Trial Outcomes & Findings for AA4500 (XIAFLEX™, Proposed Name) in the Treatment of Dupuytren's Contracture (NCT NCT00528606)

Last Updated: 2017-12-02

Results Overview

The Primary Outcome Measure for patients treated with AA4500 is the percentage of joints that were successfully treated where "successfully treated" was defined as reduction in contracture to within 0-5° of normal within 30 days of injection. The Primary Outcome Measure for placebo treated patients is the percentage of joints that were successfully treated where "successfully treated" was defined as reduction in contracture to within 0-5° of normal within 30 days of injection.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

308 participants

Primary outcome timeframe

Within 30 days after the last injection

Results posted on

2017-12-02

Participant Flow

Participant milestones

Participant milestones
Measure	AA4500 0.58 mg collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints	Placebo Placebo injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
Overall Study STARTED	204	104
Overall Study COMPLETED	191	100
Overall Study NOT COMPLETED	13	4

Reasons for withdrawal

Reasons for withdrawal
Measure	AA4500 0.58 mg collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints	Placebo Placebo injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
Overall Study Withdrew consent	4	3
Overall Study Lost to Follow-up	4	1
Overall Study Adverse Event	3	0
Overall Study Other	2	0

Baseline Characteristics

AA4500 (XIAFLEX™, Proposed Name) in the Treatment of Dupuytren's Contracture

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AA4500 0.58 mg n=204 Participants collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints	Placebo n=104 Participants placebo injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints	Total n=308 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	120 Participants n=5 Participants	57 Participants n=7 Participants	177 Participants n=5 Participants
Age, Categorical >=65 years	84 Participants n=5 Participants	47 Participants n=7 Participants	131 Participants n=5 Participants
Age, Continuous	62.3 years STANDARD_DEVIATION 9.7 • n=5 Participants	63.3 years STANDARD_DEVIATION 9.1 • n=7 Participants	62.7 years STANDARD_DEVIATION 9.5 • n=5 Participants
Sex: Female, Male Female	33 Participants n=5 Participants	30 Participants n=7 Participants	63 Participants n=5 Participants
Sex: Female, Male Male	171 Participants n=5 Participants	74 Participants n=7 Participants	245 Participants n=5 Participants
Race/Ethnicity, Customized White	203 participants n=5 Participants	104 participants n=7 Participants	307 participants n=5 Participants
Race/Ethnicity, Customized Hispanic	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment United States	204 participants n=5 Participants	104 participants n=7 Participants	308 participants n=5 Participants

PRIMARY outcome

Timeframe: Within 30 days after the last injection

Population: Modified-Intent-to-Treat population (Intent-to-treat subjects were excluded from this population if they did not have fixed-flexion measurements after the first injection or had both screening and Treatment 1, Day 0 fixed-flexion measurements between 0 and 5 degrees)

Outcome measures

Outcome measures
Measure	AA4500 0.58 mg n=203 Participants collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints	Placebo n=103 Participants placebo injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
Clinical Success (Reduction in Contracture to 5° or Less) of the Primary Joint After the Last Injection	64 Percentage of Joints	6.8 Percentage of Joints

SECONDARY outcome

Timeframe: Baseline; within 30 days after the last injection

Population: Modified ITT population( Intent-to-treat subjects were excluded from this population if they did not have fixed-flexion measurements after the first injection or had both screening and Treatment 1, Day 0 fixed-flexion measurements between 0 and 5 degrees)

Clinical Improvement is defined as \>= 50% reduction from baseline in degree of contracture within 30 days of the injection.

Outcome measures

Outcome measures
Measure	AA4500 0.58 mg n=203 Participants collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints	Placebo n=103 Participants placebo injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
Clinical Improvement After the Last Injection	84.7 Percentage of Joints	11.7 Percentage of Joints

SECONDARY outcome

Timeframe: Baseline; within 30 days after the last injection

Population: Modified ITT population (Intent-to-treat subjects were excluded from this population if they did not have fixed-flexion measurements after the first injection or had both screening and Treatment 1, Day 0 fixed-flexion measurements between 0 and 5 degrees)

Percent change in degree of contracture measured as 100\* (baseline contracture - last available post-injection contracture)/baseline contracture.

Outcome measures

Outcome measures
Measure	AA4500 0.58 mg n=203 Participants collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints	Placebo n=103 Participants placebo injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
Percent Reduction From Baseline Contracture After the Last Injection	79.3 Percent reduction from baseline Standard Deviation 32.58	8.6 Percent reduction from baseline Standard Deviation 30.78

SECONDARY outcome

Timeframe: Baselin; within 30 days after the last injection

Population: Modified ITT Population (Intent-to-treat subjects were excluded from this population if they did not have fixed-flexion measurements after the first injection or had both screening and Treatment 1, Day 0 fixed-flexion measurements between 0 and 5 degrees)

Change in degree of motion measured as last available post-injection range of motion - baseline range of motion.

Outcome measures

Outcome measures
Measure	AA4500 0.58 mg n=198 Participants collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints	Placebo n=103 Participants placebo injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
Change From Baseline Range of Motion After the Last Injection	36.70 degrees Standard Deviation 21.01	4.0 degrees Standard Deviation 14.77

SECONDARY outcome

Timeframe: Last evaluation visit on which clinical success is achieved through the Day 30 evaluation

Population: Modified ITT population

Outcome measures

Outcome measures
Measure	AA4500 0.58 mg n=203 Participants collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints	Placebo n=103 Participants placebo injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
Time to First Achieve Success After the Last Injection Injection 1, Day 1	12.8 percentage of joints	0.0 percentage of joints
Time to First Achieve Success After the Last Injection Injection 1, Day 7	12.3 percentage of joints	0.0 percentage of joints
Time to First Achieve Success After the Last Injection Injection 1, Day 30	14.3 percentage of joints	1.0 percentage of joints
Time to First Achieve Success After the Last Injection Injection 2, Day 0	0.5 percentage of joints	0.0 percentage of joints
Time to First Achieve Success After the Last Injection Injection 2, Day 1	4.9 percentage of joints	0.0 percentage of joints
Time to First Achieve Success After the Last Injection Injection 2, Day 7	5.4 percentage of joints	0.0 percentage of joints
Time to First Achieve Success After the Last Injection Injection 2, Day 30	6.4 percentage of joints	1.0 percentage of joints
Time to First Achieve Success After the Last Injection Injection 3, Day 0	0.0 percentage of joints	0.0 percentage of joints
Time to First Achieve Success After the Last Injection Injection 3, Day 1	2.0 percentage of joints	0.0 percentage of joints
Time to First Achieve Success After the Last Injection Injection 3, Day 7	2.5 percentage of joints	0.0 percentage of joints
Time to First Achieve Success After the Last Injection Injection 3, Day 30	2.5 percentage of joints	4.9 percentage of joints
Time to First Achieve Success After the Last Injection Day 90	0.5 percentage of joints	0.0 percentage of joints
Time to First Achieve Success After the Last Injection Did not reach clinical success by last injection	36.0 percentage of joints	93.2 percentage of joints

SECONDARY outcome

Timeframe: Within 30 days after first injection

Population: Modified ITT population (Intent-to-treat subjects were excluded from this population if they did not have fixed-flexion measurements after the first injection or had both screening and Treatment 1, Day 0 fixed-flexion measurements between 0 and 5 degrees)

Clinical Success is defined as reduction in contracture to within 0-5 degrees of normal within 30 days of injection.

Outcome measures

Outcome measures
Measure	AA4500 0.58 mg n=203 Participants collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints	Placebo n=103 Participants placebo injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
Clinical Success (Reduction in Contracture to 5° or Less) After the First Injection	38.9 Percentage of Joints	1.0 Percentage of Joints

SECONDARY outcome

Timeframe: Baseline; within 30 days after the first injection

Population: Modified ITT population (Intent-to-treat subjects were excluded from this population if they did not have fixed-flexion measurements after the first injection or had both screening and Treatment 1, Day 0 fixed-flexion measurements between 0 and 5 degrees)

Clinical Improvement is defined as \>= 50% reduction from contracture within 30 days of the first injectionor greater of baseline contracture within 30 days of the injection.

Outcome measures

Outcome measures
Measure	AA4500 0.58 mg n=203 Participants collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints	Placebo n=103 Participants placebo injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
Clinical Improvement After the First Injection	67.5 Percentage of Joints	2.9 Percentage of Joints

SECONDARY outcome

Timeframe: Baseline, within 30 days after the first injection

Population: Modified ITT population

Percent change in degree of contracture measured as 100\* (baseline contracture - last available post-injection contracture)/baseline contracture.

Outcome measures

Outcome measures
Measure	AA4500 0.58 mg n=203 Participants collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints	Placebo n=103 Participants placebo injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
Percent Reduction From Baseline Contracture After the First Injection	64.8 Percent reduction from baseline Standard Deviation 34.60	4.7 Percent reduction from baseline Standard Deviation 20.81

SECONDARY outcome

Timeframe: Baseline; within 30 days after the first injection

Population: Modified ITT population (Change in degree of motion measured as last available post-injection range of motion - baseline range of motion)

Change in degree of motion measured as last available post-injection range of motion - baseline range of motion.

Outcome measures

Outcome measures
Measure	AA4500 0.58 mg n=199 Participants collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints	Placebo n=102 Participants placebo injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
Change From Baseline Range of Motion After the First Injection	28.30 degrees Standard Deviation 20.23	1.50 degrees Standard Deviation 11.03

Adverse Events

AA4500 0.58 mg

Serious events: 8 serious events

Other events: 196 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	AA4500 0.58 mg n=204 participants at risk collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints	Placebo n=104 participants at risk placebo injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
Hepatobiliary disorders Acute cholecystitis	0.00% 0/204 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).	0.96% 1/104 • Number of events 1 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).
Nervous system disorders Complex regional pain syndrome	0.49% 1/204 • Number of events 1 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).	0.00% 0/104 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).
Musculoskeletal and connective tissue disorders Ligament disorder	0.49% 1/204 • Number of events 1 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).	0.00% 0/104 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).
Cardiac disorders Myocardial infarction	0.49% 1/204 • Number of events 1 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).	0.00% 0/104 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).
Psychiatric disorders Panic attack	0.49% 1/204 • Number of events 1 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).	0.00% 0/104 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).
Renal and urinary disorders Pelvi-ureteric obstruction	0.49% 1/204 • Number of events 1 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).	0.00% 0/104 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).
Surgical and medical procedures Spinal fusion surgery	0.49% 1/204 • Number of events 1 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).	0.00% 0/104 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).
Injury, poisoning and procedural complications Tendon rupture	0.98% 2/204 • Number of events 2 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).	0.00% 0/104 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).

Other adverse events

Additional Information

Clinical Trial Coordinator

Endo Pharmaceuticals, Inc.

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Auxilium Pharmaceuticals, Inc. agreements may vary with individual investigators but will not prohibit any investigator from publishing. Auxilium supports the publication of results from all centers of a multicenter trial but requests that reports based on single site data not preceed the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	AA4500 0.58 mg n=204 participants at risk collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints	Placebo n=104 participants at risk placebo injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
Skin and subcutaneous tissue disorders Blister	5.4% 11/204 • Number of events 13 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).	0.00% 0/104 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).
Injury, poisoning and procedural complications Contusion	51.0% 104/204 • Number of events 178 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).	1.9% 2/104 • Number of events 2 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).
Skin and subcutaneous tissue disorders Ecchymosis	25.0% 51/204 • Number of events 72 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).	0.96% 1/104 • Number of events 1 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).
Skin and subcutaneous tissue disorders Erythema	6.4% 13/204 • Number of events 16 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).	0.00% 0/104 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).
General disorders Injection site haemorrhage	37.3% 76/204 • Number of events 142 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).	3.8% 4/104 • Number of events 4 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).
General disorders Injection site pain	32.4% 66/204 • Number of events 117 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).	4.8% 5/104 • Number of events 7 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).
General disorders Injection site pruritus	5.4% 11/204 • Number of events 14 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).	0.00% 0/104 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).
General disorders Injection site swelling	21.1% 43/204 • Number of events 63 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).	3.8% 4/104 • Number of events 4 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).
Blood and lymphatic system disorders Lymph node pain	10.3% 21/204 • Number of events 25 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).	0.00% 0/104 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).
Blood and lymphatic system disorders Lymphadenopathy	9.8% 20/204 • Number of events 25 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).	0.00% 0/104 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).
Infections and infestations Nasopharyngitis	3.4% 7/204 • Number of events 8 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).	8.7% 9/104 • Number of events 9 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).
General disorders Oedema peripheral	72.5% 148/204 • Number of events 296 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).	3.8% 4/104 • Number of events 4 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).
Musculoskeletal and connective tissue disorders Pain in extremity	31.9% 65/204 • Number of events 95 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).	2.9% 3/104 • Number of events 3 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).
Skin and subcutaneous tissue disorders Pruritus	10.8% 22/204 • Number of events 30 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).	0.96% 1/104 • Number of events 2 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).
Injury, poisoning and procedural complications Skin laceration	10.8% 22/204 • Number of events 25 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).	0.00% 0/104 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).
General disorders Tenderness	26.5% 54/204 • Number of events 85 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).	0.00% 0/104 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).