Clinical trial NCT04849988
Conditions: Cervical Dystonia
Sponsor: AEON Biopharma, Inc.
Start date: 2021-03-29; Completion date: 2022-07-11
Enrollment: 61 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This Phase 2 trial will evaluate the safety and efficacy of ABP-450 for the treatment of cervical dystonia in adults. The study will enroll 60 patients across approximately 30 sites in the United States. Study subjects will be divided evenly across a low dose group, a medium dose group, a high dose group, and a placebo group for one treatment cycle.

Detailed description:
This Phase 2 trial will evaluate the safety and efficacy of ABP-450 for the treatment of cervical dystonia in adults. The study will enroll 60 patients across approximately 30 sites in the United States. Study subjects will be divided evenly across a low dose, a medium dose group, a high dose and placebo group for one treatment cycle.

Arms: arm 1: ABP-450 Low Dose - Intramuscular injections into affected neck muscles. arm 2: ABP-450 Mid Dose - Intramuscular injections into affected neck muscles. arm 3: ABP-450 High Dose - Intramuscular injections into affected neck muscles. arm 4: Placebo (0.9% saline, sterile, unpreserved, USP/Ph.Eur.) - Intramuscular injections into affected neck muscles.
Interventions: intervention 1: ABP-450 intervention 2: Placebo
Intervention descriptions: intervention 1: ABP-450 (prabotulinumtoxinA) contains a 900kDA botulinum toxin type-A complex produced by the bacterium Clostridium botulinum. intervention 2: 0.9% sodium chloride, sterile, unpreserved, USP/Ph.Eur.

Protocol documents:
Prot_002.pdf: 
 
 
CLINICAL STUDY PROTOCOL 
IND - 145417 
A Phase 2, Randomized, Double-Blind, Multicenter, Placebo-Controlled 
Study to Evaluate the Safety and Efficacy of Intramuscular ABP-450 
(prabotulinumtoxinA) Injection for the Treatment of Cervical Dystonia 
ABP-19000 
 
Sponsor: 
Aeon Biopharma, Inc. 
 
 
Sponsor Contact: 
 
 
 
Medical Monitor: 
 
 
 
 
 
 
Version of Protocol:  
Version 2.1 
Date of Protocol:  
13 May 2021 
18 March 2020 (Version 1.0) 
26 August 2020 (Version 1.1) 
19 November 2020 (Version 2.0)  
 
CONFIDENTIAL 
All financial and non-financial support for this study will be provided by Aeon Biopharma, 
Inc. The concepts and information contained in this document or generated during the study 
are considered proprietary and may not be disclosed in whole or in part without the 
expressed, written consent of Aeon Biopharma, Inc. 
The study will be conducted according to the International Council for Harmonisation of 
Technical Requirements for Pharmaceuticals for Human Use (ICH) guideline E6 (R2): Good 
Clinical Practice (GCP). 
 










Aeon Biopharma, Inc. 
ABP-450 
Protocol: ABP-19000 (Version 2.1) 
13 May 2021 
 
 
Declaration of Investigator 
I have read and understood all sections of the protocol entitled “A Phase 2, Randomized, 
Double-Blind, Multicenter, Placebo-Controlled Study to Evaluate the Safety and Efficacy of 
Intramuscular ABP-450 (prabotulinumtoxinA) Injection for the Treatment of Cervical 
Dystonia” and the accompanying investigator’s brochure. 
I agree to supervise all aspects of the protocol and to conduct the clinical investigation in 
accordance with the Final Protocol Version 2.1, dated 13 May 2021, the International Council 
for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) 
guideline E6(R2): Good Clinical Practice and all applicable government regulations. I will 
not make changes to the protocol before consulting with Aeon Biopharma, Inc. or implement 
protocol changes without independent ethics committee approval except to eliminate an 
immediate risk to patients. I agree to administer investigational study drug only to patients 
under my personal supervision or the supervision of a subinvestigator. 
I will not supply the investigational study drug to any person not authorized to receive it. 
Confidentiality will be protected. Patient identity will not be disclosed to third parties or 
appear in any study reports or publications. 
I will not disclose information regarding this clinical investigation or publish results of the 
investigation without authorization from Aeon Biopharma, Inc. 
 
 
 
 
Signature of Principal Investigator 
 
Date 
 
 
 
Printed Name of Principal Investigator 
 
 
 


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Table of Contents 
Table of Contents ............................................................................................................... 7 
List of Tables .................................................................................................................... 10 
List of Figures .................................................................................................................. 10 
Protocol Synopsis............................................................................................................. 11 
List of Abbreviations........................................................................................................ 23 
1 
Introduction .............................................................................................................. 25 
2 
Study Objectives and Estimands .............................................................................. 27 
2.1 
Study Objectives ............................................................................................. 27 
2.1.1 
Primary Objective ............................................................................ 27 
2.1.2 
Secondary Objective ........................................................................ 27 
2.2 
Study Estimands.............................................................................................. 27 
2.2.1 
Target Population ............................................................................. 27 
2.2.2 
Primary Estimand ............................................................................ 27 
2.2.3 
Secondary Estimands ....................................................................... 28 
3 
Investigational Plan .................................................................................................. 29 
3.1 
Study Design ................................................................................................... 29 
3.1.1 
Rationale for Study Design .............................................................. 30 
3.1.2 
Conduct of the Study During the COVID-19 Pandemic ................. 31 
4 
Patient Selection and Withdrawal Criteria ............................................................... 32 
4.1 
Selection of Study Population ......................................................................... 32 
4.1.1 
Inclusion Criteria ............................................................................. 32 
4.1.2 
Exclusion Criteria ............................................................................ 33 
4.1.3 
Rescreening ...................................................................................... 34 
4.2 
Withdrawal of Patients from the Study ........................................................... 34 
4.2.1 
Reasons for Withdrawal/Discontinuation ........................................ 34 
4.2.2 
Handling of Withdrawals ................................................................. 35 
4.2.3 
Replacements ................................................................................... 36 
5 
Study Treatments ...................................................................................................... 37 
5.1 
Method of Assigning Patients to Treatment Groups ....................................... 37 
5.2 
Treatments Administered ................................................................................ 37 


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5.3 
Identity of Investigational Product.................................................................. 38 
5.4 
Management of Clinical Supplies ................................................................... 39 
5.4.1 
Investigational Study Drug Packaging and Storage ........................ 39 
5.4.2 
Test Article Accountability .............................................................. 39 
5.4.3 
Other Supplies.................................................................................. 40 
5.5 
Overdose Management ................................................................................... 40 
5.5.1 
Treatment of Overdose .................................................................... 40 
5.6 
Blinding........................................................................................................... 40 
5.6.1 
Breaking the Blind ........................................................................... 41 
5.7 
Treatment Compliance .................................................................................... 41 
5.8 
Prior and Concomitant Therapy ...................................................................... 41 
6 
Study Assessments and Procedures .......................................................................... 42 
6.1 
Study Visits ..................................................................................................... 42 
6.2 
Safety Assessments ......................................................................................... 44 
6.2.1 
Adverse Events ................................................................................ 45 
6.2.1.1 
Definitions of Adverse Events ......................................................... 45 
6.2.1.2 
Serious Adverse Events ................................................................... 45 
6.2.1.3 
Eliciting and Documenting Adverse Events .................................... 45 
6.2.1.4 
Reporting Adverse Events ............................................................... 46 
6.2.1.5 
Reporting Serious Adverse Events .................................................. 47 
6.2.1.6 
Suspected Unexpected Serious Adverse Reactions and Non-Serious 
Adverse Events of Special Interest .................................................. 47 
6.2.1.7 
Assessment of Severity .................................................................... 48 
6.2.1.8 
Assessment of Causality .................................................................. 48 
6.2.1.9 
Follow-Up of Patients Reporting Adverse Events ........................... 49 
 
 
 
 
 
 
 
 
6.3 
Efficacy Assessments ...................................................................................... 50 
6.3.1 
TWSTRS Scale ................................................................................ 50 
6.3.2 
PGI-C and CGI-C Scales ................................................................. 50 
6.3.3 
PGI-S and CGI-S Scales .................................................................. 51 
6.3.4 
C-SSRS ............................................................................................ 51 
6.3.5 
Dysphagia Score .............................................................................. 51 


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6.4 
Safety Monitoring Committee ........................................................................ 52 
6.5 
Pregnancy ........................................................................................................ 52 
6.6 
Laboratory Analyses ....................................................................................... 52 
6.7 
Sample Collections ......................................................................................... 53 
7 
Statistical Considerations ......................................................................................... 54 
7.1 
Estimands ........................................................................................................ 54 
7.2 
Sample Size Calculations ................................................................................ 54 
7.3 
Analysis Sets ................................................................................................... 54 
7.4 
Description of Subgroups to be Analyzed ...................................................... 55 
7.5 
Statistical Analysis Methodology ................................................................... 55 
7.5.1 
Analysis of Primary Estimand ......................................................... 55 
7.5.2 
Analysis of Secondary Estimands ................................................... 55 
7.5.3 
Safety Analyses ................................................................................ 56 
7.5.4 
Other Analyses ................................................................................. 56 
7.5.5 
Interim Analyses .............................................................................. 56 
8 
Data Quality Assurance ............................................................................................ 57 
8.1 
Data Management ........................................................................................... 57 
9 
Ethics ........................................................................................................................ 58 
9.1 
Independent Ethics Committee or Institutional Review Board ...................... 58 
9.2 
Ethical Conduct of the Study .......................................................................... 58 
9.3 
Patient Information and Consent .................................................................... 58 
10 Investigator’s Obligations ........................................................................................ 59 
10.1 Confidentiality ................................................................................................ 59 
10.2 Financial Disclosure and Obligations ............................................................. 59 
10.3 Investigator Documentation ............................................................................ 60 
10.4 Study Conduct ................................................................................................. 60 
10.5 Adherence to Protocol..................................................................................... 60 
10.6 Adverse Events and Study Report Requirements ........................................... 61 
10.7 Investigator’s Final Report ............................................................................. 61 
10.8 Records Retention ........................................................................................... 61 
10.9 Publications ..................................................................................................... 61 


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11 Study Management ................................................................................................... 61 
11.1 Monitoring ...................................................................................................... 62 
11.1.1 
External Data Monitoring Committee ............................................. 62 
11.1.2 
Monitoring of the Study ................................................................... 62 
11.1.3 
Inspection of Records ...................................................................... 62 
11.2 Management of Protocol Amendments and Deviations.................................. 62 
11.2.1 
Modification of the Protocol ............................................................ 62 
11.2.2 
Protocol Deviations.......................................................................... 63 
11.3 Study Termination ........................................................................................... 63 
11.4 Final Report .................................................................................................... 63 
12 References ................................................................................................................ 65 
13 Appendices ............................................................................................................... 67 
13.1 Schedule of Events .......................................................................................... 67 
13.2 TWSTRS Scale ............................................................................................... 71 
13.3 Dysphagia Severity Scale ............................................................................... 76 
13.4 CGI-S and CGI-C Scales ................................................................................ 77 
13.5 PGI-S Scale ..................................................................................................... 78 
13.6 PGI-C Scale .................................................................................................... 79 
13.7 C-SSRS Scale.................................................................................................. 80 
 
List of Tables 
 
 
Table 13-1 
Schedule of Events .......................................................................................... 67 
 
List of Figures 
Figure 3-1 
Study Design ................................................................................................... 30 
 


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Protocol Synopsis 
Protocol Number: 
ABP-19000 
Title: 
A Phase 2, Randomized, Double-Blind, Multicenter, 
Placebo-Controlled Study to Evaluate the Safety and Efficacy of 
Intramuscular ABP-450 (prabotulinumtoxinA) Injection for the 
Treatment of Cervical Dystonia 
Sponsor: 
Aeon Biopharma, Inc. 
 
 
Study Phase: 
2 
Study Sites: 
Approximate number of total sites in the United States: 42 
Indication: 
Cervical dystonia  
Rationale: 
Cervical dystonia (spasmodic torticollis) is the most common 
form of focal dystonia, affecting the neck and shoulder muscles. 
Cervical dystonia is characterized by abnormal head and neck 
posture and involuntary head and neck movements. It is often 
associated with neck and shoulder pain. 
Botulinum toxin A is considered first-line therapy for cervical 
dystonia, helping to improve pain, posture, and disability. 
ABP-450 (prabotulinumtoxinA) is a toxin produced by 
Clostridium botulinum. It blocks neuromuscular transmission by 
binding to acceptor sites on motor nerve terminals, entering the 
nerve terminals, and inhibiting the release of acetylcholine. 
Blocking the release of acetylcholine plays a role in relaxing 
muscles by reducing muscle activity. 
 
 
 
 
 
 
 
 






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13 May 2021 
 
 
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o Any ABP-450 dose. 
Treatment-related SAEs are counted during a single 
treatment cycle (up to 20 weeks and prior to 
administering any further treatment) and irrespective of 
change in background treatment or low doses that were 
below the set low-dose amount (ie, below 150 units) or 
high doses that were above the set high-dose amount (ie, 
above 350 units). 
Secondary Estimands 
• Mean difference in change in Toronto Western 
Spasmodic Torticollis Rating Scale (TWSTRS) total 
score from baseline to Week 4 for each of low, medium, 
and high doses of ABP-450 compared with placebo. This 
is the hypothetical estimand, assuming no change in 
background treatment or further treatment before Week 4 
and administration of treatment with the correct dose 
amount. 
• Mean difference in change in the subscale scores of the 
TWSTRS (disability, severity, and pain) from baseline to 
Week 4 for each of low, medium, and high doses of 
ABP-450 compared with placebo. This is the 
hypothetical estimand assuming no change in 
background treatment or further treatment before Week 4 
and administration of treatment with the correct dose 
amount. 
• Mean difference in change in scores on the Clinical 
Global Impression of Severity, Patient Global Impression 
of Severity, Clinical Global Impression of Change, and 
Patient Global Impression of Change from baseline to 
Week 4 for each of low, medium, and high doses of 
ABP-450 compared with placebo. This is the 
hypothetical estimand, assuming no change in 
background treatment or further treatment before Week 4 


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Page 15 
and administration of treatment with the correct dose 
amount. 
For all estimands, the target population is patients diagnosed 
with cervical dystonia who have not had previous treatment with 
botulinum toxin within the last 16 weeks, are receiving stable 
doses of treatment for focal dystonia (eg, anticholinergics and 
benzodiazepines), and who meet the inclusion/exclusion criteria. 
Study Population: 
Inclusion Criteria 
Each patient must meet all of the following criteria to be 
enrolled in this study: 
1. Male or female patients between 18 and 75 years of age 
(inclusive) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4. 
 
 
 
 
 
 
 
 
 


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6. Provided written informed consent to participate in the 
study. 
 
7. Stated willingness to comply with all study procedures, 
including attendance at the study center for all study 
visits as scheduled and have technological capabilities to 
have tele visits with video capabilities 
 
Exclusion Criteria 
Patients who meet any of the following criteria will be excluded 
from the study: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 




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Study Design: 
This is a Phase 2, multicenter, randomized, double-blind, 
placebo-controlled study of ABP-450 purified neurotoxin 
complex for the treatment of cervical dystonia. 
Both previously treated patients and those who have never been 
exposed to botulinum toxin (naïve patients) will be eligible. 
Pre-treated patients must be stable responders who are receiving 
no more than 300 units of botulinum toxin type A or 750 units 
abobotulinumtoxinA. The last injection for those previously 
treated should be at least 16 weeks prior to treatment in 
ABP-19000. Botulinum toxin–naïve patients are defined as 
those not receiving treatment with a botulinum toxin in the head 
or neck. 
Patients will be randomly assigned (ratio of 1:1:1:1) into 1 of 
4 treatment arms: ABP-450 low dose (150 units), ABP-450 
medium dose (250 units), ABP-450 high dose (350 units), or 
placebo. The investigator will be blinded to the dose level. The 
doses will be prepared to the same volume using appropriate 
dilution as per the dose level. The volume injected will be 
equivalent across the doses and placebo. To ensure balance 
across the treatment groups, randomization will be stratified by 
previous treatment with BOTOX® (BOTOX® naïve vs. 
previously treated with BOTOX® within 4-12 months prior to 
baseline). The safety and efficacy of the three dose cohorts of 
ABP-450 or placebo will be evaluated over a maximum of 
20 weeks. At the completion of the Phase 2 study, all patients, 
irrespective of treatment group, will have the option to receive 
treatment with ABP-450 by rolling over into an open-label 
extension (OLE) study (ABP-19002). 
 
 
 
 
 
 
 


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Estimated Study 
Duration: 
Estimated duration of the study will be approximately 21 weeks, 
including 1 week of Screening. Patients will be followed up to 
20 weeks after the initial treatment. 
Safety Assessments: 
Safety will be evaluated by frequency, severity, and duration of 
any adverse reactions. Adverse events will be assessed at each 
office visit and telephone contact. 
 
 
 
 
 
 
 
 
 
 
 
 
Study Drug, Dosage, 
and Route of 
Administration: 
Study drug is a Clostridium botulinum toxin type A 
• Investigational study drug vials contain 100 units of 
lyophilized ABP-450 
• Placebo vials contain sodium chloride for injection, USP, 
0.9%, preservative-free 


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The dose to be administered to patients in the study will range 
between 150 units and 350 units. 
Active Treatment Arms 
Dose 
ABP-450 low dose 
150 units 
ABP-450 medium dose 
250 units 
ABP-450 high dose 
350 units 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
The dose should be divided among the affected muscles. Dosing 
in initial sessions should be tailored to the individual patient 
based on the patient's head and neck position, localization of 
pain, muscle hypertrophy, patient response, and adverse event 
history. The use of electromyographic guidance or ultrasound 
imaging should be left to the PI. 
 
 
 
 




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summarized separately for ABP-450 (all doses together and 
separately) and placebo. 
 
 
 
 
Treatment-related SAEs will be counted if they start prior to 
administering any further treatment irrespective of change to 
background treatment or low doses that were below the set 
low-dose amount (ie, below 150 units) or high doses that were 
above the set high-dose amount (ie, above 350 units). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Version and Date of 
Protocol: 
Version 2.0 dated 19 November 2020 


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List of Abbreviations 
Abbreviation 
Definition 
ABP-450 
prabotulinumtoxinA / Jeuveau (prabotulinumtoxinA-xvfs) 
AE 
adverse event 
ANCOVA 
analysis of covariance 
BOTOX® 
onabotulinumtoxinA 
Dysport® 
abobotulinumtoxinA 
CFR 
Code of Federal Regulations 
CGI-C 
Clinical Global Impression of Change 
CGI-S 
Clinical Global Impression of Severity 
CSR 
clinical study report 
C-SSRS 
Columbia–Suicide Severity Rating Scale 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EMG 
electromyographic 
EOS 
end of study 
FAS 
Full Analysis Set 
FDA 
United States Food and Drug Administration 
FEV1 
forced expiratory volume in 1 second 
FVC 
forced vital capacity 
GCP 
Good Clinical Practice 
HbA1c 
hemoglobin A1c 
ICF 
informed consent form 
ICH 
International Council for Harmonisation of Technical Requirements 
for Pharmaceuticals for Human Use 
IEC 
independent ethics committee 


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Abbreviation 
Definition 
IRB 
institutional review board 
IRT 
interactive response technology 
MedDRA 
Medical Dictionary for Regulatory Activities 
mFAS 
Modified Full Analysis Set 
OLE 
open-label extension 
PGI-C 
Patient Global Impression of Change 
PGI-S 
Patient Global Impression of Severity 
PI 
principal investigator 
PPS 
Per-Protocol Analysis Set 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SUSAR 
suspected unexpected serious adverse reaction 
TWSTRS 
Toronto Western Spasmodic Torticollis Rating Scale 
 




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PrabotulinumtoxinA has also been found to be non-inferior to onabotulinumtoxinA 
(BOTOX®) for the treatment of moderate to severe glabellar lines in adult patients and for 
upper limb spasticity in stroke patients (Nam 2015, Rzany 2019). The doses of ABP-450 
used in the Phase 3 study for upper limb spasticity were similar to the doses of BOTOX® 
used (no significant differences were seen between the two groups) (Nam 2015). 
This Phase 2, multicenter, randomized, double-blind, active- and placebo-controlled study 
aims to demonstrate the safety and efficacy of ABP-450 doses (low, medium, and high) 
compared with placebo in patients with cervical dystonia. The current Phase 2 study will help 
to determine appropriate doses of ABP-450 in this study population. 
Clostridium botulinum toxins have become the standard of care for the treatment of patients 
with cervical dystonia. In addition to onabotulinumtoxinA, abobotulinumtoxinA, 
incobotulinumtoxinA, and rimabotulinumtoxinB have been approved for the treatment of 
patients with cervical dystonia. Even though these toxin products have been approved for the 
treatment of cervical dystonia and are the standard of care in patients with this condition, 
they do have significant risks associated with their use in these patients. The labels for all 
these products carry prominent warnings concerning their side effects, such as dysphagia and 
even death, if they are not carefully administered and the patient monitored while under 
treatment. Even so, the benefit for all these products is greater than the risks and that is why 
these products are the standard of care. 
Clinical development of drugs has been impacted by the ongoing COVID-19 pandemic. The 
current study aims to implement several adjustments or mitigations to allow the study to 
continue despite pandemic-related disruption. To prioritize patient and site staff safety, 
several planned office visits have been converted to tele visits to allow the required data 
collection to meet the study objectives. 
 


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2 Study Objectives and Estimands 
2.1 Study Objectives 
2.1.1 Primary Objective 
• To demonstrate the safety of a single treatment of ABP-450 (low, medium, or high 
dose) compared with placebo in the treatment of cervical dystonia 
2.1.2 Secondary Objective 
• To demonstrate the efficacy of a single treatment of ABP-450 (low, medium, or high 
dose) at Week 4 compared with placebo in the treatment of cervical dystonia 
2.2 Study Estimands 
2.2.1 Target Population 
For all estimands, the target population is patients diagnosed with cervical dystonia. The 
patients are expected to: 
• Have not had previous treatment with a botulinum toxin within the last 16 weeks; 
• Be receiving stable doses of treatment for focal dystonia (eg, anticholinergics and 
benzodiazepines); and 
• Meet the inclusion/exclusion criteria. 
2.2.2 Primary Estimand 
• Proportion of patients who would develop treatment-related serious adverse events 
(SAEs) during the first 20 weeks of a single treatment cycle when dosed with: 
o Placebo; 
o Low-dose ABP-450 (150 units); 
o Medium-dose ABP-450 (250 units); 
o High-dose ABP-450 (350 units); or 
o Any ABP-450 dose. 


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Treatment-related SAEs are counted during a single treatment cycle (up to 20 weeks and 
prior to administering any further treatment) and irrespective of change in background 
treatment or low doses that were below the set low-dose amount (ie, below 150 units) or high 
doses that were above the set high-dose amount (ie, above 350 units). 
2.2.3 Secondary Estimands 
• Mean difference in change in Toronto Western Spasmodic Torticollis Rating Scale 
(TWSTRS) total score from baseline to Week 4 for each of low, medium, and high 
doses of ABP-450 compared with placebo. 
 
 
 
• Mean difference in change in the subscale scores of the TWSTRS (disability, severity, 
and pain) from baseline to Week 4 for each of low, medium, and high doses of 
ABP-450 compared with placebo. 
 
 
 
• Mean difference in change in scores on the Clinical Global Impression of Severity 
(CGI-S), Patient Global Impression of Severity (PGI-S), Clinical Global Impression 
of Change (CGI-C), and Patient Global Impression of Change (PGI-C) from baseline 
to Week 4 for each of low, medium, and high doses of ABP-450 compared with 
placebo. 
 
 
 


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3 Investigational Plan 
3.1 Study Design 
This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled study of 
ABP-450 purified neurotoxin complex for the treatment of cervical dystonia. 
Both previously treated patients and those who have never been exposed to botulinum toxin 
(naïve patients) will be eligible. Pre-treated patients must be stable responders who are 
receiving no more than 300 units of botulinum toxin type A or 750 units 
abobotulinumtoxinA. The last injection for those previously treated should be at least 16 
weeks prior to treatment in ABP-19000. Botulinum toxin–naïve patients are defined as those 
not receiving treatment with a botulinum toxin in the head or neck. 
Patients will be randomly assigned (ratio of 1:1:1:1) into 1 of 4 treatment arms: ABP-450 low 
dose (150 units), ABP-450 medium dose (250 units), ABP-450 high dose (350 units), or 
placebo. The investigator will be blinded to the dose level. The doses will be prepared to the 
same volume using appropriate dilution as per the dose level. The volume injected will be 
equivalent across the doses and placebo. To ensure balance across the treatment groups, 
randomization will be stratified by previous treatment with BOTOX® (BOTOX® naïve vs. 
previously treated with BOTOX® within 4-12 months prior to baseline). The safety and 
efficacy of the three dose cohorts of ABP-450 or placebo will be evaluated over a maximum 
of 20 weeks. At the completion of the Phase 2 study, all patients, irrespective of treatment 
group, will have the option to receive treatment with ABP-450 by rolling over into an 
open-label extension (OLE) study (ABP-19002). 
 
 
 
 
 
 
 
 
 
 
 
 
 




 
 
 
 
 
 
 
 
 
 
 
 
 
3.1.2 Conduct of the Study During the COVID-19 Pandemic 
Coronavirus Disease 2019 (COVID-19) is a viral illness caused by the severe acute 
respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and has impacted most of the 
countries across the globe. It was declared as a global public health emergency by the World 
Health Organization on 30 January 2020. This pandemic is recognized to have impacted the 
conduct of clinical trials of medical products in various ways. 
The safety and well-being of patients and site staff is of paramount importance during the 
COVID-19 pandemic. Measures will be implemented during the study to reduce the chance 
that study drug will be administered to patients who are infected with SARS-CoV-2. 
Testing for COVID-19 will be performed as required by the individual sites in case deemed 
necessary by the PI as per institutional standards. If a patient tests positive, study visits will 
be delayed until the patient recovers. The investigator will provide the patients with guidance 
of further clinical care for their SARS-CoV-2 infection. If the result is indeterminate, the 
PCR testing may need to be repeated as per institutional standards. 
Other potential measures will be taken to assure the safety and welfare of patients, 
maintaining compliance with GCP, and minimizing risks to trial integrity during the 
COVID-19 pandemic, such as tele visits. Any other potential measures or changes will be 
handled according to the regulations. 
Any events of COVID-19, including asymptomatic and symptomatic SARS-CoV-2 infection 
(i.e., COVID-19), are to be reported as AEs per Section 6.2.1. 
 
 
 
All the measures taken in relation to COVID-19 will be reported to the regulatory authorities 
as appropriate. 
 
 


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4 Patient Selection and Withdrawal Criteria 
4.1 Selection of Study Population 
Approximately 60 patients will be enrolled at approximately 42 sites in the United States. 
Patients will be assigned to investigational study drug only if they meet all of the inclusion 
criteria and none of the exclusion criteria. Patients who fail their initial Screening will be 
allowed to present for rescreening once, if approved in advance by the medical monitor (see 
Section 4.1.3). 
4.1.1 
Inclusion Criteria 
Each patient must meet all of the following criteria to be enrolled in this study: 
1. Male or female patients between 18 and 75 years of age (inclusive) 
2. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
6. Provided written informed consent to being treated for cervical dystonia with 
ABP-450 
7. Stated willingness to comply with all study procedures, including attendance at the 
study center for all study visits as scheduled and have technological capabilities to 
have tele visits 


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4.1.2 
Exclusion Criteria 
Patients who meet any of the following criteria will be excluded from the study: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
12. Participation in another interventional study during participation in this study 


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13. Pregnant or lactating females, or females of child-bearing potential not willing to use 
an acceptable method of contraception (ie, intrauterine device, barrier methods with 
spermicide, or abstinence) 
14. For pre-treated patients only: The patient’s most recent injection with botulinum toxin 
exceeding the number of units specified as follows (Dashtipour 2016): 
• OnabotulinumtoxinA (BOTOX®): >300 units 
• IncobotulinumtoxinA (Xeomin®): >300 units 
• AbobotulinumtoxinA (Dysport®): >750 units 
4.1.3 
Rescreening 
A screen failure is a patient who has given informed consent and failed to meet all of the 
inclusion criteria and/or met at least one of the exclusion criteria and has not been 
randomized (eg, due to a viral or other active infection, or repeat laboratory test result outside 
of reference range). Patients who fail their initial Screening will be allowed to present for 
rescreening once, if approved in advance by the medical monitor. Rescreen requests must be 
discussed with the medical monitor prior to rescreening the patient, including what has 
changed about the patient's medical status. 
Patients who present for rescreening will be assigned a new Screening number. The 
investigator or designee will record rescreening data on the source document and the 
appropriate eCRF. Details for rescreening procedures will be provided in the IRT manual. 
4.2 
Withdrawal of Patients from the Study 
Estimated duration of the study will be approximately 21 weeks, including 1 week of 
Screening. Patients will be followed up to 20 weeks after the initial treatment. 
4.2.1 
Reasons for Withdrawal/Discontinuation 
Patients may withdraw from the study at any time and for any reason without prejudice to 
their future medical care by the investigator or at the study site. Every effort should be made 
to keep patients in the study. The reasons for patients not completing the study will be 
recorded. A patient may be withdrawn from the study for any of the following reasons: 
1. The patient does not meet the protocol inclusion or exclusion criteria at the baseline 
visit. 
2. 
 


 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
9. The patient withdraws consent. 
The investigator will also withdraw a patient if Aeon Biopharma terminates the study. Upon 
occurrence of a serious or intolerable AE, the investigator will confer with the sponsor. If a 
patient is discontinued because of an AE, the event will be followed until it is resolved. 
4.2.2 
Handling of Withdrawals 
Patients are free to withdraw from the study or investigational study drug at any time upon 
their request. Patient participation in the study may be stopped at any time at the discretion of 
the investigator or at the request of the sponsor. 
 
 
 
 
 
 
 
 
 
 
 
 


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It is vital to obtain follow-up data on any patient withdrawn because of an AE or SAE. In 
every case, efforts must be made to undertake protocol-specified, safety, follow-up 
procedures. 
4.2.3 
Replacements 
Patients who discontinue prematurely from the study will not be replaced. 
 


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5 Study Treatments 
5.1 
Method of Assigning Patients to Treatment Groups 
Patients will be randomly assigned at the baseline visit (Visit 2) to receive ABP-450 low dose 
(150 units), ABP-450 medium dose (250 units), ABP-450 high dose (350 units), or placebo 
using a 1:1:1:1 allocation ratio. To ensure balance across the treatment groups, randomization 
will be stratified by previous treatment with BOTOX® (BOTOX® naïve vs. previously treated 
with BOTOX® within 4-12 months prior to baseline).
 
 
 
 
 
5.2 
Treatments Administered 
Investigational study drug is a Clostridium botulinum toxin type A 
• Investigational study drug vials contain 100 units of lyophilized ABP-450 
• Placebo vials contain sodium chloride for injection, USP, 0.9%, preservative-free 
The dose to be administered to patients in the study will range between 150 units and 
350 units. 
Active Treatment Arms 
Dose 
ABP-450 low dose 
150 units 
ABP-450 medium dose 
250 units 
ABP-450 high dose 
350 units 
 
 
 
 
 
 
 
 
 
 


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5.3 
Identity of Investigational Product 
ABP-450 is lyophilized powder packed in vials containing 100 units. Placebo will be sodium 
chloride for injection, USP, 0.9%, preservative-free (from the same lot that is used for 
reconstitution of the toxin[s]). 
 
 


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The following drug supplies will be used in the study: 
Product 
Supplied as: 
ABP-450 
100 units of lyophilized powder packed in 10-mL vials 
Placebo 
Sodium chloride injection, USP, 0.9%, preservative-free, 10-mL vials 
 
5.4 
Management of Clinical Supplies 
5.4.1 
Investigational Study Drug Packaging and Storage 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
5.4.2 
Test Article Accountability 
The investigator will maintain accurate records of receipt of all test articles, including dates 
of receipt. In addition, accurate records will be kept regarding when and how much test 
article is dispensed and used by each patient in the study. Reasons for departure from the 
expected dispensing regimen must also be recorded. At the completion of the study, to satisfy 


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regulatory requirements regarding drug accountability, all investigational study drugs will be 
reconciled and retained or destroyed according to applicable regulations. 
5.4.3 
Other Supplies 
 
 
 
5.5 
Overdose Management 
An overdose is any dose of investigational study drug given to a patient or taken by a patient 
that exceeds the dose described in the protocol.
 
 Overdoses without signs or 
symptoms do not need to be recorded as AEs; in case of any AEs associated with the 
overdose, these should be reported on relevant AE/SAE sections in the eCRF. 
5.5.1 
Treatment of Overdose 
Treatment of suspected overdose of investigational study drugs should include 
investigational study drug discontinuation and implementation of appropriate supportive 
measures. 
5.6 
Blinding 
The investigator will be blinded to the dose level. The volume injected will be equivalent 
across the doses and placebo. To ensure blinding, an appropriate and protocol-trained person 
at each site, such as a study nurse or other designee, will reconstitute investigational product 
vials in a manner blinded to the investigator and patient. 
 
 
 
 
 
 The designated person will then fill the syringe with the investigational product and 
give the filled syringe in a blinded fashion to the investigator. Appropriate spatial separation 
is required to ensure blinding. Blinding for the initial phase will be maintained throughout 
the study until the final assessment for the final patient has been entered into the database and 
the database lock has been performed. 


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5.6.1 
Breaking the Blind 
A patient’s treatment assignment will not be broken until the end of the study unless medical 
treatment of the patient depends on knowing the study treatment the patient received. In the 
event that the blind needs to be broken because of a medical emergency, the investigator may 
unblind an individual patient’s treatment allocation. 
As soon as possible, the investigator should first contact the medical monitor to discuss the 
medical emergency and the reason for revealing the actual treatment received by that patient. 
The treatment assignment will be unblinded through IRT. Reasons for treatment unblinding 
must be clearly explained and justified in the eCRF. The date on which the code was broken 
along with the identity of the person responsible must also be documented. 
5.7 
Treatment Compliance 
Patient compliance will be determined by capturing the precise dose administered and the 
time and date of dosing in the source document and the dosage administration eCRF. Delays 
in dosing and the reason for any delay in dosing is to be recorded on the dosage 
administration eCRF. 
5.8 
Prior and Concomitant Therapy 
Use of all concomitant medications will be recorded in the patient’s eCRF. The minimum 
requirement is that drug name, dose, and dates of administration are to be recorded. This will 
include all prescription drugs, herbal products, vitamins, minerals, and over-the-counter 
medications. Any changes in concomitant medications also will be recorded in the patient’s 
eCRF. 
Any concomitant medication deemed necessary for the welfare of the patient during the 
study may be given at the discretion of the investigator. However, it is the responsibility of 
the investigator to ensure that details regarding the medication are recorded in full in the 
eCRF. 


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6 Study Assessments and Procedures 
Before performing any study procedures, all potential patients will sign an informed consent 
form (ICF). Patients will have the opportunity to have any questions answered before signing 
the ICF. The investigator must address all questions raised by the patient. The investigator or 
designee will also sign the ICF. 
6.1 
Study Visits 
Estimated duration of the study is approximately 21 weeks, including 1 week of Screening. 
The schedule of assessments is detailed in Section 13.1. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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6.2 
Safety Assessments 
Safety will be evaluated by frequency, severity, and duration of any adverse reactions. 
Adverse events will be assessed at each office visit and telephone contact. 
 
 
 
 
 
 
 
 
 


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6.2.1 
Adverse Events 
6.2.1.1 
Definitions of Adverse Events 
The investigator is responsible for reporting all AEs that are observed or reported during the 
study, regardless of their relationship to investigational study drugs. The investigator will 
query the patient for changes since last visit and ask about the patient’s ability to swallow. 
An AE is defined as any untoward medical occurrence in a patient enrolled into this study 
regardless of its causal relationship to investigational study drugs. Patients will be instructed 
to contact the investigator at any time after randomization if any symptoms develop. 
A treatment-emergent AE is defined as any event not present before exposure to 
investigational study drugs or any event already present that worsens in either intensity or 
frequency after exposure to investigational study drugs. 
6.2.1.2 
Serious Adverse Events 
An SAE is defined as any event that 
• Results in death 
• Is immediately life-threatening 
• Requires inpatient hospitalization or prolongation of existing hospitalization 
• Results in persistent or significant disability/incapacity 
• Is a congenital anomaly/birth defect 
 
 
 
 
 
 
 
6.2.1.3 
Eliciting and Documenting Adverse Events 
Adverse events will be assessed from the time the patient signs the ICF until exit from the 
study (20 weeks after initial treatment). 


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Serious AEs that occur more than 90 days after the last dose of investigational study drug and 
the patient has exited the study need not be reported unless the investigator considers them 
related to investigational study drug. 
At every study visit, patients will be asked a standard non-leading question to elicit any 
medically related changes in their well-being. They will also be asked if they have been 
hospitalized, had any accidents, used any new medications, or changed concomitant 
medication regimens (both prescription and over-the-counter medications). 
In addition to patient observations, AEs identified from any study data (eg, laboratory values, 
physical examination findings, ECG changes) or identified from review of other documents 
that are relevant to patient safety will be documented on the AE page in the eCRF. 
6.2.1.4 
Reporting Adverse Events 
All AEs reported or observed during the study will be recorded on the AE page in the eCRF. 
Information to be collected includes the following: 
• Drug treatment 
• Dose 
• Event term 
• Time of onset 
• Investigator-specified assessment of severity and relationship to investigational study 
drugs 
• Time of resolution of the event 
• Seriousness 
• Any required treatment or evaluations 
• Outcome 
Adverse events resulting from concurrent illnesses, reactions to concurrent illnesses, 
reactions to concurrent medications, or progression of disease states must also be reported. 
All AEs will be followed to adequate resolution. The Medical Dictionary for Regulatory 
Activities (MedDRA) will be used to code all AEs. 
Any medical condition that is present at the time that the patient is screened but does not 
deteriorate should not be reported as an AE. However, if it deteriorates at any time after 
Screening visit, it should be recorded as an AE. 


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6.2.1.5 
Reporting Serious Adverse Events 
 
 
 
 
 
 
 
 
The sponsor or its designee is responsible for reporting relevant SAEs to the competent 
authority, other applicable regulatory authorities, and participating investigators, in 
accordance with the ICH guidelines and/or local regulatory requirements. 
The sponsor is responsible for reporting unexpected fatal or life-threatening events associated 
with the use of the investigational study drugs (expedited reports) to the regulatory agencies 
and competent authorities by telephone or fax within 7 calendar days after being notified of 
the event. The sponsor should report other relevant SAEs associated with the use of the 
investigational study drugs to the appropriate competent authorities (according to local 
guidelines), investigators, and the institutional review board (IRB) by a written safety report 
within 15 calendar days of notification. 
6.2.1.6 
Suspected Unexpected Serious Adverse Reactions and 
Non-Serious Adverse Events of Special Interest 
The sponsor will promptly evaluate all suspected unexpected serious adverse reactions 
(SUSARs) and non-serious AEs of special interest against cumulative investigational study 
drug experience to identify and expeditiously communicate possible new safety findings to 
investigators, IRBs/independent ethics committees (IECs), and applicable health authorities 
based on applicable legislation. 
 
 
 
 
 
 
 


 
 
 
 
 
 
 
 
 
6.2.1.7 
Assessment of Severity 
The severity, or intensity, of an AE refers to the extent to which an AE affects the patient’s 
daily activities. The intensity of the AE will be rated as mild, moderate, or severe using the 
following criteria: 
Mild: 
An event usually transient in nature and generally not interfering with normal 
activities. 
Moderate: 
An AE that is sufficiently discomforting to interfere with normal activities. 
Severe: 
An AE that is incapacitating and prevents normal activities. 
Changes in the severity of an AE should be documented to allow an assessment of the 
duration of the event at each level of intensity to be performed. AEs characterized as 
intermittent do not require documentation of onset and duration of each episode. 
6.2.1.8 
Assessment of Causality 
The investigator’s assessment of an AE’s relationship to investigational study drugs is part of 
the documentation process, but it is not a factor in determining what is or is not reported in 
the study. If there is any doubt as to whether a clinical observation is an AE, the event should 
be reported. 
The relationship or association of the test article in causing or contributing to the AE will be 
characterized using the following classification and criteria: 
Unrelated: 
This relationship suggests that there is no association between the 
investigational study drugs and the reported event. 
Possible: 
This relationship suggests that treatment with the investigational study drugs 
caused or contributed to the AE, ie, the event follows a reasonable temporal 
sequence from the time of drug administration or follows a known response 
pattern to the investigational study drugs, but could also have been produced by 
other factors. 
Probable: 
This relationship suggests that a reasonable temporal sequence of the event 
with drug administration exists and, based upon the known pharmacological 
action of the drug, known or previously reported adverse reactions to the drug 
or class of drugs, or judgment based on the investigator’s clinical experience, 


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the association of the event with the investigational study drugs seems likely. 
The event disappears or decreases on cessation or reduction of the dose of 
investigational study drugs. 
Definite: 
This relationship suggests that a definite causal relationship exists between drug 
administration and the AE, and other conditions (concurrent illness, 
progression/expression of disease state, or concurrent medication reaction) do 
not appear to explain the event. The event reappears or worsens if the 
investigational study drug is re-administered. 
6.2.1.9 
Follow-Up of Patients Reporting Adverse Events 
All AEs must be reported in detail on the appropriate page in the eCRF and followed to 
satisfactory resolution, until the investigator deems the event to be chronic or not clinically 
significant, or until the patient is considered to be stable. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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6.3 
Efficacy Assessments 
6.3.1 
TWSTRS Scale 
Most studies leading to the approval of currently available botulinum neurotoxins have used 
the TWSTRS scale as the primary efficacy measure (Espay 2018, Fernandez 2013). The 
standard TWSTRS is a comprehensive scale that comprises three subsets to assess motor 
severity, pain, and disability (Comella 2016). The motor severity subscale consists of 
10 items, with variable scaling and weighting. It also includes a disability subscale with 
7 items and a pain scale with 3 items. The total score is the sum of each of the subscales. 
 
 
 
 
 
 
6.3.2 
PGI-C and CGI-C Scales 
The PGI-C enables the patient to rate changes in their perception of their general health 
status over the duration of the assessment via a 7-point scale ranging from “very much 
improved” to “very much worse” (Fischer 1999). For this study, a 5-point generic PGI-C 
scale ranging from “much better” to “much worse” was used (FDA 2018). Similarly, the 
CGI-C is a 7-point scale ranging from “very much improved” to “very much worse” (Guy 
1976) based on the physician’s perception of the patient’s health status. Detailed descriptions 
of the CGI-C and PGI-C are provided in Appendix 13.4 and Appendix 13.6, respectively. 


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6.3.3 
PGI-S and CGI-S Scales 
The PGI-S is a 1-item global index that enables the patient to rate their impression of disease 
severity via a 4-point scale ranging from “normal” to “severely ill” (Guy 1976). The 
appropriateness of the PGI-S scale used depends on the context of use (eg, patient 
population) (FDA 2018). For this study, a 5-point generic PGI-S scale ranging from “none” 
to “very severe” was used. Similarly, the CGI-S enables the clinician to rate the severity of 
the patient’s illness, relative to their past experience with patients who have the same 
diagnosis, on a 7-point scale ranging from “normal” to “among the most extremely ill 
patients” (Guy 1976). Detailed descriptions of the PGI-S and CGI-S are provided in 
Appendix 13.4 and Appendix 13.5, respectively. 
6.3.4 
C-SSRS 
The C-SSRS was developed by the United States Food and Drug Administration (FDA) in 
2012 for measuring suicidal ideation and behavior in clinical trials (Posner 2011). The 
C-SSRS was designed to distinguish the domains of suicidal ideation and suicidal behavior. 
Four constructs are measured. The first is the severity of ideation (hereafter referred to as the 
“severity subscale”), which is rated on a 5-point ordinal scale in which 1=wish to be dead, 
2=non-specific active suicidal thoughts, 3=suicidal thoughts with methods, 4=suicidal intent, 
and 5=suicidal intent with plan. The second is the intensity of ideation subscale (hereafter 
referred to as the “intensity subscale”), which comprises five items, each rated on a 5-point 
ordinal scale: frequency, duration, controllability, deterrents, and reason for ideation. The 
third is the behavior subscale, which is rated on a nominal scale that includes actual, aborted, 
and interrupted attempts; preparatory behavior; and non-suicidal self-injurious behavior. The 
fourth is the lethality subscale, which assesses actual attempts; actual lethality is rated on a 
6-point ordinal scale, and if actual lethality is zero, potential lethality of attempts is rated on a 
3-point ordinal scale (Posner 2011). A detailed description is provided in Appendix 13.7. 
6.3.5 
Dysphagia Score 
 
 
 
 
 


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6.4 
Safety Monitoring Committee 
The medical monitor and sponsor will hold monthly reviews of all AEs; consequently, an 
independent Safety Committee will not be formed for this study. 
6.5 
Pregnancy 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
6.6 
Laboratory Analyses 
Any abnormal laboratory test results 
 
 
 including those that worsen from baseline or are felt to be clinically 
significant in the medical and scientific judgment of the investigator, are to be recorded as 
AEs or SAEs. 
 
 
 
 
However, any clinically significant safety assessments that are associated with the underlying 
disease, unless judged by the investigator to be more severe than expected for the patient’s 
condition, are not to be reported as AEs or SAEs. 


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6.7 
Sample Collections 
Site personnel will collect blood samples at the visits specified in Section 6.1. These samples 
will be processed at the site and shipped same day to a central laboratory, as specified in the 
laboratory manual. 
 
 
 
 
 
 


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7 Statistical Considerations 
This section briefly describes statistical and analytical methods to be used for the study. A 
statistical analysis plan (SAP) will provide details of the statistical methods and definitions 
for the analysis of efficacy and safety data. To preserve the integrity of the statistical analysis 
and study conclusions, the SAP will be finalized before database lock. 
7.1 
Estimands 
 
 
7.2 
Sample Size Calculations 
Fifteen patients will be randomly assigned to each of four treatment arms (placebo, ABP-450 
low dose, ABP-450 medium dose, and ABP-450 high dose) using a 1:1:1:1 ratio and 
therefore requiring a total of 60 patients. 
 
 
 
 
 
 
 
 
 
 
7.3 
Analysis Sets 
The following analysis sets will be used in the statistical analyses. 
Full Analysis Set (FAS): The FAS will consist of all patients who received investigational 
study drug. All analyses using the FAS will group patients according to randomized 
treatment. 
Modified Full Analysis Set (mFAS): The mFAS will consist of all patients in the FAS, but 
will exclude data points after patients have a significant change to their “stable” background 
medication, receive a dose outside of the set dose amounts, or receive further treatment. All 
analyses using the mFAS will group patients according to randomized treatment. 
Per-Protocol Analysis Set (PPS): The PPS will consist of all patients in the FAS who received 
placebo or ABP-450 (according to the set dose amount), but will exclude all patients who 


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discontinued the study prior to Week 4 or had significant protocol violations affecting 
evaluation of the primary endpoint. All analyses using the PPS will group patients according 
to actual treatment received. 
Safety Analysis Set: The Safety Analysis Set will consist of all patients who received any 
investigational study drug. All analyses using the Safety Analysis Set will group patients 
according to treatment actually received. 
7.4 
Description of Subgroups to be Analyzed 
No subgroup analyses are planned. 
7.5 
Statistical Analysis Methodology 
 Variables 
will generally be summarized using number of observations, mean, SD, median, minimum, 
maximum, and missing data (for continuous variables) and using frequencies, percentages, 
and missing data (for categorical variables). Data will be listed in data listings. 
Details of the statistical analyses, methods, and data conventions are described in the SAP. 
 
 
7.5.1 
Analysis of Primary Estimand 
The proportion of patients with treatment-related SAEs up to Week 20 and the end of a single 
treatment cycle will be summarized separately for ABP-450 (all doses together and 
separately) and placebo. 
 
 
 
Treatment-related SAEs will be counted if they start prior to administering any further 
treatment irrespective of change to background treatment or low doses that were below the 
set low-dose amount (ie, below 150 units) or high doses that were above the set high-dose 
amount (ie, above 350 units). 
7.5.2 
Analysis of Secondary Estimands 
The analysis of the first secondary efficacy estimand is based on the comparison of least 
square means 
 
 


 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
7.5.3 
Safety Analyses 
The incidence of treatment-emergent AEs for the Safety Analysis Set will be summarized by 
treatment group. Adverse events will be coded using MedDRA to classify events under 
primary system organ class and preferred term. 
 
 
 
 
 
 
 
 
 
7.5.4 
Other Analyses 
Summary statistical analyses will be provided by treatment group for demographics, 
background characteristics, medical history, and physical examination results. 
7.5.5 
Interim Analyses 
No interim analyses are planned. 


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8 Data Quality Assurance 
The sponsor or its designee will perform the quality assurance and quality control activities 
of this study, including regular monitoring visits to study sites and meeting with site 
personnel. However, the investigator generating the data will be responsible for the accuracy, 
completeness, and reliability of the study data presented to the sponsor. 
8.1 
Data Management 
As part of the responsibilities assumed by participating in the study, the investigator agrees to 
maintain adequate case histories for the patients treated as part of the research under this 
protocol. The investigator agrees to maintain accurate eCRFs and source documentation as 
part of the case histories. These source documents may include laboratory reports and 
 
 
 
All eCRF information is to be filled in. If an item is not available or is not applicable, this 
fact should be indicated. Blank spaces should not be present unless otherwise directed. A 
correction to source documentation should be made by striking through the incorrect entry 
with a single line, and the corrected information should be entered adjacent to the deleted 
item. The correction must be initialed and dated by the person making the correction. 
Investigative site personnel will enter patient data into an electronic data capture system. The 
analysis data sets will be a combination of these data and data from other sources (eg, 
laboratory data). 
Clinical data management will be performed in accordance with applicable Aeon Biopharma 
standards and data cleaning procedures to ensure the integrity of the data, eg, removing errors 
and inconsistencies in the data. Adverse event terms will be coded using MedDRA, an 
internal validated medical dictionary, and concomitant medications will be coded using the 
World Health Organization Drug Dictionary. 
 
 
 
 
 
 


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9 
Ethics 
9.1 
Independent Ethics Committee or Institutional Review Board 
Federal regulations and the ICH guidelines require that approval be obtained from an 
IRB/IEC before participation of human patients in research studies. Before study onset, the 
protocol, informed consent, advertisements to be used for the recruitment of study patients, 
and any other written information regarding this study to be provided to the patient must be 
approved by the IRB/IEC. Documentation of all IRB/IEC approvals and of the IRB/IEC 
compliance with ICH harmonised tripartite guideline E6(R2): Good Clinical Practice (GCP) 
will be maintained by the site and will be available for review by the sponsor or its designee. 
All IRB/IEC approvals should be signed by the IRB/IEC chairman or designee and must 
identify the IRB/IEC name and address, the clinical protocol by title or protocol number or 
both, and the date of approval or the date a favorable opinion was granted. 
The investigator is responsible for providing written summaries of the progress and status of 
the study at intervals not exceeding 1 year or otherwise specified by the IRB/IEC. The 
investigator must promptly supply the sponsor or its designee, the IRB/IEC, and, where 
applicable, the institution with written reports on any changes significantly affecting the 
conduct of the study or increasing the risk to patients. 
9.2 
Ethical Conduct of the Study 
The study will be performed in accordance with the ethical principles that have their origin in 
the Declaration of Helsinki, ICH GCP, the protocol, and all applicable regulations. 
9.3 
Patient Information and Consent 
A written informed consent in compliance with United States Title 21 Code of Federal 
Regulations (CFR) Part 50 shall be obtained from each patient before entering the study or 
performing any study procedure. An informed consent template may be provided by the 
sponsor to investigative sites. If any institution-specific modifications to study-related 
procedures are proposed or made by the site, the consent should be reviewed by the sponsor 
or its designee or both before IRB/IEC submission. Once reviewed, the consent will be 
submitted by the investigator to his or her IRB/IEC for review and approval before the start 
of the study. If the ICF is revised during the course of the study, all active participating 
patients must sign the revised form. 
Before recruitment and enrollment, each prospective patient will be given a full explanation 
of the study and be allowed to read the approved ICF. Once the investigator is assured that 


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the patient understands the implications of participating in the study, the patient will be asked 
to give consent to participate in the study by signing the ICF. 
The investigator shall retain the signed original ICF(s) and give a copy of the signed original 
form to the patient. 
10 Investigator’s Obligations 
The following administrative items are meant to guide the investigator in the conduct of the 
study but may be subject to change based on industry and government standard operating 
procedures, working practice documents, or guidelines. Administrative changes will be 
reported to the IRB/IEC but will not result in protocol amendments. 
10.1 Confidentiality 
All laboratory specimens, evaluation forms, reports, and other records will be identified in a 
manner designed to maintain patient confidentiality. All records will be kept in a secure 
storage area with limited access. Clinical information will not be released without the written 
permission of the patient, except as necessary for monitoring and auditing by the sponsor, its 
designee, the FDA, or the IRB/IEC. 
The investigator and all employees and coworkers involved with this study may not disclose 
or use for any purpose other than performance of the study any data, record, or other 
unpublished, confidential information disclosed to those individuals for the purpose of the 
study. Prior written agreement from the sponsor or its designee must be obtained for the 
disclosure of any said confidential information to other parties. 
10.2 Financial Disclosure and Obligations 
Investigators are required to provide financial disclosure information to allow the sponsor to 
submit the complete and accurate certification or disclosure statements required under 
21 CFR 54. In addition, the investigator must provide to the sponsor a commitment to 
promptly update this information if any relevant changes occur during the course of the 
investigation and for 1 year following the completion of the study. 
Neither the sponsor nor 
 is financially responsible for further testing or treatment of any 
medical condition that may be detected during the Screening process. In addition, in the 
absence of specific arrangements, neither the sponsor nor 
 is financially responsible for 
further treatment of the patient’s disease. 


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10.3 Investigator Documentation 
Prior to beginning the study, the investigator will be asked to comply with ICH E6(R2) 8.2 
and Title 21 of the CFR by providing the following essential documents, including but not 
limited to: 
• IRB/IEC approval 
• Original investigator-signed investigator agreement page of the protocol 
• Form FDA 1572, fully executed, and all updates on a new fully executed Form 
FDA 1572 
• Curriculum vitae for the investigator and each subinvestigator listed on Form 
FDA 1572 
• Financial disclosure information to allow the sponsor to submit complete and accurate 
certification or disclosure statements required under 21 CFR 54. In addition, the 
investigators must provide to the sponsor a commitment to promptly update this 
information if any relevant changes occur during the course of the investigation and 
for 1 year after the completion of the study 
• IRB/IEC-approved informed consent, samples of site advertisements for recruitment 
for this study, and any other written information regarding this study that is to be 
provided to the patient 
• Laboratory certifications and normal ranges for any local laboratories used by the site, 
in accordance with 42 CFR 493 
10.4 Study Conduct 
The investigator agrees that the study will be conducted according to the principles of ICH 
E6(R2). The investigator will conduct all aspects of this study in accordance with all 
national, state, and local laws or regulations. Study information from this protocol will be 
posted on publicly available clinical trial registers before enrollment of patients begins. 
10.5 Adherence to Protocol 
The investigator agrees to conduct the study as outlined in this protocol in accordance with 
ICH E6(R2) and all applicable guidelines and regulations. 


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10.6 Adverse Events and Study Report Requirements 
By participating in this study, the investigator agrees to submit reports of SAEs to the 
sponsor and/or IRB/IEC according to the timeline and method outlined in the protocol. In 
addition, the investigator agrees to submit annual reports to the study site IRB/IEC as 
appropriate. 
10.7 Investigator’s Final Report 
Upon completion of the study, the investigator, where applicable, should inform the 
institution; the investigator/institution should provide the IRB/IEC with a summary of the 
study’s outcome and the sponsor and regulatory authorities with any reports required. 
10.8 Records Retention 
Essential documents should be retained until at least 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated 
marketing applications in an ICH region or at least 2 years have elapsed since the formal 
discontinuation of clinical development of the investigational study drug. These documents 
should be retained for a longer period, however, if required by the applicable regulatory 
requirements or by an agreement with the sponsor. It is the responsibility of the sponsor to 
inform the investigator/institution as to when these documents no longer need to be retained. 
10.9 Publications 
After completion of the study, the data may be considered for reporting at a scientific 
meeting or for publication in a scientific journal. In these cases, the sponsor will be 
responsible for these activities and will work with the investigators to determine how the 
manuscript is written and edited, the number and order of authors, the publication to which it 
will be submitted, and other related issues. The sponsor has final approval authority over all 
such issues. 
Data are the property of the sponsor and cannot be published without prior authorization 
from the sponsor, but data and publication thereof will not be unduly withheld. 
11 Study Management 
The administrative structure will include a scientific steering committee and event 
adjudication committee. 


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The scientific steering committee, composed of key opinion leaders who are expert in the 
treatment of patients with cervical dystonia, will consult with the sponsor on the design of the 
study protocol, review the data, and analyze the data incorporated into the final study report. 
11.1 Monitoring 
11.1.1 
External Data Monitoring Committee 
No data monitoring committee is planned for this study. 
11.1.2 
Monitoring of the Study 
The clinical monitor, as a representative of the sponsor, has the obligation to follow the study 
closely. 
 
 
 
 
 
 
 
 
 
 
11.1.3 
Inspection of Records 
Investigators and institutions involved in the study will permit study-related monitoring, 
audits, IRB/IEC review, and regulatory inspections by providing direct access to all study 
records. 
 
 
 
 
 
 
 
11.2 Management of Protocol Amendments and Deviations 
11.2.1 
Modification of the Protocol 
Any changes in this research activity, except those necessary to remove an apparent, 
immediate hazard to the patient, must be reviewed and approved by the sponsor or its 


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designee. Amendments to the protocol must be submitted in writing to the investigator’s 
IRB/IEC for approval before patients can be enrolled into an amended protocol. 
11.2.2 
Protocol Deviations 
The investigator or designee must document and explain in the patient’s source 
documentation any deviation from the approved protocol. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
11.3 Study Termination 
Although Aeon Biopharma has every intention of completing the study, Aeon Biopharma 
reserves the right to discontinue the study at any time for clinical or administrative reasons. 
The end of the study is defined as the date on which the last patient completes the EOS visit 
(20 weeks after initial treatment), patient withdrawal (for any reason), or study 
discontinuation by the sponsor. 
11.4 Final Report 
Whether the study is completed or prematurely terminated, the sponsor will ensure that the 
clinical study reports (CSRs) are prepared and provided to the regulatory agencies as 
required by the applicable regulatory requirements. The sponsor will also ensure that the 
CSRs in marketing applications meet the standards of the ICH harmonised tripartite guideline 
E3: Structure and Content of Clinical Study Reports. 


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Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the CSR. The investigator will be provided reasonable access to 
statistical tables, figures, and relevant reports and will have the opportunity to review the 
complete study results. 
Upon completion of the CSR, the sponsor will provide the investigator with the full summary 
of the study results. The investigator is encouraged to share the summary results with the 
study patients, as appropriate. The study results will be posted on publicly available clinical 
trial registers. 




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13.2 TWSTRS Scale 


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13.3 Dysphagia Severity Scale 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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13.4 CGI-S and CGI-C Scales 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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13.5 PGI-S Scale 
 


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13.6 PGI-C Scale 
 


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13.7 C-SSRS Scale 


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SAP_003.pdf: 
 
Confidential 
 
 
 
 
 
AEON Biopharma Inc. 
 
ABP-19000 
 
A Phase 2, Randomized, Double-Blind, Multicenter, Placebo-Controlled Study to 
Evaluate the Safety and Efficacy of Intramuscular ABP-450 (prabotulinumtoxin 
A) Injection for the Treatment of Cervical Dystonia 
 
22JUL2022 
 
Statistical Analysis Plan Outline 
 
Version 2.0 
Prepared by:  
 
 
 
 
 
 
 
 


AEON Biopharma, Inc. 
 
Statistical Analysis Plan, Version 2.0 
 
ABP-19000 (Version 2.1) 13MAY2021 
 
Date Issued: 22JUL2022 
 
  
 
 
 II
TABLE OF CONTENTS 
LIST OF ABBREVIATIONS ......................................................................................................V 
1. 
INTRODUCTION ............................................................................................................ 7 
2. 
OBJECTIVES ................................................................................................................... 9 
2.1. PRIMARY OBJECTIVE .......................................................................................................... 9 
2.2. SECONDARY OBJECTIVE ..................................................................................................... 9 
3. 
INVESTIGATIONAL PLAN .......................................................................................... 9 
3.1. OVERALL STUDY DESIGN AND PLAN .................................................................................. 9 
3.2. STUDY ESTIMANDS ........................................................................................................... 11 
3.2.1. 
Primary Estimand ..................................................................................................... 11 
3.2.2. 
Secondary Estimands ................................................................................................ 11 
3.3. TREATMENTS .................................................................................................................... 12 
3.4. DOSE ADJUSTMENT/MODIFICATIONS ............................................................................... 12 
4. 
GENERAL STATISTICAL CONSIDERATIONS ..................................................... 12 
4.1. SAMPLE SIZE .................................................................................................................... 13 
4.2. RANDOMIZATION, STRATIFICATION, AND BLINDING ........................................................ 13 
4.3. ANALYSIS SETS ................................................................................................................ 14 
4.3.1. 
Screened Set .............................................................................................................. 14 
4.3.2. 
Full Analysis Set (FAS) ............................................................................................. 14 
4.3.3. 
Modified Full Analysis Set (mFAS)........................................................................... 14 
4.3.4. 
Per-Protocol Analysis Set (PPS) .............................................................................. 15 
4.3.5. 
Safety Analysis Set .................................................................................................... 15 
5. 
PATIENT DISPOSITION ............................................................................................. 15 
5.1. DISPOSITION ..................................................................................................................... 15 
5.2. PROTOCOL DEVIATIONS ................................................................................................... 15 
6. 
DEMOGRAPHICS AND BASELINE CHARACTERISTICS .................................. 16 
6.1. DEMOGRAPHICS ................................................................................................................ 16 
6.2. GENERAL MEDICAL HISTORY ........................................................................................... 16 
6.3. INCLUSION AND EXCLUSION CRITERIA ............................................................................. 16 
7. 
TREATMENTS AND MEDICATIONS ....................................................................... 17 
7.1. PRIOR AND CONCOMITANT MEDICATIONS ........................................................................ 17 
7.1.1. 
Prior Medications ..................................................................................................... 17 
7.1.2. 
Concomitant Medications ......................................................................................... 17 
7.2. STUDY TREATMENTS ........................................................................................................ 17 
7.2.1. 
Extent of Exposure .................................................................................................... 17 
7.2.2. 
Treatment Modifications ........................................................................................... 17 
8. 
SAFETY ANALYSIS ..................................................................................................... 18 
8.1. ADVERSE EVENTS............................................................................................................. 18 
8.1.1. 
Primary Estimand ..................................................................................................... 19 


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8.1.2. 
Overall Summary of Adverse Events......................................................................... 20 
8.1.3. 
Incidence of Adverse Events ..................................................................................... 20 
8.1.4. 
Relationship of Adverse Events to Study Drug ......................................................... 21 
8.1.5. 
Severity of Adverse Event.......................................................................................... 21 
8.1.6. 
Serious Adverse Events ............................................................................................. 21 
8.1.7. 
Relationship of Serious Adverse events .................................................................... 21 
8.1.8. 
Adverse Events Leading to Study Withdrawal .......................................................... 21 
8.1.9. 
Severity of Serious Adverse Events ........................................................................... 22 
8.1.10. 
Suspected Unexpected Serious Adverse Events ..................................................... 22 
8.1.11. 
Non-Serious Adverse Events of Special Interest.................................................... 22 
8.1.12. 
Death ..................................................................................................................... 22 
8.2. CLINICAL LABORATORY EVALUATIONS ........................................................................... 22 
 
 
 
 
 
 
 
 
8.2.5. 
Pregnancy ................................................................................................................. 23 
8.3. VITAL SIGN MEASUREMENTS ........................................................................................... 23 
 
 
 
 
 
 
8.7. COLUMBIA-SUICIDE SEVERITY RATING SCALE (C-SSRS)................................................ 25 
8.8. SENSITIVITY ANALYSES ................................................................................................... 25 
9. 
EFFICACY ANALYSIS................................................................................................. 26 
9.1. SECONDARY ESTIMANDS .................................................................................................. 26 
9.1.1. 
TWSTRS .................................................................................................................... 26 
9.1.2. 
CGI-S ........................................................................................................................ 28 
9.1.3. 
PGI-S......................................................................................................................... 29 
9.1.4. 
CGI-C ........................................................................................................................ 29 
9.1.5. 
PGI-C ........................................................................................................................ 30 
9.2. SENSITIVITY ANALYSES ................................................................................................... 30 
9.3. DYSPHAGIA SEVERITY SCALE .......................................................................................... 31 
10. 
INTERIM ANALYSIS ................................................................................................... 31 
11. 
CHANGES IN THE PLANNED ANALYSIS .............................................................. 31 
12. 
REFERENCES................................................................................................................ 31 
14. 
APPENDICES ................................................................................................................. 34 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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  IV
 
 
 
 
 
 
 
 
 
 
 
 


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Statistical Analysis Plan, Version 2.0 
 
ABP-19000 (Version 2.1) 13MAY2021 
 
Date Issued: 22JUL2022 
 
  
 
 
 V
List of Abbreviations 
 
ADA 
anti-drug antibodies 
AE 
adverse event 
ANCOVA 
analysis of covariance 
C-SSRS 
Columbia-Suicide Severity Rating Scale 
CD 
Cervical dystonia 
CGI-C 
Clinical Global Impression of Change 
CI 
confidence interval 
CRF 
case report form 
ECG 
electrocardiogram 
eICF 
electronic informed consent form 
EOS 
end of study 
FAS 
Full Analysis Set 
FEV1 
forced expiratory volume in 1 second 
FVC 
forced vital capacity  
ICF 
informed consent form 
ICH 
International Conference on Harmonisation 
IRT 
interactive response technology 
MedDRA 
Medical Dictionary for Regulatory Activities 
mFAS 
Modified Full Analysis Set 
PGI-C 
Patient Global Impression of Change 
PGI-S 
Patient Global Impression of Severity 
PPS 
Per Protocol Analysis Set 
Per Protocol Analysis Set 
PT 
preferred term 
OLE 
open label extension 
SAE 
serious adverse event 


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SOC 
system organ class 
TEAE 
treatment-emergent adverse events 
TWSTRS 
Toronto Western Spasmodic Torticollis Rating Scale 
WHO 
World Health Organization 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 




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PrabotulinumtoxinA has also been found to be non-inferior to onabotulinumtoxinA 
(BOTOX®) for the treatment of moderate to severe glabellar lines in adult patients and for 
upper limb spasticity in stroke patients (Nam 2015, Rzany 2019). The doses of ABP-450 
used in the Phase 3 study for upper limb spasticity were similar to the doses of BOTOX® 
used (no significant differences were seen between the two groups) (Nam 2015). 
This Phase 2, multicenter, randomized, double-blind, active- and placebo-controlled study 
aims to demonstrate the safety and efficacy of ABP-450 doses (low, medium, and high) 
compared with placebo in patients with cervical dystonia. The current Phase 2 study will 
help to determine appropriate doses of ABP-450 in this study population. 
Clostridium botulinum toxins have become the standard of care for the treatment of 
patients with cervical dystonia. In addition to onabotulinumtoxinA, abobotulinumtoxinA, 
incobotulinumtoxinA, and rimabotulinumtoxinB have been approved for the treatment of 
patients with cervical dystonia. Even though these toxin products have been approved for 
the treatment of cervical dystonia and are the standard of care in patients with this 
condition, they do have significant risks associated with their use in these patients. The 
labels for all these products carry prominent warnings concerning their side effects, such as 
dysphagia and even death, if they are not carefully administered and the patient monitored 
while under treatment. Even so, the benefit for all these products is greater than the risks 
and that is why these products are the standard of care. 
Clinical development of drugs has been impacted by the ongoing COVID-19 pandemic. 
The current study aims to implement several adjustments or mitigations to allow the study 
to continue despite pandemic-related disruption. To prioritize patient and site staff safety, 
several planned office visits have been converted to tele-visits to allow the required data 
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2. Objectives 
2.1. Primary Objective 
• To demonstrate the safety of a single treatment of ABP-450 (low, medium, or high 
dose) compared with placebo in the treatment of cervical dystonia 
2.2. Secondary Objective 
• To demonstrate the efficacy of a single treatment of ABP-450 (low, medium, or 
high dose) at Week 4 compared with placebo in the treatment of cervical dystonia 
3. Investigational Plan 
3.1. Overall Study Design and Plan 
This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled study of 
ABP-450 purified neurotoxin complex for the treatment of cervical dystonia. 
Both previously treated patients and those who have never been exposed to botulinum 
toxin (naïve patients) will be eligible. Pre-treated patients must be stable responders who 
are receiving no more than 300 units of botulinum toxin type A or 750 units 
abobotulinumtoxinA. The last injection for those previously treated should be at least 16 
weeks prior to treatment in ABP-19000. Botulinum toxin–naïve patients are defined as 
those not receiving treatment with a botulinum toxin in the head or neck. 
Sixty Patients will be randomly assigned (ratio of 1:1:1:1) into 1 of 4 treatment arms: 
ABP-450 low dose (150 units), ABP-450 medium dose (250 units), ABP-450 high dose 
(350 units), or placebo. The investigator will be blinded to the dose level. The doses will 
be prepared to the same volume using appropriate dilution as per the dose level. The 
volume injected will be equivalent across the doses and placebo. To ensure balance across 
the treatment groups, randomization will be stratified by previous treatment with BOTOX® 
(BOTOX® naïve vs. previously treated with BOTOX® within 4-12 months prior to 
baseline). The safety and efficacy of the three dose cohorts of ABP-450 or placebo will be 
evaluated over a maximum of 20 weeks. At the completion of the Phase 2 study, all 
patients, irrespective of treatment group, will have the option to receive treatment with 
ABP-450 by rolling over into an open-label extension (OLE) study (ABP-19002). 
 
 


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This study will evaluate the safety and efficacy of ABP-450 or placebo over a maximum of 
20 weeks. The primary objective will include evaluation of the safety of a single treatment 
of ABP-450 (low, medium, or high dose) compared with placebo. The secondary objective 
will include evaluation of the efficacy of a single treatment of ABP-450 (low, medium, or 
high dose) compared with placebo at Week 4. 


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3.2. Study Estimands 
3.2.1. Primary Estimand 
• Proportion of patients who would develop treatment-related serious adverse events 
(SAEs) during the first 20 weeks of a single treatment cycle when dosed with:  
o Placebo;  
o Low-dose ABP-450 (150 units);  
o Medium-dose ABP-450 (250 units);  
o High-dose ABP-450 (350 units); or  
o Any ABP-450 dose.  
 
 
 
 
 
 
  
3.2.2. Secondary Estimands 
• Mean difference in change in Toronto Western Spasmodic Torticollis Rating Scale 
(TWSTRS) total score from baseline to Week 4 for each of low, medium, and high 
doses of ABP-450 compared with placebo. This is the hypothetical estimand .  
• Mean difference in change in the subscale scores of the TWSTRS (disability, 
severity, and pain) from baseline to Week 4 for each of low, medium, and high 
doses of ABP-450 compared with placebo. This is the hypothetical estimand.  
• Mean difference in change in scores on the Clinical Global Impression of Severity 
(CGI-S) and Patient Global Impression of Severity (PGI-S) from baseline to Week 
4 for each of low, medium, and high doses of ABP-450 compared with placebo. 
This is the hypothetical estimand.  
• Mean difference in scores on the Clinical Global Impression of Change (CGI-C) 
and Patient Global Impression of Change (PGI-C) for each of low, medium, and 


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high doses of ABP-450 compared with placebo at Week 4. This is the hypothetical 
estimand. 
• 
 
 
 
• 
 
 
• 
 
 
• 
 
  
3.3. Treatments   
The four treatment groups are ABP-450 low dose (150 units), ABP-450 medium dose (250 
units), ABP-450 high dose (350 units), and placebo. Investigational study drug is a 
Clostridium botulinum toxin type A 
• Investigational study drug vials contain 100 units of lyophilized ABP-450 
• Placebo vials contain sodium chloride for injection, USP, 0.9%, preservative-free 
 
 
 
 
3.4. Dose Adjustment/Modifications 
Investigational study drug dose modifications are not allowed. 
4. General Statistical Considerations 
The statistical principles applied in the design and planned analyses of this study are 
consistent with International Council for Harmonisation (ICH) E9 guidelines (ICH 1998). 
 
 
 
 


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Data summaries will be presented by treatment group unless otherwise specified. All 
efficacy analyses will be based upon the Full Analysis Set (mFAS, Section 
 
), and all safety as well as demographic and baseline 
characteristic analyses will be based upon the Safety Analysis Set (Section 4.3.5). 
Additional analyses will be performed on selected populations as specified in the sections 
below.  
 
 
 
  
 
 
 
. 
4.1. Sample Size 
Fifteen patients will be randomly assigned to each of four treatment arms (placebo, ABP-
450 low dose, ABP-450 medium dose, and ABP-450 high dose) using a 1:1:1:1 ratio and 
therefore requiring a total of 60 patients. 
 
 
 
 
 
 
 
 
 
 
4.2. Randomization, Stratification, and Blinding 
Approximately 60 patients will be randomly assigned (ratio of 1:1:1:1) into 1 of 4 
treatment arms: ABP-450 low dose (150 units), ABP-450 medium dose (250 units), ABP-
450 high dose (350 units), or placebo. 
 




 
       
                        
 
 
 
 
 
  
 
 
 
All analyses using the 
mFAS will group patients according to randomized treatment. 
4.3.4. Per-Protocol Analysis Set (PPS) 
The PPS will consist of all patients in the FAS who received placebo or ABP-450 
(according to the set dose amount), but will exclude all patients who discontinued the study 
prior to Week 4 or had major protocol deviations which may affect evaluation of the 
TWSTRS assessment at Week 4. All analyses using the PPS will group patients according 
to actual treatment received. 
4.3.5. Safety Analysis Set 
The Safety Analysis Set will consist of all patients who received any investigational study 
drug. All analyses using the Safety Analysis Set will group patients according to treatment 
actually received. 
5. Patient Disposition 
5.1. Disposition 
Patient disposition will be summarized categorically by treatment group and overall, and 
will include the number of patients that signed informed consent, the number of patients 
that were randomized, and the number and percentage of randomized patients in the FAS, 
mFAS, PPS, and Safety Analysis Sets. The reasons for study withdrawal will also be 
summarized categorically. 
A listing of inclusion and exclusion criteria that were not met will be presented.  
5.2. Protocol Deviations 
Significant protocol deviations that may affect the evaluation of the TWSTRS assessment 
at Week 4 are considered major protocol deviations. Major protocol deviations will be 
summarized by treatment group and overall according to the following categories: 
• 
  
 
 
 
 
 
  
 
 


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 A listing of patients with protocol deviations will also be provided.  
6. Demographics and Baseline Characteristics 
6.1. Demographics 
Summaries of demographics and stratification factors will be summarized for patients in 
the mFAS and Safety Analysis Set by treatment group and overall. A listing will also be 
provided.  
Demographic characteristics consist of: 
• Age (continuous) in years 
• Sex (Male, Female) 
• Race (White, Black or African American, Asian, American Indian or Alaska 
Native, Native Hawaiian or Other pacific Islander, Other) 
• Ethnicity (Hispanic or Latino, not Hispanic or Latino) 
 
 
 
 
  
 
 
 
6.2. General Medical History 
Medical History will be tabulated for the Safety Analysis Set by system organ class, 
preferred terms, and treatment groups and overall. Medical history will also be listed. 
Medical History will be coded by MedDRA version 23.1 (or later).  
6.3. Inclusion and Exclusion Criteria 
Inclusion and exclusion criteria not met by patients will be listed. Inclusion criteria, 
exclusion criteria, and rescreening instructions may be found in Protocol Sections 4.1.1, 
4.1.2, and 4.1.3. 


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7. Treatments and Medications 
7.1. Prior and Concomitant Medications 
Prior and concomitant medications will include all prescription drugs, herbal products, 
vitamins, minerals, and over-the-counter medications. Prior and Concomitant medications 
will be coded by the World Health Organization (WHO) Drug Dictionary version 
01SEP2020 (or later). Data summaries will be based on the Safety Analysis Set.  
7.1.1. Prior Medications 
Medications with a start date and/or stop date before the treatment start date will be 
considered prior medications. If start and stop dates are missing and the medication is not 
identified to be ongoing, the medication will be considered ‘prior medications’ if the data 
was entered at Visit 1 (Screening) or Visit 2 (Baseline). Prior medications will be 
summarized by treatment group and listed. 
7.1.2. Concomitant Medications 
Medications with a start or stop date on or after the treatment dosing date will be 
considered concomitant medications. All medications which are ongoing will be 
considered concomitant. Concomitant medications will be summarized by treatment group 
and listed.  
  
 
 
 
 
  
7.2. Study Treatments 
7.2.1. Extent of Exposure 
Study treatment exposure will be summarized for all patients in Safety Analysis Set. The 
number of patients exposed to study treatment and the volume of injections will be 
summarized by treatment group. Drug accountability will also be listed. 
7.2.2. Treatment Modifications 
Investigational study drug dose modifications are not allowed.  


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8. Safety Analysis 
Safety endpoints will be summarized with descriptive statistics. All safety summaries and 
analyses will be performed using the Safety Analysis Set.  
Data will also be provided in listings. 
8.1. Adverse Events 
A treatment emergent adverse event (TEAE) is an adverse event (AE) with a start date on 
or after the date of treatment. The percentage of patients with TEAEs throughout the study 
will be summarized for ABP-450 (all doses together and separately) and placebo. 
 
 
  
 
 
 
  
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  


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• 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    
8.1.1. Primary Estimand  
The primary estimand, the proportion of patients who develop treatment-related SAEs 
during the first 20 weeks of a single treatment, will be summarized by treatment group and 
across active treatment groups. 
 
 
 
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Treatment Policy 
8.1.2. Overall Summary of Adverse Events 
An overall summary of TEAEs will be tabulated by treatment group and across active 
treatment groups by providing the number and percent of patients who experience the 
following: 
• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
8.1.3. Incidence of Adverse Events 
The incidence and frequency of TEAEs will be summarized by SOC and PT. The number 
and percentage of patients and number of events will be presented for each treatment group 
and across active treatment groups. Adverse events will also be listed. 


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8.1.4. Relationship of Adverse Events to Study Drug 
The investigator’s assessment of an AE’s relationship will be characterized using 
classification of Unrelated, Possible, Probable, and Definite. The incidence of TEAEs will 
be tabulated by SOC and PT and relationship to investigational study drug for each 
treatment group and across active treatment groups. Incidence will be based on the worst 
relationship within each level of summarization. 
The incidence of related (possible, probable or definite) TEAEs from Week 1 to Week 20 
will also be tabulated by SOC and PT.  
8.1.5. Severity of Adverse Event 
The severity, or intensity, of an AE refers to the extent to which an AE affects the patient’s 
daily activities. The severity of the AE will be rated as mild, moderate, or severe. Changes 
in the severity of an AE will be captured in the CRF. The incidence of TEAEs will be 
tabulated by SOC and PT and severity for each treatment group and across active treatment 
groups (up to 20 weeks and 6 weeks separately). Incidence will be based on the worst 
severity within each level of summarization. 
8.1.6. Serious Adverse Events 
The incidence and frequency of serious TEAEs will be summarized by SOC and PT for 
each treatment group and across active treatment groups (up to 20 weeks and 6 weeks 
separately). SAEs will also be listed.  
8.1.7. Relationship of Serious Adverse events 
The incidence of serious TEAEs will be tabulated by SOC and PT and relationship to 
investigational study drug for each treatment group and across active treatment groups (up 
to 20 weeks and 6 weeks separately). Incidence will be based on the worst relationship 
within each level of summarization.  
8.1.8. Adverse Events Leading to Study Withdrawal 
The incidence of TEAEs leading to study withdrawal will be summarized for each 
treatment group and across active treatment groups by SOC and PT.  


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8.1.9. Severity of Serious Adverse Events 
The incidence of serious TEAEs will be tabulated by SOC, PT, and severity for each 
treatment group and across active treatment groups. Incidence will be based on the worst 
severity within each level of summarization. 
8.1.10. Suspected Unexpected Serious Adverse Events 
A suspected unexpected serious adverse event (SUSAR) is defined as an AE, the nature or 
severity of which is not consistent with the applicable product information (e.g., 
investigator's brochure for an unapproved investigational medicinal product). The 
incidence of SUSARs will be summarized for each treatment group and across active 
treatment groups by SOC and PT.  
8.1.11. Non-Serious Adverse Events of Special Interest 
Adverse events potentially suggestive of distant spread of toxin effects are listed in 
Appendix 14.9. The incidence of non-serious AEs of special interest will be summarized 
for each treatment group and across active treatment groups by SOC and PT. 
8.1.12. Death 
A listing of patient deaths will be presented. 
 
 
 
 
 
 
 
 
 
 
 
 
  


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8.2.5. Pregnancy 
A urine pregnancy test will be performed at the Screening visit (Visit 1), Visit 2 (Day 1), 
and EOS (Week 20). Pregnancy test data will be provided in a listing. 
8.3. Vital Sign Measurements 
Vital sign measurements will be performed at Screening (Visit 1), Visit 2 (Day 1), Visit 4 
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pressure, oxygen saturation, and body temperature. The patient’s height and weight will be 
assessed at the Baseline visit.  
Mean change from baseline in vital signs will be summarized by scheduled visit for each 
treatment group and across active treatment groups. A listing of vital signs will also be 
provided.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 


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8.7. Columbia-Suicide Severity Rating Scale (C-SSRS) 
The C-SSRS will be performed at Screening (Visit 1), Visit 4 (Week 4), Visit 6 (Week 8), 
Visit 8 (Week 12), Visit 10 (Week 16), and EOS (Week 20). The C-SSRS was developed 
by the United States FDA in 2012 for measuring suicidal ideation and behavior in clinical 
trials (Posner et al. 2011). The C-SSRS was designed to distinguish the domains of suicidal 
ideation and suicidal behavior. Four constructs are measured. The first is the severity of 
ideation (hereafter referred to as the “severity subscale”), which is rated on a 5-point 
ordinal scale in which 1 = wish to be dead, 2 = non-specific active suicidal thoughts, 3 = 
suicidal thoughts with methods, 4 = suicidal intent, and 5 = suicidal intent with plan. The 
second is the intensity of ideation subscale (hereafter referred to as the “intensity 
subscale”), which comprises 5 items, each rated on a 5-point ordinal scale: frequency, 
duration, controllability, deterrents, and reason for ideation. The third is the behavior 
subscale, which is rated on a nominal scale that includes actual, aborted, and interrupted 
attempts; preparatory behavior; and non-suicidal self-injurious behavior. The fourth is the 
lethality subscale, which assesses actual attempts; actual lethality is rated on a 6-point 
ordinal scale, and if actual lethality is zero, potential lethality of attempts is rated on a 3-
point ordinal scale (Posner et al. 2011).  
The frequency and percentage of C-SSRS responses will be tabulated by visit for each 
treatment group and across active treatment groups. The C-SSRS responses will also be 
provided in a listing.  
8.8. Sensitivity Analyses  
 
 
  
 
 
 
 
   












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9.3. Dysphagia Severity Scale  
 
 
 
 
 
 
 
 
Dysphagia scores will be listed. 
10. Interim Analysis 
No interim analyses are planned.  
11. Changes in the Planned Analysis 
 
 
 
 
  
 
 
 
 
  
12. References 
 
 
 
 
 
 
 
 


 
       
                        
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
       
                        
 
 
 
 
 
  
 
 
 
 
 
 
 
 


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