Clinical trial NCT04182672
Conditions: Trochanteric Bursitis
Keywords: Hip bursitis hip pain
Sponsor: The University of Texas Health Science Center, Houston
Start date: 2020-08-12; Completion date: 2022-12-14
Enrollment: 22 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this study is to determine the safety and efficacy of FX006 in bursal injections and to assess the patient's impression to change in their chronic pain, following treatment.

Detailed description:

Arms: arm 1: None
Interventions: intervention 1: FX006
Intervention descriptions: intervention 1: Subjects will be injected with the 5mL of FX006. This injection may be followed with up to 3mL of ropivacaine (depending on the capacity of the bursa), under ultrasound guidance.

Protocol documents:
Prot_SAP_000.pdf: 
IRB NUMBER: HSC-MS-18-0672 
IRB APPROVAL DATE: 02/12/2021 
1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study to Assess the Safety and Efficacy of FX006 Administered to Patients With Greater 
Trochanteric Bursitis 
 
NCT04182672 
 
Version Date: 02/12/2021 
 
 


IRB NUMBER: HSC-MS-18-0672 
IRB APPROVAL DATE: 02/12/2021 
2 
 
 
DR. PRITISH BAWA/THE UNIVERSITY OF TEXAS MCGOVERN 
MEDICAL SCHOOL 
Clinical Research Protocol 
 
Study to assess the safety and efficacy of FX006 administered to 
patients with greater trochanteric bursitis 
 
Protocol Number: 
HSC-MS-18/0672 
Version Date: 2/1/2021 
lnvestigational Product: FX006 
IND Number: 
Development Phase: 
Sponsor: 
Dr. Pritish Bawa, MD 
The University of Texas McGovern Medical School 
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Principal Investigator: 
Name: Dr. Pritish Bawa |||||||||||||||||||||||||||||||||||||||||||| 
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Approval: 
 
This confidential information about an investigational 
product is provided for the exclusive use of investigators of 
this product and is subject to recall at any time. The 
information in this document may not be disclosed unless 
federal or state law or regulations require such disclosure. 
Subject to the foregoing, this information may be disclosed 
only to those persons involved in the study who have a 
need to know, with the obligation not to further disseminate 
this information. 
 
 
 
 
 
 
 
 
 
Version #:2 
Version Date: 2/1/2021 


IRB NUMBER: HSC-MS-18-0672 
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Table of Contents 
LIST OF ABBREVIATIONS .............................................................................................................................................. 4 
2 
STUDY OBJECTIVES .............................................................................................................................................. 8 
2.1 Primary Objective ...................................................................................................................................................... 8 
2.2 Secondary Objectives ............................................................................................................................................... 8 
3. STUDY DESIGN ........................................................................................................................................................... 9 
3.1 Study Overview ......................................................................................................................................................... 9 
4 
CRITERIA FOR EVALUATION ............................................................................................................................... 9 
4.1 Primary Endpoint ...................................................................................................................................................... 9 
4.2 Secondary/Exploratory Endpoints .......................................................................................................................... 9 
4.3 Safety Evaluations .................................................................................................................................................... 9 
5 
SUBJECT SELECTION ........................................................................................................................................... 9 
5.1 Study Population ....................................................................................................................................................... 9 
5.2 Inclusion Criteria ....................................................................................................................................................... 9 
5.3 Exclusion Criteria .................................................................................................................................................... 10 
6 
CONCURRENT MEDICATIONS ............................................................................................................................ 10 
6.1 Allowed Medications and Treatments................................................................................................................... 10 
6.2 Prohibited Medications and Treatments .............................................................................................................. 10 
7 
STUDY TREATMENTS .......................................................................................................................................... 11 
7.1 Treatment Plan ........................................................................................................................................................ 11 
7.1.1 
Formulation of Test Product ........................................................................................................................ 11 
7.1.2 
Packaging and Labeling ............................................................................................................................... 11 
7.2 Supply of Study Drug at the Site ........................................................................................................................... 11 
7.2.1 
Dosage/Dosage Regimen ............................................................................................................................. 11 
7.2.2 
Dispensing ..................................................................................................................................................... 11 
7.2.3 
Administration Instructions ......................................................................................................................... 12 
7.2.4 
Storage ........................................................................................................................................................... 12 
7.3 Study Drug Accountability ..................................................................................................................................... 12 
8 
STUDY PROCEDURES AND GUIDELINES ......................................................................................................... 12 
8.1 Clinical Assessments ............................................................................................................................................. 12 
8.1.1 
Concomitant Medications ............................................................................................................................ 12 
8.1.2 
Demographics ............................................................................................................................................... 12 
8.1.3 
Medical History .............................................................................................................................................. 12 
8.1.4 
Physical Examination ................................................................................................................................... 12 


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8.1.5 
Vital Signs ............................................................................................................................................. 12 
8.1.6 
Other Clinical Procedures .................................................................................................................... 13 
8.1.7 
Adverse Events ................................................................................................................................ 13 
9 
ADVERSE EXPERIENCE REPORTING AND DOCUMENTATION ................................................................... 13 
9.1 Collection ................................................................................................................................................. 13 
9.2 Definitions ............................................................................................................................................... 13 
Table 1: AE Severity Grading ................................................................................................................................... 14 
9.3 Serious Adverse Event Reporting ..................................................................................................................... 15 
9.4 Reporting to the US FDA .................................................................................................................................... 15 
9.5 Pregnancy ................................................................................................................................................ 15 
10 DISCONTINUATION AND REPLACEMENT OF SUBJECTS .............................................................................. 15 
10.1 Early Discontinuation of Study Drug ............................................................................................................... 15 
10.2 Withdrawal of Subjects from the Study .......................................................................................................... 16 
10.3 Replacement of Subjects ................................................................................................................................. 16 
11 PROTOCOL VIOLATIONS .............................................................................................................................. 16 
12 STATISTICAL METHODS AND CONSIDERATIONS .......................................................................................... 16 
12.1 Data Sets Analyzed ..................................................................................................................................... 16 
12.2 Demographic and Baseline Characteristics ................................................................................................... 17 
13 DATA COLLECTION AND RETENTION .............................................................................................................. 17 
13.2 Data Management Procedures ......................................................................................................................... 17 
13.3 Data Quality Control and Reporting ................................................................................................................ 17 
13.4 Archival of Data ........................................................................................................................................... 17 
13.5 Availability and Retention of Investigational Records .................................................................................. 18 
13.6 Subject Confidentiality ................................................................................................................................ 18 
14 ADMINISTRATIVE, ETHICAL, REGULATORY CONSIDERATIONS .................................................................. 18 
14.1 Protocol Amendments ................................................................................................................................ 18 
14.2 Institutional Review Boards and Independent Ethics Committees .............................................................. 18 
14.3 Informed Consent Form .................................................................................................................................... 19 
14.4 Publications ........................................................................................................................................... 19 
14.5 Investigator Responsibilities ...................................................................................................................... 19 
15 REFERENCES ........................................................................................................................................... 20 
16 APPENDIX 1: SCHEDULE OF STUDY ASSESSMENTS..................................................................................... 21 


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LIST OF ABBREVIATIONS 
AE 
Adverse Event 
CFR 
Code of Federal Regulations 
CRF 
Case Report Form 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IRB 
Institutional Review Board 
PI 
Principal Investigator 
SAE 
Serious Adverse Event 
NPRS 
Numeric Pain Rating Scale 
PGIC 
Patient Global Impression of Change 
IDS 
Investigational Drug Service 
MRI 
Magnetic Resonance Imaging 


IRB NUMBER: HSC-MS-18-0672 
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PROTOCOL SYNOPSIS 
 
TITLE 
Study to assess the safety and efficacy of FX006 
administered to patients with greater trochanteric bursitis 
SPONSOR 
INVESTIGATOR 
Dr. Pritish Bawa, MD 
BACKGROUND/ 
RATIONALE 
Zilretta is approved for intra-articular injection into the knee 
joint for treatment of osteoarthritis (1). There are ongoing 
studies for intra-articular injection into the other large joints 
including the shoulder and hip joints (2). To our knowledge, 
there has been no prior study to prove efficacy of injection of 
the extended release steroid into the bursa. The bursae 
surrounding the hip joint including the iliopsoas and the greater 
trochanteric bursa are some of the larger bursae in the body. 
Conventional treatment for inflammation of these bursae is 
injection of corticosteroids (3). We believe that a long acting 
corticosteroid, if efficacious, can have a great impact. There is 
a significant population of patients suffering from chronic bursal 
pain, who might benefit. At our institute, bursal injection of the 
steroid in the region of hips is one of the most common 
locations, second to joint injections. To our understanding, the 
bursa surrounding the hip are deep enough to avoid side 
effects associated with subcutaneous injection of steroid. The 
current proposal is a pilot study. 
STUDY DESIGN 
This is a prospective, open-label, pilot study, to assess the 
safety and efficacy of FX006 (triamcinolone acetonide 
extended release injectable suspension 32 mg), 
administered to patients with greater trochanteric bursitis. 
PRIMARY 
OBJECTIVE 
The primary objective will be to determine the safety and 
efficacy of this drug in bursal injections by monitoring the 
improvement in the pain from baseline, as established using 
the using a Numeric Pain Rating Scale (NPRS) score at the 
end of 12 weeks. 
SECONDARY 
OBJECTIVES 
Secondary objective is to determine any alteration in the 
Patient Global Impression of Change (PGIC) measure. This 
is used as an indicator to assess the patient’s impression to 
change in treatments, to their chronic pain. 
PRIMARY END POINT The primary endpoint will be the improvement in the pain 
from baseline, at the end of week 12, as determined by the 
NPRS pain score 
SECONDARY END 
POINT 
The secondary endpoint will be any alteration in the 
PGIC measure, at the end of week 12. 
 


IRB NUMBER: HSC-MS-18-0672 
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NUMBER OF 
SUBJECTS 
24 patients 
 
SUBJECT 
SELECTION 
CRITERIA 
Inclusion Criteria: 
• 
Written consent to participate in the study 
• 
Male or female greater than or equal to 18 years of age 
• 
Symptoms consistent with greater trochanteric bursitis for 
greater than or equal to 3 months prior to screening 
(patient reported is acceptable) 
• 
Pain in hip for greater than 15 days over the last month (as 
reported by the patient). 
• 
Hip bursitis as determined by clinical examination and 
clinical features. Where Magnetic Resonance Imaging 
(MRI) data is available, it will be used to confirm the 
bursitis diagnosis. Also, pain relief in subjects that have 
been treated with bursal injections containing an anesthetic 
(such as ropivacaine) is in itself indicative of bursitis. 
• 
Body mass index (BMI) less than or equal to 40 kg/m2 
• 
Ambulatory and in good general health 
• 
Willing and able to comply with the study procedures and visit 
schedules and able to follow verbal and written instructions. 
• 
Willing to abstain from use of protocol-restricted 
medications during the study 
Exclusion Criteria: 
• 
Hip Arthroplasty 
• 
Hip osteoarthritis, iliopsoas bursitis, reactive arthritis, 
rheumatoid arthritis, psoriatic arthritis, ankylosing 
spondylitis, or arthritis associated with inflammatory bowel 
disease 
• 
History of local infection around the bursa. 
• 
Lack of pain relief with the intrabursal treatments 
containing an anesthetic 
• 
Intra-bursal treatment of any bursa with any of the 
following agents within three (3) months of screening: 
any corticosteroid preparation (investigational or 
marketed, including FX006); and/or six (6) months for 
any biologic agent (e.g., platelet rich plasma (PRP) 
injection, stem cells, prolotherapy, amniotic fluid 
injection; investigational or marketed). 
• 
Parenteral or oral corticosteroids (investigational or 
marketed) within 3 months of Screening 
• 
Inhaled, intranasal or topical corticosteroids 
(investigational or marketed) within 2 weeks of 
screening. 
• 
Females who are pregnant or nursing or plan to become 
pregnant during the study; women who plan to conceive 


IRB NUMBER: HSC-MS-18-0672 
IRB APPROVAL DATE: 02/12/2021 
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TEST PRODUCT, 
DOSE, AND ROUTE 
OF 
ADMINISTRATION 
24 patients will be injected with the 5ml of FX006. This 
injection may be followed with up to 3ml of ropivacaine 
(depending on the capacity of the bursa), under 
ultrasound guidance. 
CONTROL 
PRODUCT, DOSE 
AND ROUTE OF 
ADMINISTRATIO 
N/A 
DURATION OF 
SUBJECT 
PARTICIPATION 
AND DURATION OF 
STUDY 
The study will be completed in week 12 and all recorded 
patients’ NPRS, PGIC and emergent findings, if any will 
be compiled into a HIPAA compliant database. 
CONCOMITANT 
MEDICATIONS 
Allowed. Exclusions are listed below. 
Prohibited: 
• Intra-bursal treatment of any bursa with any of the 
following agents within six (6) months of Screening: any 
corticosteroid preparation (investigational or marketed, 
including FX006), any biologic agent (e.g., platelet rich 
plasma (PRP) injection, stem cells, prolotherapy, 
amniotic fluid injection; investigational or marketed). 
• Parenteral or oral corticosteroids (investigational or 
marketed) within 3 months of Screening 
• Inhaled, intranasal or topical corticosteroids 
(investigational or marketed) within 2 weeks 
of Screening. 
EFFICACY 
EVALUATIONS 
Follow up telephone interviews will be performed in 1, 2, 4, 8, 
and 12 weeks to assess the patient for any adverse events 
and also to obtain the NPRS and PGIC scores. 
SAFETY 
EVALUATIONS 
Subjects will be questioned about any change in their 
perception of well-being or adverse effects if any, as 
compared to baseline 
 
 


IRB NUMBER: HSC-MS-18-0672 
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STATISTICS 
Primary Analysis 
Plan 
We plan to enroll 24 patients for the pilot study. This sample 
size is determined by the projected availability of eligible 
patients within the proposed study period (6 months). 
Descriptive statistics will be reported for demographics and all 
clinical variables collected in this study. 
For the efficacy evaluated by NPRS and PGIC, we will use 
appropriate summary statistics (e.g. mean + standard deviation 
for variables with normal distribution or median and interquartile 
range for variables with skewed distribution) to report NPRS 
and PGIC at each time point and analyze their changes over 
time. 
For safety evaluated, we will report the frequency and 
percentage of patients who have received any treatment to 
emergent adverse events within 12 weeks. 
 
 
1 BACKGROUND/RATIONALE 
 
Zilretta is approved for intra-articular injection into the knee joint for treatment of osteoarthritis (1). There 
are ongoing studies for intra-articular injection into the other large joints including the shoulder and hip 
joints (2). To our knowledge there has been no prior study to prove efficacy of injection of the extended 
release steroid into the bursa. The bursae surrounding the hip joint including the iliopsoas and the 
greater trochanteric bursa are some of the larger bursae in the body. Conventional treatment for 
inflammation of these bursae is injection of corticosteroids (3). We believe that a long acting 
corticosteroid, if efficacious, can have a great impact. There is a significant population of patients 
suffering from chronic bursal pain, who might benefit. At our institution, bursal injection of the steroid in 
the region of hips is one of the most common locations, second only to joint injections. To our 
understanding, the bursa surrounding the hip are deep enough to avoid side effects associated with 
subcutaneous injection of steroid. The current proposal is a pilot study. 
 
2 
STUDY OBJECTIVES 
 
2.1 Primary Objective 
The primary objective will be to determine the safety and efficacy of this drug in bursal injections by 
monitoring the improvement in the pain from baseline, as established using the using a Numeric Pain 
Rating Scale (NPRS) score at the end of 12 weeks. Safety of the extended-release 32 mg FX006 
administered to patients with greater trochanteric bursitis will be evaluated with a follow-up to 
determine if there were any adverse events within 12 weeks from the time of injection. 
 
2.2 Secondary Objectives 
Secondary objective is to determine any alteration in the Patient Global Impression of Change 
(PGIC) measure. This is used as an indicator to assess the patient’s impression to change in 
treatments to chronic pain. 


IRB NUMBER: HSC-MS-18-0672 
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3. STUDY DESIGN 
3.1 Study Overview 
 
This is a consented, pilot study in patients with pain and bursitis involving the greater trochanteric bursa, 
with administration of 32 mg FX006. The study will be conducted in male and female patients 18 years 
of age or older with symptomatic greater trochanteric bursitis. Each patient will be screened for eligibility 
with an ultrasound to confirm the diagnosis of bursitis, in the absence of prior MRI imaging done in the 
preceding three months. Based on the inclusion/exclusion requirements, they will be offered 
participation in the study to receive an intra-bursal injection of 32 mg FX006. Eligible and participating 
patients will receive treatment under ultrasound image guidance to the greater trochanteric bursa. 
Patients will be followed up by phone at 1, 2, 4, 8, and 12 weeks and mean NPRS pain scores and 
PGIC scores will be recorded. Adverse events, if any, will be reported immediately to the primary 
physician and any subsequent follow-up will be reported. The study will be completed in week 12 and 
all recorded patients’ NPRS, PGIC and emergent findings, if any will be compiled into a HIPAA 
compliant database. 
 
4 
CRITERIA FOR EVALUATION 
 
4.1 
Primary Endpoint 
The primary endpoint will be the improvement in the pain from baseline, at the end of week 12 as 
determined by the NPRS pain score. 
4.2 
Secondary/Exploratory Endpoints 
The secondary endpoint will be any alteration in the PGIC measure, at the end of week 12. 
4.3 
Safety Evaluations 
Incidence of adverse events will be recorded and reported to appropriate bodies including the 
UTHealth IRB and FDA, if indicated. 
 
5 
SUBJECT SELECTION 
 
5.1 
Study Population 
Subjects with a diagnosis of bursitis of greater trochanter, who meet the inclusion and exclusion 
criteria will be eligible for participation in this study. 
5.2 Inclusion Criteria 
1. Written consent to participate in the study 
2. Male or female greater than or equal to 18 years of age 
3. Symptoms consistent with bursitis of greater trochanter for greater than or equal to 3 
months prior to Screening (patient reported is acceptable) 
4. Pain in hip for greater than 15 days over the last month (as reported by the patient) 
5. Hip bursitis as determined by clinical examination and clinical features. Where Magnetic 
Resonance Imaging (MRI) data is available, it will be used to confirm the bursitis diagnosis. 
Also, pain relief in subjects that have been treated with bursal injections containing an 


IRB NUMBER: HSC-MS-18-0672 
IRB APPROVAL DATE: 02/12/2021 
11
 
 
anesthetic (such as ropivacaine) is in itself indicative of bursitis 
6. Body mass index (BMI) less than or equal to 40 kg/m2 
7. Ambulatory and in good general health 
8. Willing and able to comply with the study procedures and visit schedules and able to 
follow verbal and written instructions. 
9. Willing to abstain from use of protocol-restricted medications during the study 
 
 
5.3 Exclusion Criteria 
 
1. 
Patients who have had hip arthroplasty or conditions such as, hip osteoarthritis, iliopsoas 
bursitis, reactive arthritis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or 
arthritis associated with inflammatory bowel disease 
2. 
History of local infection around the bursa; 
3. 
Lack of pain relief with intra-bursal treatments containing an anesthetic 
4. 
Intra-bursal treatment of any bursa with any of the following agents within three (3) months 
of screening: any corticosteroid preparation (investigational or marketed, including 
FX006); and/or six (6) months for any biologic agent (e.g., platelet rich plasma (PRP) 
injection, stem cells, prolotherapy, amniotic fluid injection; investigational or marketed). 
5. 
Parenteral or oral corticosteroids (investigational or marketed) within 3 months of 
screening; Inhaled, intranasal or topical corticosteroids (investigational or marketed) within 
2 weeks of screening; 
6. 
Females who are pregnant or nursing or plan to become pregnant during the 
study; women who plan to conceive during the study. 
 
6 CONCURRENT MEDICATIONS 
All subjects should be maintained on the same medications throughout the entire study period, as 
medically feasible, with no introduction of new chronic therapies medication. 
6.1 Allowed Medications and Treatments 
Standard therapy for hip pain is allowed, except for treatments noted in the exclusion criteria 
described above and as noted in the prohibited medications section below. 
6.2 
Prohibited Medications and Treatments 
The following medications are prohibited during the study: 
 
• Intra-bursal treatment of any bursa with any of the following agents within six (6) months of 
screening: any corticosteroid preparation (investigational or marketed, including FX006), any 
biologic agent (e.g., platelet rich plasma (PRP) injection, stem cells, prolotherapy, amniotic fluid 
injection; investigational or marketed). 
• Parenteral or oral corticosteroids (investigational or marketed) within 3 months of screening 
• Inhaled, intranasal or topical corticosteroids (investigational or marketed) within 2 weeks of 
screening. 


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7.1 Treatment Plan 
The patient will make a one-time visit to the outpatient radiology department at Memorial Hermann 
Hospital at the Texas Medical Center, and will be expected to stay for a maximum of 2 hours. 
Each patient will be consented for the procedure and a baseline assessment using the NPRS and 
PGIC measures will be made. 
24 patients will be injected with the 5ml of FX006. This injection may be followed with up to 3ml of 
ropivacaine (depending on the capacity of the bursa), under ultrasound guidance. The data collected 
from the patient and subsequent follow-up will be maintained by the clinical team throughout the 12 
weeks of the subject participation. 
7.1.1 Formulation of Test Product 
FX006 is an extended-release formulation of Triamcinolone Acetonide (TA), developed by Flexion 
Therapeutics, for the management of pain of osteoarthritis. FX006 contains TA, formulated in 75:25 
polylactic-co-glycolic acid (PLGA) microspheres with a nominal drug load of 25% and is provided as a 
sterile white to off-white powder for reconstitution. The drug product is reconstituted with diluent 
containing an isotonic, sterile aqueous solution of sodium chloride, carboxymethylcellulose sodium 
and polysorbate-80 to form a suspension prior to Intra-Articular injection. 
7.1.2 Packaging and Labeling 
Study drug is supplied in a package kit containing one (1) vial of FX006, one (1) vial Diluent, and a 
vial adapter. 
The FX006 and diluent vials will be labeled with the respective unique lot numbers within the 
packaged kit, which will be affixed with its own label and kit number. 
7.2 
Supply of Study Drug at the Site 
Flexion Therapeutics, Inc. will ship Study Drug to the investigational sites. The initial FX006 study 
drug shipment will be made after site activation (i.e., all required regulatory documentation has been 
received by Flexion Therapeutics, Inc. and a contract has been executed). Subsequent study drug 
shipments will be made after site request for resupply. All drugs will be stored in the Investigational 
Drug Service (IDS) pharmacy of the Memorial Hermann Hospital at the Texas Medical Center, prior to 
use, in a monitored refrigerator, and dispensed as prescribed. 
7.2.1 Dosage/Dosage Regimen 
FX006 will be reconstituted according to the instructions for use, using aseptic techniques. It will be 
administered at the standard dosage of 32 mg and injected into the hip bursa using ultrasound 
guidance. This injection may be followed with up to 3 mL of ropivacaine (the actual volume of 
ropivacaine injected will be up to the discretion of the radiologist and will be based on the capacity of 
the bursa). Medication will be administered once per subject. 
7.2.2 Dispensing 
FX006 will be dispensed by the IDS pharmacy to the research nurse or other study personnel after 
the prescription is submitted to the pharmacy. Research personnel that are receiving FX006 will sign 
the chain of custody log in the pharmacy. FX006 will be dispensed in packaging supplied by 
manufacturer. 


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7.2.3 Administration Instructions 
 
FX006 will be administered in standard dosage of 32 mg injected into hip bursa using ultrasound 
guidance using aseptic technique. This injection may be followed with up to 3 mL of ropivacaine 
(depending on the capacity of the bursa). Medication will be administered once per subject. 
7.2.4 Storage 
Study drug will be stored by the IDS pharmacy in a designated, monitored refrigerator, 2 to 8ºC. If the 
temperature of study drug storage in the clinic/pharmacy exceeds or falls below this range, this may 
be reported to Flexion Therapeutics, Inc., for guidance on disposition. 
7.3 Study Drug Accountability 
An accurate and current accounting of the dispensing study drug for each subject will be maintained 
on an ongoing basis by a member of the study site staff. The study drug dispensed will be recorded 
on the Investigational Drug Accountability Record. Used study drug vials will be disposed of 
appropriately according to the site protocols. 
 
8 STUDY PROCEDURES AND GUIDELINES 
 
A Schedule of Events representing the required testing procedures to be performed for the duration of 
the study is detailed in Appendix 1. 
Prior to conducting any study-related activities, written informed consent and the Health Insurance 
Portability and Accountability Act (HIPAA) authorization must be signed and dated by the subject. 
8.1 
Clinical Assessments 
 
8.1.1 Concomitant Medications 
All concomitant medication and concurrent therapies will be documented at screening and during 
each follow-up telephone call and upon study discontinuation. Dose, route, unit frequency of 
administration, and indication for administration and dates of medication will be captured. 
8.1.2 Demographics 
Demographic information (date of birth and gender) will be recorded at screening. 
8.1.3 Medical History 
Relevant medical history, including history of current disease, other pertinent history, and information 
regarding underlying diseases will be recorded at screening. 
8.1.4 Physical Examination 
A focused physical examination will be performed by either the investigator or a sub-investigator 
who is a physician at screening. 
8.1.5 Vital Signs 
Measurement of body temperature, blood pressure, pulse and respiration will be performed after the 
subject has rested for 5 minutes on the treatment date. 


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8.1.6 Other Clinical Procedures 
Subjects will be asked about their Numeric Pain Rating System (NPRS) on a 1 to 10 scale, and 
will be asked about their Patient Global Impression of Change (PGIC) scores during each follow- 
up telephone call. 
 
8.1.7 Adverse Events 
Information regarding occurrence of adverse events will be captured throughout the study. Duration 
(start and stop dates and times), severity/grade, outcome, treatment and relation to the study drug will 
be recorded on the case report form (CRF). 
 
9 ADVERSE EXPERIENCE REPORTING AND DOCUMENTATION 
 
9.1 Collection 
Adverse events will be collected from the time of medication administration until completion of the 
follow-up telephone calls at week 12 or until subject participation in study ends. 
The Investigator or other medical trained personnel will probe, via discussion with the subject, for the 
occurrence of Adverse Events during each subject contact and record the information in the source 
documents. Adverse events will be recorded in the patient CRF. Adverse events will be described by 
duration (start and stop dates and times), outcome, and treatment. The Investigator, or other medical 
trained personnel will also assess the seriousness and severity of the event, and relationship of the 
event to study drug according to the definitions below. If unrelated to study drug, the more likely cause 
of the event will also be assessed and recorded. 
9.2 Definitions 
 
Adverse Event (AE): Any untoward medical occurrence in a clinical investigation of a patient 
administered a pharmaceutical product and that does not necessarily have a causal relationship with the 
treatment. An AE is therefore any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom or disease temporally associated with the administration of an investigational product, 
whether or not related to that investigational product. An unexpected AE is one 
of a type not identified in nature, severity, or frequency in the current Investigator’s Brochure or of 
greater severity or frequency than expected based on the information in the Investigator’s Brochure. 
Serious Adverse Event (SAE): An SAE is any untoward medical occurrence that at any dose: 
• Results in death, 
• Is life-threatening, (“Life-threatening” refers to an event in which the patient was at 
substantial risk of death at the time of the event; it does not refer to an event 
which hypothetically might have caused death if it were more severe.) 
• Requires inpatient hospitalization or prolongation of existing hospitalization, 
• Note: Adverse events requiring hospitalizations that are less than 24 hours in duration 
generally do not meet this criterion. A scheduled hospitalization for an elective 
procedure or a pre-existing condition that has not worsened during participation in the 


IRB NUMBER: HSC-MS-18-0672 
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15
 
 
study does not meet this criterion. 
• Results in permanent or significant disability/incapacity; a substantial disruption of the 
patient’s ability to carry out normal life functions. 
• Is a congenital anomaly/birth defect. 
• Is an important medical event: event that may not be immediately life-threatening or result in 
death or hospitalization but may jeopardize the patient or may require intervention to prevent 
one of the outcomes listed in the definition above. 
 
Severity: the intensity of the adverse event. This is not the same as “serious,” which is based on 
patient/event outcome or action criteria usually associated with events that pose a threat to a patient’s 
life or functioning. The severity of AEs will be assessed according to the following definitions: 
Table 1: AE Severity Grading 
 
Severity 
Description 
Mild 
The AE is noticeable to the patient and/or the Investigator, 
but does not interfere with routine activity. 
Moderate 
The AE interferes with routine activity, but responds 
to symptomatic therapy or rest. 
Severe 
The AE significantly limits the patient’s ability to 
perform routine activities despite symptomatic therapy 
 
 
Causal Relationship: A medically-qualified Investigator must assess the relationship of any AE 
(including SAEs) to the use of the investigational product, as related or not related, based on clinical 
judgment and using all available information. Possible causes of the AE should be considered, 
including the disease under treatment, pre-existing conditions, concomitant use of other drugs, and 
presence of environmental or genetic factors, the temporal association between drug exposure and 
onset of the AE, and whether the manifestations of the AE are consistent with known actions or 
toxicity of the investigational product. The causal relationship between the study medication and the 
AE will be assessed using one of the following categories: 
 
Causal 
relationship 
Description 
Not Related An AE is not associated with study medication if: 
o Temporal relationship is lacking (e.g., the event did not occur 
within a reasonable time frame following administration of the 
study medication); or 
o Other causative factors more likely explain the event (e.g., 
a pre-existing condition, other concomitant treatments). 


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9.3 
Serious Adverse Event Reporting 
An event that is serious must be recorded on the source document and requires expeditious handling 
to comply with regulatory requirements. 
• Reporting to IRB: In accordance with the standard operating procedures and policies of the 
local Institutional Review Board (IRB)/Independent Ethics Committee (IEC), the site 
investigator will report SAEs to the IRB as soon as possible but not later than 7 days after 
first knowledge by investigator. 
• Reporting to Flexion: All serious adverse events in patients treated with Zilretta must be 
reported to Flexion within 3 calendar days. The Investigator should attempt to collect as much 
information about the adverse event as needed to get a complete medical understanding. Any 
new information collected on an SAE should be forwarded to Flexion as it becomes available. 
9.4 Reporting to the US FDA 
All serious adverse events which are considered causally related to Zilretta must be assessed for 
whether it is expected per the Investigators Brochure. An unexpected event means that it is not 
described within the reference safety information (the Zilretta IB) as associated with Zilretta. 
If an event is assessed as serious, related to Zilretta, and unexpected, it must be reported to the FDA 
according to 21CFR312.32. 
9.5 Pregnancy 
All pregnancies, female patients or female partners of male patients during the study, must be 
evaluated by the Investigator and/or other medically qualified personnel. The Investigator must 
continue to follow the pregnancy until the completion of the pregnancy, including the outcome and 
the condition of the newborn (if applicable). Additional subsequent follow-up is not needed when a 
newborn baby is healthy. Information on the pregnancy, including follow up reports, and any data on 
the birth of the newborn should be reported to Flexion within 3 days. 
10 DISCONTINUATION AND REPLACEMENT OF SUBJECTS 
 
10.1 Early Discontinuation of Study Drug 
A subject may be discontinued from study treatment at any time if the subject, the investigator, or 
Flexion Therapeutics, Inc. feels that it is not in the subject’s best interest to continue. The following is 
a list of possible reasons for study treatment discontinuation: 
Subject withdrawal of consent (or assent) 
Subject is not compliant with study procedures 
Adverse event that in the opinion of the investigator would be in the best interest of the subject to 
An AE is attributed to the study medication if: 
o There is a positive temporal relationship (e.g., the 
event occurred within a reasonable time frame 
following administration of study medication); and 
o The AE is more likely explained by the investigational product 
than by another cause (i.e., the AE shows a pattern consistent 
with previous knowledge of the investigational product or the 
class of the investigational product). 
Related 


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discontinue study treatment 
Protocol violation requiring discontinuation of study treatment 
Lost to follow-up 
Flexion Therapeutics, Inc. request for early termination of study 
If a subject is withdrawn from treatment due to an adverse event, the subject will be followed and 
treated by the Investigator until the abnormal parameter or symptom has resolved or stabilized. 
All subjects are free to withdraw from participation at any time, for any reason, specified or 
unspecified, and without prejudice. 
Reasonable attempts will be made by the investigator to provide a reason for subject withdrawals. 
The reason for the subject’s withdrawal from the study will be specified in the subject’s source 
documents Refer to Section 10 for early termination procedures. 
10.2 Withdrawal of Subjects from the Study 
A subject may be withdrawn from the study at any time if the subject, the investigator, or the Sponsor 
feels that it is not in the subject’s best interest to continue. 
All subjects are free to withdraw from participation at any time, for any reason, specified or 
unspecified, and without prejudice. 
Reasonable attempts will be made by the investigator to provide a reason for subject 
withdrawals. The reason for the subject’s withdrawal from the study will be specified in the subject’s 
source documents. 
10.3 Replacement of Subjects 
Subjects who withdraw from the study treatment will be replaced. 
11 PROTOCOL VIOLATIONS 
A protocol violation occurs when the subject, investigator, or Sponsor fails to adhere to significant 
protocol requirements affecting the inclusion, exclusion, subject safety and primary endpoint criteria. 
Protocol violations for this study include, but are not limited to, the following: 
Failure to meet inclusion/exclusion criteria 
Use of a prohibited concomitant medication 
Failure to comply with Good Clinical Practice (GCP) guidelines will also result in a protocol violation. 
The CPHS will determine if a protocol violation will result in withdrawal of a subject. 
12 STATISTICAL METHODS AND CONSIDERATIONS 
 
Sample size justification: 
 
We plan to enroll 24 patients for the pilot study. This sample size is determined by the projected 
availability of eligible patients within the proposed study period (6 months). This pilot study will help to 
establish the safety and efficacy of the investigated treatment FX006, and the data collected in this 
study will allow us to plan a future efficacy trial. 
 
Statistical analysis plan: 
Descriptive statistics will be reported for demographics and all clinical variables collected in this study. 


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For the efficacy evaluated by NPRS and PGIC, we will use appropriate summary statistics (e.g. mean 
+ standard deviation for variables with normal distribution or median and interquartile range for 
variables with skewed distribution) to report NPRS and PGIC at each time point and analyze their 
changes over time. For safety evaluated, we will report the frequency and percentage of patients who 
have received any treatment to emergent adverse events within 12 weeks. 
 
12.1 Data Sets Analyzed 
All eligible patients who are randomized into the study and receive at least one dose of the study drug 
(the Safety Population) will be included in the safety analysis. 
12.2 Demographic and Baseline Characteristics 
The following demographic variables at screening will be summarized: gender and age. 
 
13 DATA COLLECTION AND RETENTION 
 
13.1 Data Collection Instruments 
The Investigator will prepare and maintain adequate and accurate source documents designed to 
record all observations and other pertinent data for each subject treated with the study drug. 
Study personnel will enter data from source documents corresponding to a subject’s contact into the 
protocol-specific Case Report Form (CRF) when the information corresponding to that visit is available. 
Subjects will not be identified by name in the study database or on any study documents to be collected 
by Flexion Therapeutics, Inc., but will be identified by a site number, subject number. 
If a correction is made on a CRF, the study staff member will line through the incorrect data, write in the 
correct data and initial and date the change. 
The Investigator is responsible for all information collected on subjects enrolled in this study. All data 
collected during the course of this study must be reviewed and verified for completeness and accuracy 
by the Investigator. A copy of the CRF will remain at the Investigator’s site at the completion of the 
study. 
13.2 Data Management Procedures 
The data will be entered into a validated database. The Data Management group will be responsible for 
data processing, in accordance with procedural documentation. Database lock will occur once quality 
assurance procedures have been completed. 
All procedures for the handling and analysis of data will be conducted using good computing practices 
meeting FDA guidelines for the handling and analysis of data for clinical trials. 
13.3 Data Quality Control and Reporting 
After data have been entered into the study database, a system of computerized data validation checks 
will be implemented and applied to the database on a regular basis. Query reports (Data Clarification 
Requests) pertaining to data omissions and discrepancies will be forwarded to the Investigators and 
study monitors for resolution. The study database will be updated in accordance with the resolved 
queries. All changes to the study database will be documented. 
13.4 Archival of Data 
The database is safeguarded against unauthorized access by established security procedures; 
appropriate backup copies of the database and related software files will be maintained. 


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Databases are backed up by the database administrator in conjunction with any updates or changes to 
the database. 
 
13.5 Availability and Retention of Investigational Records 
The Investigator will make study data accessible to authorized representatives of Flexion Therapeutics, 
Inc., IRB and Regulatory Agency (e.g., FDA) inspectors upon request. A file for each subject must be 
maintained that includes the signed Informed Consent, HIPAA Authorization and Assent Form and copies 
of all source documentation related to that subject. The Investigator will ensure the reliability and 
availability of source documents from which the information on the CRF was derived. 
All study documents (patient files, signed informed consent forms, copies of CRFs, etc.) will be kept 
secured for a period of two years following marketing of the investigational product or for two years after 
centers have been notified that the IND has been discontinued. There may be other circumstances for 
which Flexion, Inc. is required to maintain study records and, therefore, Flexion, Inc. will be contacted 
prior to removing study records for any reason. 
13.6 Subject Confidentiality 
In order to maintain subject confidentiality, only a site number and subject number will identify all study 
subjects on CRFs and any other documentation that may be submitted to Flexion Therapeutics, Inc. 
Additional subject confidentiality issues (if applicable) are covered in the Clinical Study Agreement. 
 
14 ADMINISTRATIVE, ETHICAL, REGULATORY CONSIDERATIONS 
To maintain confidentiality, evaluation forms, reports and other records will be identified by a coded 
number only. All study records will be kept in a locked file cabinet and code sheets linking a patient’s 
name to a patient identification number will be stored separately in another locked file cabinet. Clinical 
information will not be released without written permission of the subject, except as necessary for 
monitoring by the FDA. The Investigator will comply with all applicable privacy regulations (e.g., Health 
Insurance Portability and Accountability Act of 1996). 
14.1 Protocol Amendments 
Any amendment to the protocol will be written by the Investigator. Protocol amendments cannot be 
implemented without prior written IRB approval except as necessary to eliminate immediate safety 
hazards to patients. A protocol amendment intended to eliminate an apparent immediate hazard to 
patients may be implemented immediately, provided the IRBs are notified within five working days. 
14.2 Institutional Review Boards and Independent Ethics Committees 
The protocol and consent form will be reviewed and approved by the IRB prior to study initiation. Serious 
adverse experiences regardless of causality will be reported to the IRB in accordance with the standard 
operating procedures and policies of the IRB, and the Investigator will keep the IRB informed as to the 
progress of the study. The Investigator will obtain assurance of IRB compliance with regulations. 
Any documents that the IRB may need to fulfill its responsibilities (such as protocol, protocol amendments, 
Investigator’s Brochure, consent forms, information concerning patient recruitment, payment or 
compensation procedures, or other pertinent information) will be submitted to the IRB. The IRBs written 
unconditional approval of the study protocol and the informed consent form will be in the possession of 
the Investigator before the study is initiated. The IRBs unconditional approval statement will be transmitted 
by the Investigator to Flexion Therapeutics, Inc. prior to the shipment of study supplies to the site. This 
approval must refer to the study by exact protocol title and number and should 


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identify the documents reviewed and the date of review. 
Protocol and/or informed consent modifications or changes may not be initiated without prior written 
IRB approval except when necessary to eliminate immediate hazards to the patients or when the 
change(s) involves only logistical or administrative aspects of the study. Such modifications will be 
submitted to the IRB and written verification that the modification was submitted and subsequently 
approved should be obtained. 
The IRB must be informed of revisions to other documents originally submitted for review; serious and/or 
unexpected adverse experiences occurring during the study in accordance with the standard operating 
procedures and policies of the IRB; new information that may affect adversely the safety of the patients 
of the conduct of the study; an annual update and/or request for re-approval; and when the study has 
been completed. 
14.3 Informed Consent Form 
Informed consent will be obtained in accordance with the Declaration of Helsinki, ICH GCP, US Code 
of Federal Regulations for Protection of Human Subjects (21 CFR 50.25 [a,b], CFR 50.27, and CFR 
Part 56, Subpart A), the Health Insurance Portability and Accountability Act (HIPAA, if applicable), and 
local regulations. 
The Investigator will send an IRB-approved copy of the Informed Consent Form to Flexion Therapeutics, 
Inc. 
A properly executed, written, informed consent will be obtained from each subject prior to entering the 
subject into the trial. Information should be given in both oral and written form and subjects must be 
given ample opportunity to inquire about details of the study. If a subject is unable to sign the informed 
consent form (ICF) and the HIPAA authorization, a legal representative may sign for the subject. A copy 
of the signed consent form (and assent) will be given to the subject or legal representative of the subject 
and the original will be maintained with the subject’s records. 
Pending IRB approval, a research nurse may obtain informed consent remotely including means such 
as phone, video or other verbal means for the purposes of screening a trial subject. Written informed 
consent shall be obtained prior to the subject entering the trial 
14.4 Publications 
The preparation and submittal for publication of manuscripts containing the study results shall be in 
accordance with a process determined by mutual written agreement among Flexion Therapeutics, Inc. 
and participating institutions. The publication or presentation of any study results shall comply with all 
applicable privacy laws, including, but not limited to, the Health Insurance Portability and Accountability 
Act of 1996. 
14.5 Investigator Responsibilities 
By signing the Agreement of Investigator form, the Investigator agrees to: 
1. 
Conduct the study in accordance with the protocol and only make changes after notifying Flexion 
Therapeutics Inc., except when to protect the safety, rights or welfare of subjects. 
2. 
Personally conduct or supervise the study (or investigation). 
3. 
Ensure that the requirements relating to obtaining informed consent and IRB review and approval 
meet federal guidelines, as stated in § 21 CFR, parts 50 and 56. 
4. 
Report to Flexion Therapeutics, Inc. any AEs that occur in the course of the study, in accordance 
with §21 CFR 312.64. 


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7. Ensure that all associates, colleagues and employees assisting in the conduct of the study are 
informed about their obligations in meeting the above commitments. 
8. Maintain adequate and accurate records in accordance with §21 CFR 312.62. 
 
9. Ensure that an IRB that complies with the requirements of §21 CFR part 56 will be responsible 
for initial and continuing review and approval of the clinical study. 
10. Promptly report to the IRB and Flexion Therapeutics, Inc. all changes in the research activity and 
all unanticipated problems involving risks to subjects or others (to include amendments and IND 
safety reports). 
11. Seek IRB approval before any changes are made in the research study, except when necessary 
to eliminate hazards to the patients/subjects. 
12. Comply with all other requirements regarding the obligations of clinical investigators and all other 
pertinent requirements listed in § 21 CFR part 312. 
 
15 REFERENCES 
1. Effects of a Single Intra-Articular Injection of a Microsphere Formulation of Triamcinolone 
Acetonide on Knee Osteoarthritis Pain: A Double-Blinded, Randomized, Placebo-Controlled, 
Multinational Study, Conaghan, P,G; Hunter, D. J.; Cohen, S. B.; Kraus, V. B., Berenbaum, F.; 
Lieberman, J. R; Jones, D. G.; Spitzer, A, I.; Jevsevar, D.S., Katz, N. P. Burgess, D. J., Lufkin, J.; 
Johnson, J; Bodick, N.; J. Bone Joint Surg: April 18, 2018, 100(8), 666–677. 
 
2. Study to Compare Exposure of TA Following Administration of FX006 or TAcs in Patients With 
OA of the Shoulder or Hip, Clinical Trials.gov, NCT 03382262. 


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3. Greater Trochanteric Pain Syndrome: A Review of Anatomy, Diagnosis and Treatment 
Williams, B. S.; Anesthesia & Analgesia: May 2009 - Volume 108 (5) 1662-1670. 


 
16 APPENDIX 1: SCHEDULE OF STUDY ASSESSMENTS 
VISIT 1 
(Day 1) 
VISIT 2 
(Week 2) 
VISIT 3 
(Week 4) 
VISIT 4 
(Week 8) 
VISIT 5 
(Week 12) 
Informed Consent 
X 
Medical History 
X 
Abbreviated Physical 
Exam 
X 
Height 
X 
Weight 
X 
Vital Signs 
X 
Pregnancy Test (Urine) 
X 
Dispensing or 
Administration of Study 
Drug 
X 
Initiate Subject Diary 
X 
Subject Diary Review 
X 
X 
X 
X 
Concomitant Medication 
Review 
X 
X 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
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IRB APPROVAL DATE: 02/12/2021