC) will review unblinded safety data and make recommendations to 
the Sponsor based on the totality of available clinical data.  The DMC memberships, responsibilities, and 
operating logistics are documented in a DMC charter.
Diagnosis and Main Criteria for Inclusion/Exclusion:
Main Inclusion Criteria:
•
Subject completed the 52-week treatment period of Study M15-562.
•
In the opinion of the Investigator, subject was compliant during participation in 
Study M15-562.
•
Subject has an identified, reliable study partner (e.g., caregiver, family member, social worker, 
or friend), who has frequent contact with the subject (at least 10 hours per week) and who can 
accompany the subject to study visits to provide information as to the subject's functional 
abilities.
•
Subject voluntarily signed the Independent Ethics Committee (IEC)/Institutional Review Board 
(IRB) approved Informed Consent Form, prior to the conduct of any study procedures, or, 
where applicable (i.e., countries other than Germany*) for a given subject, the subject's legally 
authorized representative (LAR) signed the IEC/IRB approved Informed Consent form on 
behalf of the subject, prior to the conduct of any procedures.  *For Germany, where the 
subject's LAR is not permitted to sign the IEC/IRB approved Informed Consent form on behalf 
of the subject, evaluation by an independent psychiatrist will be sought if the investigator who 
is evaluating the subject for inclusion in the study doubts the subject's cognitive ability to 
independently provide informed consent.


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
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Diagnosis and Main Criteria for Inclusion/Exclusion (Continued):
Main Exclusion Criteria:
•
Subject weighs less than 44 kg (97 lbs.) at time of study entry.
•
Subject has any contraindication or inability to tolerate brain MRI (e.g., a pacemaker or any 
other implanted device or condition that would preclude proximity to a strong magnetic field).
•
Subject has any significant change in his/her medical condition that could interfere with the 
subject's participation in the study, could place the subject at increased risk, or could confound 
interpretation of study results.  The Investigator must re-evaluate the subject for continuing 
participation and consider any factors including the interim development of any clinically 
significant neurological, hematological, autoimmune, endocrine, cardiovascular, neoplastic, 
renal, hepatic, metabolic, psychiatric, pulmonary, gastrointestinal, or other major disorder.
•
More than 8 weeks have elapsed since the subject received his/her last dose of study drug in 
Study M15-562.
•
Subject is concurrently enrolled in another interventional clinical study involving a therapeutic 
agent.
•
Subject is considered by the investigator, for any reason, to be an unsuitable candidate to 
receive ABBV-8E12 or the subject is considered by the investigator to be unable or unlikely to 
comply with the dosing schedule or study evaluations.
Investigational Product:
ABBV-8E12 (vials of 300 mg/15 mL and 1000 mg/10 mL) 
Doses: 
Doses will be administered on Day 1, Day 15 (placebo for subjects 
who received ABBV-8E12 in Study M15-562), Day 29, and every 
28 days thereafter.
•
Dose level 1:  2000 mg
•
Dose level 2:  4000 mg
Doses may be decreased after evaluation by the DMC of available 
safety, tolerability, and pharmacokinetic data.
Mode of Administration:
Intravenous infusion
Duration of Treatment:  Subjects may continue study treatment until any of the criteria for 
discontinuation have been met, until the study is discontinued by the sponsor, or until the study reaches 
completion.  Planned treatment duration is up to 5 years.
Discontinuation Criteria:
The subject will be discontinued from the study if any of the following occur:
•
Subject starts receiving an approved therapy for PSP.
•
Subject develops unacceptable toxicity.
•
Female subject becomes pregnant.
•
Investigator decides it is in the subject's best interest to discontinue.
•
Subject is noncompliant with the protocol based on the investigator or medical monitor 
assessment.
•
Subject withdraws consent.
•
Subject is lost to follow-up despite reasonable efforts by the investigator to locate the subject.


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
7
Criteria for Evaluation:
Efficacy:
Clinical and Cognitive Assessments:
Primary:
•
PSPRS
Key Secondary:
•
Unified Parkinson's Disease Rating Scale (UPDRS) Part II
•
Clinical Global Impression of Change (CGI-C)
•
Schwab and England Activities of Daily Living Scale (SEADL)
Additional Secondary: 
•
Clinical Global Impression of Severity (CGI-S)
•
Patient Global Impression of Change (PGI-C)
•
PSP Staging System (PSP-SS) (composite of items from PSPRS)
•
Time to loss of ability to walk independently as measured by PSPRS item 26
Exploratory:
•
Time to death
•
EuroQuality of Life (EQ-5D)
•
Letter Fluency Test (words per minute)
•
Repeatable Battery for Assessment of Neuropsychological Status (RBANS)
•
Color Trails Test (Parts 1 and 2)
•
Natural History and Neuroprotection in Parkinson Plus Syndromes-Parkinson Plus Scale 
(NNIPPS-PPS) (not applicable in Japan)
•
Frequency of hospitalizations related to PSP
Pharmacokinetics:
The concentration of ABBV-8E12 will be determined in serum and CSF samples collected in the study.
A mixed-effect modeling approach will be used to estimate the population central value and the 
empirical Bayesian estimates of the individual values for ABBV-8E12 clearance (CL) and volume of 
distribution (V).
The concentration of ABBV-8E12 in CSF will be summarized at each collection time point.
Additional parameters may be calculated if useful in the interpretation of the data.
Immunogenicity:
ADAs will be determined in serum for assessment of immunogenicity.


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
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Criteria for Evaluation (Continued):
Biomarkers:
CSF and Plasma Biomarkers:
•
Tau in CSF and plasma
•
Additional exploratory CSF and plasma-based pharmacodynamic analyses may be conducted 
based on sample availability
Imaging Biomarkers:
•
Regional and/or whole brain volume derived from MRI
•
Fractional anisotropy and diffusivity measures in brain regions of interest derived from 
diffusion tensor imaging
Digital Biomarkers:
•
BioStamp sensor motor outcomes including posture, gait, and step count
Safety:
Adverse events and serious adverse events (SAEs) will be monitored throughout the dosing period and 
for approximately 20 weeks after the last dose.  Safety evaluations will consist of the following:  
monitoring of adverse events (including infusion and allergic reactions), vital signs, physical 
examination, complete neurologic exam, cognitive assessments, Columbia-Suicide Severity Rating Scale
(C-SSRS), laboratory abnormalities, ECG, brain MRI including fluid attenuated inversion recovery 
(FLAIR), and immunogenicity as determined by ADA responses in blood.
Statistical Methods:
Efficacy:
All subjects who receive any infusion of ABBV-8E12 in Study M15-563 and have at least one efficacy 
evaluation after dosing will be assessed for efficacy.  The analysis will be grouped by treatment 
sequences in Studies M15-562/M15-563:  2000/2000 mg, 4000/4000 mg, placebo/2000 mg, and 
placebo/4000 mg.  The primary efficacy variable is the PSPRS total score.  The primary analysis model 
is a likelihood-based, mixed-effect model, repeated measures (MMRM) analysis of the PSPRS total 
score at Study M15-563 Baseline and each post-baseline observation using all observed data.  The model 
will include fixed, categorical effects for treatment, site, visit, and treatment-by-visit interaction.  An 
unstructured (co)variance structure will be used to model the within-subject errors.  Satterthwaite's 
approximation will be used to estimate denominator degrees of freedom, and the Type III sum-of-
squares for the Least Square (LS) means will be used to estimate treatment group differences.  The 
differences for placebo/2000 mg vs 2000/2000 mg and for placebo/4000 mg vs 4000/4000 mg at 
Study M15-563 Baseline and at the end of Study M15-563 Treatment Period will be presented together 
with a 95% confidence interval.  This MMRM analysis will be applied to each efficacy variable with 
repeated measurements.


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
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Statistical Methods (Continued):
Pharmacokinetics:
Summary statistics of serum concentration data for all subjects will be provided for each scheduled time 
of sampling with a breakdown by dose level and by whether treatment in Study M15-562 was with 
ABBV-8E12 or placebo.
Population pharmacokinetic analyses will be performed using the actual sampling time relative to the 
last administered dose.  Pharmacokinetic data from this study may be combined with data from other 
ABBV-8E12 studies in the population pharmacokinetic analyses.  Pharmacokinetic models will be built 
using a non-linear mixed-effect modeling approach with the NONMEM software (version 7, or higher 
version).  The structure of the starting pharmacokinetic model will be based on the pharmacokinetic 
analysis of data from previous studies.  CL and V of ABBV-8E12 will be the pharmacokinetic 
parameters of major interest in the NONMEM analyses.  If necessary, other parameters may be fixed if 
useful in the analysis.
CSF concentration data will be summarized by treatment.
Immunogenicity:
Anti-drug antibody titers will be tabulated by dose level and summarized as appropriate.
Biomarkers:
Descriptive statistics will be provided for each scheduled time of measurement with a breakdown by 
dose level and by whether treatment in Study M15-562 was with ABBV-8E12 or placebo.  For CSF and 
plasma concentrations of tau and for volumetric MRI variables, a repeated means analysis will be 
performed with classification by dose level and by time of assessment.  An effect for the interaction of 
dose level and time will be included.  The model will include covariates for level at Baseline, and for 
volumetric MRI variables, a measure of head size will be a covariate.  The data set will include the data 
for Week 76 and later for the subjects assigned to placebo in Study M15-562, but with a shift in time to 
reflect that these subjects began treatment with ABBV-8E12 only on Day 1 of this study.  The model 
will have an effect to distinguish between assignment to ABBV-8E12 and placebo in Study M15-562.  
Digital substudy endpoints will be handled in a separate scientific report.
Safety:
Adverse events will be coded using the current version of the Medical Dictionary for Regulatory 
Activities (MedDRA).  The number and percentage of subjects with treatment-emergent adverse events 
will be tabulated by MedDRA System Organ Class (SOC) and Preferred Term with a breakdown by 
treatment sequence in Studies M15-562/M15-563:  2000/2000 mg, 4000/4000 mg, placebo/2000 mg, 
and placebo/4000 mg.  Tabulations will also be provided by rating of severity (mild, moderate, and 
severe) and by whether possibly related to study drug.  The number and percentage of subjects 
experiencing treatment-emergent SAEs (including deaths) and adverse events leading to premature 
discontinuation of study drug will be tabulated according to the MedDRA SOC and preferred term by 
treatment group.  The number and percentage of subjects with laboratory test values and measurements 
on vital signs that are potentially clinically significant, according to predefined criteria, will be tabulated 
as well.  The percentage of subjects who have suicidal behavior, suicidal ideation only, and suicidal 
behavior or ideation from the C-SSRS assessment will be summarized by treatment sequence.


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
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1.3
List of Abbreviations and Definition of Terms
Abbreviations
ADA
anti-drug-antibody
ANOVA
analysis of variance
ATEMS
AbbVie Temperature Excursion Management System
AUC
area under the concentration time curve
CBD
corticobasal degeneration
CGI-C
Clinical Global Impression of Change
CGI-S
Clinical Global Impression of Severity
CL
clearance
Cmax
maximum observed serum concentration
COMT
catechol-O-methyltransferase
CRA
clinical research associate
CRF
case report form
CS
clinically significant
CSF
cerebrospinal fluid
C-SSRS
Columbia-Suicide Severity Rating Scale
CTT
Color Trails Test
DMC
data monitoring committee
DNA
deoxyribonucleic acid
DTI
diffusion tensor imaging
ECG
electrocardiogram
eCRF
electronic case report form
EDC
electronic data capture
EMA
European Medicines Agency 
Emax
maximum effect
EQ-5D
EuroQol-5D
ERAC
exposure-response analysis center
Fc
fragment crystallizable
FLAIR
fluid attenuated inversion recovery
FSH
follicle-stimulating hormone
GABA
gamma-aminobutyric acid
GCP
Good Clinical Practice


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
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IB
investigator brochure
ICH
International Council for Harmonisation
IEC
independent ethics committee
IgG
immunoglobulin G
IgG4
subclass of IgG antibody
IMP
investigational medicinal product
IP
intraperitoneal
IRB
institutional review board
IRC
internal review committee
ITT
intent-to-treat
IUD
intrauterine device
IUS
intrauterine hormone-releasing system
IV
intravenous
IVR/IWB
interactive voice-response/interactive web-based (system)
LAR
legally authorized representative
LS
least square
MedDRA
Medical Dictionary for Regulatory Activities
MMRM
mixed-effect model repeated measures
MRI
magnetic resonance imaging
NCS
not clinically significant
NFTs
neurofibrillary tangles
NINDS-SPSP
National Institute of Neurological Disorders and the Society for Progressive 
Supranuclear Palsy
NNIPPS-PPS
Natural History and Neuroprotection in Parkinson Plus Syndromes-Parkinson 
Plus Scale
NOAEL
no observed adverse effect level
PCS
potentially clinically significant
PGI-C
Patient Global Impression of Change
PK
pharmacokinetic(s)
PRN
as needed
PSP
Progressive Supranuclear Palsy
PSPRS
Progressive Supranuclear Palsy Rating Scale
PSP-SS
Progressive Supranuclear Palsy Staging System
QT
measure of the time between the start of the Q wave and the end of the T wave 
in the heart's electrical cycle


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
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QTc
corrected QT
QTcF
QT corrected for heart rate using Fridericia's method
RBANS
Repeatable Battery for Assessment of Neuropsychological Status
RBC
red blood cell 
RNA
ribonucleic acid
RSI
Reference Safety Information
SAD
single-ascending dose
SAP
statistical analysis plan
SDAC
statistical and data analysis center
SAE
serious adverse event
SEADL
Schwab and England Activities of Daily Living Scale
SNRIs
serotonin-norepinephrine reuptake inhibitors
SOC
system organ class
SSRIs
selective serotonin reuptake inhibitors
SUSAR
suspected unexpected serious adverse reactions
TA MD
therapeutic area medical director
TEAE
treatment-emergent adverse event
UPDRS
Unified Parkinson's Disease Rating Scale
V
volume of distribution
WBC
white blood cell 
WOCBP
women of childbearing potential
Definition of Terms
Visit Window
Visits must be scheduled within ± 4 days.  Refer to Section 5.3.2.1 for 
acceptable PK and ADA windows.
Study Drug Infusion
Study drug will be administered on Day 1, Day 15, Day 29, and every 
28 days thereafter.
Scale Order
Certain scales follow a pre-defined order of administration.  Refer to 
Table 3 for recommended sequence.


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2.0
Table of Contents
1.0
Title Page..................................................................................1
1.1
Protocol Amendment:  Summary of Changes ...........................................2
1.2
Synopsis .....................................................................................................4
1.3
List of Abbreviations and Definition of Terms........................................10
2.0
Table of Contents...................................................................13
3.0
Introduction ...........................................................................18
3.1
Differences Statement..............................................................................22
3.2
Benefits and Risks....................................................................................22
4.0
Study Objectives....................................................................23
5.0
Investigational Plan...............................................................24
5.1
Overall Study Design and Plan:  Description ..........................................24
5.2
Selection of Study Population..................................................................27
5.2.1
Inclusion Criteria .....................................................................................27
5.2.2
Exclusion Criteria ....................................................................................28
5.2.3
Prior and Concomitant Therapy...............................................................30
5.2.3.1
Concomitant Therapy...............................................................................30
5.2.3.2
Prohibited Therapy...................................................................................31
5.2.4
Contraception Recommendations ............................................................32
5.3
Efficacy, Pharmacokinetic, Biomarker, Pharmacogenetic and 
Safety Assessments/Variables..................................................................34
5.3.1
Efficacy and Safety Measurements Assessed and Flow Chart ................34
5.3.1.1
Study Procedures .....................................................................................34
5.3.1.1.1
Identification of Study Partner.................................................................34
5.3.1.1.2
Medical History Update...........................................................................35
5.3.1.1.3
Physical Examination...............................................................................35
5.3.1.1.4
Orthostatic Vital Signs.............................................................................35
5.3.1.1.5
Vital Signs................................................................................................36
5.3.1.1.6
Body Weight ............................................................................................36
5.3.1.1.7
Pregnancy Testing....................................................................................36
5.3.1.1.8
Neurological Examination .......................................................................37
5.3.1.1.9
12-Lead Electrocardiogram......................................................................38


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5.3.1.1.10
Clinical Laboratory Tests.........................................................................40
5.3.1.1.11
Magnetic Resonance Imaging..................................................................42
5.3.1.1.12
Lumbar Puncture......................................................................................44
5.3.1.1.13
Diagnostic Tools and Rating Scales.........................................................45
5.3.1.2
Collection and Handling of Biomarker and Pharmacogenetic 
Research Samples ....................................................................................55
5.3.1.2.1
Biomarker Samples..................................................................................55
5.3.1.2.2
Pharmacogenetic Samples .......................................................................56
5.3.1.3
Confinement.............................................................................................57
5.3.1.4
Meals and Dietary Requirements.............................................................57
5.3.2
Drug and Anti-Drug Antibody Concentration Measurements.................57
5.3.2.1
Collection of Samples for Analysis .........................................................57
5.3.2.1.1
Blood Samples for ABBV-8E12 Assay...................................................57
5.3.2.1.2
Blood Samples for ABBV-8E12 Anti-Drug Antibodies (ADA) 
Assays ......................................................................................................58
5.3.2.1.3
CSF Samples for ABBV-8E12 Assay......................................................58
5.3.2.2
Measurement Methods.............................................................................58
5.3.3
Efficacy Variables....................................................................................59
5.3.3.1
Primary Variable......................................................................................59
5.3.3.2
Secondary Variables ................................................................................59
5.3.3.3
Exploratory Variables ..............................................................................59
5.3.4
Safety Variables.......................................................................................60
5.3.5
Pharmacokinetic Variables ......................................................................60
5.3.6
Biomarker and Pharmacogenetic Research Variables .............................61
5.3.6.1
Biomarker Research Variables.................................................................61
5.3.6.2
Pharmacogenetic Research Variables......................................................62
5.3.7
Immunogenicity .......................................................................................62
5.4
Removal of Subjects from Therapy or Assessment.................................62
5.4.1
Discontinuation of Individual Subjects....................................................62
5.4.2
Discontinuation of Entire Study...............................................................64
5.5
Treatments................................................................................................65
5.5.1
Treatments Administered.........................................................................65
5.5.2
Identity of Investigational Product...........................................................66


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5.5.2.1
Packaging and Labeling...........................................................................66
5.5.2.2
Storage and Disposition of Study Drug ...................................................67
5.5.2.3
Preparation/Reconstitution of Dosage Form............................................68
5.5.3
Method of Assigning Subjects to Treatment Groups...............................68
5.5.4
Selection and Timing of Dose for Each Subject......................................69
5.5.5
Blinding....................................................................................................69
5.5.6
Treatment Compliance.............................................................................70
5.5.7
Drug Accountability.................................................................................70
5.6
Discussion and Justification of Study Design..........................................71
5.6.1
Discussion of Study Design and Choice of Control Groups....................71
5.6.2
Appropriateness of Measurements...........................................................71
5.6.3
Suitability of Subject Population .............................................................72
5.6.4
Selection of Doses in the Study ...............................................................72
6.0
Complaints .............................................................................73
6.1
Medical Complaints.................................................................................73
6.1.1
Definitions................................................................................................73
6.1.1.1
Adverse Event..........................................................................................73
6.1.1.2
Serious Adverse Events ...........................................................................74
6.1.2
Adverse Event Severity............................................................................75
6.1.3
Relationship to Study Drug......................................................................76
6.1.4
Adverse Event Collection Period.............................................................76
6.1.5
Adverse Event Reporting.........................................................................77
6.1.6
Pregnancy.................................................................................................79
6.1.7
Toxicity Management ..............................................................................79
6.1.7.1
Potential Drug-Related Toxicities............................................................79
6.1.7.2
On-Target Toxicities................................................................................80
6.1.7.3
Non-Specific Off-Target Toxicities.........................................................80
6.1.7.4
Allergic Reactions Management..............................................................80
6.1.7.5
Management of Adverse Events of the Nervous System.........................81
6.1.8
Collection of Data Regarding Known Complications of the 
Disease Under Study................................................................................81
6.2
Product Complaint ...................................................................................82
6.2.1
Definition .................................................................................................82


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6.2.2
Reporting..................................................................................................83
7.0
Protocol Deviations................................................................83
8.0
Statistical Methods and Determination of Sample 
Size ..........................................................................................84
8.1
Statistical and Analytical Plans................................................................86
8.1.1
Efficacy Analyses ....................................................................................86
8.1.2
Safety Analyses........................................................................................87
8.1.2.1
Study Drug Exposure and Compliance....................................................88
8.1.2.2
Analysis of Adverse Events.....................................................................88
8.1.2.3
Analysis of Laboratory Tests...................................................................89
8.1.2.4
Analysis of Vital Signs and Weight.........................................................89
8.1.2.5
Analysis of ECG Variables......................................................................90
8.1.2.6
Analysis of C-SSRS.................................................................................90
8.1.3
Biomarker Analyses.................................................................................90
8.1.4
Pharmacokinetic and Exposure-Response Analyses ...............................92
8.2
Interim analysis........................................................................................94
8.2.1
Safety Interim Analyses...........................................................................94
8.2.2
Efficacy Interim Analysis ........................................................................94
8.3
Determination of Sample Size .................................................................94
9.0
Ethics.......................................................................................95
9.1
Independent Ethics Committee or Institutional Review Board ...............95
9.2
Ethical Conduct of the Study...................................................................95
9.3
Subject Information and Consent.............................................................96
10.0
Source Documents and Case Report Form 
Completion .............................................................................97
10.1
Source Documents ...................................................................................97
10.2
Case Report Forms...................................................................................97
11.0
Data Quality Assurance ........................................................98
12.0
Use of Information.................................................................99
13.0
Completion of the Study .....................................................100
14.0
Investigator's Agreement....................................................102
15.0
Reference List ......................................................................103


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List of Tables
Table 1.
Prohibited Medications ............................................................................31
Table 2.
Clinical Laboratory Tests.........................................................................41
Table 3.
Diagnostic Tools and Scale Order, and Duration of 
Administration .........................................................................................46
Table 4.
Identity of Investigational Product...........................................................66
List of Figures
Figure 1.
Study Schematic.......................................................................................26
Figure 2.
Adverse Event Collection ........................................................................77
List of Appendices
Appendix A.
Responsibilities of the Clinical Investigator ..........................................107
Appendix B.
List of Protocol Signatories....................................................................109
Appendix C.
Study Activities......................................................................................110
Appendix D.
Potentially Clinically Significant (PCS) Laboratory Values .................126
Appendix E.
Protocol Amendment:  List of Changes.................................................131


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3.0
Introduction
Progressive Supranuclear Palsy
Progressive supranuclear palsy (PSP), also known as Steele-Richardson-Olszewski 
Syndrome, is a progressive neurodegenerative disorder, with an estimated annual 
incidence of 5 to 7 per 100,000.1  Within the US, the disease affects approximately 
20,000 individuals.  No geographical, ethnic, gender, or racial disparity in PSP frequency 
is apparent.  PSP can initially present with clinical symptoms similar to other brain 
disorders, including idiopathic Parkinson's disease.  For this reason, correct diagnosis of 
PSP is sometimes delayed, often taking place 1 to 3 years after the initial onset of clinical 
symptoms.  Symptom onset is most often between the ages of 50 to 70 years, and 
although the clinical course is variable, the typical survival from time of symptom onset is 
5 to 9 years.2  Although some heterogeneity in clinical presentation exists, the most 
common and initially described PSP syndrome, now referred to as 
Steele-Richardson-Olszewski Syndrome, presents with symptoms including prominent 
postural instability and axial rigidity leading to falls, supranuclear gaze palsy causing 
range of vision impairment, frontal-subcortical cognitive impairment, and dysphagia 
leading to aspiration.  The course of disease is progressive and uniformly fatal.3
Pathologically, PSP is characterized by the abnormal accumulation of 
hyperphosphorylated, insoluble aggregates of tau protein in neurons and glia in the 
brainstem, cerebellum, basal ganglia, and cerebral cortex.3  The degree and distribution of 
tau aggregation in PSP is strongly correlated with PSP symptomatology during life.4  The 
National Institute of Neurological Disorders and the Society for Progressive Supranuclear 
Palsy (NINDS-SPSP) research criteria that describe Steele-Richardson-Olszewski 
Syndrome are highly predictive of underlying PSP pathology.5  Neuronal loss in various 
regions of the brain accompanies neurofibrillary tangles (NFTs) that are composed of tau 
aggregates.  Multiple neurotransmitter abnormalities arise as well, including those 
affecting specific dopaminergic, cholinergic, GABAergic, and noradrenergic systems.


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No treatments for PSP are currently approved.6  The negative outcomes of therapeutic 
efficacy studies in PSP preclude recommending an evidence-based standard therapy.7  In 
the absence of any effective disease modifying or neuroprotective therapies, PSP 
represents an urgent unmet medical need.
ABBV-8E12
ABBV-8E12 is a humanized monoclonal subclass of the immunoglobulin G antibody 
(IgG4) against human microtubule-associated protein tau.  It is a recombinant 
glycoprotein produced in Chinese hamster ovary cells.  It targets soluble extracellular tau 
in the brain, which has been implicated in the development and spreading of tau 
pathology.  NFTs, a characteristic pathologic feature in PSP and several other 
neurological disorders including corticobasal degeneration (CBD) and Alzheimer's 
disease, are formed inside of neurons by aggregated and post-translationally modified tau.  
Based on preclinical evidence, ABBV-8E12 may be able to block tau seeds from 
propagating between cells, and thereby decrease the spreading of tau pathology in 
neurodegenerative disorders associated with tau.
Preclinical Efficacy
In preclinical studies, the mouse version of the antibody (HJ8.5) was found to specifically 
block tau seeding activity from brain lysates of P301S transgenic mice in vitro.8  The 
P301S animal is a transgenic mouse model that carries a mutated human tau gene that 
leads to early onset frontotemporal dementia in humans.  In vivo, 3 months of treatment 
with HJ8.5 as a continuous intracerebroventricular infusion was associated with potent 
reductions in tau pathology, as evidenced by biochemical, histopathological, and 
functional/behavioral measures.  A similar study to assess the effects of peripherally 
(intraperitoneal [IP]) administered HJ8.5, found that weekly IP injections of HJ8.5 was 
highly effective at reducing insoluble tau in the brain, reducing cortical and hippocampal 
atrophy, and improving sensorimotor function.9


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Preclinical Safety
ABBV-8E12 binds to human tau but not to tau protein from preclinical toxicology species 
(i.e., rhesus/cynomolgus monkey, canine, rabbit, rat, or mouse).  Therefore, there is no 
pharmacologically relevant species in which to conduct toxicology studies to support 
safety of ABBV-8E12.  To assess toxicity in non-relevant species, a 4-week study in 
wild-type mice was conducted at doses up to 250 mg/kg for 4 weeks via weekly 
intravenous (IV) injections.  There were no adverse effects at any dose level, and the no 
observed adverse effect level (NOAEL) was 250 mg/kg.
A detailed discussion of the preclinical toxicology and pharmacology can be found in the 
Investigator's Brochure (IB).10
Clinical Experience
Compassionate-Use Protocols
Treatment with ABBV-8E12 was administered to 1 patient with PSP under an expanded 
access protocol in the United States (Study C2N-8E12-EA-001) and to 1 patient with CBD 
under a single named patient compassionate-use plan in Germany 
(Study C2N-8E12-DE-003).  ABBV-8E12 is currently being administered to 1 patient 
with chronic traumatic encephalopathy (CTE) under an expanded access, 
investigator-initiated protocol in the US (Study C16-344).
The PSP patient received 20 monthly infusions (highest dose 25 mg/kg for the last 
7 infusions), then died from PSP complications unrelated to study drug.  The CBD patient 
received 3 monthly infusions (1 at 7.5 mg/kg, 2 at 15 mg/kg), but died due to suicide 
9 days after the second 15 mg/kg infusion.  The CBD patient had a strong history of 
suicidal ideation and premeditation that preceded compassionate treatment with 
ABBV-8E12.  No evidence of imaging abnormalities or other evidence of drug-related 
toxicity was detected in these 2 patients.  The CTE patient has received multiple infusions 
of ABBV-8E12 from 2.5 to 25 mg/kg.


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Phase 1 Single Ascending Dose Study
Study C2N-8E12-WW-104 is a single-ascending dose (SAD) trial in 30 subjects with PSP 
in which 5 dose levels of ABBV-8E12 (2.5 mg/kg, 7.5 mg/kg, 15 mg/kg, 25 mg/kg, and 
50 mg/kg) were evaluated.  Twenty-three subjects received ABBV-8E12, and 7 subjects 
received placebo.
Three serious adverse events (SAEs) were reported:
●
One subject (15 mg/kg group) experienced an SAE of subdural hematoma 
resulting from a fall that was assessed by the investigator as possibly related to 
study drug; the sponsor judged the SAE to be unlikely related to study drug, 
and likely related to the underlying PSP.
●
One subject (25 mg/kg group) was hospitalized due to a severe increase in 
agitation, anxiety, and perseverative behavior, and the subject was 
discontinued from the study after being unable to participate following the 
SAE; the investigator and sponsor assessed that the worsening symptoms may 
represent progression of the subject's underlying disease, but that study drug 
cannot be ruled out as a contributing factor, so the event was therefore 
assessed as possibly drug related.
●
One subject (50 mg/kg group) was hospitalized for evaluation and treatment of 
hypertension; this SAE was assessed by the investigator as moderate in 
severity, resolved without sequelae, and unrelated to study drug.
No subject experienced a systemic hypersensitivity reaction or injection site reaction, and 
no clinically relevant patterns of adverse events or abnormal laboratory findings were 
observed.  Based on available anti-drug antibody (ADA) data in 
Study C2N-8E12-WW-104, no ADAs were detected in postdose samples on Day 14 or 
Day 28.
Pharmacokinetic data from Study C2N-8E12-WW-104 indicate dose-proportional 
increases in area under the concentration time curve (AUC) and in the maximum observed 
serum concentration (Cmax) from 2.5 to 50 mg/kg.  Half-life ranged from 27 to 37 days.  


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The mean peak ABBV-8E12 concentration (Tmax) was attained at a range of 0.3 to 
4.6 hours after dosing.  ABBV-8E12 cerebrospinal fluid (CSF) to plasma concentration 
ratios ranged from 0.181% to 0.385% with no clear trend across dose levels.
Phase 2 Multiple-Dose Study in Subjects with PSP
Study M15-562 is an ongoing Phase 2, randomized, multicenter, double-blind, 
placebo-controlled, multiple-dose trial in which 2 dose levels of ABBV-8E12 are being 
evaluated (2000 and 4000 mg).  A total of 378 subjects are planned.
3.1
Differences Statement
Study M15-563 is a Phase 2, multicenter, long-term extension of Phase 2 Study M15-562.  
Study M15-562 is a randomized, placebo-controlled clinical study to evaluate efficacy, 
safety, tolerability, immunogenicity, and pharmacokinetics (PK) of multiple doses of 
ABBV-8E12 in subjects with PSP.  The Treatment Period in Study M15-563 is up to 
5 years compared with up to 52 weeks in Study M15-562.  Subjects who complete the 
52-week treatment period in Study M15-562 and meet all entry criteria will be eligible to 
enroll in Study M15-563.  All subjects in Study M15-563 will be on active treatment 
(ABBV-8E12 2000 or 4000 mg), whereas Study M15-562 is placebo-controlled.
3.2
Benefits and Risks
Patients with PSP suffer serious debilitating symptoms that affect gait and balance, vision, 
swallowing and speaking, and cognition.  The disease is characterized by tau aggregation 
and is ultimately fatal.  No approved treatment exists.
ABBV-8E12, a humanized monoclonal antibody that is being developed for the treatment 
of PSP, may block tau seeds from propagating between cells, and therefore, may slow 
disease progression, thus providing a viable treatment option for patients with PSP.  The 
safety profile of ABBV-8E12 to date has been favorable, and no clinically relevant 
patterns of adverse events or abnormal laboratory findings have been observed.  Further, 
no ADAs were detected in postdose samples in an SAD study in subjects with PSP.


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Risks include infusion reactions and possibly life-threatening allergic reactions; however, 
no systemic hypersensitivity or injection site reactions have been reported to date.  
Subjects will be monitored closely during clinical trials for the occurrence of these events, 
study drug will be withdrawn immediately in the case of allergic reaction, and appropriate 
medical therapy will be provided for any adverse event.
Evidence of efficacy demonstrated in preclinical studies and safety data from clinical 
studies obtained to date provide a strong rationale for continuing the assessment of safety 
and efficacy of ABBV-8E12.  The benefit-risk profile of ABBV-8E12 will be further 
defined in Study M15-562, which is ongoing, and in Study M15-563, which is described 
herein.
4.0
Study Objectives
The primary objectives of this study are:
●
To assess the long-term safety and tolerability of ABBV-8E12 in subjects with 
PSP.
●
To assess the long-term efficacy of ABBV-8E12 in slowing disease 
progression in subjects with PSP as measured by the PSP Rating Scale 
(PSPRS).
The secondary objectives of this study are:
●
To assess the long-term efficacy of ABBV-8E12 in slowing disease 
progression and functional impairment in subjects with PSP as measured by 
secondary endpoints.
●
To assess the PK of ABBV-8E12 in subjects with PSP.
●
To assess the long-term efficacy of ABBV-8E12 in slowing regional and/or 
whole brain atrophy in subjects with PSP as measured by volumetric magnetic 
resonance imaging (MRI).


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The exploratory objectives of this study are:
●
To assess the long-term efficacy of ABBV-8E12 in slowing disease 
progression and functional impairment in subjects with PSP as measured by 
exploratory endpoints.
●
To assess the long-term effect of ABBV-8E12 on CSF and plasma tau protein 
levels.
●
To assess the long-term effect of ABBV-8E12 on other potential CSF and 
plasma biomarkers of disease progression.
●
To assess body position and gait in a subset of participating subjects using 
BioStamp digital sensors.
5.0
Investigational Plan
5.1
Overall Study Design and Plan:  Description
Overview
Study M15-563 is a long-term extension of Study M15-562, a Phase 2, randomized, 
multiple-dose, multicenter study in subjects with PSP.  Subjects who completed the 
52-week Treatment Period in Study M15-562 and meet all entry criteria will be eligible 
for enrollment into Study M15-563. Study M15-562 was designed to randomize 
378 subjects to meet scientific and regulatory objectives without enrolling an undue 
number of subjects in alignment with ethical considerations.  Therefore, the number of 
subjects who will participate in Study M15-563 will be up to the number of subjects 
enrolled in Study M15-562 (the actual number of subjects who enroll in Study M15-563 
will depend on the number of subjects from Study M15-562 who are eligible and consent 
to rollover).  The study will be conducted at approximately 60 multinational sites.
Study M15-563 will consist of a treatment period of up to 5 years and a post-treatment 
follow-up visit approximately 20 weeks after the last dose of study drug (including 
subjects who prematurely discontinue treatment).  All subjects will receive ABBV-8E12 
as follows:  1) subjects who received placebo in Study M15-562 will be randomized, in a 


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1:1 ratio, to 1 of 2 ABBV-8E12 doses (2000 or 4000 mg); and 2) subjects who received 
ABBV-8E12 2000 or 4000 mg in Study M15-562 will continue on the same dose.  Refer 
to Section 5.5.3 for detailed information on randomization.  Investigators and subjects 
will remain blinded to the treatment assignments in Study M15-562 and will be blinded to 
the dose level of ABBV-8E12 in Study M15-563.
Subjects from Study M15-562 will complete baseline procedures and receive the 
first infusion of study drug on Day 1 of Study M15-563.  For subjects who do not have 
interruptions in study drug administration between Study M15-562 and Study M15-563 
(i.e., the duration between the last dose of study drug in Study M15-562 and the first dose 
of study drug in Study M15-563 is no more than 45 days), procedures that were 
performed at the Week 52 Visit in Study M15-562 do not need to be repeated for the 
Day 1 Visit in Study M15-563.  Week 52 procedures from Study M15-562 cannot be used 
to satisfy the Day 1 requirements for Study M15-563 if more than 45 days (but less than 
8 weeks) have elapsed since the subject's last dose of study drug in Study M15-562; in 
that case, Day 1 activities for Study M15-563 must be performed.
Study drug will be infused 3 times during the first 4 weeks:  on Days 1, 15, and 29. 
Subjects who received placebo in Study M15-562 will receive ABBV-8E12 on Day 15 in 
Study M15-563, and subjects who received ABBV-8E12 in Study M15-562 will receive 
placebo on Day 15 in Study M15-563 (to maintain the blind in Study M15-562).  After 
Day 29 of Study M15-563, study drug will be administered every 28 days until one of the 
discontinuation criteria is met, until the study is discontinued by the sponsor, or until the 
study reaches completion.  The rate of infusion for each subject will be based upon that 
subject's most recently obtained weight and will range from 3.5 to 4.7 mL/min (210 to 
282 mL/hr) (refer to Section 5.5.1 for details on infusion rates).  Subjects will be observed 
on-site for at least 30 minutes after the end of study drug infusions.
Study drug will be administered and study procedures will be performed as shown in 
Appendix C.  Safety and tolerability will be monitored throughout the study.  Blood 
samples will be collected for pharmacokinetic and anti-drug antibodies (ADA) 
assessments every 3 months during the first 6 months, and every 6 months thereafter.  


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Lumbar puncture will be performed every 6 months during the first year, then once a year 
thereafter; it is optional every 6 months in years 2 through 5.  Volumetric MRI will be 
performed every 3 months during the first 6 months, then every 6 months thereafter.  In a 
subset of subjects (up to 50) at participating sites, subjects will be assigned digital sensor 
BioStamp units to be worn for 1 week epochs starting on Day 1, Day 29 (Week 4), 
Day 57 (Week 8), and Day 85 (Week 12).
A schematic of the study design is shown in Figure 1.
Figure 1.
Study Schematic
a.
Additional interim analyses may be performed.
DMC Review of Safety Data
A Data Monitoring Committee (DMC) will review unblinded safety data and make 
recommendations to the Sponsor based on the totality of available clinical data.  The 
DMC memberships, responsibilities, and operating logistics are documented in a DMC 
charter.  The DMC consists of at least 2 external clinicians, at least 1 external statistician, 
and at least 1 external pharmacokineticist.


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The data set reviewed by the DMC will consist of all available safety and 
pharmacokinetic data in the study, including data from any subjects who have received at 
least 1 dose of study drug.
5.2
Selection of Study Population
5.2.1
Inclusion Criteria
A subject will be eligible for study participation if he/she meets the following criteria:
1.
The subject voluntarily signed the Independent Ethics Committee 
(IEC)/Institutional Review Board (IRB) approved Informed Consent form, prior to 
the conduct of any study procedures, or, where applicable (i.e., countries other than 
Germany*) for a given subject, the subject's legally authorized representative 
(LAR) signed the IEC/IRB approved Informed Consent form on behalf of the 
subject, prior to the conduct of any procedures.  *For Germany, where the subject's 
LAR is not permitted to sign the IEC/IRB approved Informed Consent form on 
behalf of the subject, evaluation by an independent psychiatrist will be sought if the 
investigator who is evaluating the subject for inclusion in the study doubts the 
subject's cognitive ability to independently provide informed consent.
2.
The subject completed the 52-week treatment period in Study M15-562.
3.
In the opinion of the investigator, the subject was compliant during participation in 
Study M15-562.
4.
The subject has an identified, reliable study partner (e.g., caregiver, family 
member, social worker, or friend), who has frequent contact with the subject (at 
least 10 hours per week) and who can accompany the subject to study visits to 
provide information regarding the subject's functional abilities.
5.
If female, the subject must be either postmenopausal defined as:
●
age > 55 years with no menses for 12 or more months without an alternative 
medical cause


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●
age ≤ 55 years with no menses for 12 or more months without an alternative 
medical cause AND a follicle-stimulating hormone (FSH) level of > 40 IU/L.
OR
●
Permanently surgically sterile (bilateral oophorectomy, bilateral salpingectomy 
or hysterectomy).
OR
a woman of childbearing potential (WOCBP) practicing at least 
1 protocol-specified method of birth control (refer to Section 5.2.4), starting on 
Study Day 1 through at least 20 weeks after the last dose of study drug.
6.
If a male subject is sexually active, he must agree from Study Day 1 through at 
least 20 weeks after the last dose of study drug, to practice protocol specified 
contraception (refer to Section 5.2.4).
7.
Female subjects of childbearing potential must have a negative urine pregnancy test 
result on Day 1.
Rationale for the Inclusion Criteria
1
In accordance with the harmonized Good Clinical Practice (GCP)
2 – 4
To select subject population appropriate for this study
5 – 7
The effects of ABBV-8E12 on pregnancy are currently unknown
5.2.2
Exclusion Criteria
A subject will not be eligible for study participation if he/she meets any of the following 
criteria:
1.
The subject weighs less than 44 kg (97 lbs) at study entry.
2.
The subject has any contraindication or inability to tolerate brain MRI (e.g., a 
pacemaker or any other implanted device or condition that would preclude 
proximity to a strong magnetic field).


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3.
The subject has any significant change in his/her medical condition that could 
interfere with the subject's participation in the study, could place the subject at 
increased risk, or could confound interpretation of study results.  The Investigator 
must re-evaluate the subject for continuing participation and consider any factors 
including the interim development of any clinically significant neurological, 
hematological, autoimmune, endocrine, cardiovascular, neoplastic, renal, hepatic, 
metabolic, psychiatric, pulmonary, gastrointestinal, or other major disorder.
4.
More than 8 weeks have elapsed since the subject received his/her last dose of 
study drug in Study M15-562.
5.
The subject is concurrently enrolled in another interventional clinical study 
involving a therapeutic agent.
6.
The subject is considered by the investigator, for any reason, to be an unsuitable 
candidate to receive ABBV-8E12 or the subject is considered by the investigator to 
be unable or unlikely to comply with the dosing schedule or study evaluations.
7.
The subject is female and is pregnant, breastfeeding, or is considering becoming 
pregnant during the study or for approximately 20 weeks after the last dose of 
study drug.
8.
The subject is male and is considering fathering a child or donating sperm during 
the study or for approximately 20 weeks after the last dose of study drug.
Rationale for Exclusion Criteria
1, 2, 4 – 6
To ensure the appropriate subject population
3
To ensure the safety of the subjects
7, 8
The effects of ABBV-8E12 on pregnancy are currently unknown


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5.2.3
Prior and Concomitant Therapy
Any medication or vaccine (including over-the-counter or prescription medicines, 
vitamins and/or herbal supplements) that the subject is receiving at the time of enrollment, 
or receives during the study, must be recorded along with the reason for use, date(s) of 
administration including start and end dates, and dosage information including dose, route 
and frequency.
The AbbVie therapeutic area medical director (TA MD) should be contacted with any 
questions regarding concomitant or prior therapy(ies), or prohibited medications.
5.2.3.1
Concomitant Therapy
All concomitant medications should remain at stable doses for the duration of the study 
unless a change in regimen is medically necessary; any change in dose must be recorded.
The following medications are permitted:
●
Ramelteon, trazodone, amitriptyline, and mirtazapine for sleep; low doses of 
clozapine and quetiapine are also permitted for sleep.
●
Selective benzodiazepines and gamma-aminobutyric acid (GABA) agonists, 
zolpidem, zaleplon, eszopiclone, alprazolam, clonazepam, and lorazepam for 
sleep and anxiety.
●
Atypical antipsychotics, clozapine (≤ 300 mg [consult AbbVie TA MD for 
doses > 300 mg]) or quetiapine for the treatment of psychotic symptoms.
●
Selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine 
reuptake inhibitors (SNRIs), buspirone, mirtazapine, or trazodone for anxiety 
or depression.
●
Cholinesterase inhibitors (donepezil, rivastigmine, galantamine) or memantine 
for cognitive impairment.
●
Medications for parkinsonian symptoms (including levodopa/carbidopa,
dopamine agonists, monoamine oxidase inhibitors, 
catechol-O-methyltransferase [COMT] inhibitors, or amantadine).


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5.2.3.2
Prohibited Therapy
Subjects should not receive the medications listed in Table 1 unless approved by the 
Investigator in consultation with the Sponsor.  This list is not comprehensive.
Table 1.
Prohibited Medications
Anticoagulants (exclusionary for lumbar puncture)
Examples
Vitamin K antagonists
Dabigatran
Enoxaparin sodium
Rivaroxaban
Apixaban
Heparin 
Neuroleptics:a  prohibited throughout the duration of the study
Examples
Chlorpromazine
Fluphenazine
Loxapine
Perphenazine
Thioridazine
Thiothixene
Trifluoperazine
Haloperidol
Benzodiazepines/GABA agonists:a  prohibited throughout the duration of the study
Examples
Chlordiazepoxide
Diazepam
Midazolam
Flurazepam
Temazepam
Meprobamate
Triazolam
GABA = gamma-aminobutyric acid


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a.
Excluding the selected compounds mentioned in Section 5.2.3.1.
Additional recommendations are as follows:
Drugs commonly known to cause excessive sedation, orthostatic hypotension, or 
increased risk for falls should be avoided, if possible.
In general, dose changes or administration of additional medications with psychotropic 
effects (including opiates) on an as-needed (PRN) basis is prohibited.  In the exceptional 
case, low doses of anxiolytic/hypnotic agents, antipsychotic or opiate containing 
medications are permitted in the interest of subject safety or emergent symptom control; 
however, ongoing use of PRN medications should be discussed with the AbbVie TA MD.  
If a subject requires PRN use of a medication with psychotropic effects, subject efficacy 
scales must not be administered for at least 48 hours following the administration of the 
medication.  Depending on the time of dose administration, the next study visit should be 
rescheduled to assure an interval of at least 48 hours between PRN medication 
administration and clinical or psychometric assessments.  Each case of PRN medication 
administration must be documented with the reason for use, dates of administration, and 
dosages in the electronic case report form (eCRF).  Regularly scheduled medications 
administered to a subject on a daily basis should not be delayed, and administration times 
should not be altered due to cognitive assessments.
5.2.4
Contraception Recommendations
If female, subject must be either postmenopausal defined as:
●
Age > 55 years with no menses for 12 or more months without an alternative 
medical cause.
●
Age < 55 years with no menses for 12 or more months without an alternative 
medical cause AND an FSH level > 40 IU/L.
OR
●
Permanently surgically sterile (bilateral oophorectomy, bilateral salpingectomy 
or hysterectomy).


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OR
●
Practicing at least one of the following methods of birth control (per local 
regulation), on Day 1 (or earlier) through at least 20 weeks after the last dose 
of study drug:
○
Combined (estrogen and progestogen containing) hormonal contraception 
(oral, intravaginal, transdermal) associated with the inhibition of ovulation, 
initiated at least 1 month prior to Day 1.
○
Progestogen-only hormonal contraception (oral, injectable, implantable) 
associated with inhibition of ovulation, initiated at least 1 month prior to 
Day 1.
○
Bilateral tubal occlusion/ligation.
○
Vasectomized partner(s) and is the sole sexual partner of the woman of 
childbearing potential trial participant.
○
Intrauterine device (IUD).
○
Intrauterine hormone-releasing system (IUS).
○
Progestogen-only oral hormonal contraception, where inhibition of 
ovulation is not the primary mode of action, initiated at least 1 month prior 
to Day 1.
○
Male or female condom with or without spermicide.
○
Cap, diaphragm or sponge with spermicide.
○
A combination of male condom with cap, diaphragm or sponge with 
spermicide (double barrier method).
○
True abstinence:  Refraining from heterosexual intercourse when this is in 
line with the preferred and usual lifestyle of the subject (periodic 
abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation 
methods] and withdrawal are not acceptable).
If male, subject must be surgically sterile (vasectomy with medical assessment confirming 
surgical success) or have a female partner who is postmenopausal or permanently sterile 
(bilateral oophorectomy, bilateral salpingectomy, or hysterectomy), OR if sexually active 


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with female partner(s) of childbearing potential must agree from Day 1 through 20 weeks 
after the last dose of study drug to practice contraception with:
●
Condom use
●
True abstinence:  Refraining from heterosexual intercourse – when this is in 
line with the preferred and usual lifestyle of the subject.  (Note:  Periodic 
abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods 
by the female partner] and withdrawal are not acceptable).
●
Additionally, male subject agrees not to donate sperm from Day 1 through 
20 weeks after the last dose of study drug.
5.3
Efficacy, Pharmacokinetic, Biomarker, Pharmacogenetic 
and Safety Assessments/Variables
5.3.1
Efficacy and Safety Measurements Assessed and Flow 
Chart
Study procedures described are listed in the following section of this protocol and are 
summarized in tabular format in Appendix C.
5.3.1.1
Study Procedures
5.3.1.1.1
Identification of Study Partner
To be eligible for enrollment, each subject must have an identified, reliable study partner 
(e.g., caregiver, family member, social worker, or friend), who has frequent contact with 
the subject (at least 10 hours per week) and who will accompany the subject to study 
visits to provide information as to the subject's functional abilities.  In the exceptional 
case the study partner is not available to accompany the subject to a visit, he/she may 
provide the information regarding subject's functional abilities by telephone.  The 
designated study partner must be sufficiently familiar with the subject (as determined by 
the investigator) to provide accurate data and be willing to be the study partner for the 
duration of the study.  The site investigator must consider the study partner to be able to 
perform all of these functions.  The site must obtain the name and contact information of 


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the study partner and the source documents must record the study partner's consent to 
satisfy the responsibility of the study partner in this study.  It is preferable that the same 
person act as the subject's study partner for the duration of the study.
5.3.1.1.2
Medical History Update
For all subjects, an update to the medical history, including the subject's history of PSP 
and any medications taken for symptoms related to PSP, will be obtained on Day 1.  In 
addition, history of alcohol and tobacco use will be obtained from each subject.  The 
Day 1 medical history will serve as the Baseline for clinical assessment.
Ongoing concomitant medication (prescription or over-the-counter, including vitamins 
and herbal supplements) use, any medication stopped within 30 days prior to study entry, 
and any monoclonal antibodies or other biologics administered within 6 months prior to 
the first dose of study drug will also be recorded.
5.3.1.1.3
Physical Examination
Symptom-driven physical examinations will be performed at the times indicated in the 
Study Activities Table (Appendix C).  Additional symptom-directed physical 
examinations will be performed when necessary.  The physical examination performed on 
Day 1 prior to the first dose will serve as the baseline physical examination for clinical 
assessment.  Any significant physical examination findings after dosing will be recorded 
as adverse events.
5.3.1.1.4
Orthostatic Vital Signs
Body temperature and orthostatic vital signs (blood pressure and pulse rate) will be 
measured at the times indicated in the Study Activities Table (Appendix C).
Supine blood pressure and pulse rate measurements should be followed by measurements 
while standing (after 2 minutes).  Study staff should make efforts to measure on the same 
arm and with the same method, including recording of the arm and method in the subject's 
source documentation.


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The body temperature and orthostatic vital signs measurements just prior to dosing on 
Day 1 will serve as the baseline measurements for clinical assessment.
For visits in which both orthostatic vital signs and blood sample(s) are collected, 
orthostatic vital signs should be obtained prior to any blood collection.
5.3.1.1.5
Vital Signs
Body temperature and vital signs will be measured at the times indicated in the Study 
Activities Table (Appendix C).
Blood pressure and pulse rate are to be measured while the subject has been sitting for at 
least 5 minutes.  Study staff should make efforts to measure on the same arm and with the 
same method, including recording of the arm and method in the subject's source 
documentation.
For visits in which both vital signs and blood sample(s) are collected, vital signs should be 
obtained prior to any blood collection.
5.3.1.1.6
Body Weight
Body weight will be measured at the times indicated in the Study Activities Table 
(Appendix C).  The subject will wear lightweight clothing and no shoes during weighing.
5.3.1.1.7
Pregnancy Testing
WOCBP must have a negative urine pregnancy test result on Day 1.  Pregnancy testing 
should be performed during treatment at the times indicated in the Study Activities Table 
(Appendix C), including at the last dose of study drug and for at least 20 weeks after the 
last dose of study drug.  WOCBP must also have a negative urine pregnancy test result 
prior to any radiological procedures.


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5.3.1.1.8
Neurological Examination
A neurological examination will be performed at the times indicated in the Study 
Activities Table (Appendix C).  The neurological exam performed on Day 1 will serve as 
the baseline for clinical assessment.  Symptoms identified on Day 1 will be recorded as 
adverse events for Study M15-562; new symptoms or current symptoms that change in 
severity or frequency after Day 1 will be recorded as adverse events for Study M15-563.
The neurological examination will assess:
●
Mental Status – assessment of orientation, speech, and memory
●
Cranial nerves – assessment of cranial nerves II – XII.  This will include an 
assessment of supranuclear gaze palsy and slowing of vertical saccades.
○
Vertical supranuclear palsy will be established by neurological 
examination demonstrating a greater than 50% limitation of the range of 
voluntary gaze in the vertical plane, which is overcome by reflexive 
vestibular stimulation
○
Slowing of vertical saccades may be assessed by either of the 
two following methods:
●
Slowing of vertical saccades may be established by neurological 
examination of saccades toward a target held greater than 20 degrees 
from the position of primary gaze in the vertical plane.  Slowing of 
vertical saccades will be defined as present when ocular movement is 
slow enough for the examiner to see its progress, rather than just its 
initial and final positions.  A delay in initiation of saccades is not 
considered slowing.
●
Slowing of vertical saccades may be established using quantitative 
measurements of saccades, such as infrared oculography of adequate 
spatial and temporal resolution to resolve multiple saccades.
●
Motor system – brief assessment of tone and strength, tremors
●
Sensory system – brief assessment of light touch and temperature sensation
●
Reflexes – assessment of deep tendon reflexes and plantar responses (Babinski 
sign)


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●
Coordination – assessment of upper and lower extremities, including 
assessment for tremor
●
Gait – assessment of tandem gait (if clinically indicated and safe)
●
Station – assessment of posture and stability as defined by the following:
○
If clinically indicated and safe, postural instability may be assessed by 
determining the impairment of postural reflexes on neurological 
examination (i.e., retropulsion with or without unaided recovery after a 
backward pull) in the absence of any other medical cause to explain this 
impairment (e.g., primary sensory deficit, vestibular dysfunction, pontine 
infarction, cerebellar syndrome, prominent upper or lower motor neuron 
signs).
5.3.1.1.9
12-Lead Electrocardiogram
Procedure
A 12-lead resting electrocardiogram (ECG) will be obtained at the times indicated in the 
Study Activities Table (Appendix C).  For visits in which both ECGs and blood sample(s) 
are collected, ECGs should be obtained prior to any blood collection.  ECGs will be 
recorded after the subject has been supine for at least 5 minutes.  The subject should be 
instructed to remain completely stationary during the recording, without talking, laughing, 
deep breathing, or swallowing during the time of recording (10 seconds).  The ECG 
measurements obtained on Day 1 will serve as the baseline for clinical assessment.
The ECGs will be read by a qualified local physician for an immediate safety assessment 
and also by the central reader who will provide a full report to the site within 
approximately 3 business days.
ECGs will be collected as single ECGs as follows:
●
Day 1 (Dose 1)
○
Pre-dose (just prior to pre-infusion PK sample collection and the start of 
infusion) 


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●
Weeks 12, 24, 52, 104, 156, 208, and 260
○
Pre-dose (just prior to the start of infusion, when applicable [no dose at 
Week 260])
Local ECG Reading:
A qualified physician at the study site will interpret and document his/her global 
interpretation on the ECG tracing, based on the following conventions, as appropriate:
●
Normal ECG
●
Abnormal ECG – not clinically significant
●
Abnormal ECG – clinically significant
This physician will sign and date the ECG tracings.  Each ECG should be reviewed by the 
physician before study drug administration to ensure the tracing is interpretable and no 
acute, medically serious condition is present.  The investigator's (or physician designee's) 
initial interpretation of the ECG will be the basis of any decisions related to the study 
conduct and treatment of the study subjects (e.g., eligibility at Baseline, adverse event 
assessment).
Central ECG Reading:
Site personnel will transmit ECG data to an ECG central laboratory for central processing 
and reading by a qualified cardiologist (central reader) who will independently review 
each ECG.  QT interval corrected for heart rate (QTc) will be determined using 
Fridericia's correction method (QTcF).  The central ECG laboratory's data will be entered 
into the database.  The central reader will also provide the interpretation of the ECG 
(i.e., "Normal" or "Abnormal").  The central ECG laboratory will send the ECG report to 
the site within approximately 3 business days.  The Investigator (or physician designee) 
will review the central reader's report/assessment and document his/her review by signing 
and dating the central ECG laboratory report.  The investigator should review and 
reconcile if necessary his/her interpretation of the ECG (normal/abnormal) with the 


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central ECG laboratory in case of relevant divergent assessments and reconcile as he/she 
determines is appropriate.
5.3.1.1.10
Clinical Laboratory Tests
Samples will be obtained at a minimum for the clinical laboratory tests listed in Table 2 at 
the times indicated in the Study Activities Table (Appendix C).
A certified laboratory will be used to process and provide results for the clinical 
laboratory tests.  Central Laboratory reference ranges will be provided prior to initiation 
of the study.  The baseline laboratory test results for clinical assessment for a particular 
test will be defined as the last measurement prior to the initial dose of study drug.


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Table 2.
Clinical Laboratory Tests
Hematology
Clinical Chemistry
Urinalysis
Hematocrit
Hemoglobin
RBC count
WBC count
Neutrophils
Bands (if detected)
Lymphocytes
Monocytes
Basophils (if detected)
Eosinophils (if detected)
Platelet count (estimate not
acceptable)a
MCV
MCHC
PT
aPTTb
PT/INRb
BUN
Creatinine
Total bilirubin
Albumin
AST
ALT
ALP
Sodium
Potassium
Calcium
Inorganic phosphate
Uric acid
Cholesterol
Total protein
Glucose
Triglycerides
Bicarbonate/CO2 chloride
Specific gravity
Ketones
pH
Protein
Glucose
Blood
Microscopic examination, if 
dipstick results are positive
CSF Basic Laboratory Testsc
RBC, WBC with differential
Total protein
Albumin
Glucose
ALP = alkaline phosphatase; ALT = alanine aminotransferase; aPTT = activated partial thromboplastin time;
AST = aspartate aminotransferase; BUN = blood urea nitrogen; CSF = cerebrospinal fluid; CO2 = carbon dioxide; 
INR = international normalized ratio; MCHC = mean corpuscular hemoglobin concentration; MCV = mean corpuscular 
volume; PT = prothrombin time; RBC = red blood cell; WBC = white blood cell
a.
Platelet count results to be reviewed by the investigator before lumbar puncture.
b.
Coagulation results to be reviewed by the investigator before lumbar puncture.
c.
To be done at the local laboratory.  If the local laboratory is unable to perform some of the CSF measurements, 
samples may be sent to the central laboratory for analyses of total protein, albumin, and glucose only.
For any laboratory test value outside the reference range that the investigator considers to 
be clinically significant:
●
The investigator will repeat the test to verify the out-of-range value.
●
The investigator will follow the out-of-range value to a satisfactory clinical 
resolution.
●
A laboratory test value that requires a subject to be discontinued from the 
study or requires a subject to receive treatment will be recorded as an adverse 
event.


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For all laboratory abnormalities the investigator will determine if they indicate a new 
disease process, an exacerbation or worsening of an existing condition, or require further 
action to be taken and therefore need to be reported as adverse events.  Accordingly, for 
any values outside of the reference range, the Investigator will indicate on the report if the 
result is Clinically Significant (CS) or Not Clinically Significant (NCS).  If a laboratory 
abnormality meets criteria for a Potentially Clinically Significant (PCS) laboratory value, 
as defined in Appendix D, the investigator must either report an associated adverse event 
or document in source the reason(s) the finding was not considered an adverse event.
Any laboratory value that remains abnormal at Premature Discontinuation/End of Study 
and was judged to be clinically significant will be followed according to accepted medical 
standards until resolution of the abnormality.
5.3.1.1.11
Magnetic Resonance Imaging
Volumetric MRI of the brain will be obtained for all subjects at the times indicated in the
Study Activities Table (Appendix C) and interpreted by a radiologist or neurologist.  
Subjects will be positioned supine on the MRI bed and their heads will be positioned 
within a head coil with appropriate foam padding to decrease movement during the scan 
and to standardize the orientation of the head.  The subjects will then be positioned within 
the MRI scanner for imaging.  
The Day 1 MRI assessment will be used to rule out the presence of any intracranial 
masses and exclude focal or diffuse processes that could indicate a clinically significant 
neurologic disorder other than PSP, including signal abnormalities on fluid attenuated 
inversion recovery (FLAIR) or T2 weighted images consistent with infectious, vascular, 
neoplastic or other degenerative processes.  The 3D T1 weighted sequences will also be 
acquired for volumetric analysis that will enable a quantitative assessment of whole brain 
volume and regional brain volume.
All or a subset of the following brain MRI imaging sequence types will be performed:
●
T1 weighted


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●
Diffusion weighted imaging
●
T2 weighted FLAIR
●
Proton density/T2 weighted
●
T2* weighted
●
Diffusion tensor imaging (DTI)
The above listed imaging sequences may be adapted, sequences may be dropped or 
additional imaging sequences may be included based on feasibility.  The duration of each 
imaging session is not expected to exceed 60 minutes.  Details of the MRI procedures will 
be described in the MRI Procedures Manual provided by the Sponsor.  The 3D T1 
weighted sequences will also be acquired for volumetric analysis that will enable a 
quantitative assessment of whole brain volume and regional brain volume.
Scans at all protocol-required time points, including at study entry, that are of poor quality 
(e.g., due to subject motion during the scan, inadequate coverage of the brain, improper 
positioning of the head, use of incorrect scan or geometry parameters or noisy image) as 
determined by the MRI technologist at the imaging center or reviewing radiologist or 
Sponsor will be repeated at the earliest possible time but within 15 days of the protocol-
required time point to obtain a scan of good quality.
On-treatment MRIs will be performed at the time points indicated in the Study Activities 
Table (Appendix C).  The time window for the MRI procedure at each protocol-required 
time point is ± 7 days.  If a subject cannot undergo MRI due to clinical reasons, the 
AbbVie TA MD should be consulted for approval.
Sedation is not recommended but is allowed.  Subjects who might need sedation should 
discuss this with the principal investigator prior to the imaging procedure.  If sedation is 
required it should occur after all scales and cognitive testing have been performed or, if 
this is not possible, at least 48 hours before the testing.
The MRI technician is responsible for performing brain MRI scans at all 
protocol-required time points.


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5.3.1.1.12
Lumbar Puncture
Lumbar punctures to collect CSF will be performed on all subjects at the times indicated 
in the Study Activities Table (Appendix C).  Lumbar puncture on Day 1 and lumbar 
puncture at completion (Week 260) or premature discontinuation should only be done if at 
least 3 months have elapsed since the previous lumbar puncture.
A sample of CSF will be collected according to the Collection and Processing of CSF 
Samples manual provided to the study site by the Sponsor.  If sampling is not successful 
or is standard of care for the institution, other methods including CT/fluoro guided or 
ultrasound guided lumbar puncture can be used at the discretion of the local clinical site 
staff.  CSF clinical laboratory tests will be analyzed locally at the applicable clinical site 
after each lumbar puncture/CSF collection.  These measures include cell counts (RBC and 
WBC with differential), total protein, albumin, and glucose (Refer to Table 2 for Clinical 
Laboratory Tests).  If the local laboratory is unable to perform some of the CSF 
measurements, samples may be sent to the central laboratory for analyses of total protein, 
albumin, and glucose only.  Other CSF measurements (e.g., ABBV-8E12 concentration, 
tau, and other exploratory biomarkers) will be analyzed by the applicable designated 
laboratory or at AbbVie.
Subjects who are not able to undergo an LP may be enrolled with permission of the 
AbbVie TA MD without the requirement of an LP during the study.
Headaches may occur following withdrawal of CSF.  Subjects may be treated with the 
following:  IV hydration, IV caffeine administration, bed-rest, and analgesics.  
Uncommonly a blood patch (injection of some of the subject's blood to patch the CSF 
leak) may be needed.  Potential but rare risks of lumbar puncture include infection, 
damage to nerves in the back, and bleeding into the CSF space.  The risk of these is much 
less than 1%.11 Institutional policy and investigator discretion should be followed to 
provide the appropriate post-lumbar puncture observation period, and to provide 
information to the subject on possible side effects and limitations on strenuous physical 
activity and driving.


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5.3.1.1.13
Diagnostic Tools and Rating Scales
Overview
Prior to the start of the study, designated raters will be certified in the use of all scales 
used in this study.  The objective of this certification/training is to establish uniformity 
across sites in the administration, interpretation and scoring of these rating instruments.  
Raters who cannot participate in pre-study certification/training or raters who become 
involved in the study after training at the investigator's meeting will not be permitted to 
perform any study-specified ratings until they have satisfactorily completed an 
individualized certification/training program designed by the central trainers, approved by 
AbbVie and supervised by the investigator or his/her designee.  It is the responsibility of 
the investigator to ensure that the raters at his/her site are appropriately trained and 
certified in the use of selected rating scales.  Every effort must be made by the 
investigative sites to ensure that each subject is rated by the same rater for each scale 
throughout their participation in the study.
AbbVie, in conjunction with the rater training vendor, will determine the minimum rater 
qualifications for each of the rating scales.  All raters must meet these qualifications prior 
to participation in the training process.  The qualifications of the raters will be verified 
through the training vendor.  Individual exceptions to these requirements must be 
approved by the Sponsor via the training vendor.
Administration of selected scales will be audio recorded (as permitted by local 
regulations) to allow for central review of the data to ensure consistency and reliability.  
Assessments will be performed at the times indicated in Table 3 and in the Study 
Activities Table (Appendix C).


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Table 3.
Diagnostic Tools and Scale Order, and Duration of Administration
Diagnostic Tools
and Scalesa,b
Approx. 
Duration 
(min)
S/SP
Treatment Period
20 Weeks 
Post Last 
Dose F/U
Year 1
Year 2
Year 3
Year 4
Year 5
Day
1c
Wk
12
Wk
24
Wk
52
Wk
76
Wk
104
Wk
128
Wk
156
Wk
180
Wk
208
Wk
232
Wk 260
Completion/
Premature D/C
PSPRS
10
S and SP
1
1
1
1
1
1
1
1
1
1
1
1
1
CGI-S
40 – 60
S and SP
2
2
2
2
2
2
2
2
2
2
2
2
2
CGI-C
1
S and SP
3
3
3
3
3
3
3
3
3
3
3
3
3
SEADL
2
S
4
4
4
4
4
4
4
4
4
4
4
4
4
UPDRS Part II
10
S
5
5
5
5
5
5
5
5
5
5
5
5
5
RBANS
25
S
6
6
6
6
6
CTT Parts 1 & 2
5 – 10
S
7
7
7
7
7
Letter Fluency Test (wpm)
1
S
8
8
8
8
8
NNIPPS-PPSd
30 – 45
S and SP
9
9
9
9
9
PGI-Ce
1 – 2
S
X
X
X
X
X
X
X
X
X
X
X
X
X
EQ-5De
8
S
X
X
X
X
X
X
C-SSRS (at every visit)f
< 5
S
X
X
X
X
X
X
X
X
X
X
X
X
X
BioStamp nPointg
S
X
X
PSP Caregiver Questionnaires
25
SP
X
X
X
X
X
X
X
X
X
X
X
X
TSQM-9
5 
S
X
X
X
X
X
X
X
X
X
X
X
X


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Table 3.
Diagnostic Tools and Scale Order, and Duration of Administration (Continued)
Approx = approximately; CGI-C = Clinical Global Impression of Change; CGI-S = Clinical Global Impression of Severity; C-SSRS = Columbia-Suicide Severity Rating Scale; 
CTT = Color Trails Test; D/C = discontinuation; EQ-5D = EuroQol-5D; F/U = follow-up; min = minutes; NNIPPS-PPS = National Institute of Neurological Disorders and the 
Society for Progressive Supranuclear Palsy; PGI-C = Patient Global Impression of Change; RBANS = Repeatable Battery for Assessment of Neuropsychological Status; 
S = subject; SEADL = Schwab and England Activities of Daily Living Scale; SP = study partner; TSQM-9 = Treatment Satisfaction Questionnaire for Medication; 
UPDRS = Unified Parkinson's Disease Rating Scale; Wk = week; wpm = words per minute
a.
Numbering listed in the table provides a pre-defined order of administration that should occur during each visit.
b.
Audio recordings/central review of the administration/assessment of selected scales may be conducted.
c.
Assess prior to randomization and the first dose of study drug.
d.
The NNIPPS-PPS will not be administered in Japan.
e.
Scale may be administered/assessed at any time during the visit, after the other procedures are completed, with the exception of the scheduled infusion time.
f.
Scale may be administered/assessed at any time during the visit with the exception of the scheduled infusion time.
g.
BioStamp nPoint will also be administered at Weeks 4 and 8.


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The diagnostic tools and rating scales are as follows:
PSP Rating Scale12
The 28-item PSPRS was initially constructed in 1992 by Dr. Lawrence Golbe in 
consultation with numerous colleagues, and was developed over a 10-year period.  
Content validity was established by interviewing patients who met the published 
diagnostic criteria for PSP, typically every 3 to 4 months.  Subject and study partner 
together were asked to assign a value to each PSP item.  When the patient did not concur 
with study partner observations, the interviewer encouraged discussion between the 
2 parties and assigned a value to that particular item using clinical judgment.  Study data 
for patients were collected from Baseline through study completion, or participant death.  
Only the data of patients who presented with PSP symptoms and who subsequently 
developed PSP were included in the psychometric analysis.  All interviewed patients were 
taking medication for PSP-related symptoms; however, the PSPRS has been widely used 
in clinical studies.7,13-15
The PSPRS contains 28 items comprised of 6 domains:  daily activities (7 items), 
mentation (4 items), bulbar (2 items), ocular motor (4 items), limb motor (6 items), and 
gait/midline (5 items). Six items are graded 0 to 2 and 22 items are graded 0 to 4.  The 
PSPRS total score is the sum of item scores and ranges from 0 to 100.  It is administered 
to the subject and the Study Partner by a clinician and takes approximately 10 minutes to 
complete, as reported in Table 3.
The PSP staging system (PSP-SS) used as an endpoint in this study was developed by 
Dr. Golbe and it emphasizes dysphagia and postural instability, the 2 features of PSP most 
likely to lead to life-threatening complications.16 All the items used to devise the staging 
system are derivable from the PSPRS.  The staging system uses the following items from 
the PSPRS:  dysphagia for solids, dysphagia for liquids, gait and sitting down, each 
graded from 0 to 4.  Only the first is obtained by history, the others by examination.  The 
PSP-SS contains 6 stages defined by the total scores of the 4 items:  Stage 0:  total 0, 
Stage 1:  total 1 – 4, Stage 2:  5 – 8, Stage 3:  9 – 12, Stage 4:  13 – 15, Stage 5:  16.  This 


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PSP-SS was formulated for ease of use as well as criterion validity against the PSPRS and 
time.
Clinical Global Impression of Severity and Change
The Clinical Global Impression of Severity (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 to 7 (the most severely ill).  This rating is based upon observed 
and reported symptoms, behavior, and function in the past 7 days.  The Clinical Global 
Impression of change (CGI-C) rates improvement by 7 categories:  very much improved, 
much improved, minimally improved, no change, minimally worse, much worse, very 
much worse.  These assessments are administered to the subject by a clinician and take 
approximately 40 to 60 minutes to complete, as reported in Table 3.
Schwab and England Activities of Daily Living Scale17
The Schwab and England Activities of Daily Living Scale (SEADL) scale will be used as 
a means of assessing the subject's ability to perform daily activities.  The SEADL scale 
was developed by Schwab and England in 1957 and consists of 10 items intended to 
evaluate the daily life activities of a patient.  The SEADL is composed of 2 sections:  the 
first is a self-report questionnaire in which patients 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).  It is administered to the subject by a clinician and takes 
approximately 2 minutes to complete, as reported in Table 3.
Unified Parkinson's Disease Rating Scale18
The Unified Parkinson's Disease Rating Scale (UPDRS) is an Investigator-used rating tool 
to follow the longitudinal course of Parkinson's disease.  The UPDRS assessment will be 
performed by an approved, trained rater.  To be qualified by the Sponsor and the rater 


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vendor, all raters must have participated in the Rater Training and have a current, valid 
Rater Certificate.
The UPDRS is made up of the following sections:
●
Part I – Mentation, Behavior, and Mood
●
*Part II – Activities of Daily Living
●
Part III – Motor Examination
●
Part IV – Complications of Therapy (including dyskinesias)
●
Part V – Modified Hoehn and Yahr Staging
*
Only Part II will be administered in this study.
It is administered to the subject by a clinician and takes approximately 10 minutes to 
complete, as reported in Table 3.
Repeatable Battery for Assessment of Neuropsychological Status19
The Repeatable Battery for Assessment of Neuropsychological Status (RBANS) is a 
25-minute, standardized neurocognitive battery with North American population-based 
normative data.  The RBANS measures five neurocognitive domains, with age-based 
scaling.  Twelve subtests measure cognitive decline or improvement across the following 
domains:
1.
Immediate Memory – List Learning and Story Memory,
2.
Visuospatial/Constructional – Figure Copy and Line Orientation,
3.
Language – Picture naming and Semantic Fluency,
4.
Attention – Digit Span and Coding, and
5.
Delayed Memory – List Recall, List Recognition, Story Memory, and Figure 
Recall.


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The RBANS has been shown to be effective at both detecting and characterizing dementia 
of different etiologies.  The RBANS has been translated into over 25 different languages, 
with extensive clinical validity data from a wide variety of geographic regions.  It is 
administered to the subject by a clinician and takes approximately 25 minutes to 
complete, as reported in Table 3.
Color Trails Test (Parts 1 and 2)20
The Color Trails Test (CTT) (Parts 1 and 2) involves numbered circles that are printed 
with vivid pink or yellow backgrounds that are perceptible to color-blind individuals.  For 
Part 1, the respondent uses a pencil to rapidly connect circles numbered 1 – 25 in 
sequence.  For Part 2, the respondent rapidly connects numbered circles in sequence, but 
alternates between pink and yellow.  The length of time to complete each trial is recorded, 
along with qualitative features of performance indicative of brain dysfunction, such as 
near-misses, prompts, number sequence errors, and color sequence errors. The clinician 
administering this test will need a stopwatch to record the length of time for the 
completion of each part.  It is administered to the subject by a clinician and takes 
approximately 5 to 10 minutes to complete, as reported in Table 3.
Letter Fluency Test21
The Letter Fluency Test is a phonemic fluency task, requiring subjects to generate as 
many words as they can that start with a given letter over a 60 second interval.  This study 
will employ 2 trials per administration, involving different letters.  The score is the total 
number of correct words generated over the 2 trials.  It will be administered to the subject 
by a clinician and will take approximately twice 1 minute to complete, as reported in 
Table 3.
Natural History and Neuroprotection in Parkinson Plus Syndromes-Parkinson Plus 
Scale22
The Natural History and Neuroprotection in Parkinson Plus Syndromes-Parkinson Plus 
Scale (NNIPPS-PPS) is a validated rating scale used to assess disease severity and 


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progression in patients with PSP and Multiple System Atrophy (MSA).  The 
NNIPPS-PPS contains 83 items, comprised of 11 domains:  functional disability 
(activities of daily living [ADLs]), mental function (cognition, mood, and behavior), 
motor disability (rigidity and bradykinesia), tremor, oculomotor function, cerebellar signs, 
pyramidal signs, dysautonomia, bulbar/pseudobulbar symptoms, myoclonus, and 
dystonia.  Responses are graded according to their severity.  It is administered by a 
clinician and takes approximately 30 to 45 minutes to complete, as reported in Table 3.  
This scale will not be administered in Japan.
Patient Global Impression of Change23
Subjects will evaluate the change in their PSP-related symptoms since initiation of study 
drug by choosing 1 of 7 responses.  The Patient Global Impression of Change (PGI-C) is a 
7-point response scale.  The subject will be asked by the Investigator or qualified designee 
to rate their change in status using the following 7-point scale:
1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 
5 = Minimally worse, 6 = Much worse, 7 = Very much worse.
The responses of "Very much improved," "Much improved," "Minimally improved" and 
"No change" on the PGI-C will be used to define responders.  It is administered to the 
subject by a clinician and takes approximately 1 to 2 minutes to complete, as reported in 
Table 3.
EuroQuality of Life24,25
The EuroQuality of Life (EQ-5D) contains a health state descriptive part comprising 
5 items, scored from 1 (no problems or symptoms) to 3 (serious problems or symptoms); a 
question about change in health state in the preceding 12 months, and a visual analog 
scale (VAS) to evaluate current health state (from 0, worst imaginable, to 100, best 
imaginable).  The descriptive profile can be converted into a value (EQ-Index) which 
ranges from 0 (death) to 1 (perfect health), with negative values indicating health states 


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considered worse than death.  It is administered to the subject by a clinician and takes 
approximately 8 minutes to complete, as reported in Table 3.
Columbia-Suicide Severity Rating Scale26
The Columbia-Suicide Severity Rating Scale (C-SSRS) is a systematically administered 
instrument developed to track suicidal adverse events across a treatment study.  The 
instrument is designed to assess suicidal behavior and ideation, track and assess all 
suicidal events, as well as the lethality of attempts.  Additional features assessed include 
frequency, duration, controllability, reason for ideation, and deterrents.  The C-SSRS is 
considered a low-burden instrument.  It is administered to the subject by a clinician and 
takes less than 5 minutes to complete, as reported in Table 3.
Any subject noted to have suicidal ideation with plan within the prior month, either via 
answering "yes" to questions 4 or 5 to the suicidal ideation portion of the C-SSRS or via 
clinical interview, will be evaluated immediately by the study physician.  The AbbVie TA 
MD will also be informed.  Appropriate steps will be taken to protect the subject, 
including but not limited to possible discontinuation from the study and referral for 
appropriate psychiatric care.  Any such subject on Day 1 will also be excluded from the 
study.
BioStamp nPoint (for subjects participating in the substudy only)27
BioStamp nPoint is an FDA 510(k)-cleared medical device designed to collect medical 
grade, clinical quality biometric, physiologic, and other electronic clinical outcome 
assessment (eCOA) data in a clinical trial setting.  The system processes raw data into 
recognizable clinical metrics including heart rate, activity and posture classification, 
surface electromyography (sEMG), and sleep metrics.  The sensors are multi-modal, 
multi-location, rechargeable, and reusable.  BioStamp data are processed and stored in a 
secure cloud that can be synchronized with third-party electronic data capture (EDC) and 
clinical trial management (CTM) systems.


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Three BioStamp sensor locations (left precordial chest, anterior thigh, and small of back) 
will be used in the study, and will capture information on heart rate, sleep, and measures 
of motor activity including posture, gait, and step count.  Subjects will be trained during a 
clinic visit how to use the system including how to apply and remove sensors and how to 
upload data.  Detailed laboratory manuals will be provided to participating sites.
PSP Caregiver Questionnaires28,29
The PSP caregiver questionnaire assesses the burden of caregivers, their work 
productivity, and health resource use, as well as quality of life.  The questionnaire consists 
of both questions specifically developed for this study as well as validated scales.  
Caregivers will complete the following sections of the questionnaire at scheduled visits 
during the study:
●
Caregiver Information:  This section gathers caregiver's basic demographic 
information such as age, gender, ethnicity, and household information.  It takes 
approximately 2 minutes to complete.
●
Caring for Someone with PSP:  This section contains a list of questions to 
capture the relationship between the caregiver and the person with PSP, the 
living arrangement, and the amount of time spent on caring.  In addition, it 
measures how frequently the caregiver helps with daily activities.  It takes 
approximately 5 minutes to administer this section.
●
Caregiver Work Productivity and Status:  Caregiver Work Productivity is 
measured by (Work Productivity and Activity Impairment Questionnaire 
[WPAI]).  The WPAI caregiver version is a validated 6-question instrument to 
measure impairments in work and activities.  The first 4 questions measure 
employment status and hours missed from work, and the last 2 questions 
measure the impact of caregiving on work productivity and daily activities on 
a 0 - 10 scale.  In addition to WPAI, there are 2 additional questions measuring 
the caregiver's work status and if the reason of unemployment is related to 
caregiving.  It takes approximately 5 minutes to administer the questionnaire.
●
Caregiver Healthcare Resource Use:  This section assesses the caregiver's 
general health as well as their health resource use in terms of number of 


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physician, ER visits, hospitalization, and length of stay for each 
hospitalization.  It takes approximately 5 minutes to administer this section.
●
Caregiver Quality of Life (carers quality-of-life questionnaire for PSP [PQoL 
Carers]):  PQoL Carers is a QoL instrument for carers of people with atypical 
parkinsonism (AP), including PSP and MSA.  The 26-item instrument was 
generated from in-depth interviews with carers of patients with AP and a 
thorough review of the existing literature and consultation with movement 
disorder experts.  The items are scored from 0 (no problem) to 4 (extreme 
problems).  It is a concise instrument with adequate psychometric qualities.  
Convergent and concurrent validity was supported by correlations of PQoL 
Carers with the patient's health status and QoL measures such as The 
Parkinson's Disease Questionnaire-39 (PDQ-39) and EQ-5D, as well as carers' 
measures, such as Caregiver Burden Inventory (CBI) and carer EQ-5D.  The 
discriminant validity of the scale was demonstrated through its capacity to 
differentiate between carers with varying levels of self-reported health.  It 
takes approximately 8 minutes to administer the questionnaire.
Treatment Satisfaction Questionnaire for Medication30
The Treatment Satisfaction Questionnaire for Medication (TSQM-9) assesses patient 
satisfaction with medication in 3 domains:  effectiveness (3 items), convenience (3 items), 
and global satisfaction (3 items).  Each item is scored on a 7- or 5-point Likert scale.  The 
total score in each domain is converted to a score between 0 and 100, with higher scores 
indicating greater satisfaction with treatment.  It takes approximately 5 minutes to 
complete the questionnaire.
5.3.1.2
Collection and Handling of Biomarker and Pharmacogenetic 
Research Samples
5.3.1.2.1
Biomarker Samples
Blood and CSF samples will be collected at the times indicated in the Study Activities 
Table (Appendix C) and may be used to evaluate known and/or novel disease-related or 


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drug-related biomarkers.  The biomarker rationale is discussed in the Section 5.3.6.1
(Biomarker Research Variables).
All biomarker samples should be collected, processed, labeled, and shipped as outlined in 
the study-specific laboratory manual, which will be provided separately.
AbbVie (or people or companies working with AbbVie) will store the samples in a secure 
storage space with adequate measures to protect confidentiality.  The samples may be 
retained while research on ABBV-8E12, or drugs of this class, or PSP continues, but for 
no longer than 20 years from the end of the study, or per local requirement.
Blood samples (approximately 11 mL) will be collected prior to the start of the infusion 
(0 hour, no more than 30 minutes prior to the start of the infusion).  CSF samples (18 to 
20 mL) will be collected by lumbar puncture.  Details for collection and processing are 
provided in a separate laboratory manual.
5.3.1.2.2
Pharmacogenetic Samples
Subjects will have the option to provide samples for exploratory research.  Subjects may 
still participate in the main study even if they decide not to participate in this optional 
exploratory research.
AbbVie (or people or companies working with AbbVie) will store the exploratory 
research samples in a secure storage space with adequate measures to protect 
confidentiality.  The samples will be retained while research on ABBV-8E12 (or drugs of
this class) or PSP and related conditions continues, but for no longer than 20 years after 
study completion.  The procedure for obtaining and documenting informed consent for 
exploratory research samples is discussed in Section 9.3.  Instructions for the preparation 
and shipment of the exploratory research samples will be provided in a laboratory manual.
Optional whole blood samples (6.5 mL) for DNA and RNA isolation will be collected at 
the times indicated in the Study Activities Table (Appendix C).


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All pharmacogenetic samples should be collected, processed, labeled and shipped as 
outlined in the study-specific laboratory manual, which will be provided separately.
5.3.1.3
Confinement
No confinement will be required for this study.
5.3.1.4
Meals and Dietary Requirements
There are no dietary requirements or restrictions for this study.
5.3.2
Drug and Anti-Drug Antibody Concentration Measurements
5.3.2.1
Collection of Samples for Analysis
Specific instructions for collection of blood samples and subsequent preparation and 
storage of the serum samples for the pharmacokinetic assays of ABBV-8E12 will be 
provided by the central laboratory, the Sponsor, or its designee.
5.3.2.1.1
Blood Samples for ABBV-8E12 Assay
Blood samples (approximately 3 mL) for ABBV-8E12 analysis will be collected by 
venipuncture at the times indicated in the Study Activities Table (Appendix C) as follows:
●
Day 1 (Dose 1)
○
Prior to the start of the infusion (0 hour), immediately after the end of the 
infusion (within 15 minutes) and 1 and 2 hours after the end of the infusion
●
Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 232, and 260
○
Prior to the start of the infusion (0 hour), when applicable (no dose at 
Week 260)
●
Post-Treatment Follow-up Visit (20 weeks after last dose)
○
Sample may be collected any time during the visit
PK samples collected prior to infusion (0 hour) should be collected no more than 
30 minutes prior to the start of infusion.  The allowable PK window for 1-hour postdose 


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samples is ± 6 minutes, and the allowable PK window for 2-hour postdose samples is 
± 12 minutes.  The allowable window for samples scheduled for the post-treatment 
Follow-Up Visit is ± 4 days.
5.3.2.1.2
Blood Samples for ABBV-8E12 Anti-Drug Antibodies (ADA) 
Assays
Blood samples (approximately 3 mL) for ABBV-8E12 ADA analysis will be collected by 
venipuncture at the times indicated in the Study Activities Table (Appendix C) as follows:
●
Day 1 (Dose 1)
○
Prior to the start of the infusion (0 hour)
●
Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 232, and 260
○
Prior to the start of the infusion (0 hour), when applicable (no dose at 
Week 260)
●
Post-Treatment Follow-up Visit (20 weeks after last dose)
○
Sample may be collected any time during the visit
The ADA samples collected prior to infusion (0 hour) should be collected no more than 
30 minutes prior to the start of infusion.  Blood samples may be collected within ± 4 days 
for the post-treatment Follow-up Visit.
5.3.2.1.3
CSF Samples for ABBV-8E12 Assay
CSF samples (assessment referred to as lumbar puncture) will be collected at the times 
indicated in the Study Activities Table (Appendix C).
The collection time and procedures of CSF samples are located in the lumbar puncture 
section of Study Procedures Section (Section 5.3.1.1.12).
5.3.2.2
Measurement Methods
Serum concentrations and relative titers in serum of ABBV-8E12 ADA will be 
determined using validated methods at the Bioanalysis Department at AbbVie.  CSF 


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concentrations of ABBV-8E12 will be analyzed using qualified or validated methods.  
Any additional analytes may be analyzed using non-validated methods either at AbbVie 
or by outside vendors or collaborators.  Serum samples collected for ABBV-8E12 and 
ABBV-8E12 ADA analysis may be used for future assay development or validation 
activities.  ABBV-8E12 ADA samples may be used for the analysis of neutralizing anti-
drug antibodies.
5.3.3
Efficacy Variables
5.3.3.1
Primary Variable
The primary efficacy variable will be the PSPRS total score to assess the effect of 
ABBV-8E12 in slowing disease progression.
5.3.3.2
Secondary Variables
Key secondary efficacy measures are as follows:
●
UPDRS Part II
●
CGI-C
●
SEADL
Additional secondary efficacy measures are as follows:
●
CGI-S
●
PGI-C
●
PSP-SS (composite of items from PSPRS)
●
Time to loss of ability to walk independently as measured by PSPRS item 26
Analysis of the secondary efficacy variables obtained from these measures is detailed in 
Section 8.0.
5.3.3.3
Exploratory Variables
Exploratory efficacy measures are as follows:


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●
Time to death
●
EQ-5D
●
Letter Fluency Test (words per minute)
●
RBANS
●
CTT (Parts 1 and 2)
●
NNIPPS-PPS (not applicable in Japan)
●
Frequency of hospitalizations related to PSP
Analysis of the exploratory efficacy variables obtained from these measures is detailed in 
Section 8.0.
5.3.4
Safety Variables
Adverse events and SAEs will be monitored throughout the dosing period and for 
approximately 20 weeks after the last dose.  Safety evaluations will consist of the 
following:  monitoring of adverse events (including infusion and allergic reactions), vital 
signs, physical examination, complete neurologic exam, cognitive assessments, C-SSRS, 
laboratory abnormalities, ECG, brain MRI including FLAIR, and immunogenicity as 
determined by ADA responses in blood.
5.3.5
Pharmacokinetic Variables
The concentration of ABBV-8E12 will be determined in serum and CSF samples 
collected in the study.  Data from this study may be combined with data from other 
ABBV-8E12 studies for pharmacokinetic analyses.
A mixed-effect modeling approach will be used to estimate the population central value 
and obtain empirical Bayesian estimates of the individual values for ABBV-8E12 
clearance (CL) and volume of distribution (V).
The concentration of ABBV-8E12 in CSF will be summarized at each collection time 
point.


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Additional parameters may be calculated if useful in the interpretation of the data.
5.3.6
Biomarker and Pharmacogenetic Research Variables
5.3.6.1
Biomarker Research Variables
Blood and CSF samples will be collected to conduct research to investigate disease related 
and drug-related biomarkers.  The biomarkers to be analyzed may include, but are not 
limited to, the following:
●
CSF and Plasma Biomarkers:
○
Tau in CSF and plasma
○
Additional exploratory CSF and plasma-based pharmacodynamic analyses 
may be conducted based on sample availability
●
Imaging Biomarkers:
○
Regional and/or whole brain volume derived from MRI
○
Fractional anisotropy and diffusivity measures in brain regions of interest 
derived from DTI
●
Digital Biomarkers:
○
BioStamp sensor motor outcomes including posture, gait, and step count
Exploratory evaluations from blood and CSF samples may include analyzing biomarkers 
related to the pathway(s) targeted by the study drug or believed to be related to the disease 
or to drug response.  
The information learned from analyzing these data may be used to investigate factors 
impacting response to treatment, scientific questions related to PSP, support development 
of ABBV-8E12, or in the development of new therapies.  Furthermore, given the 
exploratory nature of these data the results may not be included in the study summary.
Digital substudy endpoints will be handled in a separate scientific report.


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5.3.6.2
Pharmacogenetic Research Variables
Optional samples may be collected to conduct exploratory investigations into known and 
novel biomarkers.  The types of biomarkers to be analyzed may include, but are not 
limited to, nucleic acids, proteins, lipids or metabolites.  The samples may be analyzed as 
part of a multi-study assessment of factors influencing the subjects' response to the study 
drug (or drugs of the same or similar class) or the development and progression of the 
subjects' disease or related conditions.  The samples may also be used to develop new 
diagnostic tests, therapies, research methods or technologies.  The results from these 
analyses are exploratory in nature and may not be included with the study report.
5.3.7
Immunogenicity
ADA levels will be determined for the assessment of immunogenicity.
5.4
Removal of Subjects from Therapy or Assessment
5.4.1
Discontinuation of Individual Subjects
Each subject has the right to withdraw from the study at any time.  In addition, the 
investigator may discontinue a subject from the study at any time if the investigator 
considers it necessary for any reason, including the occurrence of an adverse event or 
noncompliance with the protocol.
The subject will be discontinued from the study if any of the following occur:
●
Subject starts receiving an approved therapy for PSP.
●
Subject develops unacceptable toxicity.
●
Female subject becomes pregnant.
●
Investigator decides it is in the subject's best interest to discontinue.
●
Subject is noncompliant with the protocol based on the investigator or medical 
monitor assessment.
●
Subject withdraws consent.


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●
Subject is lost to follow-up despite reasonable efforts by the investigator to 
locate the subject.
Severe allergic reactions or other adverse events that require the immediate interruption of 
ABBV-8E12 treatment will be taken into consideration by the AbbVie TA MD for 
permanent discontinuation from further treatment and initiation of appropriate medical
therapy and follow-up.
Any treatment-emergent, clinically significant, symptomatic neurological abnormalities 
and treatment-emergent MRI findings will be reported to the AbbVie TA MD and 
subjects will be considered for discontinuation from treatment if clinically indicated.
Subjects at risk of suicide as indicated by answering yes to question 4 or 5 on the C-SSRS 
and/or determined by the investigator to be at risk of suicide, should be promptly referred 
for appropriate follow-up care.  Subjects determined to be at ongoing risk of suicide 
should be discontinued from study participation.
If for any reason the subject becomes unable to continue treatment with ABBV-8E12, 
undergo protocol required procedures, or otherwise continue to participate in the study, 
discontinuation should be discussed with the AbbVie TA MD.
In the event that a subject withdraws or is discontinued from the study, the primary reason 
for discontinuation and any other reason(s) for the discontinuation from the study will be 
recorded and a physical examination, neurological examination, body weight, vital signs 
measurement, ECG, laboratory analyses, MRI, lumbar puncture, administration and 
completion of scales/questionnaires, C-SSRS, a serum pregnancy test (WOCBP only), 
and an assessment of adverse events and concomitant medications will be performed as 
soon as possible after discontinuation from the study (Refer to Study Activities Table, 
(Appendix C).  Additional blood samples for drug measurement may be collected at the 
time of discontinuation from subjects who are discontinued due to adverse events; the 
clock time, time in relation to dose, and date the sample was collected will be recorded.


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If a subject is discontinued from the study with an ongoing adverse event or an unresolved 
laboratory result that is significantly outside of the reference range, the investigator will 
attempt to provide follow-up until a satisfactory clinical resolution of the laboratory result 
or adverse event is achieved.
In the event that a positive result is obtained on a pregnancy test for a subject or a subject 
reports becoming pregnant during the study, the administration of study drug to that 
subject must be discontinued immediately.  The investigator must report a pregnancy 
within 1 working day of the site being aware to one of the AbbVie representatives listed 
in Section 6.1.5 or Section 7.0.
Subjects who prematurely discontinue from the study can be contacted by telephone for 
periodic updates at the times shown in Appendix C providing that consent for this contact 
was obtained prior to contact being made.
5.4.2
Discontinuation of Entire Study
AbbVie may terminate this study prematurely, either in its entirety or at any study site, for 
reasonable cause provided that written notice is submitted in advance of the intended 
termination.  The investigator may also terminate the study at his/her site for reasonable 
cause, after providing written notice to AbbVie in advance of the intended termination.  
Advance notice is not required by either party if the study is stopped due to safety 
concerns.  If AbbVie terminates the study for safety reasons, AbbVie will immediately 
notify the investigator by telephone and subsequently provide written instructions for 
study termination.
The DMC will review safety data during the study.  Depending on the outcome of these 
evaluations, the DMC may make a recommendation to discontinue the entire study or stop 
enrollment in a single dose group prior to enrollment of the planned sample size.  The 
entire study will be discontinued if it is determined by AbbVie in consultation with the 
DMC that the continued exposure of subjects to study drug represents a significant safety 
risk.  Enrollment to a single dose group will be discontinued if it is determined by AbbVie 


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in consultation with the DMC that the continued exposure of subjects to that dose of study 
drug represents a significant safety risk.
5.5
Treatments
5.5.1
Treatments Administered
The solution contained in the study vial(s) of ABBV-8E12 must be diluted with 0.9% 
sodium chloride injection/solution for infusion.  Subject weight will be obtained prior to 
study drug administration to determine the appropriate infusion rate as shown in the table 
below.  Written instructions for the preparation of ABBV-8E12 solutions for infusion will 
be provided in a document that is separate from the protocol.
Subject's Weight in kg/lbs
Infusion Rateb
44 – 49 kg (97 – 109 lbs, inclusive)a
3.5 mL/min or 210 mL/hr
50 – 58 kg (110 – 128 lbs, inclusive) 
4.0 mL/min or 240 mL/hr
59 kg and over (129 lbs and over)
4.7 mL/min or 282 mL/hr
a.
Subjects who weigh less than 44 kg (97 lbs.) will be excluded from enrollment (refer to exclusion criteria, 
Section 5.2.2, Exclusion Criterion 1).
b.
Continue infusion until bag is empty.
Study continuation for subjects whose weight falls below 44 kg (97 lbs.) during their 
participation will be discussed with the AbbVie TA MD and adjustment of the infusion 
rate or potential discontinuation from the study will be considered.
Study drug will be administered by IV infusion at each visit, in the morning if possible, as 
follows:
Study Drug
Formulation
ABBV-8E12 2000 mg
IV infusions at Day 1, Day 15, and Day 29, then every 28 days for 
up to 5 years
ABBV-8E12 4000 mg
Placeboa
a.
Subjects who received active drug in Study M15-562 will receive placebo on Day 15 to maintain the blind in 
Study M15-562; this is the only time point at which placebo will be dosed.
Note:
Visits may be scheduled within ± 4 days.


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Doses may be decreased after evaluation by the DMC of available safety, tolerability, and 
pharmacokinetic data.
The start and stop time of each study drug infusion will be recorded to the nearest minute.
5.5.2
Identity of Investigational Product
Information about the ABBV-8E12 products to be used in this study is presented in 
Table 4.
Table 4.
Identity of Investigational Product
Investigational 
Product
Mode of 
Administration
Formulation
Strength
Manufacturer
ABBV-8E12
Infusion
Solution for 
infusion in a vial
300 mg/15 mL
and
1000 mg/10 mL
AbbVie 
Deutschland 
GmbH & Co. KG, 
Ludwigshafen, 
Germany
Placebo
Infusion
0.9% NaCl 
injection/solution 
for infusion
500 mL
N/A
Variousa
NaCl = sodium chloride
a.
Can be sourced from approved marketed products from various commercial manufacturers depending on 
availability.
The 0.9% sodium chloride injection/solution for infusion will be supplied with 
commercially available material in either bags or bottles, locally sourced by the sites; 
however, if mandated by local regulation or in exceptional circumstances when sites are 
unable to procure their own, AbbVie may supply 0.9% sodium chloride injection/solution 
for infusion if necessary.
5.5.2.1
Packaging and Labeling
ABBV-8E12 will be provided in a glass vial as solution for infusion.  One vial will be 
packaged per carton.  Each vial and carton will be labeled with the information necessary 


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per country requirement.  Labels must remain affixed to the vial and carton.  All blank 
spaces on the label will be completed by the site staff prior to dispensing to subjects.
The commercially sourced 0.9% sodium chloride injection/solution for infusion will not 
be labeled as an Investigational Medicinal Product (IMP) prior to the handling by the 
unblinded pharmacist or qualified designee.  Instead, after addition of ABBV-8E12 to the 
0.9% sodium chloride injection/solution for infusion to be administered, it will be labeled 
with a dispensing label by the unblinded pharmacist or qualified designee as required.  
The 0.9% sodium chloride injection/solution without addition of ABBV-8E12, to be 
administered as placebo, will be labeled with a blinded dispensing label by the unblinded 
pharmacist or qualified designee as well.  Labels must remain affixed to the material.
If an IMP label on the 0.9% sodium chloride injection/solution for infusion is mandated 
by local agencies, labels may be applied on the overwrap and will be removed by the 
unblinded pharmacist prior to administration.
5.5.2.2
Storage and Disposition of Study Drug
ABBV-8E12 must be stored at 2° to 8°C/36° to 46°F, must be protected from light and 
must not be frozen at any time.
The 0.9% sodium chloride injection/solution for infusion should be stored per the locally 
approved commercial label, Summary of Product Characteristics (SmPC), or clinical 
study label.
A storage temperature log is to be maintained to document proper storage conditions.  The 
refrigerator temperature must be recorded on each business day.  Malfunctions or 
temperature excursion must be reported to the Sponsor immediately using the AbbVie 
Temperature Excursion Management System (ATEMS).  Study drug should be 
quarantined and not dispensed until ATEMS deems the drug as acceptable.
The investigational products are for investigational use only, and are to be used only 
within the context of this study.  The study drug supplied for this study must be 


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maintained under adequate security and stored under conditions specified on the label 
until dispensed for subject use or returned to AbbVie.
5.5.2.3
Preparation/Reconstitution of Dosage Form
The preparation of blinded doses will be performed by the unblinded pharmacist or 
qualified designee.  Placebo doses, consisting of 0.9% sodium chloride injection/solution 
for infusion bags or bottles, will be essentially identical in volume to active doses.  
Written instructions for the preparation of ABBV-8E12 solutions for infusion will be 
provided in the "Pharmacy Manual."
5.5.3
Method of Assigning Subjects to Treatment Groups
Prior to enrolling subjects, each site will be provided with a user manual as well as a 
telephone number and user instructions for the Interactive Voice-Response/Interactive 
Web-Based (IVR/IWB) system.  Each user will receive a code number that will be used in 
combination with a personal identification number (PIN) to access the system by 
telephone and a unique username and confidential password to access the system through 
the internet.
As subjects are enrolled in the study, the subject number from Study M15-562 will be 
rolled over to the IVR/IWB system for Study M15-563.  Each subject has a unique 5-digit 
subject number, the first digit will be 1, the second and third digits will be the site number 
(01, 02, etc.) and the fourth and fifth digits will be assigned in ascending numerical order 
at each site.
At the Day 1 visit, each subject who received placebo in Study M15-562 will be randomly 
assigned to either ABBV-8E12 2000 or 4000 mg through the IVR/IWB system after the 
site verifies that the subject is eligible to participate in the study.  The first dose of study 
drug will be administered after randomization at the same visit.  The randomization 
schedule will be computer-generated before the start of the study by the Statistics 
Department, AbbVie.  Subjects who received ABBV-8E12 in Study M15-562 will remain 
on the same dose in Study M15-563.


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5.5.4
Selection and Timing of Dose for Each Subject
Selection of the doses for this study is discussed in Section 5.6.4.  Each subject who 
received placebo in Study M15-562 will be randomized to either ABBV-8E12 2000 or 
4000 mg as described in Section 5.5.3.  Subjects who received ABBV-8E12 in 
Study M15-562 will remain on the same dose in Study M15-563.  ABBV-8E12 will be 
administered via IV infusion; if possible this will be performed in the morning.
5.5.5
Blinding
Study M15-563 is a long-term extension study.  Investigators, study site personnel (except 
the unblinded pharmacist or qualified designee), subjects, and the sponsor will remain 
blinded to the treatment assignments in Study M15-563 to maintain the blind in 
Study M15-562.
A 0.9% sodium chloride injection/solution that is essentially identical in volume to the 
ABBV-8E12 solution will be administered on Day 15 to subjects who received 
ABBV-8E12 in Study M15-562.  Written instructions for the preparation of ABBV-8E12 
solutions for infusion will be provided as a separate document from the protocol. 
Identical commercial 0.9% sodium chloride injection/solution for infusion bag or bottle 
will be used for the placebo doses at each site.
An unblinded pharmacist or qualified designee will receive and prepare the blinded doses.  
ABBV-8E12 and 0.9% sodium chloride injection/solution for infusion (if applicable) will 
be delivered to the unblinded pharmacist or qualified designee in an open-label format.  
The unblinded pharmacist or qualified designee will prepare the doses of ABBV-8E12 (in 
a blinded manner) following the available preparation instructions as appropriate based on 
the subject's assigned treatment.
For investigational product monitoring, an unblinded clinical research associate (also 
referred to as a pharmacy clinical research associate [CRA]) will be appointed for 
verification of unblinded preparation documentation.  The unblinded pharmacy CRA will 
be a different individual than the blinded CRA to ensure blinding is maintained.  The 


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unblinding procedure for the unblinded pharmacist/qualified designee and the unblinded 
pharmacy CRA will be provided in a separate study-specific document.
The IVR/IWB system will be programmed with blind-breaker instructions.
To ensure that the DMC will be fully informed, the DMC will be unblinded in its 
assessment of safety data.  The DMC will have full access to all data as needed for safety 
assessment.  SAS® data sets blinded with respect to treatment assignment will be sent to 
an independent Statistical and Data Analysis Center (SDAC) and an independent 
exposure-response analysis center (ERAC) by AbbVie.  The study randomization will be 
sent to the SDAC and ERAC under separate cover.  The SDAC will generate a closed 
report that includes unblinded information for the DMC.  Review of the closed report will 
be limited to the DMC and, if necessary, an internal review committee (IRC) from the 
Sponsor who may need to consult with the DMC to formulate a decision based on the 
DMC's recommendations.  A detailed communication plan between the DMC and IRC 
will be specified in the DMC Charter.
5.5.6
Treatment Compliance
The investigator or his/her designated and qualified representatives will administer study 
drug only to subjects enrolled in the study in accordance with the protocol.  The study 
drug must not be used for reasons other than that described in the protocol.  Subjects will 
be supervised at the time of study drug administration.
5.5.7
Drug Accountability
The investigator or his/her representative will verify that study drug supplies are received 
intact and in the correct amounts.  This will be documented by signing and dating the 
Proof of Receipt or similar document.  A current (running) and accurate inventory of 
study drug will be kept by the investigator and will include shipping invoices and the date 
on which study drug is administered to the subject.  An overall accountability of the study 
drug will be performed and verified by an AbbVie monitor throughout the study and at the 
study site closeout visit.  Written instructions for investigational product accountability 


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requirements will be provided as a separate document from the protocol.  Upon 
completion or termination of the study, all original containers (containing used study drug 
or containing unused study drug) will be destroyed at the site according to instructions 
from AbbVie and according to local regulations.  For those sites where local destruction 
of unused study drug is not feasible, sites will return the original containers of unused 
study drug to AbbVie according to instructions from AbbVie and according to local 
regulations.
5.6
Discussion and Justification of Study Design
5.6.1
Discussion of Study Design and Choice of Control Groups
This study is designed to assess the safety, tolerability, efficacy, and PK of ABBV-8E12 
in subjects with PSP for up to 5 years.  There is a delayed-start group31 (the placebo group 
for Study M15-562) and an early-start group (the ABBV-8E12 2000 and 4000 mg groups 
for Study M15-562) in Study M15-563.  The combined data from Study M15-562 and 
Study M15-563 will enable the evaluation of a disease modification effect of ABBV-8E12 
utilizing a delayed-start analysis.  Toxicity management is described in Section 6.1.7.
5.6.2
Appropriateness of Measurements
Standard pharmacokinetic, statistical, clinical, and laboratory procedures will be used in 
this study.
The PSPRS was developed to evaluate the severity and progression of PSP symptoms.
The PSPRS has been widely used in the scientific literature to evaluate PSP symptoms 
and has adequate reliability and validity.12  The SEADL, UPDRS Part II, RBANS, and 
NNIPPS-PPS are currently accepted and validated methods of evaluating subjects with 
PSP.  All safety assessments are standard measures used in pharmaceutical research.


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5.6.3
Suitability of Subject Population
The research diagnostic criteria for possible and probable PSP developed by the National 
Institute of Neurological Disorders and the Society for Progressive Supranuclear Palsy 
(NINDS-SPSP) have been well validated and are highly predictive of underlying PSP 
pathology.5  The selection criteria are intended to identify subjects who have the potential 
to benefit from treatment would not be exposed to undue risk.
5.6.4
Selection of Doses in the Study
Dose levels for Study M15-563 (2000 and 4000 mg) were selected based on the doses 
used in Study M15-562, which were selected based on available safety, tolerability, and 
pharmacokinetic data from 2 patients with tauopathies who received ABBV-8E12 under 
an expanded access protocol (US [20 monthly infusions; maximum dose of 25 mg/kg for 
the last 7 months]) and a compassionate use trial (Germany [3 monthly infusions; 
maximum dose of 15 mg/kg for the last 2 months]) as well as safety, tolerability, and 
pharmacokinetic data from the SAD study (Study C2N-8E12-WW-104) in subjects with 
PSP, in which the safety, tolerability, and PK of single doses of ABBV-8E12 ranging 
from 2.5 to 50 mg/kg were evaluated.  The NOAEL was 250 mg/kg/week based on a 
4-week preclinical GLP toxicology study in C57BL/6 mice, and the corresponding mean 
Cmax and AUC0-168h were 3050 μg/mL and 298,000 μg•hr/mL (on Day 22) after 4 doses 
administered weekly.  The predicted safety margins are approximately 3- and 1.4-fold for 
both Cmax and AUC at the dose levels of 2000 and 4000 mg in humans, based on 
predictions from a 2-compartment PK model developed with the PK data from 
Study C2N-8E12-WW-104.
ABBV-8E12 infusions were well tolerated without any observed signs or symptoms of 
antibody-related toxicity in both compassionate-use protocols.  Dosing and follow-up 
have been completed in all dose groups in Study C2N-8E12-WW-104, and ABBV-8E12 
was generally well tolerated up to the highest tested dose of 50 mg/kg without notable 
treatment-related adverse effects or any clinically concerning safety findings in 
Study C2N-8E12-WW-104.  The actual doses administered in the SAD study were based 


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on the subject's body weight, and the range of actual doses in the 50 mg/kg group was 
2625 to 4760 mg.
6.0
Complaints
A Complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the physical characteristics, identity, quality, purity, potency, durability, 
reliability, safety, effectiveness, or performance of a product/device after it is released for 
distribution.
Complaints associated with any component of this investigational product must be 
reported to the Sponsor (Section 6.2.2).  For adverse events, please refer to Section 6.1
through Section 6.1.6.  For product complaints, please refer to Section 6.2.
6.1
Medical Complaints
The investigator will monitor each subject for clinical and laboratory evidence of adverse 
events on a routine basis throughout the study.  The investigator will assess and record 
any adverse event in detail including the date of onset, event diagnosis (if known) or 
sign/symptom, severity, time course (end date, ongoing, intermittent), relationship of the 
adverse event to study drug, and any action(s) taken.  For SAEs considered as having "no 
reasonable possibility" of being associated with study drug, the investigator will provide 
an "Other" cause of the event.  For adverse events to be considered intermittent, the events 
must be of similar nature and severity.  Adverse events, whether in response to a query, 
observed by site personnel, or reported spontaneously by the subject will be recorded.
All adverse events will be followed to a satisfactory conclusion.
6.1.1
Definitions
6.1.1.1
Adverse Event
An adverse event is defined as any untoward medical occurrence in a patient or clinical 
investigation subject administered a pharmaceutical product and which does not 


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necessarily have a causal relationship with this treatment.  An adverse event can therefore 
be any unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom, or disease temporally associated with the use of a medicinal (investigational) 
product, whether or not the event is considered causally related to the use of the product.
Such an event can result from use of the drug as stipulated in the protocol or labeling, as 
well as from accidental or intentional overdose, drug abuse, or drug withdrawal.  Any 
worsening of a pre-existing condition or illness is considered an adverse event.  
Worsening in severity of a reported adverse event should be reported as a new adverse 
event.  Laboratory abnormalities and changes in vital signs are considered to be adverse 
events only if they result in discontinuation from the study, necessitate therapeutic 
medical intervention, meet protocol specific criteria for PCS laboratory values defined in 
Appendix D and/or if the investigator considers them to be adverse events.
An elective surgery/procedure scheduled to occur during a study will not be considered an 
adverse event if the surgery/procedure is being performed for a pre-existing condition and 
the surgery/procedure has been pre-planned prior to study entry.  However, if the 
pre-existing condition deteriorates unexpectedly during the study (e.g., surgery performed 
earlier than planned), then the deterioration of the condition for which the elective 
surgery/procedure is being done will be considered an adverse event.
6.1.1.2
Serious Adverse Events
If an adverse event meets any of the following criteria, it is to be reported to AbbVie as an 
SAE within 24 hours of the site being made aware of the SAE:
Death of Subject
An event that results in the death of a subject.
Life-Threatening
An event that, in the opinion of the investigator, would have 
resulted in immediate fatality if medical intervention had not 
been taken.  This does not include an event that would have 
been fatal if it had occurred in a more severe form.


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Hospitalization or 
Prolongation of 
Hospitalization
An event that results in an admission to the hospital for any 
length of time or prolongs the subject's hospital stay.  This 
does not include an emergency room visit or admission to an 
outpatient facility.
Congenital Anomaly
An anomaly detected at or after birth, or any anomaly that 
results in fetal loss.
Persistent or 
Significant 
Disability/Incapacity
An event that results in a condition that substantially 
interferes with the activities of daily living of a study subject.  
Disability is not intended to include experiences of relatively 
minor medical significance such as headache, nausea, 
vomiting, diarrhea, influenza, and accidental trauma 
(e.g., sprained ankle).
Important Medical 
Event Requiring 
Medical or Surgical 
Intervention to 
Prevent Serious 
Outcome
An important medical event that may not be immediately 
life-threatening or result in death or hospitalization, but 
based on medical judgment may jeopardize the subject and 
may require medical or surgical intervention to prevent any 
of the outcomes listed above (i.e., death of subject, life-
threatening, hospitalization, prolongation of hospitalization, 
congenital anomaly, or persistent or significant 
disability/incapacity).  Additionally, any elective or 
spontaneous abortion or stillbirth is considered an important 
medical event.  Examples of such events include allergic 
bronchospasm requiring intensive treatment in an emergency 
room or at home, blood dyscrasias or convulsions that do not 
result in inpatient hospitalization, or the development of drug 
dependency or drug abuse.
For SAEs with the outcome of death, the date and cause of death will be recorded on the 
appropriate case report form.
6.1.2
Adverse Event Severity
The investigator will use the following definitions to rate the severity of each adverse 
event:
Mild
The adverse event is transient and easily tolerated by the subject.


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Moderate
The adverse event causes the subject discomfort and interrupts the 
subject's usual activities.
Severe
The adverse event causes considerable interference with the subject's 
usual activities and may be incapacitating or life-threatening.
6.1.3
Relationship to Study Drug
The investigator will use the following definitions to assess the relationship of the adverse 
event to the use of study drug:
Reasonable 
Possibility
After consideration of factors including timing of the event, 
biologic plausibility, clinical judgment, and potential alternative 
causes, there is sufficient evidence (information) to suggest a 
causal relationship.
No Reasonable 
Possibility
After consideration of factors including timing of the event, 
biologic plausibility, clinical judgment, and potential alternative 
causes, there is insufficient evidence (information) to suggest a 
causal relationship
For causality assessments, events assessed as having a reasonable possibility of being 
related to the study drug will be considered "associated."  Events assessed as having no 
reasonable possibility of being related to study drug will be considered "not associated."  
In addition, when the investigator has not reported a causality or deemed it not assessable, 
AbbVie will consider the event associated.
If an investigator's opinion of no reasonable possibility of being related to study drug is 
given, an "Other" cause of event must be provided by the investigator for the SAE.
6.1.4
Adverse Event Collection Period
All adverse events reported from the time of study drug administration until 20 weeks 
following discontinuation of study drug administration have elapsed (approximately 
5 half-lives) will be collected, whether solicited or spontaneously reported by the subject.  


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In addition, SAEs and protocol-related nonserious adverse events will be collected from 
the time the subject signed the study-specific informed consent.
Adverse event information will be collected as shown in Figure 2.
Figure 2.
Adverse Event Collection
6.1.5
Adverse Event Reporting
In the event of an SAE, whether associated with study drug or not, the Investigator will 
notify Clinical Pharmacovigilance within 24 hours of the site being made aware of the 
SAE by entering the SAE data into the electronic data capture (EDC) RAVE® system.  
SAEs that occur prior to the site having access to the RAVE® system or if RAVE is not 
operable should be documented on the SAE non-CRF forms and emailed (preferred route) 
or faxed to Clinical Pharmacovigilance within 24 hours of being made aware of the SAE.
Email:  
FAX to:  


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For safety concerns, contact the Neuroscience Safety Team at:
Neuroscience Safety Team
1 North Waukegan Road
North Chicago, IL 60064
Office:
Email:
For any subject safety concerns, please contact the physician listed below:
Primary TA MD:
Medical Director
Neuroscience Development
1 North Waukegan Road
North Chicago, IL 60064
Telephone Contact Information:
Phone:
Cell:
Email:
In emergency situations involving study subjects when the primary TA MD is not 
available by phone, please contact the 24-hour AbbVie Medical Escalation Hotline
where your call will be re-directed to a designated AbbVie Medical Director.
Phone:  
AbbVie will be responsible for Suspected Unexpected Adverse Reactions (SUSAR) 
reporting for the IMP in accordance with global and local guidelines, and Appendix A of 
the Investigator Brochure will serve as the Reference Safety Information (RSI).  The RSI 
in effect at the start of a Development Safety Update Report reporting period serves as the 


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RSI during the reporting period.  For follow-up reports, the RSI in place at the time of 
occurrence of the "suspected" Serious Adverse Reaction will be used to assess 
expectedness.
6.1.6
Pregnancy
Pregnancy in a study subject must be reported to AbbVie within 1 working day of the site 
becoming aware of the pregnancy.  Subjects who become pregnant during the study must 
be discontinued from the study drug (Section 5.4.1).
Information regarding a pregnancy occurrence in a study subject and the outcome of the 
pregnancy will be collected.
Pregnancy in a study subject is not considered an adverse event.  The medical outcome for 
either mother or infant, meeting any serious criteria including an elective or spontaneous 
abortion, is considered an SAE and must be reported to AbbVie within 24 hours of the 
site becoming aware of the event.
6.1.7
Toxicity Management
For the purpose of medical management, all adverse events and laboratory abnormalities 
that occur during the study must be evaluated by the investigator.
A drug-related toxicity is an adverse event or laboratory value outside of the reference 
range that is judged by the investigator or AbbVie as a "reasonable possibility" of being 
related to the study drug (Section 6.1.3).  Toxicity is deemed "clinically significant" based 
on the medical judgment of the investigator.  The following guidelines should be used for 
study drug-related toxicity management.
6.1.7.1
Potential Drug-Related Toxicities
No potential drug related toxicities were identified from preclinical or clinical studies 
conducted to date.  Examples of safety concerns that could be hypothetically associated 


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with ABBV-8E12 and safety concerns associated with monoclonal antibodies, in general, 
are summarized below.
6.1.7.2
On-Target Toxicities
The brain appears to be the only organ to express tau at significant levels.  Tau is an 
intracellular protein mainly expressed in neurons, although lower levels can be found in 
astrocytes and oligodendrocytes.  ABBV-8E12 is directed against extracellular tau and no 
function of extracellular tau has been reported.  No cellular uptake of the mouse version 
of ABBV-8E12 antibody bound to tau aggregates was detected in preclinical studies.32  
The likelihood of adverse on-target side effects of an anti tau immunotherapy is therefore 
anticipated to be low.
6.1.7.3
Non-Specific Off-Target Toxicities
Potential toxicities resulting from the non-human origin of ABBV-8E12 include allergic 
reactions or infusion reactions, including anaphylaxis or anaphylactoid reactions, flu-like 
symptoms, including fever, fatigue or loss of appetite, or rash.  ABBV-8E12 is lacking the 
Fragment Crystallizable (Fc) effector function activity and therefore Fc-mediated 
antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity is not 
expected.  In addition, ABBV-8E12 exhibited a favorable in vitro immune-safety profile.  
No infusion reactions have occurred in the single dose PSP clinical study or in the 
Expanded Access protocol (Studies C2N-8E12-EA-001 and C2N-8E12-DE-003).
6.1.7.4
Allergic Reactions Management
Subjects will be closely monitored for treatment-related adverse events, including allergic 
reactions, during the infusion.  Subjects should be monitored on site for at least 
30 minutes after the end of study drug infusions.  Longer observation periods and more 
frequent vital sign checks may be required in subjects who experience infusion reactions.
Severe or life-threatening allergic reactions require the immediate interruption of 
ABBV-8E12 treatment and permanent discontinuation from further treatment.  
Appropriate medical therapy including epinephrine, corticosteroids, IV antihistamines, 


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bronchodilators, and oxygen should be available for use in the treatment of such reactions.  
Subjects should be carefully observed until the complete resolution of all signs and 
symptoms.
Moderate infusion reactions resolving with supportive care should be discussed with the 
TA MD, and a reduction of the infusion rate for future administrations can be considered.
6.1.7.5
Management of Adverse Events of the Nervous System
Subjects will be closely monitored for adverse events suggesting neurotoxicity.  A drug 
related adverse event is an event that is judged by the investigator or AbbVie to have a 
"reasonable possibility" of being related to the study drug.
Severe or life-threatening drug related adverse events of the nervous system will require 
discontinuation from further treatment with ABBV-8E12 and prompt notification of the 
AbbVie TA MD.  Appropriate medical therapy will be initiated and subjects will be 
followed up until the resolution.
Clinically significant treatment-emergent neurological abnormalities or MRI findings will 
prompt notification of the AbbVie TA MD; subjects will be considered for 
discontinuation if clinically indicated, and may be permitted to continue in the study only 
after a management plan is discussed with the AbbVie TA MD.
6.1.8
Collection of Data Regarding Known Complications of the 
Disease Under Study
Natural progression of PSP (including new or worsening neurological symptoms and 
signs) is expected in the subjects.  Disease progression will be assessed at pre-determined 
intervals throughout the treatment period by standardized criteria (such as the PSPRS, 
SEADL, UPDRS Part II, CGI-S, NNIPPS-PPS) and recorded on the corresponding CRF 
pages for purposes or risk/benefit determinations.  Therefore, "disease progression" or 
other similar verbatim terms related to disease status SHOULD NOT be recorded on the 
adverse event CRF pages.  Similarly, since falls are a core component and defining 
feature of PSP (Steele-Richardson-Olszewski Syndrome), falls will not be recorded as 


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adverse events unless they lead to other injury or represent a change in frequency or 
character before enrollment in this study.
Similarly, the slow progression of pre-existing (before enrollment in this study) 
disease-related signs and symptoms clearly associated with the disease during the 
treatment period will not be reported as adverse events unless these signs and symptoms 
are judged by the Investigator to have become unusually severe or accelerated, or if the 
Investigator suspects the deterioration of disease-related signs and symptoms to be 
potentially related to the investigational drug.  If there is any uncertainty about the 
worsening of an adverse event being due solely to the disease under the treatment 
protocol, it should be reported as an adverse event or SAE as appropriate.
Discontinuation from this treatment protocol because of progression or deterioration of 
the disease should be recorded on the protocol Termination CRF page as discontinuation 
due to "disease progression" and NOT as discontinuation due to an adverse event.
6.2
Product Complaint
6.2.1
Definition
A Product Complaint is any Complaint (refer to Section 6.0 for the definition) related to 
the biologic or drug component of the product.
For a product this may include, but is not limited to, damaged/broken product or 
packaging, product appearance whose color/markings do not match the labeling, labeling 
discrepancies/inadequacies in the labeling/instructions (example:  printing illegible), 
missing components/product or packaging issues.
Any information available to help in the determination of causality to the events outlined 
directly above should be captured.


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6.2.2
Reporting
Product Complaints concerning the investigational product must be reported to the 
Sponsor within 1 business day of the study site's knowledge of the event via the Product 
Complaint form.  Product Complaints occurring during the study will be followed-up to a 
satisfactory conclusion.  All follow-up information is to be reported to the Sponsor (or an 
authorized representative) and documented in source as required by the Sponsor.  Product 
Complaints associated with adverse events will be reported in the study summary.  All 
other complaints will be monitored on an ongoing basis.
Product Complaints may require return of the product with the alleged complaint 
condition.  In instances where a return is requested, every effort should be made by the 
investigator to return the product within 30 days.  If returns cannot be accommodated 
within 30 days, the site will need to provide justification and an estimated date of return.
The description of the complaint is important for AbbVie in order to enable AbbVie to 
investigate and determine if any corrective actions are required.
7.0
Protocol Deviations
AbbVie does not allow intentional/prospective deviations from the protocol unless 
necessary to eliminate an immediate hazard to study subjects.  The principal investigator 
is responsible for complying with all protocol requirements, and applicable global and 
local laws regarding protocol deviations.  If a protocol deviation is identified after a 
subject has been enrolled, the principal investigator is responsible for notifying the 
appropriate IEC/IRB, regulatory authorities (as applicable), and the following AbbVie 
Clinical Monitor(s):


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Primary Contact:
Study Project Manager
AbbVie
1 North Waukegan Road
North Chicago, IL 60064
Office:
Not applicable
Mobile:
Fax:
Email:
Alternate Contact:
Study Project Manager II
AbbVie
1 North Waukegan Road
North Chicago, IL 60064
Office:
Mobile:
Fax:
Email:
Such contact must be made as soon as possible to permit a review by AbbVie to 
determine the impact of the deviation on the subject and/or the study.
8.0
Statistical Methods and Determination of Sample 
Size
The data analysis will be grouped by assigned treatment sequences/group in 
Studies M15-562/M15-563:  2000/2000 mg, 4000/4000 mg, placebo/2000 mg, and 
placebo/4000 mg.  If the treatment effect between each ABBV-8E12 dose and placebo is 
statistically significant at Week 52 in Study M15-562, the 2000/2000 mg and 
4000/4000 mg groups could be combined as the early-start ABBV-8E12 treatment group, 
and the placebo/2000 mg and placebo/4000 mg groups could be combined as the delayed-
start group for the delayed-start analysis.  Details of the analyses will be specified in the 
statistical analysis plan (SAP).
Data Sets for Efficacy Analyses
Two data sets will be used for the efficacy analysis: an intent-to-treat (ITT) data set and a 
delayed-start data set.
ITT Data Set:  The Study M15-563 ITT data set consists of all subjects who received any 
dose of study drug in Study M15-563.  This is the primary efficacy analysis set for this 


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study.  All efficacy analyses for Study M15-563 alone will be conducted on the ITT set 
unless otherwise specified.
Delayed-Start Data Set:  The delayed start analysis data set includes efficacy data from 
both Studies M15-562 and M15-563.  All subjects from Study M15-562 ITT data set will 
be included, regardless if they enroll in Study M15-563 or not.  Subjects who complete 
Study M15-562 and rollover to Study M15-563 but have a gap of more than 8 weeks 
between study drug infusions before enrolling into Study M15-563 will be excluded from 
this analysis set.
Data Sets for Safety Analyses
The safety data sets will consist of all subjects who received any dose of study drug in 
Study M15-563.  For the safety analyses, the actual treatment received will be used 
instead of the treatment assignment at the time of randomization.  There are 2 safety 
datasets:  a Stand-Alone safety data set and a cumulative safety data set as described 
below.
Stand-Alone Data Set:  The stand-alone data set is the primary data set for the safety 
analysis, and will contain data from Study M15-563 only, regardless of the treatment 
received in Study M15-562.  Baseline will be the last observation on or before the 
first dose of ABBV-8E12 in Study M15-563.  If no Baseline is recorded in 
Study M15-563, the last value in Study M15-562 will be used as the Baseline.
Cumulative Data Set:  The cumulative data set will consist of data from both 
Study M15-562 and Study M15-563.  It is the secondary data set for safety analyses.  For 
subjects who were in the placebo group in Study M15-562, their safety data from 
Study M15-562 will not be included in the cumulative data sets but their safety data from 
Study M15-563 will be included.  For Study M15-562 placebo subjects, Baseline will be 
the last observation prior to the first dose of study drug in Study M15-563.  For subjects 
who were in ABBV-8E12 treatment groups in Study M15-562, Baseline for the safety 
analyses will be their Baseline in Study M15-562.


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8.1
Statistical and Analytical Plans
8.1.1
Efficacy Analyses
All efficacy analyses of comparisons will be performed with a 2-sided test at the 
significance level of 0.05 unless otherwise specified.  All efficacy assessments that are 
taken no more than 45 days after the last dose of study drug will be included in the 
efficacy analysis.
The primary efficacy variable is the PSPRS total score in the Study M15-563 ITT 
analysis.  The primary analysis model is a likelihood-based, mixed-effect model, repeated 
measures (MMRM) analysis of the PSPRS total score at Study M15-563 Baseline and 
each post-baseline observation using all observed data.  The model will consist of fixed, 
categorical effects for treatment, site, visit, and treatment-by-visit interaction.  An 
unstructured (co)variance structure will be used to model within-subject errors.  
Satterthwaite's approximation will be used to estimate denominator degrees of freedom, 
and the Type III sum-of-squares for the Least Square (LS) means will be used to estimate 
treatment group differences.  The differences for placebo/2000 mg vs 2000/2000 mg and 
for placebo/4000 mg vs 4000/4000 mg at Study M15-563 Baseline and at the end of the 
Study M15-563 Treatment Period will be presented with a 95% confidence interval.  
Contrasts of treatment effects for other visits will be conducted as well.  This MMRM 
analysis will be applied to each efficacy variable with repeated measurements.  Details of 
the analysis will be described in the SAP.
The delayed-start analysis will be conducted on the change from Baseline in 
Study M15-562 up to Week 52 in Study M15-563 on the PSPRS total score.  An MMRM 
analysis model will be used.  The model will consist of fixed, categorical effects for 
treatment, site, visit, and treatment-by-visit interaction, with continuous fixed covariates 
for baseline PSPRS total score and the baseline score-by-visit interaction.  An 
unstructured (co)variance structure will be used to model within-subject errors.  
Satterthwaite's approximation will be used to estimate denominator degrees of freedom, 
and the Type III sum-of-squares for the LS means will be used to estimate treatment 


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group differences.  The primary comparisons will be the contrasts between an 
ABBV-8E12 dose group and the placebo group at Week 52 in both Study M15-562 and 
Study M15-563, and non-inferiority analysis of treatment effects at Week 52 between the 
2 studies.  If only one of the ABBV-8E12 dose groups in Study M15-562 is statistically 
significantly different from placebo at Week 52, the delayed-start analysis will be 
conducted only for that dose.  If treatment effects at Week 52 in Study M15-562 are 
statistically significant for both ABBV-8E12 doses (based on the primary analysis defined 
in the Study M15-562 SAP), the combined early-start groups and the combined delayed-
start groups will be used for the delayed-start analysis.  If neither ABBV-8E12 dose is 
statistically significantly different from the placebo at Week 52 in Study M15-562, the 
delayed-start analysis will not be conducted.  No multiplicity adjustment will be made for 
the delayed-start analysis based on combined groups or a selected ABBV-8E12 dose.  
Details of the analysis will be specified in the SAP.
The analysis on secondary and exploratory efficacy variables will be detailed in the SAP.
8.1.2
Safety Analyses
Comparisons between treatment groups (Studies M15-562/M15-563) of interest will be 
performed with a 2-sided test at the significance level of 0.05 unless otherwise specified.  
Unless otherwise specified, treatment group differences in continuous safety variables 
(e.g., change from Baseline to final observation on laboratory tests) will be assessed using 
an analysis of variance (ANOVA) model with treatment group as the main effect, and the 
treatment group differences in binary safety variables will be evaluated using Fisher's 
exact test.
A treatment-emergent adverse event (TEAE) is defined as any adverse event that begins 
or worsens in severity on or after the date of the first dose of study drug and no more than 
20 weeks after the date of the last dose of study drug.
All other safety assessments that are taken no more than 45 days after the last dose of 
study drug will be included in the safety evaluation of the Treatment Period, and all safety 


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assessments that are taken more than 45 days but not more than 20 weeks after the last 
dose of study drug will be included in the safety evaluation for the Post-treatment 
Follow-up Visit.
8.1.2.1
Study Drug Exposure and Compliance
The number of doses of study drug will be summarized by treatment groups and overall 
subjects.  The number and percentage of subjects with at least 90% compliance with study 
drug dosing (i.e., complete 90% of scheduled doses for each subject) will be summarized 
by treatment groups and overall subjects.  No comparisons between treatment groups will 
be performed.
8.1.2.2
Analysis of Adverse Events
The Stand-Alone data set will be the primary data set for adverse event summaries.  
Analyses that will be performed on the cumulative data set are as follows:  adverse event 
overview, adverse event incidence by system organ class (SOC) and preferred term, 
adverse event incidence in descending frequency by overall subjects, and SAE incidence 
by SOC and preferred term.
Adverse events will be coded using the current version of the Medical Dictionary for 
Regulatory Activities (MedDRA).  The number and percentage of subjects who report 
TEAEs will be tabulated by the MedDRA SOC and preferred term for treatment groups 
specified in Section 8.0.  No comparisons between treatment groups will be performed.
The number and percentage of subjects who experienced treatment-emergent SAEs 
(including deaths) and adverse events leading to premature discontinuation of study drug 
will be tabulated by the MedDRA SOC and preferred term for treatment groups specified 
in Section 8.0.  No comparisons between treatment groups will be conducted for adverse 
event summaries.


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8.1.2.3
Analysis of Laboratory Tests
Analyses will be performed on the Stand-Alone data set for laboratory tests.  Change from 
Baseline to each visit value and to the minimum, maximum, and final value will be 
presented for each continuous hematology, chemistry, and urinalysis parameter.  
Treatment differences between treatment group in change from Baseline to minimum, 
maximum, and final clinical laboratory evaluation will be analyzed using a one-way 
ANOVA with treatment group as the main effect.
For each treatment group, shift tables will be generated showing the number and 
percentage of subjects with low, normal, high, and missing values at Baseline and final 
observation based on the reference ranges provided by each laboratory.  Details will be 
specified in the SAP.  
The number and percentage of subjects in each treatment group who have values meeting 
predefined criteria for PCS (Appendix D) at any time after the first dose of study drug and 
no more than 20 weeks after the last dose of study drug will be summarized separately for 
hematology and chemistry variables.  No comparisons between treatment groups will be 
performed for PCS analysis.
8.1.2.4
Analysis of Vital Signs and Weight
Vital sign variables for this study will be pulse rate, systolic blood pressure, diastolic 
blood pressure, body temperature, weight, and body mass index (BMI).  Pulse rate and 
blood pressure will be measured in both supine and standing positions; orthostatic change 
(from supine to standing) will also be measured.
Change from Baseline to each visit value and to the minimum, maximum, and final value 
will be presented for each vital sign and weight variable and analyzed using a one-way 
ANOVA with treatment group as the main effect.  The number and percentage of subjects 
in each treatment group who have values meeting predefined criteria for PCS (definitions 
will be provided in the SAP) at any time after the first dose of study drug and no more 


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than 20 weeks after the last dose of study drug will be summarized.  No comparisons 
between treatment groups will be conducted.
8.1.2.5
Analysis of ECG Variables
ECG variables for this study will be heart rate, PR, QRS, QT, and QTcF intervals.  
Change from Baseline to final value will be presented for each ECG parameter and 
analyzed using a one-way ANOVA with treatment group as the main effect.  The number 
and percentage of subjects in each treatment group who have values meeting predefined 
criteria for PCS at any time after the first dose of study drug will be summarized.
8.1.2.6
Analysis of C-SSRS
The number and percentage of subjects in the following categories will be summarized for 
each treatment group by visit and for the entire study:
●
Answered 'Yes' to each C-SSRS item
●
Had suicidal ideation (defined as answering 'Yes' to one or more suicidal 
ideation items)
●
Had suicidal ideation only (defined as answering 'Yes' to one or more suicidal 
ideation items and answering 'No' to all suicidal behavior items)
●
Had suicidal behavior (defined as answering 'Yes' to one or more suicidal 
behavior items)
●
Had suicidal ideation or behavior (defined as answering 'Yes' to one or more 
suicidal ideation or behavior items.
8.1.3
Biomarker Analyses
For CSF and plasma concentrations of tau and for volumetric MRI variables, descriptive 
statistics will be provided for each scheduled time of measurement with a breakdown by 
groups defined by treatment in Study M15-562 and treatment in this study.  That is, the 
treatments of the 4 groups are as follows:


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●
ABBV-8E12 2000 mg in Study M15-562, continuing the same in 
Study M15-563
●
ABBV-8E12 4000 mg in Study M15-562, continuing the same in 
Study M15-563
●
Placebo in Study M15-562, ABBV-8E12 2000 mg in Study M15-563
●
Placebo in Study M15-562, ABBV-8E12 4000 mg in Study M15-563
The scheduled time of measurement will include the baseline measurement.  For subjects 
who were treated with ABBV-8E12 in Study M15-562, the baseline measurement will be 
the same as it was in Study M15-562.  For subjects whose treatment was placebo in 
Study M15-562, the baseline value will be the predose measurement on Day 1 of 
Study M15-563.  The descriptive statistics for a given time will provide information for 
both the data of the given time and the changes from Baseline.
For CSF and plasma concentrations of tau, an MMRM analysis will be performed to 
compare the effects of the 2000 and 4000 mg doses of ABBV-8E12.  The data set will 
contain the data of the first 2 groups identified above.  The data set will also include the 
data of the last 2 groups beginning with Week 76 of Study M15-563, but with a shift in 
time by 52 weeks for the purposes of this analysis so that the shifted time indicates the 
length of time on ABBV-8E12 past 52 weeks.  Thus, for this analysis, the Week 104 data 
of the last 2 groups will be considered the same as Week 52 of the first 2 groups.  
The model for the MMRM analysis performed for the tau variables will include 
classification by ABBV-8E12 dose and by time of measurement.  There will be an effect 
for the interaction of ABBV-8E12 dose and time of measurement.  The baseline value will 
be a covariate.  The model will also have an effect to distinguish between subjects who 
were assigned to ABBV-8E12 treatment in Study M15-562 and those who were assigned 
to placebo in Study M15-562.  The subjects in each treatment group will be viewed as a 
random sample, and an appropriate structure for the covariance matrix of the 
measurements of a subject will be selected.


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For volumetric MRI variables, descriptive statistics as described for the CSF tau 
concentrations will be provided.  An MMRM analysis corresponding to that described for 
the tau variables will be performed; however, the 2 models will differ with respect to 
covariates.  For the volumetric MRI variables, the baseline value and a measure of head 
size (e.g., intracranial volume) will be covariates.
For other variables for which data are reported, descriptive statistics will be provided and 
appropriate analyses performed.
Digital substudy endpoints will be handled in a separate scientific report.
8.1.4
Pharmacokinetic and Exposure-Response Analyses
For ABBV-8E12 serum concentration data, descriptive statistics will be provided for each 
scheduled time of measurement with a breakdown by groups defined by treatment in 
Study M15-562 and treatment in this study.  That is, the treatments in the 4 groups are as 
defined in Section 8.1.3.
Data from this study may be combined with data from other studies for the population 
pharmacokinetic and exposure-response analyses.  Population pharmacokinetic and 
exposure-response analyses of data from this study only may not be conducted.  The 
following general methodology will be used for the population pharmacokinetic and 
exposure-response analyses.
Population pharmacokinetic analyses will be performed using the actual sampling time 
relative to the last administered dose.  Pharmacokinetic models will be built using a non-
linear mixed-effect modeling approach with the NONMEM software (Version 7, or higher 
version).  The structure of the starting pharmacokinetic model will be based on the 
pharmacokinetic analysis of data from previous studies.  Apparent CL and apparent V of 
ABBV-8E12 will be the pharmacokinetic parameters of major interest in the NONMEM 
analyses.  If necessary, other parameters may be fixed if useful in the analysis.


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The evaluation criteria described below will be used to examine the performance of 
different models.
1.
The objective function of the best model is significantly smaller than the alternative 
model(s).
2.
The observed and predicted concentrations from the preferred model are more 
randomly distributed across the line of unity (a straight line with zero intercept and 
a slope of 1) than the alternative model(s).
3.
Visual inspection of model fits, standard errors of model parameters and change in 
inter-subject and intra-subject error.
Once an appropriate base pharmacokinetic model (including inter- and intra-subject error 
structure) is developed, empirical Bayesian estimates of individual model parameters will 
be calculated by the posterior conditional estimation technique using NONMEM.  The 
relationship between these conditional estimates of CL/F and V/F values and potentially 
physiologically relevant or clinically meaningful covariates (such as subject age, sex, 
body weight, concomitant medications, laboratory markers of hepatic or renal function) 
will be explored using either a stepwise forward selection method, or a generalized 
additive method (GAM), or another suitable regression/smoothing method at a 
significance level of 0.05.  After identification of all relevant covariates, a stepwise
backward elimination of covariates from the full model will be employed to evaluate the 
significance (at P < 0.005, corresponding to a decrease in objective function > 7.88 for 
one degree of freedom) of each covariate in the full model.
Linear or nonlinear relationships of primary pharmacokinetic parameters with various 
covariates will be explored.
Relationships between exposure, biomarker, and clinical observations (efficacy or safety 
variables of interest) may be explored.  Initially, the time-course of placebo response will 
be modeled.  Subsequently the relationship between exposure (e.g., population 
pharmacokinetic model predicted average concentrations or AUC or trough 


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concentrations of the individual model-predicted pharmacokinetic profiles, or some other 
appropriate measure of exposure) and drug effect will be explored after accounting for the 
time-course of placebo response.  Several classes of models (e.g., linear, log-linear, 
exponential, maximum effect [Emax], sigmoid Emax) will be evaluated to characterize the 
exposure-response relationship based on the observed data.
Additional analyses will be performed if useful and appropriate.
8.2
Interim analysis
Regular interim safety analyses will be performed and preplanned interim efficacy 
evaluation(s) may be performed.  Assessment of safety and efficacy data at interim(s) will 
be conducted by the DMC.
8.2.1
Safety Interim Analyses
Safety data will be reviewed by the DMC based on interim safety review schedules for 
Study M15-563.  A detailed timeline of the safety interim analysis will be provided in a 
DMC charter.
8.2.2
Efficacy Interim Analysis
An efficacy interim analysis may be conducted when the last subject completes Week 52 
assessments in Study M15-563.  Additional efficacy interim analyses may be conducted 
as needed.  A delayed-start analysis will be conducted and details of the delayed-start 
analysis will be specified in the SAP.
8.3
Determination of Sample Size
The sample size for this study is dependent on the number of subjects who complete 
Study M15-562 and are qualified for enrollment into Study M15-563.  A total of 
378 subjects will be randomized in Study M15-562; and the number of subjects who 
enroll in Study M15-563 will be up to the number of subjects enrolled in Study M15-562.


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9.0
Ethics
9.1
Independent Ethics Committee or Institutional Review 
Board
GCP requires that the clinical protocol, any protocol amendments, the IB, the informed 
consent and all other forms of subject information related to the study 
(e.g., advertisements used to recruit subjects) and any other necessary documents be 
reviewed by an IEC/IRB.  The IEC/IRB will review the ethical, scientific and medical 
appropriateness of the study before it is conducted.  IEC/IRB approval of the protocol, 
informed consent and subject information and/or advertising, as relevant, will be obtained 
prior to the authorization of drug shipment to a study site.
Any amendments to the protocol will require IEC/IRB approval prior to implementation 
of any changes made to the study design.  The investigator will be required to submit, 
maintain and archive study essential documents according to International Council for 
Harmonisation (ICH) GCP.
Any SAEs that meet the reporting criteria, as dictated by local regulations, will be 
reported to both responsible Ethics Committees and Regulatory Agencies, as required by 
local regulations.  During the conduct of the study, the investigator should promptly 
provide written reports (e.g., ICH Expedited Reports, and any additional reports required 
by local regulations) to the IEC/IRB of any changes that affect the conduct of the study 
and/or increase the risk to subjects.  Written documentation of the submission to the 
IEC/IRB should also be provided to AbbVie.
9.2
Ethical Conduct of the Study
The study will be conducted in accordance with the protocol, ICH guidelines, applicable 
regulations and guidelines governing clinical study conduct and the ethical principles that 
have their origin in the Declaration of Helsinki.  Responsibilities of the clinical 
investigator are specified in Appendix A.


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9.3
Subject Information and Consent
Prior to the initiation of any study-specific procedures, the investigator or his/her 
representative will explain the nature of the study to the subject, their study partner, and 
the subject's LAR (if applicable), and answer all questions regarding this study.  Each 
informed consent will be reviewed, signed and dated by the subject, the person who 
administered the informed consent, and any other signatories according to local 
requirements.  For Germany, where the subject's LAR is not permitted to sign the 
IEC/IRB approved Informed Consent form on behalf of the subject, evaluation by an 
independent psychiatrist will be sought if the investigator who is evaluating the subject 
for inclusion in the study doubts the subject's cognitive ability to independently provide 
informed consent.  An informed consent statement will also be reviewed, signed and 
dated, by the subject's study partner prior to beginning any study related activities.  A 
copy of each informed consent will be given to the subject and their study partner and 
each original will be placed in the subject's medical record.  An entry must also be made 
in the subject's dated source documents to confirm that informed consent was obtained 
prior to any study-related procedures and that the subject received a signed copy.
If at any time during the study, a subject experiences diminished decision-making 
capacity, an informed consent must be obtained from an LAR.
Information regarding incentives for subjects and information regarding provisions for 
treating and/or compensating subjects who are harmed as a consequence of participation 
in the study can be found in the informed consent form.
In the event a subject withdraws consent to participate from the study, stored biomarker 
and optional exploratory research samples will continue to be used for research and 
analysis.  In the event that a subject would like to withdraw consent for research using 
these samples, the subject may request that their samples be withdrawn.  Once AbbVie 
receives the request, remaining biomarker and optional exploratory research samples will 
be destroyed.  If the subject changes his/her consent, and the samples have already been 
tested, those results will still remain as part of the overall research data.


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An informed consent, approved by an IEC/IRB, must be voluntarily signed and dated 
before samples are collected for optional pharmacogenetic exploratory research.  The 
nature of the testing should be explained and the subject given an opportunity to ask 
questions.  The informed consent must be signed before the samples are collected and any 
testing is performed.  If the subject does not consent to provide samples for 
pharmacogenetic exploratory research, it will not impact their participation in the study.
10.0
Source Documents and Case Report Form 
Completion
10.1
Source Documents
Source documents are defined as original documents, data and records.  This may include 
hospital records, clinical and office charts, laboratory data/information, subjects' diaries or 
evaluation checklists, pharmacy dispensing and other records, recorded data from 
automated instruments, microfiches, photographic negatives, microfilm or magnetic 
media, and/or x-rays.  Data collected during this study must be recorded to the appropriate 
source document.  The Investigator Awareness Date (SAE CRF) may serve as the source 
for this data point.  This adverse event data point required for eCRF completion can be 
entered directly in the eCRF.
The investigator(s)/institution(s) will permit study-related monitoring, audits, IEC/IRB 
review, and regulatory inspection(s), providing direct access to source data documents.
10.2
Case Report Forms
eCRFs must be completed for each subject enrolled in this study.  These forms will be 
used to transmit information collected during the study to AbbVie and regulatory 
authorities, as applicable.  The CRF data for this study are being collected with an EDC 
system called Rave® provided by the technology vendor Medidata Solutions Incorporated, 
NY, USA.  The EDC system and the study-specific eCRFs will comply with Title 21 CFR 
Part 11.  The documentation related to the validation of the EDC system is available 


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through the vendor, Medidata, while the validation of the study-specific eCRFs will be 
conducted by AbbVie and will be maintained in the Trial Master File at AbbVie.
The investigator will document subject data in his/her own subject files.  These subject 
files will serve as source data for the study.  All eCRF data required by this protocol will 
be recorded by investigative site personnel in the EDC system.  All data entered into the 
eCRF will be supported by source documentation.
The investigator or an authorized member of the investigator's staff will make any 
necessary corrections to the eCRF.  All change information, including the date and person 
performing the corrections, will be available via the audit trail, which is part of the EDC 
system.  For any correction, a reason for the alteration will be provided.  The eCRFs will 
be reviewed periodically for completeness, legibility, and acceptability by AbbVie 
personnel (or their representatives).  AbbVie (or their representatives) will also be allowed 
access to all source documents pertinent to the study in order to verify eCRF entries.  The 
principal investigator will review the eCRFs for completeness and accuracy and provide 
his or her electronic signature and date to eCRFs as evidence thereof.
Medidata will provide access to the EDC system for the duration of the trial through a 
password-protected method of internet access.  Such access will be removed from 
investigator sites at the end of the site's participation in the study.  Data from the EDC 
system will be archived on appropriate data media (CD-ROM, etc.) and provided to the 
investigator at that time as a durable record of the site's eCRF data.  It will be possible for 
the investigator to make paper printouts from that media.
11.0
Data Quality Assurance
An initiation meeting will be held with AbbVie personnel, the investigator(s), and the 
study coordinators/project manager(s) prior to enrolling any subject in the study.  This 
meeting will include a detailed discussion and review of the protocol and essential 
documents, performance of study procedures, CRF completion, and specimen collection 
methods.


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The AbbVie monitor will monitor the study site throughout the study according to a 
monitoring plan.  Source document review will be made against entries in RAVE and a 
quality assurance check will be performed to ensure that the investigator is complying 
with the protocol and regulations.  During the study, an ongoing review of the data will be 
conducted by a physician or representative at AbbVie.
Computer logic and manual checks will be created to identify items such as inconsistent 
study dates.  Any necessary corrections will be made to the eCRF.
12.0
Use of Information
All information concerning ABBV-8E12 and AbbVie operations, such as AbbVie patent 
applications, formulas, manufacturing processes, basic scientific data, or formulation 
information, supplied by AbbVie and not previously published is considered confidential 
information.
The information developed during the conduct of this clinical study is also considered 
confidential and will be used by AbbVie in connection with the development of 
ABBV-8E12.  This information may be disclosed as deemed necessary by AbbVie to 
other clinical investigators, other pharmaceutical companies, and to governmental 
agencies.  To allow for the use of the information derived from this clinical study and to 
ensure complete and thorough analysis, the investigator is obligated to provide AbbVie 
with complete test results and all data developed in this study and to provide direct access 
to source data/documents for study-related monitoring, audits, IEC/IRB review, and 
regulatory inspection.
This confidential information shall remain the sole property of AbbVie, shall not be 
disclosed to others without the written consent of AbbVie, and shall not be used except in 
the performance of this study.
The investigator will maintain a confidential subject identification code list of all subjects 
enrolled in the study, including each subject's name, subject number, address, phone 
number and emergency contact information.  This list will be maintained at the study site 


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with other study records under adequate security and restricted access, and will not be 
retrieved by AbbVie.
Any research that may be done using research samples from this study will be 
experimental in nature and the results will not be suitable for clinical decision making or 
patient management.  Hence, the subject will not be informed of individual results, should 
analyses be performed, nor will anyone not directly involved in this research.  
Correspondingly, researchers will have no access to subject identifiers.  Individual results 
will not be reported to anyone not directly involved in this research other than for 
regulatory purposes.  Aggregate data from research may be provided to investigators and 
used in scientific publications or presented at medical conventions.  Research information 
will be published or presented only in a way that does not identify any individual subject.
13.0
Completion of the Study
The investigator will conduct the study in compliance with the protocol and complete the 
study within the timeframe specified in the contract between the investigator/designated 
person and AbbVie.  Continuation of this study beyond this date must be mutually agreed 
upon in writing by both the investigator/designated person and AbbVie.  The 
investigator/designated person will provide a final report to the IEC/IRB following 
conclusion of the study, and will forward a copy of this report to AbbVie or their 
representative.
The investigator/designated person must retain any records related to the study according 
to local requirements.  If the investigator/designated person is not able to retain the 
records, he/she must notify AbbVie to arrange alternative archiving options.
AbbVie will select the signatory coordinating investigator from the investigators who 
participate in each multicenter study.  Selection criteria for this signatory investigator will 
be based on level of participation, and significant knowledge of the clinical research, 
investigational drug, and study protocol.  The signatory investigator for the study will 


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review and sign the final study report in accordance with the European Medicines Agency 
(EMA) Guidance on Investigator's Signature for Study Reports.
The end of study is defined as the date of the last subject's last visit.


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14.0
Investigator's Agreement
1.
I have received and reviewed the Investigator's Brochure for ABBV-8E12.
2.
I have read this protocol and agree that the study is ethical.
3.
I agree to conduct the study as outlined and in accordance with all applicable 
regulations and guidelines.
4.
I agree to maintain the confidentiality of all information received or developed in 
connection with this protocol.
5.
I agree that all electronic signatures will be considered the equivalent of a 
handwritten signature and will be legally binding.
Protocol Title: 
An Extension Study of ABBV-8E12 in Progressive Supranuclear 
Palsy (PSP)
Protocol Date: 
21 February 2019
Signature of Principal Investigator
Date
Name of Principal Investigator (printed or typed)


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15.0
Reference List
1.
Golbe LI.  Progressive supranuclear palsy.  Semin Neurol.  2014;34(2):151-9.
2.
Houghton DJ, Litvan I.  Unraveling progressive supranuclear palsy:  from bedside 
back to the bench.  Parkinsonism Relat Disord.  2007;13 (Suppl 3):S341-6.
3.
Williams DR, Lees AJ.  Progressive supranuclear palsy:  clinicopathological 
concepts and diagnostic challenges.  Lancet Neurol.  2009;8(3):270-9.
4.
Schofield EC, Hodges JR, Bak TH, et al.  The relationship between clinical and 
pathological variables in Richardson's syndrome.  J Neurol.  2012;259(3):482-90.
5.
Litvan IY, Agid J, Jankovic C, et al.  Accuracy of clinical criteria for the diagnosis 
of progressive supranuclear palsy (Steele-Richardson-Olszewski Syndrome).  
Neurology.  1996;46(4):922-30.
6.
Stamelou MR, de Silva O, Arias-Carrión E, et al.  Rational therapeutic approaches 
to progressive supranuclear palsy.  Brain.  2010;133 (Pt 6):1578-90.
7.
Boxer AL, Lang AE, Grossman M, et al.  Davunetide in patients with progressive 
supranuclear palsy:  a randomised, double-blind, placebo-controlled phase 2/3 trial.  
Lancet Neurol.  2014;4422(14):1-10.
8.
Yanamandra KN, Kfoury H, Jiang TE, et al.  Anti-tau antibodies that block tau 
aggregate seeding in vitro markedly decrease pathology and improve cognition 
in vivo.  Neuron.  2013;80(2):402-14.
9.
Yanamandra K, Jiang H, Mahan TE, et al.  Anti-tau antibody reduces insoluble tau 
and decreases brain atrophy.  Ann Clin Trans Neurol.  2015;2(3):278-88.
10.
AbbVie.  ABBV-8E12 Investigator's Brochure Edition 1.  25 March 2016; 
Addendum 1 to the Investigator's Brochure Edition 1.  August 2016.
11.
Duits FH, Martinez-Lage P, Paquet C, et al.  Performance and complications of 
lumbar puncture in memory clinics:  results of the multicenter lumbar puncture 
feasibility study.  Alzheimer's Dement.  2016;12(2):154-63.


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12.
Hall DA, Forjaz MJ, Golbe LI, et al.  Scales to assess clinical features of 
progressive supranuclear palsy:  MDS Task Force Report.  Movement Disorders 
Clinical Practice.  2015;2(2):127-34.
13.
Tolosa E, Litvan I, Hölglinger GU, et al.  A phase 2 trial of the GSK-3 inhibitor 
tideglusib in progressive supranuclear palsy.  Mov Disord.  2014;29(4):470-8.
14.
Leclair-Visonneau L, Rouaud T, Debily B, et al.  Randomized placebo-controlled 
trial of sodium valproate in progressive supranuclear palsy.  Clinical Neurology 
and Neurosurgery.  146;(2016):35-9.
15.
Nuebling G, Hensler M, Paul S, et al.  PROSPERA:  a randomized, controlled trial 
evaluating rasagiline in progressive supranuclear palsy.  J Neurol.  
2016;263(8):1565-74.
16.
Golbe LI, Ohman-Strickland PA.  A clinical rating scale for progressive 
supranuclear palsy.  Brain.  2007;130(6):1552-62.
17.
Schwab RS, England AC.  Projection technique for evaluating surgery in 
Parkinson's disease.  In:  Gillingham FJ, Donaldson MC, eds.  Third symposium on 
Parkinson's disease.  Edinburgh. Livingston.  1969:152-7.
18.
Martinez-Martin P, Gil-Nagel A, Gracia LM, et al.  Unified Parkinson's disease 
rating scale characteristics and structure.  The Cooperative Multicentric Group.  
Mov Disord.  1994;9(1):76-83.
19.
Randolph C, Tierney MC, Mohr E, et al.  The Repeatable Battery for the 
Assessment of Neuropsychological Status (RBANS):  preliminary clinical validity.  
J Clin Exp Neuropsychol.  1998;20(3):310-9.
20.
Uchiyama CL, Mitrushina MN, D'Elia LF, et al.  Frontal lobe functioning in 
geriatric and nongeriactric samples:  an argument for multimodal analyses.  Arch 
Clin Neuropsychol.  1994;9(3):215-27.
21.
Shao Z, Janse E, Visser K, et al.  What do verbal fluency tasks measure?  
Predictors of verbal fluency performance in older adults.  Front Psychol.  
2014;5:772.


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22.
Payan C, Viallet F, Landwehrmeyer B, et al.  Disease severity and progression in 
progressive supranuclear palsy and multiple system atrophy:  validation of the 
NNIPPS--Parkinson Plus Scale.  PLoS One.  2011;6(8):1-12.
23.
Guy W.  ECDEU Assessment Manual for Psychopharmacology.  Revised 
Rockville, MD, US Department of Health, Education, and Welfare, Public Health 
Service, Alcohol, Drug Abuse, and Mental Health Administration, NIMH 
Psychopharmacology Research Brand, Division of Extramural Research.
24.
EuroQol Group.  EuroQol – a new facility for the measurement of health-related 
quality of life.  Health Policy.  Elsevier Science.  1990;16(3):199-208.
25.
Schrag A, Selai C, Quinn N, et al.  Measuring quality of life in progressive 
supranuclear palsy.  In:  Jenkinson C, Peters M, Bromberg M, eds.  Quality of Life 
Measurement in Neurodegenerative and Related Conditions.  Cambridge:  
Cambridge University Press.  2011;52-9.
26.
Columbia-Suicide Severity Rating Scale (C-SSRS) [homepage on the Internet].  
Columbia University Medical Center.  Available from:  
http//www.cssrs.columbia.edu/.
27.
Adams JL, Dinesh K, Xiong M, et al.  Multiple wearable sensors in Parkinson and 
Huntington disease individuals:  a pilot study in clinic and at home.  Digit 
Biomark.  2017;1:52-63.
28.
Reilly MC, Zbrozek AS, Dukes EM.  The validity and reproducibility of a work 
productivity and activity impairment instrument.  Pharmacoeconomics.  
1993;4(5):353-65.
29.
Pillas M, Selai C, Quinn NP, Lees A, et al.  Development and validation of a carers 
quality-of-life questionnaire for parkinsonism (PQoL Carers).  Qual Life Res.  
2016;25(1):81–8.
30.
Bharmal M, Payne K, Atkinson MJ, et al.  Validation of an abbreviated treatment 
satisfaction questionnaire for medication (TSQM-9) among patients on 
antihypertensive medications.  Health Qual Life Outcomes.  2009;7:36.


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31.
Liu-Seifert H, Andersen SW, Lipkovich I, et al.  A novel approach to delayed-start 
analyses for demonstrating disease-modifying effects in Alzheimer's disease.  PLoS 
One.  2015;10(3):1-16.
32.
Williams DR.  Tauopathies:  classification and clinical update on 
neurodegenerative diseases associated with microtubule-associated protein tau.  
J Intern Med J.  2006;36(10):652-60.


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Appendix A.
Responsibilities of the Clinical Investigator
Clinical research studies sponsored by AbbVie are subject to the Good Clinical Practices 
(GCP) and local regulations and guidelines governing the study at the site location.  In 
signing the Investigator Agreement in Section 14.0 of this protocol, the investigator is 
agreeing to the following:
1.
Conducting the study in accordance with the relevant, current protocol, making 
changes in a protocol only after notifying AbbVie, except when necessary to 
protect the safety, rights or welfare of subjects.
2.
Personally conducting or supervising the described investigation(s).
3.
Informing all subjects, or persons used as controls, that the drugs are being used for 
investigational purposes and complying with the requirements relating to informed 
consent and ethics committees (e.g., independent ethics committee (IEC) or 
institutional review board (IRB)) review and approval of the protocol and 
amendments.
4.
Reporting adverse experiences that occur in the course of the investigation(s) to 
AbbVie and the site director.
5.
Reading the information in the Investigator's Brochure/safety material provided, 
including the instructions for use and the potential risks and side effects of the 
investigational product(s).
6.
Informing all associates, colleagues, and employees assisting in the conduct of the 
study about their obligations in meeting the above commitments.
7.
Maintaining adequate and accurate records of the conduct of the study, making 
those records available for inspection by representatives of AbbVie and/or the 
appropriate regulatory agency, and retaining all study-related documents until 
notification from AbbVie.
8.
Maintaining records demonstrating that an ethics committee reviewed and 
approved the initial clinical investigation and all amendments.


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9.
Reporting promptly, all changes in the research activity and all unanticipated 
problems involving risks to human subjects or others, to the appropriate individuals 
(e.g., coordinating investigator, institution director) and/or directly to the ethics 
committees and AbbVie.
10.
Following the protocol and not making any changes in the research without ethics 
committee approval, except where necessary to eliminate apparent immediate 
hazards to human subjects.


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Appendix B.
List of Protocol Signatories
Name
Title
Functional Area
Clinical
Clinical
Clinical
Statistics
Statistics
Pharmacokinetics
Neuroscience Development
Bioanalysis
Medical Writing


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Appendix C.
Study Activities
Visits & Proceduresb
Treatment Perioda
20 Wks
Post Last 
Dose F/U
Year 1
Dose
1
Dose
2
Dose
3
Dose
4
Dose
5
Dose
6
Dose
7
Dose
8
Dose
9
Dose
10
Dose
11
Dose
12
Dose
13
Dose
14
Dose
15
D/C
Day
1
Day
15
Day
29
Day 
57
Day
85
Day
113
Day
141
Day
169
Day
197
Day
225
Day
253
Day
281
Day
309
Day
337
Day
365
Day
1
Wk
2
Wk
4
Wk
8
Wk
12
Wk
16
Wk
20
Wk
24
Wk
28
Wk
32
Wk
36
Wk
40
Wk
44
Wk
48
Wk
52
Subject/study partner ICFc
X
Medical history updated
X
Randomization
X
Physical examination
X
Symptom-driven physical 
examinatione
X
X
X
X
Orthostatic vital signsf,g
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital signsg
X
X
Body weight (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pregnancy test (WOCBP)h 
U
U
U
U
S
U
Neurological examination
X
X
X
X
X
X
12-lead ECG
X
X
X
X
X
Clinical laboratory tests
X
X
X
X
X
Brain MRIi
X
X
X
X
X
X
LP/CSF collectionj
X
X
X
X
X


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Visits & Proceduresb
Treatment Perioda
20 Wks
Post Last 
Dose F/U
Year 1
Dose
1
Dose
2
Dose
3
Dose
4
Dose
5
Dose
6
Dose
7
Dose
8
Dose
9
Dose
10
Dose
11
Dose
12
Dose
13
Dose
14
Dose
15
D/C
Day
1
Day
15
Day
29
Day 
57
Day
85
Day
113
Day
141
Day
169
Day
197
Day
225
Day
253
Day
281
Day
309
Day
337
Day
365
Day
1
Wk
2
Wk
4
Wk
8
Wk
12
Wk
16
Wk
20
Wk
24
Wk
28
Wk
32
Wk
36
Wk
40
Wk
44
Wk
48
Wk
52
Blood PK sample
X
X
X
X
X
X
ADA Sample collection
X
X
X
X
X
X
Plasma biomarkers
X
X
X
X
X
X
CSF biomarkers
X
X
X
X
X
Optional exploratory PGx DNA and 
RNA blood sample 
X
X
X
X
X
Administer IV Study Drug
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PSPRS
1
1
1
1
1
1
CGI-S
2
2
2
2
2
2
CGI-C
3
3
3
3
3
3
SEADL
4
4
4
4
4
4
UPDRS Part II
5
5
5
5
5
5
RBANS
6
6
CTT Parts 1 & 2
7
7
Letter Fluency Test (wpm)
8
8
NNIPPS-PPSk
9
9
PGI-Cl
X
X
X
X
X
X


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Visits & Proceduresb
Treatment Perioda
20 Wks
Post Last 
Dose F/U
Year 1
Dose
1
Dose
2
Dose
3
Dose
4
Dose
5
Dose
6
Dose
7
Dose
8
Dose
9
Dose
10
Dose
11
Dose
12
Dose
13
Dose
14
Dose
15
D/C
Day
1
Day
15
Day
29
Day 
57
Day
85
Day
113
Day
141
Day
169
Day
197
Day
225
Day
253
Day
281
Day
309
Day
337
Day
365
Day
1
Wk
2
Wk
4
Wk
8
Wk
12
Wk
16
Wk
20
Wk
24
Wk
28
Wk
32
Wk
36
Wk
40
Wk
44
Wk
48
Wk
52
EQ-5Dl
X
X
X
C-SSRSm
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
BioStamp Digitaln
X
X
X
X
PSP Caregiver Questionnaires
X
X
X
X
X
TSQM-9
X
X
X
X
X
Concomitant medication
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
AE assessment (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Telephone contacto
X
X
X
X
X
X
AE = adverse event; ICF = informed consent form; LP = lumbar puncture; PK = pharmacokinetic; PGx = pharmacogenetic; S = serum; U = urine
a.
Study drug will be administered on Days 1, 15, and 29, then every 28 days thereafter until 1 of the discontinuation criteria is met, until the Sponsor discontinues the study, or 
until the study reaches completion.  For those Visits that include both study drug infusion and other activities, the Visits may be completed over 2 consecutive days with the 
second day to include the start and end of the infusion.
b.
Audio recordings/central review of the administration/assessment of selected scales may be conducted.
c.
Subject informed consent, or as applicable, legally authorized representative informed consent, and study partner informed consent must be obtained prior to Study M15-563 
Day 1 dosing.
d.
Review medical history to confirm subject does not meet exclusion criteria prior to randomization.
e.
Additional symptom-driven physical examinations may be performed as needed.
f.
All supine and standing blood pressure and pulse rate measurements are to be measured as part of an orthostatic assessment.


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g.
An attempt should be made to obtain all vital sign measurements at the same time of day and using the same arm.
h.
For all females of childbearing potential, a negative urine pregnancy test result is also required prior to any radiological procedures.
i.
If a subject cannot undergo MRI due to a clinical reason, the AbbVie TA MD should be consulted for approval.
j.
Subjects who are not able to undergo an LP may be enrolled with permission of the AbbVie TA MD without the requirement of an LP during the study.
k.
The NNIPPS-PPS will not be administered in Japan.
l.
Scale may be administered/assessed at any time during the visit, after the other procedures are completed, with the exception of the scheduled infusion time.
m.
Scale may be administered/assessed at any time during the visit with the exception of the scheduled infusion time.
n.
Device to be worn for 7 days.
o.
Only applicable to subjects who prematurely discontinue.  Verify consent was obtained prior to making contact.
Note:
Numbering listed in the table provides a pre-defined order of administration that these scales should occur during each visit.


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Visits & Proceduresb
Treatment Perioda
Year 2
Dose
16
Dose
17
Dose
18
Dose
19
Dose
20
Dose
21
Dose
22
Dose
23
Dose
24
Dose
25
Dose
26
Dose
27
Dose
28
D/C
20 Wks
Post Last 
Dose F/U
Day
393
Day
421
Day
449
Day
477
Day
505
Day
533
Day
561
Day
589
Day
617
Day
645
Day
673
Day
701
Day
729
Wk
56
Wk
60
Wk
64
Wk
68
Wk
72
Wk
76
Wk
80
Wk
84
Wk
88
Wk
92
Wk
96
Wk
100
Wk
104
Symptom-driven physical examinationc
X
X
X
X
Vital signsd
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Body weight (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pregnancy test (WOCBP)e 
U
U
S
U
Neurological examination
X
X
X
X
12-lead ECG
X
X
Clinical laboratory tests
X
X
Brain MRIf
X
X
X
X
LP/CSF collection
X
X
X
X
Blood PK sample
X
X
X
X
ADA Sample collection
X
X
X
X
Plasma biomarkers
X
X
X
CSF biomarkers
X
X
X
X
Optional exploratory PGx DNA and RNA 
sample 
X
X
Administer IV Study Drug
X
X
X
X
X
X
X
X
X
X
X
X
X
PSPRS
1
1
1
1


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Visits & Proceduresb
Treatment Perioda
Year 2
Dose
16
Dose
17
Dose
18
Dose
19
Dose
20
Dose
21
Dose
22
Dose
23
Dose
24
Dose
25
Dose
26
Dose
27
Dose
28
D/C
20 Wks
Post Last 
Dose F/U
Day
393
Day
421
Day
449
Day
477
Day
505
Day
533
Day
561
Day
589
Day
617
Day
645
Day
673
Day
701
Day
729
Wk
56
Wk
60
Wk
64
Wk
68
Wk
72
Wk
76
Wk
80
Wk
84
Wk
88
Wk
92
Wk
96
Wk
100
Wk
104
CGI-S
2
2
2
2
CGI-C
3
3
3
3
SEADL
4
4
4
4
UPDRS Part II
5
5
5
5
RBANS
6
6
CTT Parts 1 & 2
7
7
Letter Fluency Test (wpm)
8
8
NNIPPS-PPSg
9
9
PGI-Ch
X
X
X
X
EQ-5Dh
X
X
C-SSRSi
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PSP Caregiver Questionnaires
X
X
X
X
TSQM-9
X
X
X
X
Concomitant medication 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
AE assessment (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Telephone contactj
X
X
X
X
AE = adverse event; LP = lumbar puncture; PK = pharmacokinetic; PGx = pharmacogenetic; S = serum; U = urine


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
116
a.
Study drug will be administered on Days 1, 15, and 29, then every 28 days thereafter until 1 of the discontinuation criteria is met, until the Sponsor discontinues the study, or 
until the study reaches completion.  For those Visits that include both study drug infusion and other activities, the Visits may be completed over 2 consecutive days with the 
second day to include the start and end of the infusion.
b.
Audio recordings/central review of the administration/assessment of selected scales may be conducted.
c.
Additional symptom-driven physical examinations may be performed as needed.
d.
An attempt should be made to obtain all vital sign measurements at the same time of day and using the same arm.
e.
For all females of childbearing potential, a negative urine pregnancy test result is also required prior to any radiological procedures.
f
If a subject cannot undergo MRI due to a clinical reason, the AbbVie TA MD should be consulted for approval.
g.
The NNIPPS-PPS will not be administered in Japan
h.
Scale may be administered/assessed at any time during the visit, after the other procedures are completed, with the exception of the scheduled infusion time.
i.
Scale may be administered/assessed at any time during the visit with the exception of the scheduled infusion time.
j.
Only applicable to subjects who prematurely discontinue.  Verify consent was obtained prior to making contact.
Note:
Numbering listed in the table provides a pre-defined order of administration that these scales should occur during each visit.


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
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Visits & Proceduresb
Treatment Perioda
20 Weeks
Post Last 
Dose F/U
Year 3
Dose
29
Dose
30
Dose
31
Dose
32
Dose
33
Dose
34
Dose
35
Dose
36
Dose
37
Dose
38
Dose
39
Dose
40
Dose
41
D/C
Day
757
Day
785
Day
813
Day
841
Day
869
Day
897
Day
925
Day
953
Day
981
Day
1009
Day
1037
Day
1065
Day
1093
Wk
108
Wk
112
Wk
116
Wk
120
Wk
124
Wk
128
Wk
132
Wk
136
Wk
140
Wk
144
Wk
148
Wk
152
Wk
156
Symptom-driven physical examinationc
X
X
X
X
Vital signsd
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Body weight ( prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pregnancy test (WOCBP)e 
U
U
S
U
Neurological examination
X
X
X
X
12-lead ECG
X
X
Clinical laboratory tests
X
X
Brain MRIf
X
X
X
X
LP/CSF collection
X
X
X
X
Blood PK sample
X
X
X
X
ADA Sample collection
X
X
X
X
Plasma biomarkers
X
X
X
CSF biomarkers
X
X
X
X
Optional exploratory PGx DNA and RNA 
sample 
X
X
Administer IV Study Drug
X
X
X
X
X
X
X
X
X
X
X
X
X
PSPRS
1
1
1
1


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
118
Visits & Proceduresb
Treatment Perioda
20 Weeks
Post Last 
Dose F/U
Year 3
Dose
29
Dose
30
Dose
31
Dose
32
Dose
33
Dose
34
Dose
35
Dose
36
Dose
37
Dose
38
Dose
39
Dose
40
Dose
41
D/C
Day
757
Day
785
Day
813
Day
841
Day
869
Day
897
Day
925
Day
953
Day
981
Day
1009
Day
1037
Day
1065
Day
1093
Wk
108
Wk
112
Wk
116
Wk
120
Wk
124
Wk
128
Wk
132
Wk
136
Wk
140
Wk
144
Wk
148
Wk
152
Wk
156
CGI-S
2
2
2
2
CGI-C
3
3
3
3
SEADL
4
4
4
4
UPDRS Part II
5
5
5
5
RBANS
6
6
CTT Parts 1 & 2
7
7
Letter Fluency Test (wpm)
8
8
NNIPPS-PPSg
9
9
PGI-Ch
X
X
X
X
EQ-5Dh
X
X
C-SSRSi
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PSP Caregiver Questionnaires
X
X
X
X
TSQM-9
X
X
X
X
Concomitant medication 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
AE assessment (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Telephone contactj
X
X
X
X
AE = adverse event; LP = lumbar puncture; PK = pharmacokinetic; PGx = pharmacogenetic; S = serum; U = urine


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
119
a.
Study drug will be administered on Days 1, 15, and 29, then every 28 days thereafter until 1 of the discontinuation criteria is met, until the Sponsor discontinues the study, or 
until the study reaches completion.  For those Visits that include both study drug infusion and other activities, the Visits may be completed over 2 consecutive days with the 
second day to include the start and end of the infusion.
b.
Audio recordings/central review of the administration/assessment of selected scales may be conducted.
c.
Additional symptom-driven physical examinations may be performed as needed.
d.
An attempt should be made to obtain all vital sign measurements at the same time of day and using the same arm.
e.
For all females of childbearing potential, a negative urine pregnancy test result is also required prior to any radiological procedures.
f.
If a subject cannot undergo MRI due to a clinical reason, the AbbVie TA MD should be consulted for approval.
g.
The NNIPPS-PPS will not be administered in Japan
h.
Scale may be administered/assessed at any time during the visit, after the other procedures are completed, with the exception of the scheduled infusion time.
i.
Scale may be administered/assessed at any time during the visit with the exception of the scheduled infusion time.
j.
Only applicable to subjects who prematurely discontinue.  Verify consent was obtained prior to making contact.
Note:
Numbering listed in the table provides a pre-defined order of administration that these scales should occur during each visit.


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
120
Visits & Proceduresb
Treatment Perioda
20 Weeks
Post Last 
Dose F/U
Year 4
Dose
42
Dose
43
Dose
44
Dose
45
Dose
46
Dose
47
Dose
48
Dose
49
Dose
50
Dose
51
Dose
52
Dose
53
Dose
54
D/C
Day
1121
Day
1149
Day
1177
Day
1205
Day
1233
Day
1261
Day
1289
Day
1317
Day
1345
Day
1373
Day
1401
Day
1429
Day
1457
Wk
160
Wk
164
Wk
168
Wk
172
Wk
176
Wk
180
Wk
184
Wk
188
Wk
192
Wk
196
Wk
200
Wk
204
Wk
208
Symptom-driven physical examinationc
X
X
X
X
Vital signsd
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Body weight (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pregnancy test (WOCBP)e 
U
U
S
U
Neurological examination
X
X
X
X
12-lead ECG
X
X
Clinical laboratory tests
X
X
Brain MRIf
X
X
X
X
LP/CSF collection
X
X
X
X
Blood PK sample
X
X
X
X
ADA Sample collection
X
X
X
X
Plasma biomarkers
X
X
X
CSF biomarkers
X
X
X
X
Optional exploratory PGx DNA and RNA 
sample 
X
X
Administer IV Study Drug
X
X
X
X
X
X
X
X
X
X
X
X
X
PSPRS
1
1
1
1


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
121
Visits & Proceduresb
Treatment Perioda
20 Weeks
Post Last 
Dose F/U
Year 4
Dose
42
Dose
43
Dose
44
Dose
45
Dose
46
Dose
47
Dose
48
Dose
49
Dose
50
Dose
51
Dose
52
Dose
53
Dose
54
D/C
Day
1121
Day
1149
Day
1177
Day
1205
Day
1233
Day
1261
Day
1289
Day
1317
Day
1345
Day
1373
Day
1401
Day
1429
Day
1457
Wk
160
Wk
164
Wk
168
Wk
172
Wk
176
Wk
180
Wk
184
Wk
188
Wk
192
Wk
196
Wk
200
Wk
204
Wk
208
CGI-S
2
2
2
2
CGI-C
3
3
3
3
SEADL
4
4
4
4
UPDRS Part II
5
5
5
5
RBANS
6
6
CTT Parts 1 & 2
7
7
Letter Fluency Test (wpm)
8
8
NNIPPS-PPSg
9
9
PGI-Ch
X
X
X
X
EQ-5Dh
X
X
C-SSRSi
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PSP Caregiver Questionnaires
X
X
X
X
TSQM-9
X
X
X
X
Concomitant medication 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
AE assessment (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Telephone contactj
X
X
X
X
AE = adverse event; LP = lumbar puncture; PK = pharmacokinetic; PGx = pharmacogenetic; S = serum; U = urine


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
122
a.
Study drug will be administered on Days 1, 15, and 29, then every 28 days thereafter until 1 of the discontinuation criteria is met, until the Sponsor discontinues the study, or 
until the study reaches completion.  For those Visits that include both study drug infusion and other activities, the Visits may be completed over 2 consecutive days with the 
second day to include the start and end of the infusion.
b.
Audio recordings/central review of the administration/assessment of selected scales may be conducted.
c.
Additional symptom-driven physical examinations may be performed as needed.
d.
An attempt should be made to obtain all vital sign measurements at the same time of day and using the same arm.
e.
For all females of childbearing potential, a negative urine pregnancy test result is also required prior to any radiological procedures.
f.
If a subject cannot undergo MRI due to a clinical reason, the AbbVie TA MD should be consulted for approval.
g.
The NNIPPS-PPS will not be administered in Japan.
h.
Scale may be administered/assessed at any time during the visit, after the other procedures are completed, with the exception of the scheduled infusion time.
i.
Scale may be administered/assessed at any time during the visit with the exception of the scheduled infusion time.
j.
Only applicable to subjects who prematurely discontinue.  Verify consent was obtained prior to making contact.
Note:
Numbering listed in the table provides a pre-defined order of administration that these scales should occur during each visit.


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
123
Visits & Proceduresb
Treatment Perioda
Year 5
Dose
55
Dose
56
Dose
57
Dose
58
Dose
59
Dose
60
Dose
61
Dose
62
Dose
63
Dose
64
Dose
65
Dose
66/
Final
No
Dose
20 
Weeks
Post 
Last 
Dose 
F/U
Day
1485
Day
1513
Day
1541
Day
1569
Day
1597
Day
1625
Day
1653
Day
1681
Day
1709
Day
1737
Day
1765
Day
1793
Day
1821
Wk
212
Wk
216
Wk
220
Wk
224
Wk
228
Wk
232
Wk
236
Wk
240
Wk
244
Wk
248
Wk
252
Wk
256
Wk
260
D/C
Symptom-driven physical examinationc
X
X
X
X
Vital signsd
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Body weight (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pregnancy test (WOCBP)e 
U
S
S
U
Neurological examination
X
X
X
X
12-lead ECG
X
X
Clinical laboratory tests
X
X
Brain MRIf
X
X
X
X
LP/CSF collection
X
X
X
X
Blood PK sample
X
X
X
X
ADA Sample collection
X
X
X
X
Plasma biomarkers
X
X
X
CSF biomarkers
X
X
X
X
Optional exploratory PGx DNA and RNA 
sample 
X
X
Administer IV Study Drug
X
X
X
X
X
X
X
X
X
X
X
X


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
124
Visits & Proceduresb
Treatment Perioda
Year 5
Dose
55
Dose
56
Dose
57
Dose
58
Dose
59
Dose
60
Dose
61
Dose
62
Dose
63
Dose
64
Dose
65
Dose
66/
Final
No
Dose
20 
Weeks
Post 
Last 
Dose 
F/U
Day
1485
Day
1513
Day
1541
Day
1569
Day
1597
Day
1625
Day
1653
Day
1681
Day
1709
Day
1737
Day
1765
Day
1793
Day
1821
Wk
212
Wk
216
Wk
220
Wk
224
Wk
228
Wk
232
Wk
236
Wk
240
Wk
244
Wk
248
Wk
252
Wk
256
Wk
260
D/C
PSPRS
1
1
1
1
CGI-S
2
2
2
2
CGI-C
3
3
3
3
SEADL
4
4
4
4
UPDRS Part II
5
5
5
5
RBANS
6
6
CTT Parts 1 & 2
7
7
Letter Fluency Test (wpm)
8
8
NNIPPS-PPSg
9
9
PGI-Ch
X
X
X
X
EQ-5Dh
X
X
C-SSRSi
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PSP Caregiver Questionnaires
X
X
X
X
TSQM-9
X
X
X
X
Concomitant medication 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
AE assessment (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
125
Visits & Proceduresb
Treatment Perioda
Year 5
Dose
55
Dose
56
Dose
57
Dose
58
Dose
59
Dose
60
Dose
61
Dose
62
Dose
63
Dose
64
Dose
65
Dose
66/
Final
No
Dose
20 
Weeks
Post 
Last 
Dose 
F/U
Day
1485
Day
1513
Day
1541
Day
1569
Day
1597
Day
1625
Day
1653
Day
1681
Day
1709
Day
1737
Day
1765
Day
1793
Day
1821
Wk
212
Wk
216
Wk
220
Wk
224
Wk
228
Wk
232
Wk
236
Wk
240
Wk
244
Wk
248
Wk
252
Wk
256
Wk
260
D/C
Telephone contactj
X
X
X
X
AE = adverse event; LP = lumbar puncture; PK = pharmacokinetic; PGx = pharmacogenetic; S = serum; U = urine
a.
Study drug will be administered on Days 1, 15, and 29, then every 28 days thereafter until 1 of the discontinuation criteria is met, until the Sponsor discontinues the study, or 
until the study reaches completion.  For those Visits that include both study drug infusion and other activities, the Visits may be completed over 2 consecutive days with the 
second day to include the start and end of the infusion.
b.
Audio recordings/central review of the administration/assessment of selected scales may be conducted.
c.
Additional symptom-driven physical examinations may be performed as needed.
d.
An attempt should be made to obtain all vital sign measurements at the same time of day and using the same arm.
e.
For all females of childbearing potential, a negative urine pregnancy test result is also required prior to any radiological procedures.
f.
If a subject cannot undergo MRI due to a clinical reason, the AbbVie TA MD should be consulted for approval.
g.
The NNIPPS-PPS will not be administered in Japan.
h.
Scale may be administered/assessed at any time during the visit, after the other procedures are completed, with the exception of the scheduled infusion time.
i.
Scale may be administered/assessed at any time during the visit with the exception of the scheduled infusion time.
j.
Only applicable to subjects who prematurely discontinue.  Verify consent was obtained prior to making contact.
Note:
Numbering listed in the table provides a pre-defined order of administration that these scales should occur during each visit.












ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
131
Appendix E.
Protocol Amendment:  List of Changes
The summary of changes is listed in Section 1.1.
Specific Protocol Changes
Section 1.0  Title Page
"Sponsor/Emergency Contact:" previously read:
Sponsor/Emergency
Contact:
Medical Director
Neuroscience Development
AbbVie Deutschland GmbH 
& Co. KG
Knollstrasse
67061 Ludwigshafen
Germany
Phone:
Fax:
Has been changed to read:
Sponsor/Emergency
Contact:
Medical Director
Neuroscience Development
1 North Waukegan Road
North Chicago, IL 60064
Phone:
Fax:
Cell:
Section 1.2  Synopsis
Subsection Objectives:
Third paragraph
Add:  new last bullet
To assess body position and gait in a subset of participating subjects using BioStamp 
digital sensors.


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
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Section 1.2  Synopsis
Subsection Methodology:
Third paragraph
Add:  new last sentence
In a subset of subjects (up to 50) at participating sites, subjects will be assigned digital 
sensor BioStamp units to be worn for 1-week epochs starting on Day 1, Day 29 (Week 4), 
Day 57 (Week 8), and Day 85 (Week 12).
Section 1.2  Synopsis
Subsection Diagnosis and Main Criteria for Inclusion/Exclusion:
Heading "Main Inclusion Criteria:"
Last bullet, first sentence previously read:
Subject voluntarily signed the Independent Ethics Committee (IEC)/Institutional Review 
Board (IRB) approved Informed Consent Form, prior to the conduct of any study 
procedures, or, where applicable (i.e., countries other than Germany*) for a given subject,
the subject's legally authorized representative (LAR) signed the IEC/IRB approved 
Informed Consent form on behalf of the subject and the subject signed the IEC/IRB 
approved assent form, prior to the conduct of any procedures.  
Has been changed to read:
Subject voluntarily signed the Independent Ethics Committee (IEC)/Institutional Review 
Board (IRB) approved Informed Consent Form, prior to the conduct of any study 
procedures, or, where applicable (i.e., countries other than Germany*) for a given subject, 
the subject's legally authorized representative (LAR) signed the IEC/IRB approved 
Informed Consent form on behalf of the subject, prior to the conduct of any procedures.  
Section 1.2  Synopsis
Subsection Criteria for Evaluation:
Heading "Digital Biomarkers:"
Add:  new heading and text
Digital Biomarkers:
●
BioStamp sensor motor outcomes including posture, gait, and step count


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
133
Section 1.2  Synopsis
Subsection Statistical Methods:
Heading "Biomarkers:"
Add:  new last sentence
Digital substudy endpoints will be handled in a separate scientific report.
Section 1.2  Synopsis
Subsection Statistical Methods:
Heading "Safety:"
First sentence previously read:
Adverse events will be coded using the most current version of the Medical Dictionary for 
Regulatory Activities (MedDRA).  
Has been changed to read:
Adverse events will be coded using the current version of the Medical Dictionary for 
Regulatory Activities (MedDRA).  
Section 3.0  Introduction
Subsection Clinical Experience
Heading "Phase 2 Multiple-Dose Study in Subjects with PSP"
Last sentence previously read:
A total of 330 subjects (220 on ABBV-8E12 and 110 on placebo) are planned.
Has been changed to read:
A total of 378 subjects are planned.
Section 4.0  Study Objectives
Third paragraph
Add:  new last bullet
To assess body position and gait in a subset of participating subjects using BioStamp 
digital sensors.


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
134
Section 5.1  Overall Study Design and Plan:  Description
Subsection Overview
First paragraph, third sentence previously read:
Study M15-562 was designed to randomize approximately 330 subjects to meet scientific 
and regulatory objectives without enrolling an undue number of subjects in alignment 
with ethical considerations.  
Has been changed to read:
Study M15-562 was designed to randomize 378 subjects to meet scientific and regulatory 
objectives without enrolling an undue number of subjects in alignment with ethical 
considerations.  
Section 5.1  Overall Study Design and Plan:  Description
Subsection Overview
Fourth paragraph, fourth sentence previously read:
The rate of infusion for each subject will be based upon that subject's most recently 
obtained weight and will range from 2.0 to 2 .7 mL/min (125 to 166 mL/hr) (refer to 
Section 5.5.1 for details on infusion rates).  
Has been changed to read:
The rate of infusion for each subject will be based upon that subject's most recently 
obtained weight and will range from 3.5 to 4.7 mL/min (210 to 282 mL/hr) (refer to 
Section 5.5.1 for details on infusion rates).  
Section 5.1  Overall Study Design and Plan:  Description
Subsection Overview
Last paragraph
Add:  new last sentence
In a subset of subjects (up to 50) at participating sites, subjects will be assigned digital 
sensor BioStamp units to be worn for 1 week epochs starting on Day 1, Day 29 (Week 4), 
Day 57 (Week 8), and Day 85 (Week 12).


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Section 5.2.1  Inclusion Criteria
Criterion 1
First sentence previously read:
The subject voluntarily signed the Independent Ethics Committee (IEC)/Institutional 
Review Board (IRB) approved Informed Consent form, prior to the conduct of any study 
procedures, or, where applicable (i.e., countries other than Germany*) for a given subject, 
the subject's legally authorized representative (LAR) signed the IEC/IRB approved 
Informed Consent form on behalf of the subject and the subject signed the Independent 
IEC/IRB approved assent form, prior to the conduct of any procedures.  
Has been changed to read:
The subject voluntarily signed the Independent Ethics Committee (IEC)/Institutional 
Review Board (IRB) approved Informed Consent form, prior to the conduct of any study 
procedures, or, where applicable (i.e., countries other than Germany*) for a given subject, 
the subject's legally authorized representative (LAR) signed the IEC/IRB approved 
Informed Consent form on behalf of the subject, prior to the conduct of any procedures.  
Section 5.3.1.1.9  12-Lead Electrocardiogram
Subsection Procedure
Third paragraph
First bullet, sub-bullet previously read:
Pre-dose (just prior to pre-infusion PK sample collection and the start of infusion) and 
within 15 minutes after the end of infusion prior to the PK sample collection)
Has been changed to read:
Pre-dose (just prior to pre-infusion PK sample collection and the start of infusion)


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Section 5.3.1.1.11  Magnetic Resonance Imaging
First paragraph
Delete:  last sentence
The study entry MRI should be completed after all other relevant study entry procedures 
(except lumbar puncture) have been completed and reviewed by the investigator.
Section 5.3.1.1.11  Magnetic Resonance Imaging
Second paragraph, first sentence previously read:
The Day 1 MRI assessment will be used to rule out the presence of any intracranial 
masses that might preclude the subject from undergoing a lumbar puncture, and exclude 
focal or diffuse processes that could indicate a clinically significant neurologic disorder 
other than PSP, including signal abnormalities on fluid attenuated inversion recovery 
(FLAIR) or T2 weighted images consistent with infectious, vascular, neoplastic or other 
degenerative processes.  
Has been changed to read:
The Day 1 MRI assessment will be used to rule out the presence of any intracranial 
masses and exclude focal or diffuse processes that could indicate a clinically significant 
neurologic disorder other than PSP, including signal abnormalities on fluid attenuated 
inversion recovery (FLAIR) or T2 weighted images consistent with infectious, vascular, 
neoplastic or other degenerative processes.  
Section 5.3.1.1.11  Magnetic Resonance Imaging
Sixth paragraph
Add:  new last sentence
If a subject cannot undergo MRI due to clinical reasons, the AbbVie TA MD should be 
consulted for approval.


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Section 5.3.1.1.12  Lumbar Puncture
First paragraph, last sentence previously read:
The lumbar puncture on Day 1 must be done after all other entry criteria have been 
satisfied, and the lumbar puncture at completion (Week 260) or premature discontinuation 
should only be done if at least 3 months have elapsed since the previous lumbar puncture.
Has been changed to read:
Lumbar puncture on Day 1 and lumbar puncture at completion (Week 260) or premature 
discontinuation should only be done if at least 3 months have elapsed since the previous 
lumbar puncture.
Section 5.3.1.1.12  Lumbar Puncture
Add:  new third paragraph
Subjects who are not able to undergo an LP may be enrolled with permission of the 
AbbVie TA MD without the requirement of an LP during the study.


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Table 3.  Diagnostic Tools and Scale Order, and Duration of Administration
Previously read:
Diagnostic Tools
and Scalesa,b
Approx. 
Duration 
(min)
S/SP
Treatment Period
20 Weeks 
Post Last 
Dose F/U
Year 1
Year 2
Year 3
Year 4
Year 5
Day
1c
Wk
12
Wk
24
Wk
52
Wk
76
Wk
104
Wk
128
Wk
156
Wk
180
Wk
208
Wk
232
Wk 260
Completion/
Premature D/C
PSPRS
10
S and SP
1
1
1
1
1
1
1
1
1
1
1
1
1
CGI-S
40 – 60
S
2
2
2
2
2
2
2
2
2
2
2
2
2
CGI-C
1
S
3
3
3
3
3
3
3
3
3
3
3
3
3
SEADL
2
S
4
4
4
4
4
4
4
4
4
4
4
4
4
UPDRS Part II
10
S
5
5
5
5
5
5
5
5
5
5
5
5
5
RBANS
25
S
6
6
6
6
6
CTT Parts 1 & 2
5 – 10
S
7
7
7
7
7
Letter Fluency Test (wpm)
1
S
8
8
8
8
8
NNIPPS-PPSd
30 – 45
S and SP
9
9
9
9
9
PGI-Ce
1 – 2
S
X
X
X
X
X
X
X
X
X
X
X
X
X
EQ-5De
8
S
X
X
X
X
X
X
C-SSRS (at every visit prior to 
infusion)
< 5
S
X
X
X
X
X
X
X
X
X
X
X
X
X
Approx = approximately; CGI-C = Clinical Global Impression of Change; CGI-S = Clinical Global Impression of Severity; C-SSRS = Columbia-Suicide Severity Rating Scale; 
CTT = Color Trails Test; D/C = discontinuation; EQ-5D = EuroQol-5D; F/U = follow-up; min = minutes; NNIPPS-PPS = National Institute of Neurological Disorders and the 
Society for Progressive Supranuclear Palsy; PGI-C = Patient Global Impression of Change; RBANS = Repeatable Battery for Assessment of Neuropsychological Status; 
S = subject; SEADL = Schwab and England Activities of Daily Living Scale; SP = study partner; UPDRS = Unified Parkinson's Disease Rating Scale; Wk = week; wpm = words 
per minute


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a.
Numbering listed in the table provides a pre-defined order of administration that should occur during each visit.
b.
Audio recordings/central review of the administration/assessment of selected scales may be conducted.
c.
Assess prior to randomization and the first dose of study drug.
d.
The NNIPPS-PPS will not be administered in Japan.
e.
Scale may be administered/assessed at any time during the visit, after the other procedures are completed, with the exception of the scheduled infusion time.


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Has been changed to read:
Diagnostic Tools
and Scalesa,b
Approx. 
Duration 
(min)
S/SP
Treatment Period
20 Weeks 
Post Last 
Dose F/U
Year 1
Year 2
Year 3
Year 4
Year 5
Day
1c
Wk
12
Wk
24
Wk
52
Wk
76
Wk
104
Wk
128
Wk
156
Wk
180
Wk
208
Wk
232
Wk 260
Completion/
Premature D/C
PSPRS
10
S and SP
1
1
1
1
1
1
1
1
1
1
1
1
1
CGI-S
40 – 60
S and SP
2
2
2
2
2
2
2
2
2
2
2
2
2
CGI-C
1
S and SP
3
3
3
3
3
3
3
3
3
3
3
3
3
SEADL
2
S
4
4
4
4
4
4
4
4
4
4
4
4
4
UPDRS Part II
10
S
5
5
5
5
5
5
5
5
5
5
5
5
5
RBANS
25
S
6
6
6
6
6
CTT Parts 1 & 2
5 – 10
S
7
7
7
7
7
Letter Fluency Test (wpm)
1
S
8
8
8
8
8
NNIPPS-PPSd
30 – 45
S and SP
9
9
9
9
9
PGI-Ce
1 – 2
S
X
X
X
X
X
X
X
X
X
X
X
X
X
EQ-5De
8
S
X
X
X
X
X
X
C-SSRS (at every visit)f
< 5
S
X
X
X
X
X
X
X
X
X
X
X
X
X
BioStamp nPointg
S
X
X
PSP Caregiver Questionnaires
25
SP
X
X
X
X
X
X
X
X
X
X
X
X
TSQM-9
5 
S
X
X
X
X
X
X
X
X
X
X
X
X


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Approx = approximately; CGI-C = Clinical Global Impression of Change; CGI-S = Clinical Global Impression of Severity; C-SSRS = Columbia-Suicide Severity Rating Scale; 
CTT = Color Trails Test; D/C = discontinuation; EQ-5D = EuroQol-5D; F/U = follow-up; min = minutes; NNIPPS-PPS = National Institute of Neurological Disorders and the 
Society for Progressive Supranuclear Palsy; PGI-C = Patient Global Impression of Change; RBANS = Repeatable Battery for Assessment of Neuropsychological Status; 
S = subject; SEADL = Schwab and England Activities of Daily Living Scale; SP = study partner; TSQM-9 = Treatment Satisfaction Questionnaire for Medication; 
UPDRS = Unified Parkinson's Disease Rating Scale; Wk = week; wpm = words per minute
a.
Numbering listed in the table provides a pre-defined order of administration that should occur during each visit.
b.
Audio recordings/central review of the administration/assessment of selected scales may be conducted.
c.
Assess prior to randomization and the first dose of study drug.
d.
The NNIPPS-PPS will not be administered in Japan.
e.
Scale may be administered/assessed at any time during the visit, after the other procedures are completed, with the exception of the scheduled infusion time.
f.
Scale may be administered/assessed at any time during the visit with the exception of the scheduled infusion time.
g.
BioStamp nPoint will also be administered at Weeks 4 and 8.


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Section 5.3.1.1.13  Diagnostic Tools and Rating Scales
Subsection Schwab and England Activities of Daily Living Scale
Subsection title previously read:
Schwab and England Activities of Daily Living Scale
Has been changed to read:
Schwab and England Activities of Daily Living Scale17
Section 5.3.1.1.13  Diagnostic Tools and Rating Scales
Subsection BioStamp nPoint (for subjects participating in the substudy only)27
Add:  new subsection title and text
BioStamp nPoint (for subjects participating in the substudy only)27
BioStamp nPoint is an FDA 510(k)-cleared medical device designed to collect medical 
grade, clinical quality biometric, physiologic, and other electronic clinical outcome 
assessment (eCOA) data in a clinical trial setting.  The system processes raw data into 
recognizable clinical metrics including heart rate, activity and posture classification, 
surface electromyography (sEMG), and sleep metrics.  The sensors are multi-modal, 
multi-location, rechargeable, and reusable.  BioStamp data are processed and stored in a 
secure cloud that can be synchronized with third-party electronic data capture (EDC) and 
clinical trial management (CTM) systems.
Three BioStamp sensor locations (left precordial chest, anterior thigh, and small of back) 
will be used in the study, and will capture information on heart rate, sleep, and measures 
of motor activity including posture, gait, and step count.  Subjects will be trained during a 
clinic visit how to use the system including how to apply and remove sensors and how to 
upload data.  Detailed laboratory manuals will be provided to participating sites.


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Section 5.3.1.1.13  Diagnostic Tools and Rating Scales
Subsection PSP Caregiver Questionnaires28,29
Add:  new subsection title and text
PSP Caregiver Questionnaires28,29
The PSP caregiver questionnaire assesses the burden of caregivers, their work 
productivity, and health resource use, as well as quality of life.  The questionnaire consists 
of both questions specifically developed for this study as well as validated scales.  
Caregivers will complete the following sections of the questionnaire at scheduled visits 
during the study:
●
Caregiver Information:  This section gathers caregiver's basic demographic 
information such as age, gender, ethnicity, and household information.  It takes 
approximately 2 minutes to complete.
●
Caring for Someone with PSP:  This section contains a list of questions to 
capture the relationship between the caregiver and the person with PSP, the 
living arrangement, and the amount of time spent on caring.  In addition, it 
measures how frequently the caregiver helps with daily activities.  It takes 
approximately 5 minutes to administer this section.
●
Caregiver Work Productivity and Status:  Caregiver Work Productivity is 
measured by (Work Productivity and Activity Impairment Questionnaire 
[WPAI]).  The WPAI caregiver version is a validated 6-question instrument to 
measure impairments in work and activities.  The first 4 questions measure 
employment status and hours missed from work, and the last 2 questions 
measure the impact of caregiving on work productivity and daily activities on 
a 0 - 10 scale.  In addition to WPAI, there are 2 additional questions measuring 
the caregiver's work status and if the reason of unemployment is related to 
caregiving.  It takes approximately 5 minutes to administer the questionnaire.
●
Caregiver Healthcare Resource Use:  This section assesses the caregiver's 
general health as well as their health resource use in terms of number of 
physician, ER visits, hospitalization, and length of stay for each 
hospitalization.  It takes approximately 5 minutes to administer this section.


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●
Caregiver Quality of Life (carers quality-of-life questionnaire for PSP [PQoL 
Carers]):  PQoL Carers is a QoL instrument for carers of people with atypical 
parkinsonism (AP), including PSP and MSA.  The 26-item instrument was 
generated from in-depth interviews with carers of patients with AP and a 
thorough review of the existing literature and consultation with movement 
disorder experts.  The items are scored from 0 (no problem) to 4 (extreme 
problems).  It is a concise instrument with adequate psychometric qualities.  
Convergent and concurrent validity was supported by correlations of PQoL 
Carers with the patient's health status and QoL measures such as The 
Parkinson's Disease Questionnaire-39 (PDQ-39) and EQ-5D, as well as carers' 
measures, such as Caregiver Burden Inventory (CBI) and carer EQ-5D.  The 
discriminant validity of the scale was demonstrated through its capacity to 
differentiate between carers with varying levels of self-reported health.  It 
takes approximately 8 minutes to administer the questionnaire.
Section 5.3.1.1.13  Diagnostic Tools and Rating Scales
Subsection Treatment Satisfaction Questionnaires for Medication30
Add:  new subsection title and text
Treatment Satisfaction Questionnaire for Medication30
The Treatment Satisfaction Questionnaire for Medication (TSQM-9) assesses patient 
satisfaction with medication in 3 domains:  effectiveness (3 items), convenience (3 items), 
and global satisfaction (3 items).  Each item is scored on a 7- or 5-point Likert scale.  The 
total score in each domain is converted to a score between 0 and 100, with higher scores 
indicating greater satisfaction with treatment.  It takes approximately 5 minutes to 
complete the questionnaire.
Section 5.3.1.2.1  Biomarker Samples
Last paragraph
Add:  new last sentence
Details for collection and processing are provided in a separate laboratory manual.


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Section 5.3.6.1  Biomarker Research Variables
Add:  new last bullet and sub-bullet
●
Digital Biomarkers:
○
BioStamp sensor motor outcomes including posture, gait, and step count
Section 5.3.6.1  Biomarker Research Variables
Add:  new last paragraph
Digital substudy endpoints will be handled in a separate scientific report.
Section 5.4.1  Discontinuation of Individual Subjects
Add:  new last paragraph
Subjects who prematurely discontinue from the study can be contacted by telephone for 
periodic updates at the times shown in Appendix C providing that consent for this contact 
was obtained prior to contact being made.
Section 5.5.1  Treatments Administered
First table previously read:
Subject's Weight in kg/lbs
Infusion Rateb
44 – 49 kg (97 – 109 lbs, inclusive)a
2.0 mL/min or 125 mL/hr
50 – 58 kg (110 – 128 lbs, inclusive) 
2.3 mL/min or 142 mL/hr
59 kg and over (129 lbs and over)
2.7 mL/min or 166 mL/hr
a.
Subjects who weigh less than 44 kg (97 lbs.) will be excluded from enrollment (refer to exclusion criteria, 
Section 5.2.2, Exclusion Criterion 1).
b.
Continue infusion until bag is empty.


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Has been changed to read:
Subject's Weight in kg/lbs
Infusion Rateb
44 – 49 kg (97 – 109 lbs, inclusive)a
3.5 mL/min or 210 mL/hr
50 – 58 kg (110 – 128 lbs, inclusive) 
4.0 mL/min or 240 mL/hr
59 kg and over (129 lbs and over)
4.7 mL/min or 282 mL/hr
a.
Subjects who weigh less than 44 kg (97 lbs.) will be excluded from enrollment (refer to exclusion criteria, 
Section 5.2.2, Exclusion Criterion 1).
b.
Continue infusion until bag is empty.
Section 5.5.2.2  Storage and Disposition of Study Drug
Third paragraph, third and fourth sentence previously read:
Malfunctions or any temperature excursion must be reported to the Sponsor immediately 
using the AbbVie Temperature Excursion Management System (ATEMS).  Study drug 
should be quarantined and not dispensed until AbbVie (ATEMS) deems the drug as 
acceptable.
Has been changed to read:
Malfunctions or temperature excursion must be reported to the Sponsor immediately 
using the AbbVie Temperature Excursion Management System (ATEMS).  Study drug 
should be quarantined and not dispensed until ATEMS deems the drug as acceptable.


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Section 6.1.5  Adverse Event Reporting
"Primary TA MD:" previously read:
Medical Director
Neuroscience Development
AbbVie Deutschland GmbH & Co. KG
Knollstrasse
67061 Ludwigshafen
Germany
Telephone Contact Information:
Phone:
Cell:
Email:
Has been changed to read:
Medical Director
Neuroscience Development
1 North Waukegan Road
North Chicago, IL 60064
Telephone Contact Information:
Phone:
Cell:
Email:
Section 6.1.7.5  Management of Adverse Events of the Nervous System
First paragraph, last sentence previously read:
A drug related adverse event is an adverse that is judged by the investigator or AbbVie to 
have a "reasonable possibility" of being related to the study drug.


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Has been changed to read:
A drug related adverse event is an event that is judged by the investigator or AbbVie to 
have a "reasonable possibility" of being related to the study drug.
Section 6.2.2  Reporting
First paragraph, first sentence previously read:
Product Complaints concerning the investigational product must be reported to the 
Sponsor within 24 hours of the study site's knowledge of the event via the Product 
Complaint form.  
Has been changed to read:
Product Complaints concerning the investigational product must be reported to the 
Sponsor within 1 business day of the study site's knowledge of the event via the Product 
Complaint form.  
Section 8.1.2.2  Analysis of Adverse Events
Second paragraph, first sentence previously read:
Adverse events will be coded using the most current version of the Medical Dictionary for 
Regulatory Activities (MedDRA).  
Has been changed to read:
Adverse events will be coded using the current version of the Medical Dictionary for 
Regulatory Activities (MedDRA).  
Section 8.1.3  Biomarker Analyses
Add:  new last paragraph
Digital substudy endpoints will be handled in a separate scientific report.


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Section 8.2.2  Efficacy Interim Analysis
Add:  new second sentence
Additional efficacy interim analyses may be conducted as needed.
Section 8.3  Determination of Sample Size
Last sentence previously read:
Approximately 330 subjects will be randomized in Study M15-562; and the number of 
subjects who enroll in Study M15-563 will be up to the number of subjects enrolled in 
Study M15-562.
Has been changed to read:
A total of 378 subjects will be randomized in Study M15-562; and the number of subjects 
who enroll in Study M15-563 will be up to the number of subjects enrolled in 
Study M15-562.
Section 15.0  Reference List
Add:  new Reference 17, 27, 28, 29, 30
17.
Schwab RS, England AC.  Projection technique for evaluating surgery in 
Parkinson's disease.  In: Gillingham FJ, Donaldson MC, eds.  Third symposium on 
Parkinson's disease.  Edinburgh. Livingston. 1969:152-7.
27.
Adams JL, Dinesh K, Xiong M, et al.  Multiple wearable sensors in Parkinson and 
Huntington disease individuals:  a pilot study in clinic and at home.  Digit 
Biomark.  2017;1:52-63.
28.
Reilly MC, Zbrozek AS, Dukes EM.  The validity and reproducibility of a work 
productivity and activity impairment instrument.  Pharmacoeconomics 
1993;4(5):353-65.
29.
Pillas M, Selai C, Quinn NP, Lees A, et al.  Development and validation of a 
carers quality-of-life questionnaire for parkinsonism (PQoL Carers).  Qual Life 
Res.  2016;25(1): 81–8.


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30.
Bharmal M, Payne K, Atkinson MJ, et al.  Validation of an abbreviated treatment 
satisfaction questionnaire for medication (TSQM-9) among patients on 
antihypertensive medications.  Health Qual Life Outcomes.  2009;7:36.
Appendix B.  List of Protocol Signatories
Previously read:
Name
Title
Functional Area
Clinical
Clinical
Clinical
Statistics
Statistics
Pharmacokinetics
Clinical
Bioanalysis
Medical Writing
Has been changed to read:
Name
Title
Functional Area
Clinical
Clinical
Clinical
Statistics
Statistics
Pharmacokinetics
Neuroscience Development
Bioanalysis
Medical Writing


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Appendix C.  Study Activities
Previously read:
Visits & Proceduresb
Treatment Perioda
20 Wks
Post Last 
Dose F/U
Year 1
Dose
1
Dose
2
Dose
3
Dose
4
Dose
5
Dose
6
Dose
7
Dose
8
Dose
9
Dose
10
Dose
11
Dose
12
Dose
13
Dose
14
Dose
15
D/C
Day
1
Day
15
Day
29
Day 
57
Day
85
Day
113
Day
141
Day
169
Day
197
Day
225
Day
253
Day
281
Day
309
Day
337
Day
365
Day
1
Wk
2
Wk
4
Wk
8
Wk
12
Wk
16
Wk
20
Wk
24
Wk
28
Wk
32
Wk
36
Wk
40
Wk
44
Wk
48
Wk
52
Subject/study partner ICFc
X
Medical history updated
X
Randomization
X
Physical examination
X
Symptom-driven physical 
examinatione
X
X
X
X
Orthostatic vital signsf,g
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital signsg
X
X
Body weight (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pregnancy test (WOCBP)h 
U
U
U
U
S
U
Neurological examination
X
X
X
X
X
X
12-lead ECG
X
X
X
X
X
Clinical laboratory tests
X
X
X
X
X
Brain MRI
X
X
X
X
X
X
LP/CSF collection
X
X
X
X
X


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Visits & Proceduresb
Treatment Perioda
20 Wks
Post Last 
Dose F/U
Year 1
Dose
1
Dose
2
Dose
3
Dose
4
Dose
5
Dose
6
Dose
7
Dose
8
Dose
9
Dose
10
Dose
11
Dose
12
Dose
13
Dose
14
Dose
15
D/C
Day
1
Day
15
Day
29
Day 
57
Day
85
Day
113
Day
141
Day
169
Day
197
Day
225
Day
253
Day
281
Day
309
Day
337
Day
365
Day
1
Wk
2
Wk
4
Wk
8
Wk
12
Wk
16
Wk
20
Wk
24
Wk
28
Wk
32
Wk
36
Wk
40
Wk
44
Wk
48
Wk
52
Blood PK sample
X
X
X
X
X
X
ADA Sample collection
X
X
X
X
X
X
CSF and plasma biomarkers
X
X
X
X
X
X
Optional exploratory PGx DNA and 
RNA blood sample 
X
X
X
X
X
Administer IV Study Drug
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PSPRS
1
1
1
1
1
1
CGI-S
2
2
2
2
2
2
CGI-C
3
3
3
3
3
3
SEADL
4
4
4
4
4
4
UPDRS Part II
5
5
5
5
5
5
RBANS
6
6
CTT Parts 1 & 2
7
7
Letter Fluency Test (wpm)
8
8
NNIPPS-PPSil
9
9
PGI-Cj
X
X
X
X
X
X
EQ-5Dj
X
X
X


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Visits & Proceduresb
Treatment Perioda
20 Wks
Post Last 
Dose F/U
Year 1
Dose
1
Dose
2
Dose
3
Dose
4
Dose
5
Dose
6
Dose
7
Dose
8
Dose
9
Dose
10
Dose
11
Dose
12
Dose
13
Dose
14
Dose
15
D/C
Day
1
Day
15
Day
29
Day 
57
Day
85
Day
113
Day
141
Day
169
Day
197
Day
225
Day
253
Day
281
Day
309
Day
337
Day
365
Day
1
Wk
2
Wk
4
Wk
8
Wk
12
Wk
16
Wk
20
Wk
24
Wk
28
Wk
32
Wk
36
Wk
40
Wk
44
Wk
48
Wk
52
C-SSRS (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
BioStamp
Concomitant medication
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
AE assessment (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
AE = adverse event; ICF = informed consent form; LP = lumbar puncture; PK = pharmacokinetic; PGx = pharmacogenetic; S = serum; U = urine
a.
Study drug will be administered on Days 1, 15, and 29, then every 28 days thereafter until 1 of the discontinuation criteria is met, until the Sponsor discontinues the study, or 
until the study reaches completion.  For those Visits that include both study drug infusion and other activities, the Visits may be completed over 2 consecutive days with the 
second day to include the start and end of the infusion.
b.
Audio recordings/central review of the administration/assessment of selected scales may be conducted.
c.
Subject informed consent, or as applicable, legally authorized representative informed consent and subject assent, and study partner informed consent must be obtained prior 
to Study M15-563 Day 1 dosing.
d.
Review medical history to confirm subject does not meet exclusion criteria prior to randomization.
e.
Additional symptom-driven physical examinations may be performed as needed.
f.
All supine and standing blood pressure and pulse rate measurements are to be measured as part of an orthostatic assessment.
g.
An attempt should be made to obtain all vital sign measurements at the same time of day and using the same arm.
h.
For all females of childbearing potential, a negative urine pregnancy test result is also required prior to any radiological procedures.
i.
The NNIPPS-PPS will not be administered in Japan.
j.
Scale may be administered/assessed at any time during the visit, after the other procedures are completed, with the exception of the scheduled infusion time.
Note:
Numbering listed in the table provides a pre-defined order of administration that these scales should occur during each visit.


ABBV-8E12
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EudraCT 2017-001590-16
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Visits & Proceduresb
Treatment Perioda
Year 2
Dose
16
Dose
17
Dose
18
Dose
19
Dose
20
Dose
21
Dose
22
Dose
23
Dose
24
Dose
25
Dose
26
Dose
27
Dose
28
D/C
20 Wks
Post Last 
Dose F/U
Day
393
Day
421
Day
449
Day
477
Day
505
Day
533
Day
561
Day
589
Day
617
Day
645
Day
673
Day
701
Day
729
Wk
56
Wk
60
Wk
64
Wk
68
Wk
72
Wk
76
Wk
80
Wk
84
Wk
88
Wk
92
Wk
96
Wk
100
Wk
104
Symptom-driven physical examinationc
X
X
X
X
Vital signsd
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Body weight (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pregnancy test (WOCBP)e 
U
U
S
U
Neurological examination
X
X
X
X
12-lead ECG
X
X
Clinical laboratory tests
X
X
Brain MRI
X
X
X
X
LP/CSF collection
O
X
X
X
Blood PK sample
X
X
X
X
ADA Sample collection
X
X
X
X
CSF and plasma biomarkers
X
X
X
Optional exploratory PGx DNA and RNA 
sample 
X
X
Administer IV Study Drug
X
X
X
X
X
X
X
X
X
X
X
X
X
PSPRS
1
1
1
1
CGI-S
2
2
2
2


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EudraCT 2017-001590-16
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Visits & Proceduresb
Treatment Perioda
Year 2
Dose
16
Dose
17
Dose
18
Dose
19
Dose
20
Dose
21
Dose
22
Dose
23
Dose
24
Dose
25
Dose
26
Dose
27
Dose
28
D/C
20 Wks
Post Last 
Dose F/U
Day
393
Day
421
Day
449
Day
477
Day
505
Day
533
Day
561
Day
589
Day
617
Day
645
Day
673
Day
701
Day
729
Wk
56
Wk
60
Wk
64
Wk
68
Wk
72
Wk
76
Wk
80
Wk
84
Wk
88
Wk
92
Wk
96
Wk
100
Wk
104
CGI-C
3
3
3
3
SEADL
4
4
4
4
UPDRS Part II
5
5
5
5
RBANS
6
6
CTT Parts 1 & 2
7
7
Letter Fluency Test (wpm)
8
8
NNIPPS-PPSf
9
9
PGI-Cg
X
X
X
X
EQ-5Dg
X
X
C-SSRS (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant medication 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
AE assessment (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
AE = adverse event; LP = lumbar puncture; O = optional; PK = pharmacokinetic; PGx = pharmacogenetic; S = serum; U = urine
a.
Study drug will be administered on Days 1, 15, and 29, then every 28 days thereafter until 1 of the discontinuation criteria is met, until the Sponsor discontinues the study, or 
until the study reaches completion.  For those Visits that include both study drug infusion and other activities, the Visits may be completed over 2 consecutive days with the 
second day to include the start and end of the infusion.
b.
Audio recordings/central review of the administration/assessment of selected scales may be conducted.
c.
Additional symptom-driven physical examinations may be performed as needed.


ABBV-8E12
M15-563 Protocol Amendment 2
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d.
An attempt should be made to obtain all vital sign measurements at the same time of day and using the same arm.
e.
For all females of childbearing potential, a negative urine pregnancy test result is also required prior to any radiological procedures.
f.
The NNIPPS-PPS will not be administered in Japan
g.
Scale may be administered/assessed at any time during the visit, after the other procedures are completed, with the exception of the scheduled infusion time.
Note:
Numbering listed in the table provides a pre-defined order of administration that these scales should occur during each visit.


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
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Visits & Proceduresb
Treatment Perioda
20 Weeks
Post Last 
Dose F/U
Year 3
Dose
29
Dose
30
Dose
31
Dose
32
Dose
33
Dose
34
Dose
35
Dose
36
Dose
37
Dose
38
Dose
39
Dose
40
Dose
41
D/C
Day
757
Day
785
Day
813
Day
841
Day
869
Day
897
Day
925
Day
953
Day
981
Day
1009
Day
1037
Day
1065
Day
1093
Wk
108
Wk
112
Wk
116
Wk
120
Wk
124
Wk
128
Wk
132
Wk
136
Wk
140
Wk
144
Wk
148
Wk
152
Wk
156
Symptom-driven physical examinationc
X
X
X
X
Vital signsd
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Body weight ( prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pregnancy test (WOCBP)e 
U
U
S
U
Neurological examination
X
X
X
X
12-lead ECG
X
X
Clinical laboratory tests
X
X
Brain MRI
X
X
X
X
LP/CSF collection
O
X
X
X
Blood PK sample
X
X
X
X
ADA Sample collection
X
X
X
X
CSF and plasma biomarkers
X
X
X
Optional exploratory PGx DNA and RNA 
sample 
X
X
Administer IV Study Drug
X
X
X
X
X
X
X
X
X
X
X
X
X
PSPRS
1
1
1
1
CGI-S
2
2
2
2


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M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
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Visits & Proceduresb
Treatment Perioda
20 Weeks
Post Last 
Dose F/U
Year 3
Dose
29
Dose
30
Dose
31
Dose
32
Dose
33
Dose
34
Dose
35
Dose
36
Dose
37
Dose
38
Dose
39
Dose
40
Dose
41
D/C
Day
757
Day
785
Day
813
Day
841
Day
869
Day
897
Day
925
Day
953
Day
981
Day
1009
Day
1037
Day
1065
Day
1093
Wk
108
Wk
112
Wk
116
Wk
120
Wk
124
Wk
128
Wk
132
Wk
136
Wk
140
Wk
144
Wk
148
Wk
152
Wk
156
CGI-C
3
3
3
3
SEADL
4
4
4
4
UPDRS Part II
5
5
5
5
RBANS
6
6
CTT Parts 1 & 2
7
7
Letter Fluency Test (wpm)
8
8
NNIPPS-PPSf
9
9
PGI-Cg
X
X
X
X
EQ-5Dg
X
X
C-SSRS (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant medication 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
AE assessment (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
AE = adverse event; LP = lumbar puncture; O = optional; PK = pharmacokinetic; PGx = pharmacogenetic; S = serum; U = urine
a.
Study drug will be administered on Days 1, 15, and 29, then every 28 days thereafter until 1 of the discontinuation criteria is met, until the Sponsor discontinues the study, or 
until the study reaches completion.  For those Visits that include both study drug infusion and other activities, the Visits may be completed over 2 consecutive days with the 
second day to include the start and end of the infusion.
b.
Audio recordings/central review of the administration/assessment of selected scales may be conducted.
c.
Additional symptom-driven physical examinations may be performed as needed.


ABBV-8E12
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EudraCT 2017-001590-16
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d.
An attempt should be made to obtain all vital sign measurements at the same time of day and using the same arm.
e.
For all females of childbearing potential, a negative urine pregnancy test result is also required prior to any radiological procedures.
f.
The NNIPPS-PPS will not be administered in Japan
g.
Scale may be administered/assessed at any time during the visit, after the other procedures are completed, with the exception of the scheduled infusion time.
Note:
Numbering listed in the table provides a pre-defined order of administration that these scales should occur during each visit.


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
160
Visits & Proceduresb
Treatment Perioda
20 Weeks
Post Last 
Dose F/U
Year 4
Dose
42
Dose
43
Dose
44
Dose
45
Dose
46
Dose
47
Dose
48
Dose
49
Dose
50
Dose
51
Dose
52
Dose
53
Dose
54
D/C
Day
1121
Day
1149
Day
1177
Day
1205
Day
1233
Day
1261
Day
1289
Day
1317
Day
1345
Day
1373
Day
1401
Day
1429
Day
1457
Wk
160
Wk
164
Wk
168
Wk
172
Wk
176
Wk
180
Wk
184
Wk
188
Wk
192
Wk
196
Wk
200
Wk
204
Wk
208
Symptom-driven physical examinationc
X
X
X
X
Vital signsd
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Body weight (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pregnancy test (WOCBP)e 
U
U
S
U
Neurological examination
X
X
X
X
12-lead ECG
X
X
Clinical laboratory tests
X
X
Brain MRI
X
X
X
X
LP/CSF collection
O
X
X
X
Blood PK sample
X
X
X
X
ADA Sample collection
X
X
X
X
CSF and plasma biomarkers
X
X
X
Optional exploratory PGx DNA and RNA 
sample 
X
X
Administer IV Study Drug
X
X
X
X
X
X
X
X
X
X
X
X
X
PSPRS
1
1
1
1
CGI-S
2
2
2
2


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
161
Visits & Proceduresb
Treatment Perioda
20 Weeks
Post Last 
Dose F/U
Year 4
Dose
42
Dose
43
Dose
44
Dose
45
Dose
46
Dose
47
Dose
48
Dose
49
Dose
50
Dose
51
Dose
52
Dose
53
Dose
54
D/C
Day
1121
Day
1149
Day
1177
Day
1205
Day
1233
Day
1261
Day
1289
Day
1317
Day
1345
Day
1373
Day
1401
Day
1429
Day
1457
Wk
160
Wk
164
Wk
168
Wk
172
Wk
176
Wk
180
Wk
184
Wk
188
Wk
192
Wk
196
Wk
200
Wk
204
Wk
208
CGI-C
3
3
3
3
SEADL
4
4
4
4
UPDRS Part II
5
5
5
5
RBANS
6
6
CTT Parts 1 & 2
7
7
Letter Fluency Test (wpm)
8
8
NNIPPS-PPSf
9
9
PGI-Cg
X
X
X
X
EQ-5Dg
X
X
C-SSRS (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant medication 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
AE assessment (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
AE = adverse event; LP = lumbar puncture; O = optional; PK = pharmacokinetic; PGx = pharmacogenetic; S = serum; U = urine
a.
Study drug will be administered on Days 1, 15, and 29, then every 28 days thereafter until 1 of the discontinuation criteria is met, until the Sponsor discontinues the study, or 
until the study reaches completion.  For those Visits that include both study drug infusion and other activities, the Visits may be completed over 2 consecutive days with the 
second day to include the start and end of the infusion.
b.
Audio recordings/central review of the administration/assessment of selected scales may be conducted.
c.
Additional symptom-driven physical examinations may be performed as needed.


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
162
d.
An attempt should be made to obtain all vital sign measurements at the same time of day and using the same arm.
e.
For all females of childbearing potential, a negative urine pregnancy test result is also required prior to any radiological procedures.
f.
The NNIPPS-PPS will not be administered in Japan.
g.
Scale may be administered/assessed at any time during the visit, after the other procedures are completed, with the exception of the scheduled infusion time.
Note:
Numbering listed in the table provides a pre-defined order of administration that these scales should occur during each visit.


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
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Visits & Proceduresb
Treatment Perioda
Year 5
Dose
55
Dose
56
Dose
57
Dose
58
Dose
59
Dose
60
Dose
61
Dose
62
Dose
63
Dose
64
Dose
65
Dose
66/
Final
No
Dose
20 
Weeks
Post 
Last 
Dose 
F/U
Day
1485
Day
1513
Day
1541
Day
1569
Day
1597
Day
1625
Day
1653
Day
1681
Day
1709
Day
1737
Day
1765
Day
1793
Day
1821
Wk
212
Wk
216
Wk
220
Wk
224
Wk
228
Wk
232
Wk
236
Wk
240
Wk
244
Wk
248
Wk
252
Wk
256
Wk
260
D/C
Symptom-driven physical examinationc
X
X
X
X
Vital signsd
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Body weight (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pregnancy test (WOCBP)e 
U
S
S
U
Neurological examination
X
X
X
X
12-lead ECG
X
X
Clinical laboratory tests
X
X
Brain MRI
X
X
X
X
LP/CSF collection
O
X
X
X
Blood PK sample
X
X
X
X
ADA Sample collection
X
X
X
X
CSF and plasma biomarkers
X
X
X
Optional exploratory PGx DNA and RNA 
sample 
X
X
Administer IV Study Drug
X
X
X
X
X
X
X
X
X
X
X
X
PSPRS
1
1
1
1


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
164
Visits & Proceduresb
Treatment Perioda
Year 5
Dose
55
Dose
56
Dose
57
Dose
58
Dose
59
Dose
60
Dose
61
Dose
62
Dose
63
Dose
64
Dose
65
Dose
66/
Final
No
Dose
20 
Weeks
Post 
Last 
Dose 
F/U
Day
1485
Day
1513
Day
1541
Day
1569
Day
1597
Day
1625
Day
1653
Day
1681
Day
1709
Day
1737
Day
1765
Day
1793
Day
1821
Wk
212
Wk
216
Wk
220
Wk
224
Wk
228
Wk
232
Wk
236
Wk
240
Wk
244
Wk
248
Wk
252
Wk
256
Wk
260
D/C
CGI-S
2
2
2
2
CGI-C
3
3
3
3
SEADL
4
4
4
4
UPDRS Part II
5
5
5
5
RBANS
6
6
CTT Parts 1 & 2
7
7
Letter Fluency Test (wpm)
8
8
NNIPPS-PPSf
9
9
PGI-Cg
X
X
X
X
EQ-5Dg
X
X
C-SSRS (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant medication 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
AE assessment (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
AE = adverse event; LP = lumbar puncture; O = optional; PK = pharmacokinetic; PGx = pharmacogenetic; S = serum; U = urine
a.
Study drug will be administered on Days 1, 15, and 29, then every 28 days thereafter until 1 of the discontinuation criteria is met, until the Sponsor discontinues the study, or 
until the study reaches completion.  For those Visits that include both study drug infusion and other activities, the Visits may be completed over 2 consecutive days with the 
second day to include the start and end of the infusion.


ABBV-8E12
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EudraCT 2017-001590-16
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b.
Audio recordings/central review of the administration/assessment of selected scales may be conducted.
c.
Additional symptom-driven physical examinations may be performed as needed.
d.
An attempt should be made to obtain all vital sign measurements at the same time of day and using the same arm.
e.
For all females of childbearing potential, a negative urine pregnancy test result is also required prior to any radiological procedures.
f.
The NNIPPS-PPS will not be administered in Japan.
g.
Scale may be administered/assessed at any time during the visit, after the other procedures are completed, with the exception of the scheduled infusion time.
Note:
Numbering listed in the table provides a pre-defined order of administration that these scales should occur during each visit.


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
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Has been changed to read:
Visits & Proceduresb
Treatment Perioda
20 Wks
Post Last 
Dose F/U
Year 1
Dose
1
Dose
2
Dose
3
Dose
4
Dose
5
Dose
6
Dose
7
Dose
8
Dose
9
Dose
10
Dose
11
Dose
12
Dose
13
Dose
14
Dose
15
D/C
Day
1
Day
15
Day
29
Day 
57
Day
85
Day
113
Day
141
Day
169
Day
197
Day
225
Day
253
Day
281
Day
309
Day
337
Day
365
Day
1
Wk
2
Wk
4
Wk
8
Wk
12
Wk
16
Wk
20
Wk
24
Wk
28
Wk
32
Wk
36
Wk
40
Wk
44
Wk
48
Wk
52
Subject/study partner ICFc
X
Medical history updated
X
Randomization
X
Physical examination
X
Symptom-driven physical 
examinatione
X
X
X
X
Orthostatic vital signsf,g
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital signsg
X
X
Body weight (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pregnancy test (WOCBP)h 
U
U
U
U
S
U
Neurological examination
X
X
X
X
X
X
12-lead ECG
X
X
X
X
X
Clinical laboratory tests
X
X
X
X
X
Brain MRIi
X
X
X
X
X
X
LP/CSF collectionj
X
X
X
X
X


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
167
Visits & Proceduresb
Treatment Perioda
20 Wks
Post Last 
Dose F/U
Year 1
Dose
1
Dose
2
Dose
3
Dose
4
Dose
5
Dose
6
Dose
7
Dose
8
Dose
9
Dose
10
Dose
11
Dose
12
Dose
13
Dose
14
Dose
15
D/C
Day
1
Day
15
Day
29
Day 
57
Day
85
Day
113
Day
141
Day
169
Day
197
Day
225
Day
253
Day
281
Day
309
Day
337
Day
365
Day
1
Wk
2
Wk
4
Wk
8
Wk
12
Wk
16
Wk
20
Wk
24
Wk
28
Wk
32
Wk
36
Wk
40
Wk
44
Wk
48
Wk
52
Blood PK sample
X
X
X
X
X
X
ADA Sample collection
X
X
X
X
X
X
Plasma biomarkers
X
X
X
X
X
X
CSF biomarkers
X
X
X
X
X
Optional exploratory PGx DNA and 
RNA blood sample 
X
X
X
X
X
Administer IV Study Drug
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PSPRS
1
1
1
1
1
1
CGI-S
2
2
2
2
2
2
CGI-C
3
3
3
3
3
3
SEADL
4
4
4
4
4
4
UPDRS Part II
5
5
5
5
5
5
RBANS
6
6
CTT Parts 1 & 2
7
7
Letter Fluency Test (wpm)
8
8
NNIPPS-PPSk
9
9
PGI-Cl
X
X
X
X
X
X


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
168
Visits & Proceduresb
Treatment Perioda
20 Wks
Post Last 
Dose F/U
Year 1
Dose
1
Dose
2
Dose
3
Dose
4
Dose
5
Dose
6
Dose
7
Dose
8
Dose
9
Dose
10
Dose
11
Dose
12
Dose
13
Dose
14
Dose
15
D/C
Day
1
Day
15
Day
29
Day 
57
Day
85
Day
113
Day
141
Day
169
Day
197
Day
225
Day
253
Day
281
Day
309
Day
337
Day
365
Day
1
Wk
2
Wk
4
Wk
8
Wk
12
Wk
16
Wk
20
Wk
24
Wk
28
Wk
32
Wk
36
Wk
40
Wk
44
Wk
48
Wk
52
EQ-5Dl
X
X
X
C-SSRSm
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
BioStamp Digitaln
X
X
X
X
PSP Caregiver Questionnaires
X
X
X
X
X
TSQM-9
X
X
X
X
X
Concomitant medication
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
AE assessment (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Telephone contacto
X
X
X
X
X
X
AE = adverse event; ICF = informed consent form; LP = lumbar puncture; PK = pharmacokinetic; PGx = pharmacogenetic; S = serum; U = urine
a.
Study drug will be administered on Days 1, 15, and 29, then every 28 days thereafter until 1 of the discontinuation criteria is met, until the Sponsor discontinues the study, or
until the study reaches completion.  For those Visits that include both study drug infusion and other activities, the Visits may be completed over 2 consecutive days with the 
second day to include the start and end of the infusion.
b.
Audio recordings/central review of the administration/assessment of selected scales may be conducted.
c.
Subject informed consent, or as applicable, legally authorized representative informed consent, and study partner informed consent must be obtained prior to Study M15-563 
Day 1 dosing.
d.
Review medical history to confirm subject does not meet exclusion criteria prior to randomization.
e.
Additional symptom-driven physical examinations may be performed as needed.
f.
All supine and standing blood pressure and pulse rate measurements are to be measured as part of an orthostatic assessment.


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
169
g.
An attempt should be made to obtain all vital sign measurements at the same time of day and using the same arm.
h.
For all females of childbearing potential, a negative urine pregnancy test result is also required prior to any radiological procedures.
i.
If a subject cannot undergo MRI due to a clinical reason, the AbbVie TA MD should be consulted for approval.
j.
Subjects who are not able to undergo an LP may be enrolled with permission of the AbbVie TA MD without the requirement of an LP during the study.
k.
The NNIPPS-PPS will not be administered in Japan.
l.
Scale may be administered/assessed at any time during the visit, after the other procedures are completed, with the exception of the scheduled infusion time.
m.
Scale may be administered/assessed at any time during the visit with the exception of the scheduled infusion time.
n.
Device to be worn for 7 days.
o.
Only applicable to subjects who prematurely discontinue.  Verify consent was obtained prior to making contact.
Note:
Numbering listed in the table provides a pre-defined order of administration that these scales should occur during each visit.


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
170
Visits & Proceduresb
Treatment Perioda
Year 2
Dose
16
Dose
17
Dose
18
Dose
19
Dose
20
Dose
21
Dose
22
Dose
23
Dose
24
Dose
25
Dose
26
Dose
27
Dose
28
D/C
20 Wks
Post Last 
Dose F/U
Day
393
Day
421
Day
449
Day
477
Day
505
Day
533
Day
561
Day
589
Day
617
Day
645
Day
673
Day
701
Day
729
Wk
56
Wk
60
Wk
64
Wk
68
Wk
72
Wk
76
Wk
80
Wk
84
Wk
88
Wk
92
Wk
96
Wk
100
Wk
104
Symptom-driven physical examinationc
X
X
X
X
Vital signsd
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Body weight (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pregnancy test (WOCBP)e 
U
U
S
U
Neurological examination
X
X
X
X
12-lead ECG
X
X
Clinical laboratory tests
X
X
Brain MRIf
X
X
X
X
LP/CSF collection
X
X
X
X
Blood PK sample
X
X
X
X
ADA Sample collection
X
X
X
X
Plasma biomarkers
X
X
X
CSF biomarkers
X
X
X
X
Optional exploratory PGx DNA and RNA 
sample 
X
X
Administer IV Study Drug
X
X
X
X
X
X
X
X
X
X
X
X
X
PSPRS
1
1
1
1


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
171
Visits & Proceduresb
Treatment Perioda
Year 2
Dose
16
Dose
17
Dose
18
Dose
19
Dose
20
Dose
21
Dose
22
Dose
23
Dose
24
Dose
25
Dose
26
Dose
27
Dose
28
D/C
20 Wks
Post Last 
Dose F/U
Day
393
Day
421
Day
449
Day
477
Day
505
Day
533
Day
561
Day
589
Day
617
Day
645
Day
673
Day
701
Day
729
Wk
56
Wk
60
Wk
64
Wk
68
Wk
72
Wk
76
Wk
80
Wk
84
Wk
88
Wk
92
Wk
96
Wk
100
Wk
104
CGI-S
2
2
2
2
CGI-C
3
3
3
3
SEADL
4
4
4
4
UPDRS Part II
5
5
5
5
RBANS
6
6
CTT Parts 1 & 2
7
7
Letter Fluency Test (wpm)
8
8
NNIPPS-PPSg
9
9
PGI-Ch
X
X
X
X
EQ-5Dh
X
X
C-SSRSi
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PSP Caregiver Questionnaires
X
X
X
X
TSQM-9
X
X
X
X
Concomitant medication 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
AE assessment (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Telephone contactj
X
X
X
X
AE = adverse event; LP = lumbar puncture; PK = pharmacokinetic; PGx = pharmacogenetic; S = serum; U = urine


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
172
a.
Study drug will be administered on Days 1, 15, and 29, then every 28 days thereafter until 1 of the discontinuation criteria is met, until the Sponsor discontinues the study, or 
until the study reaches completion.  For those Visits that include both study drug infusion and other activities, the Visits may be completed over 2 consecutive days with the 
second day to include the start and end of the infusion.
b.
Audio recordings/central review of the administration/assessment of selected scales may be conducted.
c.
Additional symptom-driven physical examinations may be performed as needed.
d.
An attempt should be made to obtain all vital sign measurements at the same time of day and using the same arm.
e.
For all females of childbearing potential, a negative urine pregnancy test result is also required prior to any radiological procedures.
f
If a subject cannot undergo MRI due to a clinical reason, the AbbVie TA MD should be consulted for approval.
g.
The NNIPPS-PPS will not be administered in Japan
h.
Scale may be administered/assessed at any time during the visit, after the other procedures are completed, with the exception of the scheduled infusion time.
i.
Scale may be administered/assessed at any time during the visit with the exception of the scheduled infusion time.
j.
Only applicable to subjects who prematurely discontinue.  Verify consent was obtained prior to making contact.
Note:
Numbering listed in the table provides a pre-defined order of administration that these scales should occur during each visit.


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
173
Visits & Proceduresb
Treatment Perioda
20 Weeks
Post Last 
Dose F/U
Year 3
Dose
29
Dose
30
Dose
31
Dose
32
Dose
33
Dose
34
Dose
35
Dose
36
Dose
37
Dose
38
Dose
39
Dose
40
Dose
41
D/C
Day
757
Day
785
Day
813
Day
841
Day
869
Day
897
Day
925
Day
953
Day
981
Day
1009
Day
1037
Day
1065
Day
1093
Wk
108
Wk
112
Wk
116
Wk
120
Wk
124
Wk
128
Wk
132
Wk
136
Wk
140
Wk
144
Wk
148
Wk
152
Wk
156
Symptom-driven physical examinationc
X
X
X
X
Vital signsd
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Body weight ( prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pregnancy test (WOCBP)e 
U
U
S
U
Neurological examination
X
X
X
X
12-lead ECG
X
X
Clinical laboratory tests
X
X
Brain MRIf
X
X
X
X
LP/CSF collection
X
X
X
X
Blood PK sample
X
X
X
X
ADA Sample collection
X
X
X
X
Plasma biomarkers
X
X
X
CSF biomarkers
X
X
X
X
Optional exploratory PGx DNA and RNA 
sample 
X
X
Administer IV Study Drug
X
X
X
X
X
X
X
X
X
X
X
X
X
PSPRS
1
1
1
1


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
174
Visits & Proceduresb
Treatment Perioda
20 Weeks
Post Last 
Dose F/U
Year 3
Dose
29
Dose
30
Dose
31
Dose
32
Dose
33
Dose
34
Dose
35
Dose
36
Dose
37
Dose
38
Dose
39
Dose
40
Dose
41
D/C
Day
757
Day
785
Day
813
Day
841
Day
869
Day
897
Day
925
Day
953
Day
981
Day
1009
Day
1037
Day
1065
Day
1093
Wk
108
Wk
112
Wk
116
Wk
120
Wk
124
Wk
128
Wk
132
Wk
136
Wk
140
Wk
144
Wk
148
Wk
152
Wk
156
CGI-S
2
2
2
2
CGI-C
3
3
3
3
SEADL
4
4
4
4
UPDRS Part II
5
5
5
5
RBANS
6
6
CTT Parts 1 & 2
7
7
Letter Fluency Test (wpm)
8
8
NNIPPS-PPSg
9
9
PGI-Ch
X
X
X
X
EQ-5Dh
X
X
C-SSRSi
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PSP Caregiver Questionnaires
X
X
X
X
TSQM-9
X
X
X
X
Concomitant medication 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
AE assessment (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Telephone contactj
X
X
X
X
AE = adverse event; LP = lumbar puncture; PK = pharmacokinetic; PGx = pharmacogenetic; S = serum; U = urine


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
175
a.
Study drug will be administered on Days 1, 15, and 29, then every 28 days thereafter until 1 of the discontinuation criteria is met, until the Sponsor discontinues the study, or 
until the study reaches completion.  For those Visits that include both study drug infusion and other activities, the Visits may be completed over 2 consecutive days with the 
second day to include the start and end of the infusion.
b.
Audio recordings/central review of the administration/assessment of selected scales may be conducted.
c.
Additional symptom-driven physical examinations may be performed as needed.
d.
An attempt should be made to obtain all vital sign measurements at the same time of day and using the same arm.
e.
For all females of childbearing potential, a negative urine pregnancy test result is also required prior to any radiological procedures.
f.
If a subject cannot undergo MRI due to a clinical reason, the AbbVie TA MD should be consulted for approval.
g.
The NNIPPS-PPS will not be administered in Japan
h.
Scale may be administered/assessed at any time during the visit, after the other procedures are completed, with the exception of the scheduled infusion time.
i.
Scale may be administered/assessed at any time during the visit with the exception of the scheduled infusion time.
j.
Only applicable to subjects who prematurely discontinue.  Verify consent was obtained prior to making contact.
Note:
Numbering listed in the table provides a pre-defined order of administration that these scales should occur during each visit.


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
176
Visits & Proceduresb
Treatment Perioda
20 Weeks
Post Last 
Dose F/U
Year 4
Dose
42
Dose
43
Dose
44
Dose
45
Dose
46
Dose
47
Dose
48
Dose
49
Dose
50
Dose
51
Dose
52
Dose
53
Dose
54
D/C
Day
1121
Day
1149
Day
1177
Day
1205
Day
1233
Day
1261
Day
1289
Day
1317
Day
1345
Day
1373
Day
1401
Day
1429
Day
1457
Wk
160
Wk
164
Wk
168
Wk
172
Wk
176
Wk
180
Wk
184
Wk
188
Wk
192
Wk
196
Wk
200
Wk
204
Wk
208
Symptom-driven physical examinationc
X
X
X
X
Vital signsd
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Body weight (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pregnancy test (WOCBP)e 
U
U
S
U
Neurological examination
X
X
X
X
12-lead ECG
X
X
Clinical laboratory tests
X
X
Brain MRIf
X
X
X
X
LP/CSF collection
X
X
X
X
Blood PK sample
X
X
X
X
ADA Sample collection
X
X
X
X
Plasma biomarkers
X
X
X
CSF biomarkers
X
X
X
X
Optional exploratory PGx DNA and RNA 
sample 
X
X
Administer IV Study Drug
X
X
X
X
X
X
X
X
X
X
X
X
X
PSPRS
1
1
1
1


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
177
Visits & Proceduresb
Treatment Perioda
20 Weeks
Post Last 
Dose F/U
Year 4
Dose
42
Dose
43
Dose
44
Dose
45
Dose
46
Dose
47
Dose
48
Dose
49
Dose
50
Dose
51
Dose
52
Dose
53
Dose
54
D/C
Day
1121
Day
1149
Day
1177
Day
1205
Day
1233
Day
1261
Day
1289
Day
1317
Day
1345
Day
1373
Day
1401
Day
1429
Day
1457
Wk
160
Wk
164
Wk
168
Wk
172
Wk
176
Wk
180
Wk
184
Wk
188
Wk
192
Wk
196
Wk
200
Wk
204
Wk
208
CGI-S
2
2
2
2
CGI-C
3
3
3
3
SEADL
4
4
4
4
UPDRS Part II
5
5
5
5
RBANS
6
6
CTT Parts 1 & 2
7
7
Letter Fluency Test (wpm)
8
8
NNIPPS-PPSg
9
9
PGI-Ch
X
X
X
X
EQ-5Dh
X
X
C-SSRSi
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PSP Caregiver Questionnaires
X
X
X
X
TSQM-9
X
X
X
X
Concomitant medication 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
AE assessment (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Telephone contactj
X
X
X
X
AE = adverse event; LP = lumbar puncture; PK = pharmacokinetic; PGx = pharmacogenetic; S = serum; U = urine


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
178
a.
Study drug will be administered on Days 1, 15, and 29, then every 28 days thereafter until 1 of the discontinuation criteria is met, until the Sponsor discontinues the study, or 
until the study reaches completion.  For those Visits that include both study drug infusion and other activities, the Visits may be completed over 2 consecutive days with the 
second day to include the start and end of the infusion.
b.
Audio recordings/central review of the administration/assessment of selected scales may be conducted.
c.
Additional symptom-driven physical examinations may be performed as needed.
d.
An attempt should be made to obtain all vital sign measurements at the same time of day and using the same arm.
e.
For all females of childbearing potential, a negative urine pregnancy test result is also required prior to any radiological procedures.
f.
If a subject cannot undergo MRI due to a clinical reason, the AbbVie TA MD should be consulted for approval.
g.
The NNIPPS-PPS will not be administered in Japan.
h.
Scale may be administered/assessed at any time during the visit, after the other procedures are completed, with the exception of the scheduled infusion time.
i.
Scale may be administered/assessed at any time during the visit with the exception of the scheduled infusion time.
j.
Only applicable to subjects who prematurely discontinue.  Verify consent was obtained prior to making contact.
Note:
Numbering listed in the table provides a pre-defined order of administration that these scales should occur during each visit.


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
179
Visits & Proceduresb
Treatment Perioda
Year 5
Dose
55
Dose
56
Dose
57
Dose
58
Dose
59
Dose
60
Dose
61
Dose
62
Dose
63
Dose
64
Dose
65
Dose
66/
Final
No
Dose
20 
Weeks
Post 
Last 
Dose 
F/U
Day
1485
Day
1513
Day
1541
Day
1569
Day
1597
Day
1625
Day
1653
Day
1681
Day
1709
Day
1737
Day
1765
Day
1793
Day
1821
Wk
212
Wk
216
Wk
220
Wk
224
Wk
228
Wk
232
Wk
236
Wk
240
Wk
244
Wk
248
Wk
252
Wk
256
Wk
260
D/C
Symptom-driven physical examinationc
X
X
X
X
Vital signsd
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Body weight (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pregnancy test (WOCBP)e 
U
S
S
U
Neurological examination
X
X
X
X
12-lead ECG
X
X
Clinical laboratory tests
X
X
Brain MRIf
X
X
X
X
LP/CSF collection
X
X
X
X
Blood PK sample
X
X
X
X
ADA Sample collection
X
X
X
X
Plasma biomarkers
X
X
X
CSF biomarkers
X
X
X
X
Optional exploratory PGx DNA and RNA 
sample 
X
X
Administer IV Study Drug
X
X
X
X
X
X
X
X
X
X
X
X


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
180
Visits & Proceduresb
Treatment Perioda
Year 5
Dose
55
Dose
56
Dose
57
Dose
58
Dose
59
Dose
60
Dose
61
Dose
62
Dose
63
Dose
64
Dose
65
Dose
66/
Final
No
Dose
20 
Weeks
Post 
Last 
Dose 
F/U
Day
1485
Day
1513
Day
1541
Day
1569
Day
1597
Day
1625
Day
1653
Day
1681
Day
1709
Day
1737
Day
1765
Day
1793
Day
1821
Wk
212
Wk
216
Wk
220
Wk
224
Wk
228
Wk
232
Wk
236
Wk
240
Wk
244
Wk
248
Wk
252
Wk
256
Wk
260
D/C
PSPRS
1
1
1
1
CGI-S
2
2
2
2
CGI-C
3
3
3
3
SEADL
4
4
4
4
UPDRS Part II
5
5
5
5
RBANS
6
6
CTT Parts 1 & 2
7
7
Letter Fluency Test (wpm)
8
8
NNIPPS-PPSg
9
9
PGI-Ch
X
X
X
X
EQ-5Dh
X
X
C-SSRSi
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PSP Caregiver Questionnaires
X
X
X
X
TSQM-9
X
X
X
X
Concomitant medication 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
AE assessment (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X


ABBV-8E12
M15-563 Protocol Amendment 2
EudraCT 2017-001590-16
181
Visits & Proceduresb
Treatment Perioda
Year 5
Dose
55
Dose
56
Dose
57
Dose
58
Dose
59
Dose
60
Dose
61
Dose
62
Dose
63
Dose
64
Dose
65
Dose
66/
Final
No
Dose
20 
Weeks
Post 
Last 
Dose 
F/U
Day
1485
Day
1513
Day
1541
Day
1569
Day
1597
Day
1625
Day
1653
Day
1681
Day
1709
Day
1737
Day
1765
Day
1793
Day
1821
Wk
212
Wk
216
Wk
220
Wk
224
Wk
228
Wk
232
Wk
236
Wk
240
Wk
244
Wk
248
Wk
252
Wk
256
Wk
260
D/C
Telephone contactj
X
X
X
X
AE = adverse event; LP = lumbar puncture; PK = pharmacokinetic; PGx = pharmacogenetic; S = serum; U = urine
a.
Study drug will be administered on Days 1, 15, and 29, then every 28 days thereafter until 1 of the discontinuation criteria is met, until the Sponsor discontinues the study, or 
until the study reaches completion.  For those Visits that include both study drug infusion and other activities, the Visits may be completed over 2 consecutive days with the 
second day to include the start and end of the infusion.
b.
Audio recordings/central review of the administration/assessment of selected scales may be conducted.
c.
Additional symptom-driven physical examinations may be performed as needed.
d.
An attempt should be made to obtain all vital sign measurements at the same time of day and using the same arm.
e.
For all females of childbearing potential, a negative urine pregnancy test result is also required prior to any radiological procedures.
f.
If a subject cannot undergo MRI due to a clinical reason, the AbbVie TA MD should be consulted for approval.
g.
The NNIPPS-PPS will not be administered in Japan.
h.
Scale may be administered/assessed at any time during the visit, after the other procedures are completed, with the exception of the scheduled infusion time.
i.
Scale may be administered/assessed at any time during the visit with the exception of the scheduled infusion time.
j.
Only applicable to subjects who prematurely discontinue.  Verify consent was obtained prior to making contact.
Note:
Numbering listed in the table provides a pre-defined order of administration that these scales should occur during each visit.

SAP_001.pdf: 
ABBV-8E12
M15-563 – Statistical Analysis Plan
Draft Version 1.0 – 15 Aug 2019
1
1.0
Title Page
Statistical Analysis Plan
Study M15-563
An Extension Study of ABBV-8E12 in Progressive 
Supranuclear Palsy (PSP)
Date:  15 Aug 2019
Draft Version 1.0
NCT03391765


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1.1
List of Abbreviations and Definition of terms
AE
Adverse Event
ALT
Alanine Aminotransferase
aPTT
Activated Partial Thromboplastin Time
AST
Aspartate Aminotransferase
ATC
Anatomical Therapeutic Chemical
BMI
Body Mass Index
BUN
Blood Urea Nitrogen
CGI-C
Clinical Global Impression of Change
CGI-S
Clinical Global Impression of Severity
CMC
Chemistry Manufacturing and Control
CPK
Creatine Phosphokinase
CRF
Case Report Form
CSF
Cerebrospinal Fluid
CSR
Clinical Study Report
C-SSRS
Columbia-Suicide Severity Rating Scale
CTCAE
Common Terminology Criteria for Adverse Events
CTT
Color Trails Test
DBP
Diastolic Blood Pressure
DMC
Data Monitoring Committee
DNA
Deoxyribonucleic Acid
ECG
Electrocardiogram
eCRF
Electronic Case Report Form
EQ-5D
EuroQol-5D
GABA
Gamma-Aminobutyric Acid
HR
Heart Rate
IA
Interim Analysis
ITT
Intent-to-Treat
INR
International Normalized Ratio
LFT
Letter Fluency Test
LLN
Lower Limit of Normal
LP
Lumbar Puncture
LTE
Long-term Extension
LS
Least Square


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LSLV
Last Subject Last Visit
MAPT
Microtubule Associated Protein Tau
MCHC
Mean Corpuscular Hemoglobin Concentration
MCV
Mean Corpuscular Volume
MD
Mean Diffusivity
MMRM
Mixed-effect Model Repeated-Measures
MRI
Magnetic Resonance Imaging
NFL
Neurofilament Light Protein
NNIPPS-PPS
Natural History and Neuroprotection in Parkinson Plus Syndromes-Parkinson Plus 
Scale
PBO
Placebo
PCS
Potentially Clinically Significant
PGI-C
Patient Global Impression of Change
PK
Pharmacokinetic
PSP
Progressive Supranuclear Palsy
PSP-QoL
Progressive Supranuclear Palsy Health Related Quality of Life Scale
PSPRS
Progressive Supranuclear Palsy Rating Scale
PT
Prothrombin Time
PT/INR
Prothrombin Time/International Normalized Ratio
PTT
Partial Thromboplastin Time
PTAE
Post-treatment AE
PTs
Preferred Terms
QRS
ECG QRS Complex
QT
Measure of the time between the start of the Q wave and the end of the T wave in 
the heart's electrical cycle
QTcF
QT corrected for heart rate using Fridericia's Method
RBANS
Repeatable Battery for Assessment of Neuropsychological Status
RBC
Red Blood Cell Count
RD
Radial Diffusivity
RNA 
Ribonucleic Acid
SAE
Serious Adverse Event
SBP
Systolic Blood Pressure
SDAC
Statistical and Data Analysis Center
SEADL
Schwab and England Activities of Daily Living Scale
SOC
System Organ Class


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TEAE
Treatment-emergent Adverse Event
ULN
Upper Limit of Normal
UPDRS
Unified Parkinson's Disease Rating Scale
VAS
Visual Analog Scale


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2.0
Table of Contents
1.0
Title Page..................................................................................1
1.1
List of Abbreviations and Definition of terms...........................................2
2.0
Table of Contents.....................................................................5
3.0
Introduction .............................................................................8
4.0
Study Objectives, Design and Procedures.............................8
4.1
Objectives ..................................................................................................8
4.2
Study Design..............................................................................................9
4.3
Sample Size..............................................................................................11
4.4
Interim Analyses ......................................................................................11
4.5
Efficacy Variables....................................................................................13
4.6
Safety Variables.......................................................................................13
4.7
Pharmacokinetic Variables ......................................................................13
4.8
Biomarker and Pharmacogenetic Research Variables .............................14
4.8.1
Biomarker Research Variables.................................................................14
4.8.2
Pharmacogenetic Research Variables......................................................14
5.0
Analysis Populations .............................................................15
5.1
Analysis Data Sets ...................................................................................15
6.0
Demographics, Baseline Characteristics, Medical 
History, and Previous/Concomitant Medications ..............17
6.1
Demographic and Baseline Characteristics .............................................17
6.2
Medical History .......................................................................................18
6.3
Previous and Concomitant Medications ..................................................19
7.0
Subject Disposition................................................................20
8.0
Study Drug Exposure and Compliance...............................21
9.0
Efficacy Analysis....................................................................22
10.0
Safety Analysis.......................................................................22
10.1
General Considerations............................................................................22
10.2
Analysis of Adverse Events.....................................................................23
10.2.1
Adverse Event Overview .........................................................................23
10.2.2
Adverse Event Incidence .........................................................................24
10.2.3
Listing of Adverse Events........................................................................25


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10.3
Analysis of Laboratory Tests...................................................................26
10.3.1
Analysis of Mean Changes for Laboratory Tests.....................................26
10.3.2
Shifts Between Normal and Abnormal for Laboratory Tests ..................27
10.3.3
Potentially Clinically Significant Laboratory Values ..............................27
10.4
Analysis of Vital Signs and Weight.........................................................27
10.4.1
Analysis of Mean Changes for Vital Sign and Weight............................28
10.4.2
Potentially Clinically Significant Vital Sign and Weight Values............28
10.5
Analysis of Electrocardiogram (ECG) Variables.....................................28
10.5.1
Analysis of Mean Changes for ECG........................................................29
10.5.2
Potentially Clinically Significant ECG Values........................................29
10.6
Analysis for Other Safety Variables ........................................................29
10.6.1
Analysis of Columbia-Suicide Severity Rating Scale (C-SSRS) ............29
10.6.2
Summary of MRI Safety Evaluations ......................................................30
11.0
Pharmacokinetic Analysis.....................................................30
12.0
Analysis of Biomarker Research Variables ........................30
12.1
Descriptive Statistics................................................................................30
12.2
Analysis on Treatment by ABBV-8E12 for at Least One Year...............32
13.0
Table and Appendix ..............................................................35
List of Tables
Table 1.
Laboratory tests........................................................................................26
Table 2.
Study Activities........................................................................................36
List of Figures
Figure 1.
Study Schematic.......................................................................................11
List of Appendices
Appendix A.
Potentially Clinically Significant (PCS) Laboratory Value.....................52
Appendix B.
Criteria for Potentially Clinically Significant Vital Sign and 
Weight Values..........................................................................................53


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Appendix C.
Criteria for Potentially Clinically Significant ECG Values.....................54


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3.0
Introduction
This analysis plan describes the statistical analyses to be completed by AbbVie Statistical 
Science and Programming for ABBV-8E12 Study Protocol M15-563, that incorporates 
two amendments (original Protocol, Amendment 1, Administrative Change 1, 
Amendment 2, Administrative Change 2).
This statistical analysis plan (SAP) provides details to further elaborate statistical methods 
as outlined in the protocol and describes analysis conventions to guide the statistical 
programming work.  Population pharmacokinetic and exposure-response analysis for this 
study, if performed, will be conducted separately and are not included in this SAP.
Analyses will be performed using SAS version 9.3 or higher (SAS Institute Inc., Cary, NC 
27513) under the UNIX operating system.
4.0
Study Objectives, Design and Procedures
4.1
Objectives
The primary objectives of this study are:
●
To assess the long-term safety and tolerability of ABBV-8E12 in subjects with 
progressive supranuclear palsy (PSP).
●
To assess the long-term efficacy of ABBV-8E12 in slowing disease 
progression in subjects with PSP as measured by the PSP Rating Scale 
(PSPRS).
The secondary objectives of this study are:
●
To assess the long-term efficacy of ABBV-8E12 in slowing disease 
progression and functional impairment in subjects with PSP as measured by 
secondary endpoints.
●
To assess the pharmacokinetics of ABBV-8E12 in subjects with PSP.


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●
To assess the long-term efficacy of ABBV-8E12 in slowing regional and/or 
whole brain atrophy in subjects with PSP as measured by volumetric magnetic 
resonance imaging (MRI).
The exploratory objectives of this study are:
●
To assess the long-term efficacy of ABBV-8E12 in slowing disease 
progression and functional impairment in subjects with PSP as measured by 
exploratory endpoints.
●
To assess the long-term effect of ABBV-8E12 on cerebrospinal fluid (CSF) 
and plasma tau protein levels.
●
To assess the long-term effect of ABBV-8E12 on other potential CSF and 
plasma biomarkers of disease progression.
●
To assess body position and gait in a subset of participating subjects using 
BioStamp digital sensors. 
4.2
Study Design
This study is a long-term extension of the Phase 2, double-blind study, Study M15-562.  
Subjects who completed the 52-week Treatment Period in Study M15-562 will be eligible 
for enrollment into Study M15-563.  All subjects in Study M15-563 will receive 
ABBV-8E12 as follows:  1) subjects who received placebo in Study M15-562 will be 
randomized, in a 1:1 ratio, to 1 of 2 ABBV-8E12 doses (2000 or 4000 mg); and 
2) subjects who received ABBV-8E12 2000 or 4000 mg in Study M15-562 will continue 
on the same dose.  Investigators and subjects will remain blinded to the treatment 
assignments in Study M15-562 after database lock and will be blinded to the dose level of 
ABBV-8E12 in Study M15-563. 
Subjects who enroll in Study M15-563 from Study M15-562 will complete baseline 
procedures and receive their first infusion of study drug on Day 1 of Study M15-563.  For 
subjects who do not have interruptions in study drug administration between 
Study M15-562 and Study M15-563, i.e., the duration between the last dose of study drug 


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infusion in Study M15-562 and the first dose of study drug in Study M15-563 is no more 
than 45 days, assessments that were performed at the Week 52 Visit in Study M15-562 
will be used for the Day 1 Visit assessments in Study M15-563.  If a subject enrolled in 
Study M15-563 is more than 45 days but less than 8 weeks since the subject's last dose of 
study drug in Study M15-562; in that case, Day 1 activities for Study M15-563 must be 
performed.
Subjects will receive 3 infusions of study drug during the first 4 weeks of Study M15-563, 
the first on Day 1, the second on Day 15 (subjects who received placebo in 
Study M15-562 will receive ABBV-8E12 on Day 15 of Study M15-563, and subjects who 
received ABBV-8E12 in Study M15-562 will receive placebo on Day 15 of 
Study M15-563 to maintain the blind in Study M15-562), and the third on Day 29.  After 
Day 29, subjects will receive study drug infusions every 28 days and will continue to 
receive ABBV-8E12 until one of the discontinuation criteria is met, until the study is 
discontinued by the Sponsor, or until the study reaches completion.  Subjects will return 
to the site approximately 20 weeks after their last dose for a post-treatment Follow-up 
Visit.
A Data Monitoring Committee (DMC) will review unblinded safety data and make 
recommendations to the Sponsor based on the totality of available clinical data.  The 
DMC memberships, responsibilities, and operating logistics are documented in a DMC 
charter.
A schematic of the study design is shown below in Figure 1, and a schedule of study 
procedures is shown in Table 2.


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Figure 1.
Study Schematic
a.
Additional interim analyses may be performed.
4.3
Sample Size
The sample size for this study is dependent on the number of subjects who complete 
Study M15-562 and are qualified for enrollment into Study M15-563.  A total of 
330 subjects were planned for Study M15-562.  Enrollment of M15-562 has been 
completed with totally 378 subjects randomized.  The number of subjects who enroll in 
Study M15-563 could be up to 378.
4.4
Interim Analyses
Safety Interim Reviews
Regular interim safety reviews will be performed for this study by the DMC.  An 
independent statistical and data analysis center (SDAC) will be responsible for generating 
and providing unblinded statistical tables, figures, and listings to the DMC for the interim 
safety reviews.  To maintain the integrity of the trial, a specific data access plan with a 
strict firewall will be in place to protect the unblinded data and the details will be 
described in the DMC charter.


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Before database lock of Study M15-562, safety reviews of Study M15-563 will follow the 
same schedules as Study M15-562.  DMC safety reviews after subjects from 
Study M15-562 roll over to Study M15-563.  After the last scheduled DMC safety review 
meeting for Study M15-562, independent DMC safety review meetings for 
Study M15-563 will occur every 6 months.  The database snapshots will be taken for the 
safety interim reviews. 
The DMC will communicate their recommendations to the AbbVie Contact regarding 
continuing, modifying or terminating the trial due to safety concerns in accordance with 
the DMC charter.
The following analyses will be conducted for the safety interim reviews:
●
Subject disposition and baseline demographics (gender, race, ethnicity, age, 
weight, height, body mass index)
●
Treatment emergent adverse events analysis:  overview, by system organ class 
(SOC) and preferred term (PT), SAE by SOC and PT, AEs leading to 
discontinuation, AEs with reasonable possibility
●
Laboratory mean change analysis and summary of potentially clinically 
significant (PCS) events
●
Mean change analysis of vital signs and summary of PCS events of vital sign 
values
●
Mean change analysis of electrocardiogram (ECG) and summary of PCS 
events of ECG values
●
Summary of concomitant medications
●
Summary of PK parameters (as available)
●
Exposure-response analyses on any safety endpoint if necessary
●
Summary of Columbia Suicide Severity Rating Scale (C-SSRS)
●
Summary of MRI results
More details of safety interim analyses will be specified in the DMC Charter.


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4.5
Efficacy Variables
Efficacy variable PSP Rating Scale (PSPRS) total score will be used to assess the 
treatment effect of ABBV-8E12 in slowing disease progression. 
Other efficacy variables include Unified Parkinson's Disease Rating Scale (UPDRS) 
Part II score, Clinical Global Impression of Severity and Change (CGI-S, CGI-C) score, 
the Schwab and England Activities of Daily Living Scale (SEADL) score, Patient Global 
Impression of Change (PGI-C), PSP Staging System (PSP-SS) (composite of items from 
PSPRS), Time from first dose of M1-562 to loss of ability to walk independently as 
measured by PSPRS item 26.
Exploratory efficacy variables include the time from first dose of M1-562 to death, 
EuroQuality of Life (EQ-5D), Letter Fluency Test (LFT) score, Repeatable Battery for 
Assessment of Neuropsychological Status (RBANS) score, Color Trails Test (CTT) 
(Parts 1 and 2) score, Natural History and Neuroprotection in Parkinson Plus Syndromes-
Parkinson Plus Scale (NNIPPS-PPS) total score, and Frequency of hospitalizations related 
to PSP.
4.6
Safety Variables
The following safety variables will be analyzed for the study:  adverse event (including 
infusion and allergic reactions), vital signs, C-SSRS, laboratory abnormalities, ECG, and 
MRI safety evaluations. 
4.7
Pharmacokinetic Variables
The concentration of ABBV-8E12 in serum and CSF samples will be summarized at each 
collection time point in the study.  Data from this study may be combined with data from 
other ABBV-8E12 studies for pharmacokinetic analyses. 


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4.8
Biomarker and Pharmacogenetic Research Variables
4.8.1
Biomarker Research Variables
Blood and CSF samples will be collected to conduct research to investigate disease-
related and drug-related biomarkers.  The biomarkers to be analyzed may include, but are 
not limited to, the following:
●
CSF and Plasma Biomarkers:
○
Tau in CSF and plasma
○
Additional exploratory CSF and plasma-based pharmacodynamic variables 
for which concentration data are reported
●
Imaging Biomarkers:
○
Regional and/or whole brain volume derived from MRI
○
Fractional anisotropy and diffusivity measures in brain regions of interest 
derived from DTI
●
Digital Biomarkers:
○
BioStamp sensor motor outcomes including posture, gait, and step count
4.8.2
Pharmacogenetic Research Variables
Optional samples may be collected to conduct exploratory investigations into known and 
novel biomarkers.  The types of biomarkers to be analyzed may include, but are not 
limited to, nucleic acids, proteins, lipids or metabolites.  The samples may be analyzed as 
part of a multi-study assessment of factors influencing the subjects' response to the study 
drug (or drugs of the same or similar class) or the development and progression of the 
subjects' disease or related conditions.  The samples may also be used to develop new 
diagnostic tests, therapies, research methods or technologies.  
If such data are obtained, the results from these analyses would be exploratory in nature 
and may not be included with the study report.  The analysis for such data is not addressed 
in this SAP.


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5.0
Analysis Populations
5.1
Analysis Data Sets
Data Sets for Efficacy Analyses
Two data sets will be created for the efficacy analysis: an intent-to-treat (ITT) data set and 
a delayed-start data set.
ITT Data Set:  the ITT data set consists of all subjects who received any dose of study 
drug in Study M15-563.  All efficacy analyses will be conducted on the ITT data set using 
data from Study M15-563 alone unless otherwise specified.
Delayed-Start Data Set:  The Delayed-Start data set includes all subjects from the 
Study M15-562 ITT data set who received placebo or ABBV-8E12 in Study M15-562 
regardless of whether they enroll in Study M15-563 or not.  For the Delayed-Start 
analysis, efficacy data for PSPRS total score from both Study M15-562 and 
Study M15-563 studies will be included.
Data Sets for Safety Analyses
The safety data set will consist of all subjects who received any dose of study drug 
infusion in Study M15-563.  For safety analyses, the actual treatment received will be 
used instead of the treatment assignment at enrollment.  There are two safety data sets:  a 
Stand-Alone data set and a Cumulative data set.
Stand-Alone Data Set:  The Stand-Alone data set is the primary data set for safety 
analyses, and will contain data from Study M15-563 only, regardless of the treatment 
received in Study M15-562.  Baseline for the Stand-Alone data set will be the last 
observation on or before the first dose of ABBV-8E12 in Study M15-563.  If no Baseline 
is recorded in Study M15-563, the last value in Study M15-562 will be used as the 
Baseline.


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Cumulative Data Set:  The Cumulative data set will consist of data from both 
Study M15-562 and Study M15-563.  It is the secondary data set for safety analyses.  For 
subjects who were in the placebo group in Study M15-562, their safety data from 
Study M15-562 will not be included in the Cumulative data set but their safety data from 
Study M15-563 will be included.  For subjects who were in the placebo group in 
Study M15-562, Baseline will be the last observation prior to the first dose of study drug 
in Study M15-563.  For subjects who were in ABBV-8E12 treatment groups in 
Study M15-562, Baseline for the Cumulative data set will be their Baseline in 
Study M15-562.
Data Sets for Biomarker Analyses
For the analysis of biomarker data, the actual treatment received will be used rather than 
the treatment assignment at enrollment.  Descriptive statistics will be provided for all 
scheduled post-baseline times of measurement in Study M15-563, with all subjects who 
were administered a dose in Study M15-563 included.  The descriptive statistics will also 
be provided for the baseline measurement.  For subjects whose treatment in 
Study M15-562 was one of the ABBV-8E12 doses, the baseline value for Study M15-563 
will be the baseline value of Study M15-562.  For subjects whose treatment in 
Study M15-562 was placebo, the baseline value will be the last measurement obtained 
before the first dose of Study M15-563, which might be the last measurement of 
Study M15-562 as explained in Section 4.2.
Longer-Term Biomarker Data Set:  Only data of subjects whose treatment in 
Study M15-562 was with one of the ABBV-8E12 dose levels will be included in this data 
set.  The data set will include the data for all scheduled times of measurement of 
Study M15-563.  The baseline value for this data set will be the baseline value of 
Study M15-562.  


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6.0
Demographics, Baseline Characteristics, Medical 
History, and Previous/Concomitant Medications
The data analysis will be conducted among treatment groups defined as 
Studies M15-562/M15-563:  2000/2000 mg, 4000/4000 mg, placebo/2000 mg, and 
placebo/4000 mg.
6.1
Demographic and Baseline Characteristics
The following demographic and baseline characteristics will be summarized for each 
treatment group, and for overall subjects the Stand-Alone data set.  
●
Gender (male, female)
●
Race (white, black, American Indian/Alaska native, Native Hawaiian or 
another Pacific Islander, Asian, Other, Multi-Race)
●
Ethnicity (Hispanic or Latino)
●
Age (years)
●
Age group (≤ 65, > 65)
●
Weight for all subjects (kg)
●
Weight for all male subjects (kg)
●
Weight for all female subjects (kg)
●
Height (cm)
●
Body mass index (BMI, kg/m2)
●
Body mass index category (BMI, kg/m2) (≤ 25, > 25)
Alcohol and tobacco use will be summarized for each treatment group and overall 
subjects for the Stand-Alone safety data set.  For alcohol use, the number and percentage 
of subjects who are drinkers, ex-drinkers and non-drinkers (defined as those who have 
never been a drinker) will be presented.  For tobacco use, the number and percentage of 
users, ex-users and non-users (defined as those who have never been a user) will be 
presented.  A subject reporting multiple use category for the different types of tobacco 
(cigarette, pipe, cigar and chewing tobacco) will be counted in the tobacco user category.


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The following baseline efficacy and clinical variables will be summarized for each 
treatment group and overall subjects for the ITT data set and Delayed-Start data set (if 
Delayed-Start analysis will be conducted).
●
PSPRS total and domain scores
●
UPDRS Part II score
●
SEADL score
●
CGI-S score
●
RBANS total scale score 
●
Color Trails Test (Parts 1 and 2) score 
●
Letter Fluency Test score
●
NNIPPS-PPS total score
●
EQ-5D index score and VAS score 
Categorical variables will be summarized by the number and percentage of subjects in 
each category.  No comparisons of treatment groups will be performed for alcohol and 
nicotine uses.  Continuous variables will be summarized with descriptive statistics 
(number of non-missing observations, mean, standard deviation, median, minimum and 
maximum).  No statistical comparisons of treatment groups will be performed. 
6.2
Medical History
Medical history of this study is transferred from medical history in Study M15-562.  The 
conditions/diagnoses recorded in medical/surgical history data will be coded using the 
most current version of the Medical Dictionary for Regulatory Activities (MedDRA).  
Data will be summarized and presented using system organ classes (SOCs) and preferred 
terms (PTs).  The SOC will be presented in alphabetical order and the PTs will be 
presented in alphabetical order within each SOC.  The number and percentage of subjects 
with any condition/diagnosis and condition/diagnosis in a particular SOC and PT will be 
summarized for each treatment group and overall subjects for the safety Stand-Alone data 
set.  Subjects reporting more than one PT within a SOC will be counted only once for that 
SOC.  No comparison among treatment groups will be performed.


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The following progressive supranuclear palsy disease history variables will be 
summarized for each treatment group and overall subjects for the Stand-Alone data set.
●
Age at onset of symptoms of PSP (years)
●
Age when first diagnosed as having PSP (years)
●
Years since onset of PSP symptoms (Age at study – Age at onset)
●
Years since PSP diagnosis (Age at study – Age at diagnosis)
●
Family history of PSP (None, biological mother, biological father, full sibling, 
biological child)
Categorical variables will be summarized with the number and percentage of subjects in 
each category. Continuous variables will be summarized with descriptive statistics 
(number of non-missing observations, mean, standard deviation, median, minimum, and 
maximum).  No comparisons of treatment groups will be performed.
6.3
Previous and Concomitant Medications
Previous medications are defined as all medications with a start date before the first study 
drug administration date.  Concomitant medications are defined as all medications, other 
than study drug, taken during the treatment period (i.e., from the first day of study drug 
administration through 45 days after the last day of study drug administration).  Previous 
and concomitant medications will be coded using the World Health Organization (WHO) 
dictionary and will be summarized by generic name and Anatomical Therapeutic 
Chemical (ATC) classification system level 3.  The number and percentage of subjects 
who take at least 1 medication and who take at least 1 dose of each specific medication in 
the following categories will be summarized for each treatment group and overall subjects 
for the Stand-Alone data set.
●
Previous medications for PSP (CMCAT = "PROGRESSIVE 
SUPRANUCLEAR PALSY MEDICATIONS") will be summarized by the 
following categories:
○
Antipsychotic medication


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○
Antidepressants
○
Medications for Parkinsonian symptoms (including levodopa/carbidopa, 
dopamine agonists, monoamine oxidase inhibitors, COMT inhibitors, and 
amantadine).
○
Anti-dementia drugs (CMCLAS3 = ANTI-DEMENTIA DRUGS): 
cholinesterase inhibitors (donepezil, rivastigmine, galantamine) or 
memantine for cognitive impairment.
○
Selective benzodiazepines and gamma-aminobutyric acid (GABA) 
agonists (zolpidem, zaleplon, eszopiclone, alprazolam, clonazepam and 
lorazepam for sleep and anxiety).  Other medications
●
Other previous medications
●
Concomitant medications for PSP (CMCAT = "PROGRESSIVE 
SUPRANUCLEAR PALSY MEDICATIONS") will be summarized by the 
same categories as previous medications for PSP.
●
Concomitant non-medicinal therapy. 
●
Other concomitant medications.
No comparisons of treatment groups will be performed.
7.0
Subject Disposition
For subjects who are enrolled in the study, the number and percentage of subjects in each 
disposition category (prematurely discontinued and completed) will be summarized for 
each treatment group and overall subjects.  The interim analyses, the disposition category 
"ongoing" will also be included.
The number and percentage of subjects who prematurely discontinued study drug or 
prematurely discontinued from the study will be summarized by reason (primary or any 
reason) for each treatment group and overall subjects.  
In addition, the following additional summaries will be presented for all enrolled subjects:
●
The number and percentage of subjects who are enrolled at each site.


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●
The number and percentage of subjects who prematurely discontinued at each 
site.
8.0
Study Drug Exposure and Compliance
Summaries of study drug exposure and compliance will be prepared for the Stand-Alone 
data set.
Study drug exposure will be summarized for each treatment group and overall subjects.  
Duration of exposure is calculated as the last study drug administration date minus the 
first study drug administration date + 30.  Total subject years of exposure is calculated by 
summing the duration of exposure across all subjects and dividing this sum by 365 (1 year 
will be considered as 365 days).  The number and percentage of subjects who have taken a 
total of ≤ 6, 7 to 12, 13 to 18, 19 to 24, 25 to 30, 31 to 36, 37 to 42, 43 to 48, 49 to 54, 55 
to 60, and ≥ 61 doses of study drug will be summarized.  No comparisons of treatment 
groups will be performed for this summary.  In addition, duration of exposure will be 
summarized with descriptive statistics (number of non-missing observations, mean, 
standard deviation, median, minimum and maximum duration and total years). 
At each scheduled dosing visit, the investigator will document whether the subject has 
received entire infusion and the volume administered will be recorded in the eCRF if the 
entire dose is not administered.  The percentage of the assigned dose administered will be 
calculated.  The mean of this percentage across infusions for each subject will be 
obtained.  The descriptive statistics (number of non-missing observations, minimum, 
mean, median, standard deviation, maximum) based on each subject's mean volume 
percentage of study drug infusion will be summarized for each treatment group and 
overall subjects.


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9.0
Efficacy Analysis
No efficacy analyses will be conducted.  Baseline values and change from baseline of the 
following primary and secondary efficacy variables will be summarized on both ITT data 
set and Delayed-start data set:
●
PSPRS total score
●
UPDRS Part II score
●
CGI-C score
●
SEADL score
●
CGI-S score
●
PGI-C score
●
PSP-SS (composite of items from PSPRS) score
A Figure of mean of PSPRS total score for each visit will be displayed by treatment 
groups 2000/2000 mg, 4000/4000 mg, placebo/2000 mg, and placebo/4000 mg.  This will 
be conducted on delayed-start data set.
10.0
Safety Analysis
10.1
General Considerations
Comparisons between treatment groups (Studies M15-562/M15-563) of interest will not 
be performed.  
All other safety assessments that are taken no more than 45 days after the last dose of 
study drug will be included in the safety evaluation of the Treatment Period, and all safety 
assessments that are taken more than 45 days but not more than 20 weeks after the last 
dose of study drug will be included in the safety evaluation for the Post-treatment 
Follow-up Visit.


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10.2
Analysis of Adverse Events
The Stand-Alone data set will be the primary data set for adverse event summaries.  
Analyses that will also be performed on the Cumulative data set are as follows:  adverse 
event overview, adverse event incidence by system organ class (SOC) and preferred term, 
adverse event incidence in descending frequency by overall subjects, and SAE incidence 
by SOC and preferred term.
All adverse events will be coded using the most current version of the Medical Dictionary 
for Regulatory Activities (MedDRA).  A treatment-emergent adverse event (TEAE) is 
defined as any adverse event that begins or worsens in severity on or after the first study 
drug dose date and no more than 20 weeks after the last study drug dose date.  Analysis of 
adverse events will also be conducted by geographical region (North America including 
US and Canada, European countries plus Australia, and Japan). 
10.2.1
Adverse Event Overview
The number and percentage of subjects experiencing one or more adverse events in the 
following adverse event categories will be summarized for each treatment group and 
overall subjects in both Stand-Alone data set and the Cumulative data set.  No 
comparisons of treatment groups will be performed.
●
Any TEAE
●
Any TEAE that was rated reasonable possibility of being related to study drug 
by the investigator 
●
Any severe TEAE
●
Any serious TEAE
●
Any TEAE that led to discontinuation of study drug
●
Any fatal TEAE
●
All deaths


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10.2.2
Adverse Event Incidence
TEAE incidence will be summarized and presented using primary MedDRA system organ 
classes (SOCs) and preferred terms (PTs).  The system organ classes will be presented in 
alphabetical order and the preferred terms will be presented in the alphabetical order 
within each system organ class.  Subjects reporting more than one adverse event for a 
given MedDRA PT will be counted only once for that term.  Subjects reporting more than 
one adverse event within a SOC will be counted only once for the SOC total.  Subjects 
reporting more than one adverse event will be counted only once in the overall adverse 
event total.
The number and percentage of subjects experiencing one or more TEAEs will be 
summarized by PT for each treatment group and overall subjects.  The PTs will be 
presented by decreasing frequency in overall subjects.
The number and percentage of subjects experiencing one or more adverse events in the 
following adverse event categories will be summarized by primary SOC and PT for each 
treatment group and overall subjects. 
●
Any TEAE
●
Any serious TEAE
●
Any TEAE that led to discontinuation of study drug
●
Any TEAE assessed by the investigator to be Reasonable Possibility of Being 
Related to study drug
The number of subjects experiencing one or more TEAEs will also be summarized by 
maximum severity category (mild, moderate, severe and unknown) and primary SOC and 
PT for each treatment group and overall subjects.  Subjects reporting more than 
one TEAE for a given PT will be counted only once for that term in the most severe 
category reported.  If a subject has an adverse event with unknown severity, then the 
subject will be counted in the severity category of "unknown" even if the subject has 
another occurrence of the same event with a severity present.  The only exception is if the 


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subject has another occurrence of the same adverse event with the most extreme severity –
"Severe."  In this case, the subject will be counted under the "Severe" category.  No 
comparisons of treatment groups will be performed.
The number of subjects experiencing one or more TEAEs will also be summarized by 
maximum relationship category (Reasonable Possibility of Being Related, No Reasonable 
Possibility of Being Related and Unknown), as assessed by the investigator, and primary 
SOC and PT for each treatment group and overall subjects.  Subjects reporting more than 
one TEAE for a given PT will be counted only once for that term in the most related 
category reported.  If a subject has an adverse event with unknown relationship, then the 
subject will be counted in the relationship category of "unknown," even if the subject has 
another occurrence of the same event with a relationship present.  The only exception is 
that if a subject has another occurrence of the same adverse event with a relationship 
assessment of "Reasonable Possibility of Being Related."  In this case, the subject will be 
counted under the "Reasonable Possibility of Being Related."  No comparisons between 
treatment groups will be performed.
10.2.3
Listing of Adverse Events
The following additional summaries of adverse events will be prepared only on Stand-
Alone data set.
●
List of subject numbers associated with each PT for all TEAEs
●
List of subject numbers associated with each PT for all TEAEs assessed by the 
investigator as Reasonable Possibility of Being Related. 
●
Listing of all serious adverse events
●
Listing of all adverse events that led to discontinuation of study drug
●
Listing of all fatal adverse events
●
Listing of all deaths


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10.3
Analysis of Laboratory Tests
Analyses of Laboratory tests will be performed on the Stand-Alone data set. 
The laboratory tests are described in the following table.
Table 1.
Laboratory tests
Hematology
Clinical Chemistry
Urinalysis
Hematocrit
Hemoglobin
Red blood cell (RBC) count
White blood cell (WBC) count
Neutrophils
Bands (if detected)
Lymphocytes
Monocytes
Basophils (if detected)
Eosinophils (if detected)
Platelet count (estimate not 
acceptable)
Mean corpuscular volume (MCV)
Mean corpuscular hemoglobin 
concentration (MCHC)
Prothrombin time (PT)
Activated partial thromboplastin time 
(aPTT)
PT/INR (Prothrombin 
Time/International Normalized 
Ratio)
Blood urea nitrogen (BUN)
Creatinine
Total bilirubin
Albumin
Aspartate aminotransferase (AST)
Alanine aminotransferase (ALT)
Alkaline phosphatase
Sodium
Potassium
Calcium
Inorganic phosphate
Uric acid
Cholesterol
Total protein
Glucose
Triglycerides
Bicarbonate/Carbon Dioxide 
(CO2) Chloride
Specific gravity
pH
10.3.1
Analysis of Mean Changes for Laboratory Tests
The following summaries of laboratory data will be included in the output:  mean change 
from baseline to each double-blind visit value and to the minimum, maximum and final 
double-blind value for each continuous hematology, chemistry and urinalysis variable, 
mean change from final double-blind value to final post-treatment value presented for 
each continuous hematology, chemistry and urinalysis variable, shift tables, and 
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10.3.2
Shifts Between Normal and Abnormal for Laboratory Tests
Laboratory observations will be categorized as normal, low, or high relative to the 
reference (normal) range associated with the laboratory that performed the assay.  For 
each hematology, chemistry and urinalysis variable with a reference range, shift tables 
will be prepared for shifts from baseline to lowest, highest and final value during the 
entire study for each treatment group and overall subjects.  No comparisons of treatment 
groups will be performed.  Shift tables will also be prepared by geographical region.  The 
tables will present:
●
The numbers and percentages of subjects with low or normal observations at 
baseline who have a high observation at any post-baseline visit
●
The numbers and percentages of subjects with normal or high observations at 
baseline who have a low observation at any post-baseline visit
●
The numbers and percentages of subjects with low or normal observations at 
baseline who have a high observation at the final visit
●
The numbers and percentages of subjects with normal or high observations at 
baseline who have a low observation at the final visit
10.3.3
Potentially Clinically Significant Laboratory Values
Criteria for potentially clinically significant (PCS) values have been predefined for 
selected laboratory variables as outlined in Appendix A.  For each variable, a summary of 
the number and percentage of subjects in each treatment group who have at least 
one double-blind observation that meets the PCS criteria and is more extreme than their 
baseline value will be provided.  A listing will also be prepared that will include, for each 
variable, all observations for each subject that met the PCS criteria for that variable at any 
time during the study.
10.4
Analysis of Vital Signs and Weight
Vital sign and weight data analyses will be performed on Stand-Alone data set.  Vital sign 
variables include:  diastolic blood pressure, systolic blood pressure and pulse rate at 


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supine and standing positions, orthostatic diastolic blood pressure, orthostatic systolic 
blood pressure, orthostatic pulse rate, and body temperature.  The calculations of 
orthostatic vital sign values are:
●
Orthostatic SBP (mmHg) = Standing SBP – Supine SBP
●
Orthostatic DBP (mmHg) = Standing DBP – Supine DBP
●
Orthostatic Pulse Rate (bpm) = Standing Pulse Rate – Supine Pulse Rate.
Weight variables include weight and BMI.
10.4.1
Analysis of Mean Changes for Vital Sign and Weight
Diastolic blood pressure, systolic blood pressure and pulse will be analyzed separately for 
each position of measurement.  Analyses of mean change from baseline to each double 
blinded visit value and to the minimum, maximum and final double-blind value will be 
presented for each vital sign and weight variable.  Analysis of orthostatic SBP, DBP and 
pulse rate will be conducted similarly.
10.4.2
Potentially Clinically Significant Vital Sign and Weight 
Values
Criteria for potentially clinically significant values have been predefined for selected vital 
sign and weight variables as outlined in Appendix.  For each variable, a summary of the 
number and percentage of subjects in each treatment group who have at least one double 
blind observation that meets the PCS criteria and is more extreme than their baseline 
value will be provided.  A listing will also be prepared that will include, for each variable, 
all observations for each subject that met the PCS criteria for that variable at any time 
during the study.  
10.5
Analysis of Electrocardiogram (ECG) Variables
Electrocardiogram (ECG) variables include:  heart rate (HR), PR interval, QRS interval, 
uncorrected QT interval, and QT interval corrected for heart rate using Fridericia's 


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formula (QTcF).  Analyses of ECG variables will be performed on the Stand-Alone data 
set.  
10.5.1
Analysis of Mean Changes for ECG
Analyses of mean change from baseline to each double-blind visit value and to the 
minimum, maximum and final double-blind value will be presented for each ECG 
variable.  Analyses of mean change from final double-blind value to final post-treatment 
value will also be presented for each ECG variable.
10.5.2
Potentially Clinically Significant ECG Values
Criteria for potentially clinically significant values have been predefined for selected ECG 
variables as outlined in Appendix C.  For each variable, a summary of the number and 
percentage of subjects in each treatment group who have at least one double-blind 
observation that meets the PCS criteria and is more extreme than their baseline value will 
be provided.  Listings will also be prepared to include all observations for each variable 
for each subject that met the PCS criteria for that variable at any time during the study.  
No comparisons of treatment groups will be performed.
10.6
Analysis for Other Safety Variables
10.6.1
Analysis of Columbia-Suicide Severity Rating Scale (C-
SSRS)
Analyses of C-SSRS will be performed on the Stand-Alone data set.  
Number and percentage of subjects in the following categories will be summarized for 
each treatment group and overall subjects by visit and for the entire study:
●
Answered 'Yes' to each C-SSRS item
●
Had suicidal ideation (defined as answering 'Yes' to one or more suicidal 
ideation items)
●
Had suicidal ideation only (defined as answering 'Yes' to one or more suicidal 
ideation items and answering 'No' to all suicidal behavior items)


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●
Had suicidal behavior (defined as answering 'Yes' to one or more suicidal 
behavior items)
●
Had suicidal ideation or behavior (defined as answering 'Yes' to one or more 
suicidal ideation or behavior items)
10.6.2
Summary of MRI Safety Evaluations 
MRI safety evaluations will be summarized by treatment group based on MRI evaluations 
in the double blinded period.  The summaries include the number and percentage of 
subjects pertaining cerebral edema, micro- and macro-haemorrhages, white matter 
hyperintensities (ARWMC score) across visits; number and percentage of subjects with 
presence and increasing severity of cerebral edema; number and percentage of subjects 
with new micro- and macro-haemorrhage lesions; number and percentage of subject with 
white matter hyperintensities change (ARWMC score) from previous time point.  
Descriptive statistics (mean, median, minimum, maximum) of number of new micro- and 
macro-hemorrhages or new lesions, as well as changes in ARWMC score in the double-
blinded period will be presented.
11.0
Pharmacokinetic Analysis
For ABBV-8E12 serum and/or CSF concentration data, descriptive statistics will be 
provided for each scheduled time of measurement with a breakdown by groups defined by 
treatment in Study M15-562 and treatment in this study.  
12.0
Analysis of Biomarker Research Variables
12.1
Descriptive Statistics
For CSF and plasma concentrations of tau and volumetric MRI variables, descriptive 
statistics will be provided for each scheduled time of measurement for each treatment 
group.  The descriptive statistics will be provided for the baseline measurement also. The 
data set for which the descriptive statistics will be provided is described in Section 5.1
under the heading "Data Sets for Biomarker Analyses."  The four treatment groups are 


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those defined in the first paragraph of Section 4.2.  That is, the treatments of the 4 groups 
are:
●
Subjects who received ABBV-8E12 2000 mg in Study M15-562 and continue 
on the same dose in Study M15-563
●
Subjects who received ABBV-8E12 4000 mg in Study M15-562 and continue 
on the same dose in Study M15-563
●
Subjects who received placebo in Study M15-562 and receive ABBV-8E12 
2000 mg doses in Study M15-563
●
Subjects who received placebo in Study M15-562 and receive ABBV-8E12 
4000 mg doses in Study M15-563
The descriptive statistics for a post-baseline time will be provided for both the data of the 
given time and the changes from baseline. 
Time of measurement will be indicated for two different reference points.  The 
first reference point will simply be the day of the first dose of Study M15-563.  The 
second reference point is the time relative to the first dose of ABBV-8E12, which will be 
the first dose of Study M15-562 or the first dose in Study M15-563, depending upon 
whether the subject was administered ABBV-8E12 or placebo in Study M15-562.  For 
subjects who were treated with ABBV-8E12 in Study M15-562, the time relative to the 
second reference point will be 52 weeks longer than the time relative to the first reference 
point.  For the subjects whose treatment in Study M15-562 was placebo, the time relative 
to both reference points will be the same.
The statistics will consist of:  number of observations (n), mean, standard deviation, 
coefficient of variation as a percentage (quotient of standard deviation and mean, 
multiplied by 100), minimum, median and maximum.  If the logarithmic transformation is 
employed for a variable in the statistical analysis that is described in Section 12.2, the 
geometric mean will also be reported.  All of these descriptive statistics except for the 
coefficient of variation and the geometric mean will be provided for the change from 
baseline at each scheduled time of measurement in Study M15-563. 


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12.2
Analysis on Treatment by ABBV-8E12 for at Least One Year   
The data set on which this analysis will be performed is the Longer-Term Biomarker Data 
Set described in Section 5.1.  All the measurements in this data set were obtained after a 
subject was on treatment with ABBV-8E12 for 52 weeks or longer.  
Transformation of Variables for Analysis
If the probability distribution for a variable appears to have considerable non-symmetry 
(e.g., skewness coefficient > 1.00 in magnitude), a transformation will be sought that has 
an approximately normal distribution.  If a transformation is employed, estimates of 
central values on the original scale (back transformation of SAS least squares means) will 
be provided.  If the logarithmic transformation is used, the comparison of the treatments 
will be in terms of the ratio of central values.  
Analysis of CSF and Plasma Concentration Variables
For CSF and plasma concentrations of tau, an MMRM analysis will be performed to 
compare the effects of the 2000 and 4000 mg doses of ABBV-8E12.  The model will 
include classification by ABBV-8E12 dose and time of measurement.  There will be an 
effect for the interaction of ABBV-8E12 dose and time of measurement.  The subjects in 
each treatment group will be viewed as a random sample.  The baseline value will be a 
covariate.  The model will also initially have a term for the interaction of baseline value 
and visit.
After the structure of the covariance matrix is decided upon, as discussed below, a test 
will be performed on the term for the interaction of baseline value and visit.  The term for 
this interaction will be removed from the model if the statistic is not significant at 
level 0.100.
Within the framework of the final model, the mean across the scheduled times of 
measurement will be estimated for each ABBV-8E12 dose level.  The hypothesis of no 
difference between the main effects of the two ABBV-8E12 dose levels (i.e., a composite 


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assessment for the several times of times of evaluation) will be tested at significance 
level 0.050.  The SAS least squares means (LS means) for the two ABBV-8E12 dose 
levels across time will be provided and presented graphically.
There will be three candidates for the structure of the covariance matrix for the 
conditional distribution of the vector of scheduled responses, given the values of the 
covariate(s).  The simplest model will be the compound symmetry model (SAS option CS 
with the REPEATED statement), and another option will be the one that imposes no 
conditions on the covariance matrix (SAS option UN with the REPEATED statement).  
The third model will allow the variances for the several times of response to differ, but 
impose the condition that all pairs of the response variables have the same correlation 
coefficient (SAS option CSH with the REPEATED statement).  An approximate test will 
be performed to compare the model with no restrictions to the compound symmetry 
model, with a multivariate normal distribution assumed for the conditional distribution.  
Such a test will also be performed to compare the model of intermediate complexity (SAS 
CSH option) to the compound symmetry model.  The approximate test will be that based 
upon the difference in the values of –2log(likelihood) for the two models, using the chi-
square approximation for the null distribution, with degrees of freedom being the 
difference in the number of parameters required for the two structures of the covariance 
matrix.  If the test statistic is not significant at level 0.050 for either test, the compound 
symmetry model will be used.  If the statistic is significant at level 0.050 for one of the 
two tests, the compound symmetry model will not be used, and the two more complex 
models will be compared using the approximate test.  If the statistic for this test is 
significant at level 0.050, the model with no restrictions will be used.  Otherwise, the 
model of intermediate complexity will be used.  
Analysis of Imaging Variables
For imaging variables, an MMRM analysis corresponding to that described for the tau 
variables will be performed.  However, for the volumetric MRI variables, there will be 
two covariates.  In addition to the baseline value, a variable reflecting head size 


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(e.g., intracranial volume) will be a covariate.  For this second covariate, interaction with 
visit will not be included in the model. 
For other variables for which data are reported, descriptive statistics will be provided, and 
appropriate analyses will be performed.


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M15-563 – Statistical Analysis Plan
Draft Version 1.0 – 15 Aug 2019
35
13.0
Table and Appendix


ABBV-8E12
M15-563 – Statistical Analysis Plan
Draft Version 1.0 – 15 Aug 2019
36
Table 2.
Study Activities
Visits & Proceduresb
Treatment Perioda
20 Wks 
Post 
Last 
Dose 
F/U
Year 1
Dose 
1
Dose 
2
Dose 
3
Dose 
4
Dose 
5
Dose 
6
Dose 
7
Dose 
8
Dose 
9
Dose 
10
Dose 
11
Dose 
12
Dose 
13
Dose 
14
Dose 
15
D/C
Day 
1
Day 
15
Day 
29
Day 
57
Day 
85
Day 
113
Day 
141
Day 
169
Day 
197
Day 
225
Day 
253
Day 
281
Day 
309
Day 
337
Day 
365
Day 
1
Wk 
2
Wk 
4
Wk 
8
Wk 
12
Wk 
16
Wk 
20
Wk 
24
Wk 
28
Wk 
32
Wk 
36
Wk 
40
Wk 
44
Wk 
48
Wk 
52
Subject/study partner ICFc
X
Medical history updated
X
Randomization
X
Physical examination
X
Symptom-driven physical 
examinatione
X
X
X
X
Orthostatic vital signsf,g
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital signsg
X
X
Body weight (prior to 
infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pregnancy test (WOCBP)h
U
U
U
U
S
U
Neurological examination
X
X
X
X
X
X
12-lead ECG
X
X
X
X
X
Clinical laboratory tests
X
X
X
X
X
Brain MRIi
X
X
X
X
X
X
LP/CSF collectionj
X
X
X
X
X


ABBV-8E12
M15-563 – Statistical Analysis Plan
Draft Version 1.0 – 15 Aug 2019
37
Table 2.
Study Activities (Continued)
Visits & Proceduresb
Treatment Perioda
20 Wks 
Post 
Last 
Dose 
F/U
Year 1
Dose 
1
Dose 
2
Dose 
3
Dose 
4
Dose 
5
Dose 
6
Dose 
7
Dose 
8
Dose 
9
Dose 
10
Dose 
11
Dose 
12
Dose 
13
Dose 
14
Dose 
15
D/C
Day 
1
Day 
15
Day 
29
Day 
57
Day 
85
Day 
113
Day 
141
Day 
169
Day 
197
Day 
225
Day 
253
Day 
281
Day 
309
Day 
337
Day 
365
Day 
1
Wk 
2
Wk 
4
Wk 
8
Wk 
12
Wk 
16
Wk 
20
Wk 
24
Wk 
28
Wk 
32
Wk 
36
Wk 
40
Wk 
44
Wk 
48
Wk 
52
Blood PK sample
X
X
X
X
X
X
ADA Sample collection
X
X
X
X
X
X
Plasma biomarkers
X
X
X
X
X
X
CSF biomarkers
X
X
X
X
X
Optional exploratory PGx 
DNA and RNA blood 
sample 
X
X
X
X
X
Administer IV Study Drug
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PSPRS
1
1
1
1
1
1
CGI-S
2
2
2
2
2
2
CGI-C
3
3
3
3
3
3
SEADL
4
4
4
4
4
4
UPDRS Part II
5
5
5
5
5
5
RBANS
6
6
CTT Parts 1 & 2
7
7
Letter Fluency Test (wpm)
8
8


ABBV-8E12
M15-563 – Statistical Analysis Plan
Draft Version 1.0 – 15 Aug 2019
38
Table 2.
Study Activities (Continued)
Visits & Proceduresb
Treatment Perioda
20 Wks 
Post 
Last 
Dose 
F/U
Year 1
Dose 
1
Dose 
2
Dose 
3
Dose 
4
Dose 
5
Dose 
6
Dose 
7
Dose 
8
Dose 
9
Dose 
10
Dose 
11
Dose 
12
Dose 
13
Dose 
14
Dose 
15
D/C
Day 
1
Day 
15
Day 
29
Day 
57
Day 
85
Day 
113
Day 
141
Day 
169
Day 
197
Day 
225
Day 
253
Day 
281
Day 
309
Day 
337
Day 
365
Day 
1
Wk 
2
Wk 
4
Wk 
8
Wk 
12
Wk 
16
Wk 
20
Wk 
24
Wk 
28
Wk 
32
Wk 
36
Wk 
40
Wk 
44
Wk 
48
Wk 
52
NNIPPS-PPSk
9
9
PGI-Cl
X
X
X
X
X
X
EQ-5Dl
X
X
X
C-SSRSm
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
BioStamp Digitaln 
X
X
X
X
PSP Caregiver 
Questionnaires
X
X
X
X
X
TSQM-9
X
X
X
X
X
Concomitant medication
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
AE assessment (prior to 
infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Telephone contacto
X
X
X
X
X
X
AE = adverse event; ICF = informed consent form; LP = lumbar puncture; PK = pharmacokinetic; PGx = pharmacogenetic; S = serum; U = urine
a.
Study drug will be administered on Days 1, 15, and 29, then every 28 days thereafter until 1 of the discontinuation criteria is met, until the Sponsor discontinues the study, or 
until the study reaches completion.  For those Visits that include both study drug infusion and other activities, the Visits may be completed over 2 consecutive days with the 
second day to include the start and end of the infusion.


ABBV-8E12
M15-563 – Statistical Analysis Plan
Draft Version 1.0 – 15 Aug 2019
39
Table 2.
Study Activities (Continued)
b.
Audio recordings/central review of the administration/assessment of selected scales may be conducted.
c.
Subject informed consent, or as applicable, legally authorized representative informed consent, and study partner informed consent must be obtained prior to Study M15-563 
Day 1 dosing.
d.
Review medical history to confirm subject does not meet exclusion criteria prior to randomization.
e.
Additional symptom-driven physical examinations may be performed as needed.
f.
All supine and standing blood pressure and pulse rate measurements are to be measured as part of an orthostatic assessment.
g.
An attempt should be made to obtain all vital sign measurements at the same time of day and using the same arm.
h.
For all females of childbearing potential, a negative urine pregnancy test result is also required prior to any radiological procedures.
i.
If a subject cannot undergo MRI due to a clinical reason, the AbbVie TA MD should be consulted for approval.
j.
Subjects who are not able to undergo an LP may be enrolled with permission of the AbbVie TA MD without the requirement of an LP during the study.
k.
The NNIPPS-PPS will not be administered in Japan.
l.
Scale may be administered/assessed at any time during the visit, after the other procedures are completed, with the exception of the scheduled infusion time.
m.
Scale may be administered/assessed at any time during the visit with the exception of the scheduled infusion time.
n.
Device to be worn for 7 days.
o.
Only applicable to subjects who prematurely discontinue.  Verify consent was obtained prior to making contact.
Note:
Numbering listed in the table provides a pre-defined order of administration that these scales should occur during each visit.


ABBV-8E12
M15-563 – Statistical Analysis Plan
Draft Version 1.0 – 15 Aug 2019
40
Visits & Proceduresb
Treatment Perioda
20 Wks 
Post 
Last 
Dose 
F/U
Year 2
Dose 
16
Dose 
17
Dose 
18
Dose 
19
Dose 
20
Dose 
21
Dose 
22
Dose 
23
Dose 
24
Dose 
25
Dose 
26
Dose 
27
Dose 
28
D/C
Day 
393
Day 
421
Day 
449
Day 
477
Day 
505
Day 
533
Day 
561
Day
589
Day 
617
Day 
645
Day 
673
Day 
701
Day 
729
Wk 
56
Wk 
60
Wk 
64
Wk 
68
Wk 
72
Wk 
76
Wk 
80
Wk 
84
Wk 
88
Wk 
92
Wk 
96
Wk 
100
Wk 
104
Symptom-driven physical examinationc
X
X
X
X
Vital signsd
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Body weight (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pregnancy test (WOCBP)e
U
U
S
U
Neurological examination
X
X
X
X
12-lead ECG
X
X
Clinical laboratory tests
X
X
Brain MRIf
X
X
X
X
LP/CSF collection
O
X
X
X
Blood PK sample
X
X
X
X
ADA Sample collection
X
X
X
X
Plasma biomarkers
X
X
X
CSF biomarkers
O
X
X
X
Optional exploratory PGx DNA and RNA 
sample 
X
X
Administer IV Study Drug
X
X
X
X
X
X
X
X
X
X
X
X
X
PSPRS
1
1
1
1


ABBV-8E12
M15-563 – Statistical Analysis Plan
Draft Version 1.0 – 15 Aug 2019
41
Visits & Proceduresb
Treatment Perioda
20 Wks 
Post 
Last 
Dose 
F/U
Year 2
Dose 
16
Dose 
17
Dose 
18
Dose 
19
Dose 
20
Dose 
21
Dose 
22
Dose 
23
Dose 
24
Dose 
25
Dose 
26
Dose 
27
Dose 
28
D/C
Day 
393
Day 
421
Day 
449
Day 
477
Day 
505
Day 
533
Day 
561
Day
589
Day 
617
Day 
645
Day 
673
Day 
701
Day 
729
Wk 
56
Wk 
60
Wk 
64
Wk 
68
Wk 
72
Wk 
76
Wk 
80
Wk 
84
Wk 
88
Wk 
92
Wk 
96
Wk 
100
Wk 
104
CGI-S
2
2
2
2
CGI-C
3
3
3
3
SEADL
4
4
4
4
UPDRS Part II
5
5
5
5
RBANS
6
6
CTT Parts 1 & 2
7
7
Letter Fluency Test (wpm)
8
8
NNIPPS-PPSg
9
9
PGI-Ch
X
X
X
X
EQ-5Dh
X
X
C-SSRSi
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PSP Caregiver Questionnaires
X
X
X
X
TSQM-9
X
X
X
X
Concomitant medication 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
AE assessment (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Telephone contactj
X
X
X
X
AE = adverse event; LP = lumbar puncture; PK = pharmacokinetic; PGx = pharmacogenetic; S = serum; U = urine


ABBV-8E12
M15-563 – Statistical Analysis Plan
Draft Version 1.0 – 15 Aug 2019
42
a.
Study drug will be administered on Days 1, 15, and 29, then every 28 days thereafter until 1 of the discontinuation criteria is met, until the Sponsor discontinues the study, or 
until the study reaches completion.  For those Visits that include both study drug infusion and other activities, the Visits may be completed over 2 consecutive days with the 
second day to include the start and end of the infusion.
b.
Audio recordings/central review of the administration/assessment of selected scales may be conducted.
c.
Additional symptom-driven physical examinations may be performed as needed.
d.
An attempt should be made to obtain all vital sign measurements at the same time of day and using the same arm.
e.
For all females of childbearing potential, a negative urine pregnancy test result is also required prior to any radiological procedures.
f
If a subject cannot undergo MRI due to a clinical reason, the AbbVie TA MD should be consulted for approval.
g.
The NNIPPS-PPS will not be administered in Japan.
h.
Scale may be administered/assessed at any time during the visit, after the other procedures are completed, with the exception of the scheduled infusion time.
i.
Scale may be administered/assessed at any time during the visit with the exception of the scheduled infusion time.
j.
Only applicable to subjects who prematurely discontinue.  Verify consent was obtained prior to making contact.
Note:
Numbering listed in the table provides a pre-defined order of administration that these scales should occur during each visit.


ABBV-8E12
M15-563 – Statistical Analysis Plan
Draft Version 1.0 – 15 Aug 2019
43
Visits & Proceduresb
Treatment Perioda
20 Weeks 
Post Last 
Dose F/U
Year 3
Dose 
29
Dose 
30
Dose 
31
Dose 
32
Dose 
33
Dose 
34
Dose 
35
Dose 
36
Dose 
37
Dose 
38
Dose 
39
Dose 
40
Dose 
41
D/C
Day 
757
Day 
785
Day 
813
Day 
841
Day 
869
Day 
897
Day 
925
Day 
953
Day 
981
Day 
1009
Day 
1037
Day 
1065
Day 
1093
Wk 
108
Wk 
112
Wk 
116
Wk 
120
Wk 
124
Wk 
128
Wk 
132
Wk 
136
Wk 
140
Wk 
144
Wk 
148
Wk 
152
Wk 
156
Symptom-driven physical examinationc
X
X
X
X
Vital signsd
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Body weight (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pregnancy test (WOCBP)e 
U
U
S
U
Neurological examination
X
X
X
X
12-lead ECG
X
X
Clinical laboratory tests
X
X
Brain MRIf
X
X
X
X
LP/CSF collection
O
X
X
X
Blood PK sample
X
X
X
X
ADA Sample collection
X
X
X
X
Plasma biomarkers
X
X
X
CSF biomarkers
O
X
X
X
Optional exploratory PGx DNA and RNA 
sample 
X
X
Administer IV Study Drug
X
X
X
X
X
X
X
X
X
X
X
X
X
PSPRS
1
1
1
1


ABBV-8E12
M15-563 – Statistical Analysis Plan
Draft Version 1.0 – 15 Aug 2019
44
Visits & Proceduresb
Treatment Perioda
20 Weeks 
Post Last 
Dose F/U
Year 3
Dose 
29
Dose 
30
Dose 
31
Dose 
32
Dose 
33
Dose 
34
Dose 
35
Dose 
36
Dose 
37
Dose 
38
Dose 
39
Dose 
40
Dose 
41
D/C
Day 
757
Day 
785
Day 
813
Day 
841
Day 
869
Day 
897
Day 
925
Day 
953
Day 
981
Day 
1009
Day 
1037
Day 
1065
Day 
1093
Wk 
108
Wk 
112
Wk 
116
Wk 
120
Wk 
124
Wk 
128
Wk 
132
Wk 
136
Wk 
140
Wk 
144
Wk 
148
Wk 
152
Wk 
156
CGI-S
2
2
2
2
CGI-C
3
3
3
3
SEADL
4
4
4
4
UPDRS Part II
5
5
5
5
RBANS
6
6
CTT Parts 1 & 2
7
7
Letter Fluency Test (wpm)
8
8
NNIPPS-PPSg
9
9
PGI-Ch
X
X
X
X
EQ-5Dh
X
X
C-SSRSi
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PSP Caregiver Questionnaires
X
X
X
X
TSQM-9
X
X
X
X
Concomitant medication 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
AE assessment (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Telephone contactj
X
X
X
X
AE = adverse event; LP = lumbar puncture; PK = pharmacokinetic; PGx = pharmacogenetic; S = serum; U = urine


ABBV-8E12
M15-563 – Statistical Analysis Plan
Draft Version 1.0 – 15 Aug 2019
45
a.
Study drug will be administered on Days 1, 15, and 29, then every 28 days thereafter until 1 of the discontinuation criteria is met, until the Sponsor discontinues the study, or 
until the study reaches completion.  For those Visits that include both study drug infusion and other activities, the Visits may be completed over 2 consecutive days with the 
second day to include the start and end of the infusion.
b.
Audio recordings/central review of the administration/assessment of selected scales may be conducted.
c.
Additional symptom-driven physical examinations may be performed as needed.
d.
An attempt should be made to obtain all vital sign measurements at the same time of day and using the same arm.
e.
For all females of childbearing potential, a negative urine pregnancy test result is also required prior to any radiological procedures.
f.
If a subject cannot undergo MRI due to a clinical reason, the AbbVie TA MD should be consulted for approval.
g.
The NNIPPS-PPS will not be administered in Japan.
h.
Scale may be administered/assessed at any time during the visit, after the other procedures are completed, with the exception of the scheduled infusion time.
i.
Scale may be administered/assessed at any time during the visit with the exception of the scheduled infusion time.
j.
Only applicable to subjects who prematurely discontinue.  Verify consent was obtained prior to making contact.
Note:
Numbering listed in the table provides a pre-defined order of administration that these scales should occur during each visit.


ABBV-8E12
M15-563 – Statistical Analysis Plan
Draft Version 1.0 – 15 Aug 2019
46
Visits & Proceduresb
Treatment Perioda
20 Weeks 
Post Last 
Dose F/U
Year 4
Dose 
42
Dose 
43
Dose 
44
Dose 
45
Dose 
46
Dose 
47
Dose 
48
Dose 
49
Dose 
50
Dose 
51
Dose 
52
Dose 
53
Dose 
54
D/C
Day 
1121
Day 
1149
Day 
1177
Day 
1205
Day 
1233
Day 
1261
Day 
1289
Day 
1317
Day 
1345
Day 
1373
Day 
1401
Day
1429
Day 
1457
Wk 
160
Wk 
164
Wk 
168
Wk 
172
Wk 
176
Wk 
180
Wk 
184
Wk 
188
Wk 
192
Wk 
196
Wk 
200
Wk 
204
Wk 
208
Symptom-driven physical examinationc
X
X
X
X
Vital signsd
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Body weight (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pregnancy test (WOCBP)e
U
U
S
U
Neurological examination
X
X
X
X
12-lead ECG
X
X
Clinical laboratory tests
X
X
Brain MRIf
X
X
X
X
LP/CSF collection
O
X
X
X
Blood PK sample
X
X
X
X
ADA Sample collection
X
X
X
X
Plasma biomarkers
X
X
X
CSF biomarkers
O
X
X
X
Optional exploratory PGx DNA and RNA sample 
X
X
Administer IV Study Drug
X
X
X
X
X
X
X
X
X
X
X
X
X
PSPRS
1
1
1
1
CGI-S
2
2
2
2


ABBV-8E12
M15-563 – Statistical Analysis Plan
Draft Version 1.0 – 15 Aug 2019
47
Visits & Proceduresb
Treatment Perioda
20 Weeks 
Post Last 
Dose F/U
Year 4
Dose 
42
Dose 
43
Dose 
44
Dose 
45
Dose 
46
Dose 
47
Dose 
48
Dose 
49
Dose 
50
Dose 
51
Dose 
52
Dose 
53
Dose 
54
D/C
Day 
1121
Day 
1149
Day 
1177
Day 
1205
Day 
1233
Day 
1261
Day 
1289
Day 
1317
Day 
1345
Day 
1373
Day 
1401
Day
1429
Day 
1457
Wk 
160
Wk 
164
Wk 
168
Wk 
172
Wk 
176
Wk 
180
Wk 
184
Wk 
188
Wk 
192
Wk 
196
Wk 
200
Wk 
204
Wk 
208
CGI-C
3
3
3
3
SEADL
4
4
4
4
UPDRS Part II
5
5
5
5
RBANS
6
6
CTT Parts 1 & 2
7
7
Letter Fluency Test (wpm)
8
8
NNIPPS-PPSg
9
9
PGI-Ch
X
X
X
X
EQ-5Dh
X
X
C-SSRSi
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PSP Caregiver Questionnaires
X
X
X
X
TSQM-9
X
X
X
X
Concomitant medication 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
AE assessment (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Telephone contactj
X
X
X
X
AE = adverse event; LP = lumbar puncture; PK = pharmacokinetic; PGx = pharmacogenetic; S = serum; U = urine


ABBV-8E12
M15-563 – Statistical Analysis Plan
Draft Version 1.0 – 15 Aug 2019
48
a.
Study drug will be administered on Days 1, 15, and 29, then every 28 days thereafter until 1 of the discontinuation criteria is met, until the Sponsor discontinues the study, or 
until the study reaches completion.  For those Visits that include both study drug infusion and other activities, the Visits may be completed over 2 consecutive days with the 
second day to include the start and end of the infusion.
b.
Audio recordings/central review of the administration/assessment of selected scales may be conducted.
c.
Additional symptom-driven physical examinations may be performed as needed.
d.
An attempt should be made to obtain all vital sign measurements at the same time of day and using the same arm.
e.
For all females of childbearing potential, a negative urine pregnancy test result is also required prior to any radiological procedures.
f.
If a subject cannot undergo MRI due to a clinical reason, the AbbVie TA MD should be consulted for approval.
g.
The NNIPPS-PPS will not be administered in Japan.
h.
Scale may be administered/assessed at any time during the visit, after the other procedures are completed, with the exception of the scheduled infusion time.
i.
Scale may be administered/assessed at any time during the visit with the exception of the scheduled infusion time.
j.
Only applicable to subjects who prematurely discontinue.  Verify consent was obtained prior to making contact.
Note:
Numbering listed in the table provides a pre-defined order of administration that these scales should occur during each visit.


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Visits & Proceduresb
Treatment Perioda
Year 5
Dose 
55
Dose 
56
Dose 
57
Dose 
58
Dose 
59
Dose 
60
Dose 
61
Dose 
62
Dose 
63
Dose 
64
Dose 
65
Dose 66/
Final
No 
Dose
D/C
20 Weeks 
Post Last 
Dose F/U
Day 
1485
Day 
1513
Day 
1541
Day 
1569
Day 
1597
Day 
1625
Day 
1653
Day 
1681
Day 
1709
Day 
1737
Day
1765
Day 
1793
Day 
1821
Wk 
212
Wk 
216
Wk 
220
Wk 
224
Wk 
228
Wk 
232
Wk 
236
Wk 
240
Wk 
244
Wk 
248
Wk 
252
Wk 256
Wk 
260
Symptom-driven physical examinationc
X
X
X
X
Vital signsd
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Body weight (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pregnancy test (WOCBP)e 
U
S
S
U
Neurological examination
X
X
X
X
12-lead ECG
X
X
Clinical laboratory tests
X
X
Brain MRIf
X
X
X
X
LP/CSF collection
O
X
X
X
Blood PK sample
X
X
X
X
ADA Sample collection
X
X
X
X
Plasma biomarkers
X
X
X
CSF biomarkers
O
X
X
X
Optional exploratory PGx DNA and RNA 
sample 
X
X
Administer IV Study Drug
X
X
X
X
X
X
X
X
X
X
X
X
PSPRS
1
1
1
1


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M15-563 – Statistical Analysis Plan
Draft Version 1.0 – 15 Aug 2019
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Visits & Proceduresb
Treatment Perioda
Year 5
Dose 
55
Dose 
56
Dose 
57
Dose 
58
Dose 
59
Dose 
60
Dose 
61
Dose 
62
Dose 
63
Dose 
64
Dose 
65
Dose 66/
Final
No 
Dose
D/C
20 Weeks 
Post Last 
Dose F/U
Day 
1485
Day 
1513
Day 
1541
Day 
1569
Day 
1597
Day 
1625
Day 
1653
Day 
1681
Day 
1709
Day 
1737
Day
1765
Day 
1793
Day 
1821
Wk 
212
Wk 
216
Wk 
220
Wk 
224
Wk 
228
Wk 
232
Wk 
236
Wk 
240
Wk 
244
Wk 
248
Wk 
252
Wk 256
Wk 
260
CGI-S
2
2
2
2
CGI-C
3
3
3
3
SEADL
4
4
4
4
UPDRS Part II
5
5
5
5
RBANS
6
6
CTT Parts 1 & 2
7
7
Letter Fluency Test (wpm)
8
8
NNIPPS-PPSg
9
9
PGI-Ch
X
X
X
X
EQ-5Dh
X
X
C-SSRSi
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PSP Caregiver Questionnaires
X
X
X
X
TSQM-9
X
X
X
X
Concomitant medication 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
AE assessment (prior to infusion)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Telephone contactj
X
X
X
X
AE = adverse event; LP = lumbar puncture; PK = pharmacokinetic; PGx = pharmacogenetic; S = serum; U = urine


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a.
Study drug will be administered on Days 1, 15, and 29, then every 28 days thereafter until 1 of the discontinuation criteria is met, until the Sponsor discontinues the study, or 
until the study reaches completion.  For those Visits that include both study drug infusion and other activities, the Visits may be completed over 2 consecutive days with the 
second day to include the start and end of the infusion.
b.
Audio recordings/central review of the administration/assessment of selected scales may be conducted.
c.
Additional symptom-driven physical examinations may be performed as needed.
d.
An attempt should be made to obtain all vital sign measurements at the same time of day and using the same arm.
e.
For all females of childbearing potential, a negative urine pregnancy test result is also required prior to any radiological procedures.
f.
If a subject cannot undergo MRI due to a clinical reason, the AbbVie TA MD should be consulted for approval.
g.
The NNIPPS-PPS will not be administered in Japan.
h.
Scale may be administered/assessed at any time during the visit, after the other procedures are completed, with the exception of the scheduled infusion time.
i.
Scale may be administered/assessed at any time during the visit with the exception of the scheduled infusion time.
j.
Only applicable to subjects who prematurely discontinue.  Verify consent was obtained prior to making contact.
Note:
Numbering listed in the table provides a pre-defined order of administration that these scales should occur during each visit.


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Appendix A.
Potentially Clinically Significant (PCS) Laboratory Value
Clinical Laboratory Tests
Very Low (VL)
Very High (VH)
Hematology
Activated partial thromboplastin time
NA
> ULN
Hemoglobin  
< 100 g/L (6.2 mmol/L)
> 40 g/L above ULN
Prothrombin Intl. Normalized Ratio  
NA
> ULN
Leukocytes
< 2 × 109/L
> 100 × 109/L
Lymphocyte
< 0.5 × 109/L
> 20 × 109/L
Neutrophil
< 1 × 109/L
NA
Platelets
< 75 × 109/L
NA
Chemistry
Bilirubin
NA
> 1.5 × ULN
Cholesterol
NA
> 12.92 mmol/L (500 mg/dL)
Creatinine
NA
> 1.5 × ULN
Calcium (corrected serum)
< 1.75 mmol/L (7.0 mg/dL)
> 3.1 mmol/L (12.5 mg/dL)
Glucose (fasting)
< 2.2 mmol/L (40 mg/dL)
> 13.9 mmol/L (250 mg/dL)
Potassium
< 3.0 mmol/L
> 6.0 mmol/L
Triglycerides
NA
> 5.7 mmol/L (500 mg/dL)
Urate
NA
> 590 umol/L (10 mg/dL)
Albumin
< 20 g/L
NA
Sodium
< 130 mmol/L
> 155 mmol/L
Phosphate
< 0.6 mmol/L (2.0 mg/dL)
NA
Enzymes
Alanine aminotransferase (ALT)
NA
> 3 × ULN
Alkaline phosphatase
NA
> 2.5 × ULN
Aspartate aminotransferase (AST)
NA
> 3 × ULN


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M15-563 – Statistical Analysis Plan
Draft Version 1.0 – 14 Aug 2019
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Appendix B.
Criteria for Potentially Clinically Significant Vital Sign and Weight 
Values
Vital Signs
Very Low (VL)
Very High (VH)
Systolic Blood Pressure 
(SBP) (mmHG)
≤ 90 and decreased ≥ 30 from 
baseline
≥ 180 and increased ≥ 40 from 
baseline
Diastolic Blood Pressure 
(DBP) (mmHG)
≤ 50 and decreased ≥ 20 from 
baseline
≥ 105 and increased ≥ 30 from 
baseline
Pulse (bpm)
≤ 50 and decreased ≥ 30 from 
baseline
≥ 100 and increased ≥ 30 from 
baseline
Temperature (C)
≥ 1.1 decrease from baseline
> 38.5 or increase ≥ 1.1 from baseline
Orthostatic SBP 
(Hypotension) (mmHg)
Decrease of ≥ 30 in SBP 
(supine to standing)
NA
Orthostatic DBP 
(Hypotension) (mmHg)
Decrease of ≥ 20 in DBP 
(supine to standing)
NA
Weight (kg)
Decreased ≥ 7% from baseline
Increased ≥ 7% from baseline


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Appendix C.
Criteria for Potentially Clinically Significant ECG Values
ECG Parameters
Significant Values
QTcF Interval (msec)
> 499
QTcF Interval Increased from Baseline (msec)
> 60