Conditions: Cervical Dystonia
Allocation: NA | Intervention model: SEQUENTIAL
Enrollment: 51
Healthy volunteers: no

Brief summary:
This Open-label Extension 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 42 sites in the United States from Phase 2 (ABP-19000) trial. Study subjects who had their initial dose of study drug in the Phase 2 trial, irrespective of treatment allocation, will be eligible to enroll in this OLE study.

Detailed description:
This Open-label Extension 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 42 sites in the United States from Phase 2 (ABP-19000) trial. Study subjects who had their initial dose of study drug in the Phase 2 trial, irrespective of treatment allocation, will be eligible to enroll in this OLE study. Study subjects will receive a predetermined dose of ABP-450 between the Low Dose and High Dose, based on the investigator's discretion and clinical judgment.

Arms:
arm 1: ABP-450 Between Low Dose and High Dose - Intramuscular injections into affected neck muscles with investigator's determined dose within the range of low dose and high dose - 4 injection cycles at 3-month intervals.

Interventions: intervention 1: ABP-450
Intervention descriptions: intervention 1: ABP-450 (prabotulinumtoxinA) contains a 900kDA botulinum toxin type-A complex produced by the bacterium Clostridium botulinum.

Protocol document:
Prot_000.pdf: 
Aeon Biopharma, Inc. 
ABP-450 
Protocol: ABP-19002 (Version 2.1) 
13 May 2021 
 
 
CLINICAL STUDY PROTOCOL 
IND - 145417 
An Open-Label, Multicenter Study to Evaluate the Safety and Efficacy of 
Repeat Intramuscular ABP-450 (prabotulinumtoxinA) Injection for the 
Treatment of Cervical Dystonia 
ABP-19002 
 
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)  
03 December 2020 (Version 2.0) 












Aeon Biopharma, Inc. 
ABP-450 
Protocol: ABP-19002 (Version 2.1) 
13 May 2021 
 
 
Declaration of Investigator 
I have read and understood all sections of the protocol entitled “An Open-Label, Multicenter 
Study to Evaluate the Safety and Efficacy of Repeat 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 (GCP) 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 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 
 
 
 


Aeon Biopharma, Inc. 
ABP-450 
Protocol: ABP-19002 (Version 2.1) 
13 May 2021 
 
 
Page 8 
Table of Contents 
Table of Contents .......................................................................................................................8 
List of Tables ............................................................................................................................ 11 
Protocol Synopsis.....................................................................................................................12 
List of Abbreviations................................................................................................................22 
1 
Introduction ......................................................................................................................24 
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 of Study Design .......................................................................29 
3.1.2 
Conduct of the Study During the COVID-19 Pandemic .........................30 
4 
Patient Selection and Withdrawal Criteria .......................................................................31 
4.1 
Selection of Study Population .................................................................................31 
4.1.1 
Inclusion Criteria .....................................................................................31 
4.1.2 
Exclusion Criteria ....................................................................................32 
4.1.3 
Rescreening ..............................................................................................33 
4.2 
Withdrawal of Patients from the Study ...................................................................33 
4.2.1 
Reasons for Withdrawal/Discontinuation ................................................33 
4.2.2 
Handling of Withdrawals .........................................................................34 
4.2.3 
Replacements ...........................................................................................34 
5 
Study Treatments ..............................................................................................................35 
5.1 
Method of Assigning Patients to Treatment Group.................................................35 
5.2 
Treatment Administered ..........................................................................................35 
5.3 
Identity of Investigational Product..........................................................................37 


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13 May 2021 
 
 
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5.4 
Management of Clinical Supplies ...........................................................................37 
5.4.1 
Investigational Study Drug Packaging and Storage ................................37 
5.4.2 
Test Article Accountability ......................................................................37 
5.4.3 
Other Supplies..........................................................................................38 
5.5 
Overdose Management ...........................................................................................38 
5.5.1 
Treatment of Overdose ............................................................................38 
5.6 
Blinding...................................................................................................................38 
5.6.1 
Breaking the Blind ...................................................................................38 
5.7 
Treatment Compliance ............................................................................................38 
5.8 
Prior and Concomitant Therapy ..............................................................................39 
6 
Study Assessments and Procedures ..................................................................................40 
6.1 
Study Visits .............................................................................................................40 
6.2 
Safety Assessments .................................................................................................42 
6.2.1 
Adverse Events ........................................................................................43 
6.2.1.1 
Definitions of Adverse Events .................................................................43 
6.2.1.2 
Serious Adverse Events ...........................................................................43 
6.2.1.3 
Eliciting and Documenting Adverse Events ............................................43 
6.2.1.4 
Reporting Adverse Events .......................................................................44 
6.2.1.5 
Reporting Serious Adverse Events ..........................................................45 
6.2.1.6 
Suspected Unexpected Serious Adverse Reactions and Non-Serious 
Adverse Events of Special Interest ..........................................................45 
6.2.1.7 
Assessment of Severity ............................................................................46 
6.2.1.8 
Assessment of Causality ..........................................................................46 
6.2.1.9 
Follow-Up of Patients Reporting Adverse Events ...................................47 
 
 
 
 
 
 
 
 
6.3 
Secondary Efficacy Assessments ............................................................................48 
6.3.1 
TWSTRS Scale ........................................................................................48 
6.3.2 
PGI-C and CGI-C Scales .........................................................................49 
 
 
6.3.4 
C-SSRS ....................................................................................................49 
6.3.5 
Dysphagia Score ......................................................................................50 
6.4 
Safety Monitoring Committee ................................................................................50 


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13 May 2021 
 
 
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6.5 
Pregnancy ................................................................................................................50 
6.6 
Laboratory Analyses ...............................................................................................50 
6.7 
Sample Collections .................................................................................................51 
7 
Statistical Considerations .................................................................................................52 
7.1 
Estimands ................................................................................................................52 
7.2 
Sample Size Calculations ........................................................................................52 
7.3 
Analysis Sets ...........................................................................................................52 
7.4 
Description of Subgroups to be Analyzed ..............................................................53 
7.5 
Statistical Analysis Methodology ...........................................................................53 
7.5.1 
Analysis of Primary Estimand .................................................................53 
7.5.2 
Analysis of Secondary Estimands ...........................................................53 
7.5.3 
Other Analyses .........................................................................................54 
7.5.4 
Interim Analyses ......................................................................................54 
8 
Data Quality Assurance ....................................................................................................55 
8.1 
Data Management ...................................................................................................55 
9 
Ethics ................................................................................................................................56 
9.1 
Independent Ethics Committee or Institutional Review Board ..............................56 
9.2 
Ethical Conduct of the Study ..................................................................................56 
9.3 
Patient Information and Consent ............................................................................56 
10 Investigator’s Obligations ................................................................................................58 
10.1 Confidentiality ........................................................................................................58 
10.2 Financial Disclosure and Obligations .....................................................................58 
10.3 Investigator Documentation ....................................................................................58 
10.4 Study Conduct .........................................................................................................59 
10.5 Adherence to Protocol.............................................................................................59 
10.6 Adverse Events and Study Report Requirements ...................................................59 
10.7 Investigator’s Final Report .....................................................................................60 
10.8 Records Retention ...................................................................................................60 
10.9 Publications .............................................................................................................60 
11 Study Management ...........................................................................................................61 
11.1 Monitoring ..............................................................................................................61 


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13 May 2021 
 
 
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11.1.1 
External Data Monitoring Committee .....................................................61 
11.1.2 
Monitoring of the Study ...........................................................................61 
11.1.3 
Inspection of Records ..............................................................................61 
11.2 Management of Protocol Amendments and Deviations..........................................62 
11.2.1 
Modification of the Protocol ....................................................................62 
11.2.2 
Protocol Deviations..................................................................................62 
11.3 Study Termination ...................................................................................................62 
11.4 Final Report ............................................................................................................63 
12 References ........................................................................................................................64 
13 Appendices .......................................................................................................................66 
 
13.2 TWSTRS Scale .......................................................................................................70 
 
13.4 PGI-C Scale ............................................................................................................76 
13.5 
 CGI-C Scales ........................................................................................76 
13.6 Dysphagia Severity Scale .......................................................................................78 
13.7 C-SSRS Scale..........................................................................................................79 
 
List of Tables 
 
 
 
 
 


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ABP-450 
Protocol: ABP-19002 (Version 2.1) 
13 May 2021 
 
 
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Protocol Synopsis 
Protocol Number: 
ABP-19002 
Title: 
An Open-Label, Multicenter Study to Evaluate the Safety and 
Efficacy of Repeat Intramuscular ABP-450 (prabotulinumtoxinA) 
Injection for the Treatment of Cervical Dystonia 
Sponsor: 
Aeon Biopharma, Inc. 
 
 
Study Phase: 
2/3 
Study Sites: 
Approximate total: 71 
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 with 
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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ABP-450 
Protocol: ABP-19002 (Version 2.1) 
13 May 2021 
 
 
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Secondary Objective 
• To evaluate the efficacy of repeat intramuscular injections of 
ABP-450 (150-350 units per dose) in the treatment of cervical 
dystonia 
Estimands: 
For all estimands, the target population is patients diagnosed with 
cervical dystonia. Patients are expected to: 
• Have not had previous treatment with BOTOX® within the last 
8 weeks 
• Have not had previous treatment with ABP-450 within the last 
8 weeks 
• Be receiving stable doses of treatment for focal dystonia 
treatment (eg, anticholinergics and benzodiazepines) 
• Meet other inclusion/exclusion criteria 
Primary Estimand 
• 
 
 
 
 
 
 
 
 
Secondary Estimands 
These are the hypothetical estimands regarding alternative prohibited 
medications (eg, BOTOX®), assuming (treatment policy) no change 
in background treatment and administration of treatment within the 
150- to 350-unit dose range: 
• 
 
 


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Protocol: ABP-19002 (Version 2.1) 
13 May 2021 
 
 
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Study Population: 
Inclusion Criteria 
Each patient must meet all of the following criteria to be enrolled in 
this OLE study: 
1. Qualified for and had their initial dose of study drug in the 
ABP-19000 
 
 
 
 
2. Provided written informed consent to participate in the study. 
3. Were a male or female patient between 18 and 75 years of age 
(inclusive) when they entered the ABP-19000 
 
studies. 
 
 
 
 
 
 
 


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ABP-450 
Protocol: ABP-19002 (Version 2.1) 
13 May 2021 
 
 
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6. 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 
this OLE study: 
1. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
8. Participated in another interventional study during 
participation in this study. 


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ABP-450 
Protocol: ABP-19002 (Version 2.1) 
13 May 2021 
 
 
Page 17 
9. Were a pregnant or lactating female, or female of child-bearing 
potential not willing to use an acceptable method of 
contraception (ie, intrauterine device, barrier methods with 
spermicide, or abstinence). 
10. Would not benefit from treatment with ABP-450 for their 
cervical dystonia, in the investigator’s opinion. 
11. Viral or other active infection or any medical condition that, in 
the opinion of the investigator, classifies the patient as 
unsuitable for participation in the study or patients who do not 
seem to be in good general health at the time of Screening, and 
prior to any investigational study drug administration. 
Note: Patients will not routinely be tested for COVID-19 during 
the study. Patients presenting with fever or who are 
symptomatic for COVID-19 should be treated through their 
general practitioner. 
Study Design: 
This is an open-label, Phase 2/3, multicenter, 52-week study of 
ABP-450 purified neurotoxin complex for the treatment of cervical 
dystonia. The study population will consist of all patients who had 
their initial dose of study drug in the ABP-19000 
 
studies, irrespective of treatment allocation, and who consented to 
being treated for cervical dystonia with ABP-450 in the ABP-19002 
OLE study
 
 
At the investigator’s discretion and with the patient’s consent, 
patients will enter the OLE study at Week 8 (Week 8 will be Day 0 
“rollover” for the OLE study) with the opportunity to either maintain 
the original Phase 2 dose or modify the dose. If there is no efficacy 
(or loss of efficacy) between 6 and 20 weeks in the ABP-19000 
study, then patients can roll over to the OLE study at a dose 
determined per the investigator’s discretion. 
 
 
 


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ABP-450 
Protocol: ABP-19002 (Version 2.1) 
13 May 2021 
 
 
Page 18 
 
 
 
 
 
This OLE study will evaluate the safety and efficacy of repeat 
injections of ABP-450 for the long-term treatment of cervical 
dystonia. 
Estimated Study 
Duration: 
Patients will be followed up for 52 weeks after they enter the 
ABP-19002 OLE study. 
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: 
Investigational study drug is Clostridium botulinum toxin type A. 
Each vial will contain 100 units of lyophilized ABP-450. 


Aeon Biopharma, Inc. 
ABP-450 
Protocol: ABP-19002 (Version 2.1) 
13 May 2021 
 
 
Page 19 
All study patients, regardless of dose group and including placebo 
patients, will be administered between 150 and 350 units of 
ABP-450, based on the investigator’s discretion and clinical 
judgment. 
The dose should be divided among the affected muscles (see table 
below). 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. 
 
 
 
 
 
 
 


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ABP-450 
Protocol: ABP-19002 (Version 2.1) 
13 May 2021 
 
 
Page 20 
 
 
 
 
 
 
  
Sample Size: 
All eligible patients who had their initial dose of study drug in the 
ABP-19000 
 studies, irrespective of treatment 
allocation, and consented to being treated with ABP-450 can be 
enrolled in this OLE (ie, ABP-19002) study. 
 
 
 
 
 
Statistical Methods: 
The proportion of patients with treatment-related SAEs up to 
Week 52 will be summarized for the Safety Analysis Set with 
Retreatment. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Protocol: ABP-19002 (Version 2.1) 
13 May 2021 
 
 
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Version and Date of 
Protocol: 
Version 2.0 dated 03 December 2020 


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Protocol: ABP-19002 (Version 2.1) 
13 May 2021 
 
 
Page 22 
List of Abbreviations 
Abbreviation 
Definition 
ABP-450 
prabotulinumtoxinA/Jeuveau (prabotulinumtoxinA-xvfs) 
AE 
adverse event 
BOTOX® 
onabotulinumtoxinA 
CFR 
Code of Federal Regulations 
CGI-C 
Clinical Global Impression of Change 
 
 
CSR 
clinical study report 
C-SSRS 
Columbia–Suicide Severity Rating Scale 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EMG 
electromyographic 
EOS 
end of study 
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 
IRB 
institutional review board 


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ABP-450 
Protocol: ABP-19002 (Version 2.1) 
13 May 2021 
 
 
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Abbreviation 
Definition 
MedDRA 
Medical Dictionary for Regulatory Activities 
mFAS 
Modified Full Analysis Set 
OLE 
open-label extension 
PGI-C 
Patient Global Impression of Change 
 
 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SAS 
Safety Analysis Set  
SASR 
Safety Analysis Set with Retreatment 
SUSAR 
suspected unexpected serious adverse reaction 
TWSTRS 
Toronto Western Spasmodic Torticollis Rating Scale 




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Protocol: ABP-19002 (Version 2.1) 
13 May 2021 
 
 
Page 25 
 
 
 
 
 
 
 
PrabotulinumtoxinA has also been found to be non-inferior to BOTOX® for the treatment of 
moderate to severe glabellar lines in adult patients and upper limb spasticity in patients with 
stroke (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 2 groups) (Nam 2015). 
ABP-19000 is an ongoing, Phase 2, randomized, double-blind, multicenter, 
placebo-controlled study to evaluate the safety and effectiveness of intramuscular ABP-450 
injection for the treatment of cervical dystonia.
 
 
 
ABP-19002 is the open-label extension (OLE) study, wherein eligible patients from 
 
ABP-19000 
 studies, irrespective of treatment allocation, will have the option 
to continue treatment with ABP-450. 
 
 
 The ABP-19002 study will help to 
evaluate safety and efficacy of repeat dosing of ABP-450 for the long-term treatment of 
cervical dystonia. 
Clostridium botulinum toxins have become the standard of care for the treatment of patients 
with cervical dystonia, but also have significant risks associated with their use in these 
patients. The labels of marketed products carry prominent warnings concerning their side 
effects, such as dysphagia and even death, if they are not carefully administered and the 
patients are not monitored while under treatment. Even so, the benefit for all these products 
is greater than the potential risk. 
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, 


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ABP-450 
Protocol: ABP-19002 (Version 2.1) 
13 May 2021 
 
 
Page 26 
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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Protocol: ABP-19002 (Version 2.1) 
13 May 2021 
 
 
Page 27 
2 
Study Objectives and Estimands 
2.1 
Study Objectives 
2.1.1 Primary Objective 
• To evaluate the safety of repeat intramuscular injections of ABP-450 (150-350 units per 
dose) in the treatment of cervical dystonia 
2.1.2 Secondary Objective 
• To evaluate the efficacy of repeat intramuscular injections of ABP-450 (150-350 units per 
dose) 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. Patients 
are expected to: 
• Have not had previous treatment with BOTOX® within the last 8 weeks 
• Have not had previous treatment with ABP-450 within the last 8 weeks 
• Be receiving stable doses of treatment for focal dystonia treatment (eg, 
anticholinergics and benzodiazepines) 
• Meet other inclusion/exclusion criteria 
2.2.2 Primary Estimand 
The primary estimand of the study will be: 
 
 
 
 
 
 
 


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ABP-450 
Protocol: ABP-19002 (Version 2.1) 
13 May 2021 
 
 
Page 28 
2.2.3 
Secondary Estimands 
These are the hypothetical estimands regarding alternative prohibited medications (eg, 
BOTOX®), assuming (treatment policy) no change in background treatment and 
administration of treatment within the 150- to 350-unit dose range: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Protocol: ABP-19002 (Version 2.1) 
13 May 2021 
 
 
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3 
Investigational Plan 
3.1 
Study Design 
This is an open-label, Phase 2/3, multicenter, 52-week study of ABP-450 purified neurotoxin 
complex for the treatment of cervical dystonia. The study population in the ABP-19002 OLE 
study will consist of all patients who had their initial dose of study drug in the ABP-19000 
 
 studies, irrespective of treatment allocation, who consented to being treated for 
cervical dystonia with ABP-450,
 
 
At the investigator’s discretion and with the patient’s consent, patients will enter the OLE 
study at Week 8 (Week 8 will be Day 0 “rollover” for the OLE study) with the opportunity to 
either maintain the original Phase 2 dose or modify the dose. If there is no efficacy (or loss of 
efficacy) between 6 and 20 weeks in the ABP-19000 study, then patients can roll over to the 
OLE study at a dose determined per the investigator’s discretion. 
 
 
 
 During this OLE study, patients will receive any dose 
between 150 and 350 units of ABP-450, based on the investigator’s discretion. There will be 
no additional retreatments after Week 48. 
This OLE study will evaluate the safety and efficacy of repeat injections of ABP-450 for the 
long-term treatment of cervical dystonia. 
3.1.1 Rationale of Study Design 
 
 
 
 
 
 
 


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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 
related to retreatment will be delayed until 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 
All patients who had their initial dose of study drug in the ABP-19000 
 studies, 
irrespective of treatment allocation, and who consented to being treated for cervical dystonia 
with ABP-450 will be eligible to enroll in this OLE study 
 
 
 The study will be conducted at approximately 42 sites in the United States 
 
 
 Patients will be administered 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 OLE study: 
1. Qualified for and had their initial dose of study drug in the ABP-19000 
 
 
 
 
2. Provided written informed consent to being treated for cervical dystonia with 
ABP-450. 
3. Were a male or female patient between 18 and 75 years of age (inclusive) when 
they entered the ABP-19000 
 studies. 
 
 
 
 
 
 
 
 
 
 
 


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13 May 2021 
 
 
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4.1.2 Exclusion Criteria 
Patients who meet any of the following criteria will be excluded from this OLE study: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
8. Participated in another interventional study during participation in this study. 
9. Were a pregnant or lactating female, or female of child-bearing potential not 
willing to use an acceptable method of contraception (ie, intrauterine device, 
barrier methods with spermicide, or abstinence). 
10. Would not benefit from treatment with ABP-450 for their cervical dystonia, in the 
investigator’s opinion. 
11. Viral or other active infection or any medical condition that, in the opinion of the 
investigator, classifies the patient as unsuitable for participation in the study or 
patients who do not seem to be in good general health at the time of Day 0 
“rollover”, and prior to any investigational study drug administration. 
Note: Patients will not routinely be tested for COVID-19 during the study. 
Patients presenting with fever or who are symptomatic for COVID-19 should be 
treated through their general practitioner. 


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13 May 2021 
 
 
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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 
Patients will be followed up for 52 weeks after they enter the ABP-19002 OLE study. 
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: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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8. The patient withdraws consent. 
The investigator will also withdraw a patient if Aeon Biopharma, Inc. 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. 
Any patient may withdraw his or her consent at any time. 
4.2.2 Handling of Withdrawals 
Patients are free to withdraw from the study or study treatment at any time at 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. 
 
 
 
 
 
 
 
 
 
 
 
 
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. All data collected from all patients, including early withdrawals and early 
discontinuations of treatment, will be used in the reporting and analysis of the study. 
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 Group 
Patients who meet all eligibility criteria will continue the current OLE study with the 
randomization code assigned by an interactive response technology system in the ABP-19000 
 studies as their study number. All eligible patients who had their initial dose of 
study drug in the ABP-19000
 studies, irrespective of treatment allocation, and 
who consented to being treated for cervical dystonia,
 
 will 
receive ABP-450 in an unblinded fashion. 
5.2 
Treatment Administered 
Investigational study drug is a Clostridium botulinum toxin type A. Each vial will contain 
100 units of lyophilized ABP-450. 
The ABP-450 dose to be administered to patients in the ABP-19002 OLE study will range 
between 150 and 350 units. Patients will be enrolled in the ABP-19002 OLE study with the 
opportunity to either maintain or modify the dose at the investigator’s discretion. As the blind 
will not be broken, the placebo patients (who were entered into one of the dose groups in the 
ABP-19000 
 studies) can be administered any dose between 150 and 350 units 
of ABP-450, based on the investigator’s discretion and clinical judgment. 
 
 
 
 
 
 
 
 
 
 
 
 
 


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5.3 
Identity of Investigational Product 
ABP-450 is a lyophilized powder packed in vials, each containing 100 units. 
 
 
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 test article, 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, investigational study drug 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. Any overdose, with or without associated 
AEs, must be promptly reported to the
. 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 of the eCRF. 
5.5.1 Treatment of Overdose 
Treatment of suspected overdose of investigational study drug should include investigational 
study drug discontinuation and implementation of appropriate supportive measures. 
5.6 
Blinding 
This is an OLE study. All eligible patients from the 
 ABP-19002 studies will 
receive ABP-450 in an unblinded fashion. As the blind will not be broken, the placebo 
patients (who were entered into one of the dose groups in the ABP-19000 
studies) can be administered any dose between 150 and 350 units of ABP-450, based on the 
investigator’s discretion. 
5.6.1 Breaking the Blind 
Not applicable, as this is an OLE study. 
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 are to be recorded on the dosage 
administration eCRF. 


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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, route of administration, reason for taking, 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) for this OLE study. Patients will have the opportunity to have any questions 
answered before they sign the ICF. The investigator must address all questions raised by the 
patient. The investigator will also sign the ICF. 
6.1 
Study Visits 
Patients will be followed up for 52 weeks after they enter the ABP 19002 OLE study. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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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 drug. 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 drug. Patients will be instructed 
to contact the investigator at any time after enrollment if any symptoms develop. 
A treatment-emergent AE is defined as any event not present before exposure to 
investigational study drug or any event already present that worsens in either intensity or 
frequency after exposure to investigational study drug. 
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 (ie, 52 weeks or end of treatment [ET] after Day 0 “rollover”). 


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Serious AEs that occur more than 56 days (ie, 8 weeks) 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, changes in 12-lead ECG results) 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 
drug 
• 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. 




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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 drug 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 investigational 
study drug and the reported event. 
Possible: 
This relationship suggests that treatment with investigational study drug 
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 investigational study drug but could also have been produced by 
other factors. 


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Unrelated: 
This relationship suggests that there is no association between investigational 
study drug and the reported event. 
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, 
the association of the event with investigational study drug seems likely. The 
event disappears or decreases on cessation or reduction of the dose of 
investigational study drug. 
Definite: 
This relationship suggests that a definite causal relationship exists between 
drug administration and the AE, and other conditions (concurrent illness, 
progression or 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 
Secondary 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 (Fernandez 2013; Espay 2018). 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. 
 
 
 
 
 
 


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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 PGI-C and CGI-C are provided in Appendix 13.4 and Appendix 0, 
respectively. 
 
 
 
 
 
 
 
 
 
 
 
6.3.4 C-SSRS 
The C-SSRS was developed by the 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, 


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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 
 
 
 
 
 
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 Day 0 “rollover,” felt to be clinically 


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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. 
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 
All eligible patients who had their initial dose of study drug in the ABP-19000 
 
studies, irrespective of treatment allocation, and consented to being treated with ABP-450 
will be eligible to enroll in this OLE study. 
Approximately 60 patients could enroll in this OLE study from the ABP-19000 study, 
 
 
 
 
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. 
Modified Full Analysis Set (mFAS): The mFAS will consist of all patients in the FAS but will 
exclude data points 
 
 
 
Per-Protocol Analysis Set: The Per-Protocol Analysis Set will consist of all patients in the 
FAS who received ABP-450 within the study dose range of 150 to 350 units but will exclude 
all patients who had significant protocol violations or do not receive more than one treatment 
of ABP-450 within the OLE study. 
Safety Analysis Set (SAS): The SAS will consist of all patients who received investigational 
study drug. 


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Safety Analysis Set with Retreatment (SASR): The SASR will consist of all patients in the 
SAS but will exclude patients who do not receive more than one treatment of ABP-450 
within the OLE study. 
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, standard deviation, 
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 will be described in the 
SAP. 
7.5.1 Analysis of Primary Estimand 
The proportion of patients with treatment-related SAEs up to Week 52 will be summarized 
for the SASR. 
 
 
 
 
7.5.2 Analysis of Secondary Estimands 
The analysis of the first secondary efficacy estimand is based on a regression model with 
change 
 
 
 
 
 
 
 
 
 


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7.5.3 Other Analyses 
Summary statistical analyses will be provided for demographics, background characteristics, 
medical history, and physical examination. 
7.5.4 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 OLE 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 
 
 
 
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, 
Inc. 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 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 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. 


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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 
 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 
 is financially responsible for 
further treatment of the patient’s disease. 
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 


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• 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 (applicable to study sites in the United States only) 
• Curriculum vitae for the investigator and each subinvestigator listed on Form FDA 1572 
(applicable to study sites in the United States only) 
• 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. 
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. 


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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. 


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11 Study Management 
The administrative structure will include a scientific steering committee and event 
adjudication committee. 
The scientific steering committee, composed of key opinion leaders 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. 
 
 
 
 
 


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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 
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, Inc. has every intention of completing the study, Aeon 
Biopharma, Inc. 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 
(ie, 52 weeks after Day 0 “rollover”), patient withdrawal (for any reason), or study 
discontinuation by the sponsor. 


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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 guideline E3: Structure and 
Content of Clinical Study Reports. 
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 Appendices 
 
 


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13.2 TWSTRS Scale 


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13.4 PGI-C Scale 
 
 
 


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13.5 
 CGI-C Scales 


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13.6 Dysphagia Severity Scale 


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13.7 C-SSRS Scale 


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SAP_001.pdf: 
 
Confidential 
 
 
 
 
 
 
 
 
 
AEON Biopharma, Inc 
 
ABP-19002 
 
An Open-Label, Multicenter Study to Evaluate the Safety and Efficacy of Repeat 
Intramuscular ABP-450 (prabotulinumtoxinA) Injection for the Treatment of 
Cervical Dystonia 
 
24 Aug 2023 
 
Final Statistical Analysis Plan 
 
Version 2.0 
Protocol Version 2.1 
 
Prepared by:  
 
 
 
 
 
 
 


Aeon Biopharma, Inc 
 
Statistical Analysis Plan, Version 2.0 
 
ABP-19002 (Version 2.1) 13MAY2021 
 
Date Issued: 24Aug2023. 
 
 
 
 II
Table of Contents 
TABLE OF CONTENTS ............................................................................................................ II 
LIST OF ABBREVIATIONS .................................................................................................... IV 
1. 
INTRODUCTION ............................................................................................................ 1 
2. 
OBJECTIVES ................................................................................................................... 2 
2.1.1. 
Primary objective ........................................................................................................ 2 
2.1.2. 
Secondary objective .................................................................................................... 3 
3. 
INVESTIGATIONAL PLAN .......................................................................................... 3 
3.1. OVERALL STUDY DESIGN AND PLAN .................................................................................. 3 
3.2. STUDY ESTIMANDS ............................................................................................................. 3 
3.2.1. 
Primary Estimand ....................................................................................................... 3 
3.2.2. 
Secondary Estimands .................................................................................................. 4 
3.3. TREATMENTS ...................................................................................................................... 4 
3.4. DOSE ADJUSTMENT/MODIFICATIONS ................................................................................. 4 
4. 
GENERAL STATISTICAL CONSIDERATIONS ....................................................... 5 
4.1. GENERAL CONSIDERATIONS ................................................................................................ 5 
4.2. KEY DEFINITIONS ............................................................................................................... 6 
4.3. SAMPLE SIZE ...................................................................................................................... 7 
4.4. RANDOMIZATION, STRATIFICATION, AND BLINDING .......................................................... 7 
4.5. ANALYSIS SET .................................................................................................................... 8 
4.5.1. 
Enrolled Set ................................................................................................................. 8 
4.5.2. 
Modified Full Analysis Set (mFAS)............................................................................. 8 
4.5.3. 
Safety Analysis Set (SAF) ............................................................................................ 8 
4.5.4. 
Safety Analysis Set with Retreatment (SAFR) ............................................................. 8 
5. 
PATIENT DISPOSITION ............................................................................................... 8 
5.1. DISPOSITION ....................................................................................................................... 8 
5.2. PROTOCOL DEVIATIONS ..................................................................................................... 9 
6. 
DEMOGRAPHICS AND BASELINE CHARACTERISTICS .................................... 9 
6.1. DEMOGRAPHICS .................................................................................................................. 9 
6.2. GENERAL MEDICAL HISTORY ............................................................................................. 9 
6.3. INCLUSION AND EXCLUSION CRITERIA ............................................................................. 10 
7. 
TREATMENTS AND MEDICATIONS ....................................................................... 10 
7.1. PRIOR AND CONCOMITANT MEDICATIONS ........................................................................ 10 
7.1.1. 
Prior Medications ..................................................................................................... 10 
7.1.2. 
Concomitant Medications ......................................................................................... 10 
7.2. STUDY TREATMENTS ........................................................................................................ 10 
7.2.1. 
Extent of Exposure to ABP-450 ................................................................................ 10 
7.2.2. 
Treatment Compliance .............................................................................................. 11 
8. 
SAFETY ANALYSIS ..................................................................................................... 11 


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8.1. ADVERSE EVENTS ............................................................................................................. 11 
8.1.1. 
Primary Estimand ..................................................................................................... 12 
8.1.2. 
Overall Summary of Adverse Events......................................................................... 13 
8.1.3. 
Incidence of Adverse Events ..................................................................................... 13 
8.1.4. 
Relationship of Adverse Events to Study Drug ......................................................... 13 
8.1.5. 
Severity of Adverse Event.......................................................................................... 14 
8.1.6. 
Serious Adverse Events ............................................................................................. 14 
8.1.7. 
Adverse Events Leading to Treatment Discontinuation............................................ 14 
8.1.8. 
Adverse Events Leading to Study Withdrawal .......................................................... 14 
8.1.9. 
Suspected Unexpected Serious Adverse Events ........................................................ 14 
8.1.10. Non-Serious Adverse Events of Special Interest ....................................................... 14 
8.1.11. Death ......................................................................................................................... 14 
8.2. CLINICAL LABORATORY EVALUATIONS ........................................................................... 14 
 
 
 
 
 
 
 
 
 
 
8.2.6. 
Urine Pregnancy Test ............................................................................................... 15 
 
 
 
 
 
 
 
 
8.7. COLUMBIA-SUICIDE SEVERITY RATING SCALE (C-SSRS)................................................ 16 
9. 
EFFICACY ANALYSIS................................................................................................. 17 
9.1. SECONDARY ESTIMAND .................................................................................................... 17 
9.1.1. 
TWSTRS Total Score ................................................................................................. 18 
9.1.2. 
TWSTRS Subscale (Disability, Severity, and Pain) Scores ....................................... 19 
 
 
9.1.4. 
PGI-C ........................................................................................................................ 20 
 
 
9.1.6. 
CGI-C ........................................................................................................................ 20 
9.1.7. 
Time to loss of 80% peak treatment effect of TWSTRS Total Score. ........................ 21 
9.1.8. 
Dysphagia Severity Scale scores .............................................................................. 21 
10. 
INTERIM ANALYSIS ................................................................................................... 22 
11. 
CHANGES IN THE PLANNED ANALYSIS .............................................................. 22 
12. 
REFERENCES ................................................................................................................ 23 
13. 
APPENDICES ................................................................................................................. 25 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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  IV
List of Abbreviations 
 
AE 
adverse event 
ATC 
Anatomical Therapeutic Chemical 
BMI 
Body mass index 
CGI-C 
Clinical Global Impression of Change 
C-SSRS 
Columbia-Suicide Severity Rating Scale 
 
 
CI 
Confidence interval 
COVID-19 
Coronavirus Disease 2019 
CRF 
case report form 
DSMB 
data safety monitoring board 
ECG 
electrocardiogram 
eCRF 
Electronic case report form 
EOS 
End of study 
FAS 
full analysis set 
FEV1 
forced expiratory volume in 1 second   
FVC 
forced vital capacity 
HEENT 
head, ears, eyes, nose, throat 
ICH 
International Conference on Harmonisation 
ITT 
intent-to-treat 
MedDRA 
Medical Dictionary for Regulatory Activities 
mFAS 
Modified full analysis set 
MITT 
modified intent-to-treat 
OLE 
Open label extension 
PGI-C 
Patient Global Impression of Change 
 
 
PPS 
per protocol set 
PT 
preferred term 
PVG 
Pharmacovigilance 
SAF 
Safety analysis set 
SAFR 
Safety analysis set with retreatment 
SAP 
Statistical analysis plan 
SAE 
serious adverse event 
SE 
Standard error 
SOC 
system organ class 
SOP 
Standard operating procedures 
TEAE 
treatment-emergent adverse events 
TWSTRS 
Toronto Western Spasmodic Torticollis Rating Scale 
WHO 
World Health Organization 
WHODRUG 
World Health Organization drug dictionary 
 
 


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1. Introduction 
Cervical dystonia (spasmodic torticollis) is the most common form of focal dystonia, affecting the 
neck and shoulder muscles (Defazio 2004, Mittal 2019). Cervical dystonia is characterized by 
abnormal head and neck posture with 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 
(Comella 
2011, 
Simpson 
2016, 
Mittal 
2019). 
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.  
 
 
 
 
 
 
 
 
ABP-450  was evaluated in multiple non-clinical safety and toxicological tests to determine the 
pharmacologic and safety profile of the product to in complying with International Council for 
Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) 
guidelines/requirements for biologic products. 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
PrabotulinumtoxinA has also been found to be non-inferior to BOTOX® for the treatment of 
moderate to severe glabellar lines in adult patients and upper limb spasticity in patients with stroke 


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(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 2 groups) (Nam 2015). 
 
ABP-19000 is an ongoing, Phase 2, randomized, double-blind, multicenter, placebo-controlled 
study to evaluate the safety and effectiveness of intramuscular ABP-450 injection for the treatment 
of cervical dystonia. 
 
 
 ABP-19002 is the open-label extension (OLE) 
study, wherein eligible patients from 
 ABP-19000 
 studies, irrespective of 
treatment allocation, will have the option to continue treatment with ABP-450. 
 
 
 
 The ABP-19002 study will help to evaluate safety and efficacy of repeat dosing 
of ABP-450 for the long-term treatment of cervical dystonia. 
 
Clostridium botulinum toxins have become the standard of care for the treatment of patients with 
cervical dystonia, but also have significant risks associated with their use in these patients. The 
labels of marketed products carry prominent warnings concerning their side effects, such as 
dysphagia and even death, if they are not carefully administered and the patients are not monitored 
while under treatment. Even so, the benefit for all these products is greater than the potential risk. 
 
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. 
 
This statistical analysis plan (SAP) defines the statistical methods and data presentations to be used 
 in the analysis and presentation of data for Aeon Biopharma, 
Inc protocol number ABP19002 entitled ‘An Open-Label, Multicenter Study to Evaluate the Safety 
and Efficacy of Repeat Intramuscular ABP-450 (prabotulinumtoxinA) Injection for the Treatment 
of Cervical Dystonia’. This SAP has been written in accordance with ICH E9 
 
 standard operating procedures (SOPs) and using the final study 
protocol version 2.1 dated 13 May 2021 and electronic case report form (eCRF) version 2.0 (28 
Jun 2021). 
2. Objectives 
2.1.1. Primary objective 
• To evaluate the safety of repeat intramuscular injections of ABP-450 (150-350 units per 
dose) in the treatment of cervical dystonia. 
 


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2.1.2. Secondary objective 
• To evaluate the efficacy of repeat intramuscular injections of ABP-450 (150-350 units per 
dose) in the treatment of cervical dystonia. 
3. Investigational Plan 
3.1. Overall Study Design and Plan 
Since cervical dystonia is a chronic disease, patients typically receive medications regularly (i.e., 
repeated therapy), including botulinum toxin injections. For this reason, it is useful to evaluate the 
safety and efficacy of repeat injections of ABP-450 for the ongoing (long-term) treatment of 
cervical dystonia. 
 
This is an open-label, Phase 2/3, multicenter, 52-week study of ABP-450 purified neurotoxin 
complex for the treatment of cervical dystonia. The study population will consist of all patients 
who had their initial dose of study drug in the ABP-19000 study, irrespective of treatment 
allocation, and who consented to being treated for cervical dystonia with ABP-450 in the ABP-
19002 OLE study 
  
 
At the investigator’s discretion and with the patient’s consent, patients will enter the OLE study at 
Week 8 (Week 8 will be Day 1 “rollover” for the OLE study) with the opportunity to either 
maintain the original Phase 2 dose or modify the dose. If there is no efficacy (or loss of efficacy) 
between 6 and 20 weeks in the ABP-19000 study, then patients can roll over to the OLE study at 
a dose determined per the investigator’s discretion. 
 
 
 
 
 During this OLE study, patients will 
receive any dose between 150 and 350 units of ABP-450, based on the investigator’s discretion. 
There will be no additional retreatments after Week 48. 
3.2. Study Estimands 
For all estimands, the target population is patients diagnosed with cervical dystonia. Patients are 
expected to: 
• Have not had previous treatment with BOTOX® within the last 8 weeks. 
• Have not had previous treatment with ABP-450 within the last 8 weeks. 
• Be receiving stable doses of treatment for focal dystonia treatment (e.g., anticholinergics 
and benzodiazepines) 
• Meet other inclusion/exclusion criteria. 
3.2.1. Primary Estimand 
 
 
 
 


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3.2.2. Secondary Estimands 
These are the hypothetical estimands regarding alternative prohibited medications (e.g., 
BOTOX®), assuming (treatment policy) no change in background treatment and administration of 
treatment within the 150- to 350-unit dose range: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3.3. Treatments   
Investigational study drug is a Clostridium botulinum toxin type A. Each vial contains 100 units 
of lyophilized ABP-450. All study patients, will be administered between 150 and 350 units of 
ABP-450, based on the investigator’s discretion and clinical judgment. 
 
 
 
 
 
 
 
  
 
  
 
  
 
 
 
 
There will be no additional retreatments after Week 48. 
3.4. Dose Adjustment/Modifications 
Patients were enrolled in the ABP-19002 OLE study with the opportunity to either maintain the 
original Phase 2 dose or modify the dose at the investigator’s discretion. As the blind will not be 
broken, the placebo patients (who were entered into one of the dose groups in the ABP-19000 


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study) can be administered any dose between 150 and 350 units of ABP-450, based on the 
investigator’s discretion and clinical judgment. Retreatments are also based on investigator’s 
discretion and clinical judgement. 
4. General Statistical Considerations 
4.1. General 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). All descriptive 
summaries will be presented by dose group, treatment cycle and nominal visit/timepoint (where 
applicable). 
 
 
 
 All efficacy analyses will 
be based upon the modified Full Analysis Set (mFAS, Section 4.5.2), and all safety as well as 
demographic and baseline characteristic analyses will be based upon the Safety Analysis Set 
(Section 4.5.3). Summary of safety and efficacy analyses will be displayed by treatment group and 
treatment cycle. Additional analyses will be performed on selected populations as specified in the 
sections below. 
 
Unless otherwise stated, the following methods will apply: 
 
• Treatment groups: For a given assessment or event, treatment group will be assigned to a 
patient based on the last dose received as follows: 
Range of total dose 
treatment group 
a. 
Non-missing dose ≤ 200 units 
ABP-450 150 units 
b. 
> 200 to ≤ 300 units 
ABP-450 250 units 
c. 
> 300 units 
ABP-450 350 units 
 
In addition, three dose groups (low, medium, high) based on total dose across the whole 
study will be assigned to a patient for a given assessment or event as follows: 
 
Range of overall total dose 
Overall treatment group 
a. 
Non-missing dose ≤ 800 units 
ABP-450 low 
b. 
> 800 to ≤ 1200 units 
ABP-450 medium 
c. 
> 1200 units 
ABP-450 high 
 
• Continuous variables: will be summarized using summary statistics (i.e., non-missing 
values (n), mean, standard deviation, median, minimum, and maximum). For the summary 
statistics of all continuous data, minimum and maximum values will be displayed to the 
same level of precision as reported, unless otherwise specified. Mean and median will be 
displayed to one level of precision greater than the data collected. Standard deviation will 
be displayed to two levels of precision greater than the data collected. 
 
• Categorical variables: will be described using the patient count and percentage in each 
category. When counts are presented, in cases where the count is zero, the percentage will 


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not be displayed to draw attention to the non-zero counts. A row denoted ‘Missing’ will be 
included in count tabulations where specified on the shells to account for missing values. 
The denominator for all percentages will be the number of populated patients in that 
treatment within the analysis set of interest, unless otherwise specified. Frequency statistics 
will be displayed using one decimal place except for the display of 100% frequency which 
will be displayed as ‘XX (100)’.  
 
• Rules for multiple assessments: To summarize data collected over time, summary tables 
will be presented by scheduled visit. Unscheduled visits may be included in specific 
summaries (such as worst post-baseline measurement) and will be described in the relevant 
sections. Both scheduled and unscheduled visits will be included in the data listings. 
 
• Date and time display conventions: The following display conventions will be applied in 
all outputs where dates and/or times are displayed: 
Date only: DDMMMYYYY 
Date and time: DDMMMYYYY HH:MM 
Partial dates will be listed as such (i.e., where day or day and month is missing, only 
MMMYYYY or YYYY will be displayed, respectively).  
 
• Multiple comparisons: There will be no statistical adjustment for multiplicity. 
 
• Treatment terminology and order to be used in TLF outputs:  
▪ Unless specified, the following labels will be used for summary tables: 
a. ABP-450 150 units 
b. ABP-450 250 units 
c. ABP-450 350 units 
▪ For summary of disposition, demography, medical history, prior medications, and first 
secondary estimand, the following will be used: 
a. ABP-450 low 
b. ABP-450 medium 
c. ABP-450 high 
4.2. Key Definitions 
The following key definitions will be used: 
 
 
 
  
 
 
 
 
 
 
 
 
   


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• Study Day: Within each treatment cycle, the study day of an event is defined as the relative 
day of the event starting with the date the study drug administration (reference date) for 
that Cycle as Study Day 1 (there will be no Day 0 for analysis purposes). The study day of 
events occurring before the first study drug administration in the first treatment cycle will 
be calculated as:  
 
 
 
Study Day = (date of event – date of first study drug administration).  
 
For events occurring on or after Study Day 1 in the first treatment cycle (including protocol 
specified Day 0 “rollover” visit), study day will be calculated within cycles as: 
 
Study Day = (date of event/visit within a cycle – Date of study drug administration of that 
cycle) + 1. 
 
Study days will only be calculated for events with complete or imputed dates and will be 
undefined for events that are “ongoing” at the end of the study. 
 
• Baseline: The last observation on or before date of first dose in the ABP-19000 study will 
be considered as the baseline measurement unless otherwise specified. Repeat or 
unscheduled assessments may be included in the derivation of the baseline value.  
 
• Change from baseline: The change from baseline value is defined as the difference between 
the result collected/derived at a post-baseline visit/timepoint within a cycle and the baseline 
value. The change from baseline value at each post-baseline visit/timepoint within a Cycle 
will be calculated for all continuous parameters using the formula: 
 
Change from baseline Value = Result at Visit or Timepoint within a cycle– Baseline 
Value 
 
The change from baseline value will only be calculated if the specific post-baseline 
visit/timepoint within a treatment cycle results and the baseline value for the parameter are 
both available and will be treated as missing otherwise. 
 
All analyses will be conducted using 
 
4.3. Sample Size 
All eligible patients who had their initial dose of study drug in the ABP-19000 study, irrespective 
of treatment allocation, and consented to being treated with ABP-450 can be enrolled in this OLE 
(i.e., ABP-19002) study. 
 
Approximately 59 patients could enroll in this OLE study from the ABP-19000 study. As there 
will be no comparative analyses, study power and sample size justifications are not required. 
4.4. Randomization, Stratification, and Blinding 
This is an OLE study. All eligible patients from the ABP-19002 study will receive ABP-450 in an 
unblinded fashion. As the blind will not be broken, the placebo patients (who were entered into 


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one of the dose groups in the ABP-19000 study) can be administered any dose between 150 and 
350 units of ABP-450, based on the investigator’s discretion. 
4.5. Analysis Set 
The following analysis sets will be used for this study. Inclusion in each analysis set will be 
reviewed and confirmed prior to database lock. The number and percent of patients in each analysis 
set will be summarized. A listing will also be produced displaying patients excluded from each 
set. 
4.5.1. Enrolled Set 
Enrolled Set will include every patient who signed informed consent form and attended Visit. The 
Enrolled Set will only be used for summaries of patient disposition and protocol deviations. 
4.5.2. Modified Full Analysis Set (mFAS) 
The mFAS will consist of all patients in the Safety Analysis Set but will exclude patients 
 
 
 
 The mFAS will be used for analysis of 
secondary estimands. 
4.5.3. Safety Analysis Set (SAF) 
The SAF will consist of all patients who received at least one dose of the investigational study 
drug. The SAF will be used to tabulate all safety data excluding the primary estimand.  
4.5.4. Safety Analysis Set with Retreatment (SAFR) 
The SAFR will consist of all patients in the SAF but will exclude patients who do not receive 
more than one treatment of ABP-450 within the OLE study. The SAFR will be used for analysis 
of the primary estimand. 
5. Patient Disposition 
5.1. Disposition 
Patient disposition will be summarized by overall treatment group and presented in a listing for 
patients in the Enrolled Set. The disposition of patients will include the number and percentage of 
patients for the following categories:  
• Patients enrolled. 
• Patients included in the mFAS. 
• Patients included in the SAF. 
• Patients included in the SAFR. 
• Patients who discontinued treatment with corresponding reasons for treatment 
discontinuation. 
• Patient included in the SAF with corresponding reasons for treatment discontinuation. 
• Patients who withdrew from the study with corresponding reasons for study withdrawal. 
 
The reasons for discontinuation of ABP-450 treatment or withdrawal from the study include: 
• Adverse Event 


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• Death 
• Lack of Efficacy 
• Lost to Follow-up 
• Non-Compliance with Study Drug 
• Physician Decision 
• Pregnancy 
• Study Terminated by Sponsor 
• Withdrawal by Subject 
• Other 
5.2. Protocol Deviations 
A listing of patients with protocol deviations will be provided. 
6. Demographics and Baseline Characteristics 
Demographic and baseline information will be summarized descriptively by overall treatment 
group (low, medium, high) as described in Section 4.1 using the mFAS and SAF and presented 
in listings using SAF. 
6.1. Demographics 
The following demographic parameters will be summarized: 
Continuous descriptive analysis 
• Age (years, as collected on the eCRF) 
• Height (cm) 
• Weight (kg) 
• Body Mass Index (BMI) (kg/m2). The BMI will be calculated as (body weight in 
kilograms) / (height in meters)2. 
Categorical descriptive analysis 
• Sex (Male, Female) 
• Ethnicity (Hispanic or Latino, Not Hispanic or Latino, and Not Reported) 
• Race (White, Black or African American, Asian, American Indian or Alaska Native, Native 
Hawaiian or Other Pacific Islander, Other, and Not Reported) 
6.2. General Medical History 
Medical history and current medical conditions will be coded using the ICH Medical Dictionary 
for Regulatory Activities (MedDRA) version 25.0 or later. Relevant prior medical history and 
current medical conditions will be summarized by overall treatment group (low, medium, high) 
system organ class (SOC) and preferred term (PT), using the SAF. Summary tables will include 
the number and proportion of patients (%) experiencing an event. Patients will be counted once 
for each SOC and PT level. General medical history data will also be listed using the SAF. 


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6.3. Inclusion and Exclusion Criteria 
Inclusion and exclusion criteria not met by patients will be listed using the Enrolled Set. Inclusion 
criteria and exclusion criteria may be found in Protocol Sections 4.1.1 and 4.1.2, respectively. 
7. Treatments and Medications 
7.1. Prior and Concomitant Medications 
Prior and concomitant medications will be documented and updated during the study. Prior and 
concomitant medications will be coded according to the latest World Health Organization drug 
dictionary (WHODRUG Sep 2022 or later). 
 
Medications that started prior to and continued after the first dose of ABP-450 will be included as 
both prior and concomitant medications. Summaries of prior and concomitant medications will be 
presented by overall treatment group (low, medium, high), PT and based on the SAF..  
7.1.1. Prior Medications 
A prior medication is defined as any medication that is taken prior to the first dose of ABP-450 
regardless of when they stopped. 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 (Baseline). Prior medications will be tabulated and listed. Medications that were 
started during and prior to the ABP-19000 study will be flagged in the listings.  
7.1.2. Concomitant Medications 
A concomitant medication is defined as any medication (other than ABP-450) that was used at 
least once on or after the date of first dose of ABP-450. Medications that were stopped on the same 
date as the first dose of ABP-450 will be included as concomitant medications. All medications 
which are ongoing will be considered concomitant. In addition, if a clear determination cannot be 
made (e.g., missing or partial medication start and/ or end dates), the medication will be included 
as concomitant. 
 
  
 
 
 
 
 
7.2. Study Treatments 
7.2.1. Extent of Exposure to ABP-450 
The number and percentage of patients exposed to study treatment at each visit within each 
treatment cycle will be summarized descriptively for categorical parameters by treatment group, 
while the cumulative number of doses and cumulative dose at each visit within each treatment 
cycle and total ABP-450 administered overall will be summarized descriptively for continuous 
parameters as described in Section 4.1, using the SAF. 
 
 
 


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7.2.2. Treatment Compliance  
ABP-450 will be administered to the patient at the trial site by trained trial staff. Precise dose 
administered, the time and date of dosing in the source document and the dosage administration 
will be recorded in the eCRF. No analysis of compliance is planned for ABP-450. 
 
8. Safety Analysis 
8.1. Adverse Events 
AEs will be collected from the time of signing of the ICF until 52 weeks or end of treatment after 
Day 1 “rollover” (exit from the study). All AEs will be classified by SOC and PT according to the 
MedDRA, version 24.0 or later. 
 
Serious AEs that occur more than 56 days (i.e., 8 weeks) after the last dose of investigational study 
drug and the patient has exited the study may be reported if the investigator considers them related 
to investigational study drug. 
 
The severity or intensity of an AE refers to the extent to which an AE affects the patient’s daily 
activities. Adverse event severity will be classified as “Mild”, “Moderate”, and “Severe”. TEAEs 
with missing severity will be imputed as ‘Severe’. 
 
The investigator will provide an assessment of the relationship of the event to the trial drug. The 
possible relationships are “Unrelated”, “Possibly Related”, “Probably Related” and “Definitely 
Related”. Any TEAE reported as “Definitely Related”, “Possibly Related” or “Probably Related” 
will be considered related to the ABP-450. TEAEs that are missing a relationship will be counted 
in the summary table as “Definitely Related” but will be presented in the data listing with a missing 
relationship.  
 
Treatment emergent adverse events (TEAEs) are defined as those AEs that started on or after the 
day of first dose of ABP-450 up to 5 days after the end of treatment or end of study visits. Only 
TEAEs will be included in the AE summary tables. However, all adverse events will be listed and 
TEAEs will be flagged. 
 
The TEAEs will be summarized by SOC and PT and will include the number and percentage of 
patients experiencing an event and the number of events (based on start date of the event) by 
treatment cycle and treatment group. Patients will be counted only once for each SOC and PT level 
(categorical descriptive analyses). In general, TEAE summary tables will be sorted by SOC and 
PT in descending order of frequency from the SOC and PT with the highest total frequency to the 
SOC and PT with the lowest total frequency. 
 
  
 
 
 
 
 
 
 
 
 
 


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For the purpose of inclusion in TEAE tables, incomplete AE onset and end dates will be imputed 
following date imputation guidelines (see Section 13.2). 
8.1.1. Primary Estimand 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 


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8.1.2. Overall Summary of Adverse Events 
An overall summary of TEAEs will be summarized by treatment group and treatment cycle by 
providing the number and percent of patients who experience the following: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
8.1.3. Incidence of Adverse Events 
An overall summary of the number and percentage of patients with at least one TEAE will be 
presented by SOC and PT. At each level of patient summarization, a patient is counted once if the 
patient reported one or more events starting in each treatment group in each treatment cycle, and 
across all cycles (by overall total doses of low, medium, and high). Percentages will be calculated 
out of the number of patients in the SAF. The table will be sorted by SOC and PT in descending 
order of incidence from the SOC and PT with the highest total incidence to the SOC and PT with 
the lowest total incidence. Summaries and listings will be presented for the SAF. 
8.1.4. Relationship of Adverse Events to Study Drug 
Summaries of TEAEs related to ABP-450 will be presented by SOC and PT in descending order 
of frequency by treatment group within each treatment cycle. Summaries for TEAEs related to 


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ABP-450 will be presented using patients in the SAF who received at least one dose of ABP-450. 
Data will be listed for the SAF. 
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 by treatment group within each treatment cycle. Incidence will be based on the worst 
severity within each level of summarization.  
 
Listings will be presented for the SAF. 
8.1.6. Serious Adverse Events 
Treatment-emergent SAEs will be presented by SOC and PT in a manner similar to that described 
in Section 8.1. Incidence and frequency summaries and listings of all treatment-emergent SAEs 
will be presented for the SAF by treatment group in each treatment cycle, and across all cycles (by 
overall total doses of low, medium, and high).  
8.1.7. Adverse Events Leading to Treatment Discontinuation 
Incidence of TEAEs with a study drug action taken as “Drug Withdrawn” will be summarized by 
SOC and PT by treatment group within each treatment cycle as described in Section 8.1. At each 
level of patient summarization, a patient is counted once if the patient reported one or more 
events. Percentages will be calculated out of the number of patients in the SAF. 
8.1.8. Adverse Events Leading to Study Withdrawal 
Summaries of incidence of TEAEs leading to study withdrawal will be tabulated by SOC and PT 
for each treatment group within each treatment cycle as described in Section 8.1. Percentages will 
be calculated out of the number of patients in the SAF. 
8.1.9. 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 
by SOC,  PT, and treatment group for each treatment cycle. 
8.1.10. Non-Serious Adverse Events of Special Interest 
Adverse events potentially suggestive of distant spread of toxin effects are listed in Appendix 13.3. 
The incidence of non-serious AEs of special interest will be summarized by SOC and PT for each 
treatment group within each treatment cycle. 
8.1.11. Death 
A listing of patient deaths will be presented using the SAF. 
8.2. Clinical Laboratory Evaluations 
 
 


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8.2.6. Urine Pregnancy Test 
A urine pregnancy test will be performed as scheduled (see Appendix 13.1). Pregnancy test data 
will be provided in a listing. 
 
 
 
  


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8.7. Columbia-Suicide Severity Rating Scale (C-SSRS) 
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 
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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 C-SSRS will be performed as per schedule of assessment (see Appendix 13.1) and a detailed 
description of the C-SSRS scale is provided in study protocol Appendix 13.7. The eCRF for ‘Since 
Last Visit’ scale will be used for all visits. The frequency and percentage of C-SSRS responses 
will be tabulated by treatment cycle and treatment group  using the SAF. The C-SSRS responses 
of patients with any suicidal ideation, suicidal behavior, or self-injurious behavior without suicidal 
intent will also be provided in a listing for the SAF.  
9. Efficacy Analysis 
Unless otherwise indicated, all inferential efficacy analyses will include all patients in the mFAS 
and will be presented by treatment cycle and treatment group.  Missing data imputation will be 
performed as described in each section. Visit windows for efficacy analyses are described in 
Appendix 13.1. Efficacy analyses will be tabulated, and figures will be produced for measures 
over time. 
9.1. Secondary Estimand 
The secondary estimands for this study are:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  


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9.1.1. TWSTRS Total Score 
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 6 items and a pain scale with 3 items. The 
total score is the sum of each of the subscales. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 


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9.1.2. TWSTRS Subscale (Disability, Severity, and Pain) Scores 
Summary statistics for TWSTRS subscale scores (actual subscale scores and change from baseline 
in TWSTRS subscale score to each scheduled post baseline visit) will be calculated 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 


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9.1.4. PGI-C 
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). Detailed descriptions of the PGI-C are provided in study protocol 
Section 13.4. PGI-C scores will be measured as per scheduled of assessment (see Appendix 13.1). 
 
Summary statistics for actual PGI-C scores at each scheduled post baseline visit will be calculated 
as described for continuous variables in section 4.1. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
9.1.6. CGI-C 
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 are provided in study protocol section 13.5 and CGI-C scores will be measured as per 
scheduled of assessment (see Appendix 13.1). 
 
Summary statistics for actual CGI-C scores at each scheduled post baseline visit will be calculated 
as described for continuous variables in Section 4.1. 
 
 
 


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9.1.7. Time to loss of 80% peak treatment effect of TWSTRS Total Score. 
Summary statistics for time to loss of ≥ 80% of peak treatment effect for patients dosed on ABP-
450 will be tabulated by treatment cycle and treatment group. 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
9.1.8. Dysphagia Severity Scale scores 
 
 
 
 
 
 
 
 
 
 
 
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10. Interim Analysis 
There is no planned interim analysis for this OLE study. 
 
11. Changes in the Planned Analysis 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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12. References 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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13. Appendices 
 
 


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