Trial Outcomes & Findings for AA4500 (XIAFLEX™, Proposed Name) in the Treatment of Advanced Dupuytren's Disease (NCT NCT00528424)

Results Overview

Successfully treated or clinical success in non-primary joints defined as reduction in contracture to within 0-5° of normal within 30 days of injection.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

286 participants

Primary outcome timeframe

Within 30 days after last injection

Results posted on

2017-12-02

Participant Flow

Participant milestones

Participant milestones
Measure	AA4500 0.58 mg Collagenase clostridium histolyticum 0.58 mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
Overall Study STARTED	286
Overall Study COMPLETED	257
Overall Study NOT COMPLETED	29

Reasons for withdrawal

Reasons for withdrawal
Measure	AA4500 0.58 mg Collagenase clostridium histolyticum 0.58 mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
Overall Study Lost to Follow-up	13
Overall Study Withdrew consent	2
Overall Study Administrative reason	2
Overall Study Other	12

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AA4500 0.58 mg n=286 Participants Collagenase clostridium histolyticum 0.58 mg injected into MP and/or PIP joints
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	166 Participants n=5 Participants
Age, Categorical >=65 years	120 Participants n=5 Participants
Age, Continuous	62.7 years STANDARD_DEVIATION 9.5 • n=5 Participants
Sex: Female, Male Female	60 Participants n=5 Participants
Sex: Female, Male Male	226 Participants n=5 Participants
Race/Ethnicity, Customized White	285 participants n=5 Participants
Race/Ethnicity, Customized Hispanic	1 participants n=5 Participants
Region of Enrollment United States	286 participants n=5 Participants

PRIMARY outcome

Timeframe: Within 30 days after last injection

Population: Evaluable non-primary joints treated with AA4500 with baseline fixed flexion contracture \>5° and at least 1 post-injection contracture measurement. For the purpose of analysis, 13 subjects with non-primary joints treated with AA4500 in double-blind study AUX-CC-857 are included in overall number of participants.

Successfully treated or clinical success in non-primary joints defined as reduction in contracture to within 0-5° of normal within 30 days of injection.

Outcome measures

Outcome measures
Measure	AA4500 0.58 mg n=320 Joints Collagenase clostridium histolyticum 0.58 mg injected into MP and/or PIP joints
Reduction in Contracture to 5° or Less	41.9 Percentage of joints

SECONDARY outcome

Timeframe: Baseline, within 30 days after last injection

Population: Evaluable non-primary joints treated with AA4500 with baseline fixed flexion contracture \>5° and at least 1 post-injection contracture measurement. For the purpose of analysis, 13 subjects with non-primary joints treated with AA4500 in double-blind study AUX-CC-857 are included in overall number of participants.

Clinical improvement in non-primary joints defined as ≥50% reduction from baseline in the degree of contracture within 30 days after injection

Outcome measures

Outcome measures
Measure	AA4500 0.58 mg n=320 Joints Collagenase clostridium histolyticum 0.58 mg injected into MP and/or PIP joints
Clinical Improvement After the Last Injection	65.0 Percentage of joints

SECONDARY outcome

Timeframe: Baseline, Day 30 after last injection

Population: Evaluable non-primary joints treated with AA4500 with baseline fixed flexion contracture \>5° and at least 1 post-injection contracture measurement. For the purpose of analysis, 13 subjects with non-primary joints treated with AA4500 in double-blind study AUX-CC-857 are included in overall number of participants.

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

Outcome measures

Outcome measures
Measure	AA4500 0.58 mg n=320 Joints Collagenase clostridium histolyticum 0.58 mg injected into MP and/or PIP joints
Percent Reduction From Baseline Contracture After the Last Injection	60.8 Percentage of change Standard Deviation 39.00

SECONDARY outcome

Timeframe: Baseline, Day 30 after last injection

Population: Evaluable non-primary joints treated with AA4500 with baseline fixed flexion contracture \>5° and at least 1 post-injection contracture measurement. For the purpose of analysis, 13 subjects with non-primary joints treated with AA4500 in double-blind study AUX-CC-857 are included in overall number of participants.

Change in degree of range of motion in non-primary joints measured as last available post-injection range of motion - baseline range of motion

Outcome measures

Outcome measures
Measure	AA4500 0.58 mg n=320 Joints Collagenase clostridium histolyticum 0.58 mg injected into MP and/or PIP joints
Change From Baseline Range of Motion After the Last Injection	24.0 Degrees Standard Deviation 20.83

SECONDARY outcome

Timeframe: Within 30 days after last injection

Population: Evaluable non-primary joints treated with AA4500 with baseline fixed flexion contracture \>5° and at least 1 post-injection contracture measurement. For the purpose of analysis, 13 subjects with non-primary joints treated with AA4500 in double-blind study AUX-CC-857 are included in overall number of participants.

Clinical success in non-primary joints defined as reduction in contracture to within 0-5° of normal within 30 days of injection, displayed in post injection time point categories

Outcome measures

Outcome measures
Measure	AA4500 0.58 mg n=320 Joints Collagenase clostridium histolyticum 0.58 mg injected into MP and/or PIP joints
Time to Reach Clinical Success Injection 1, Day 1	12.5 Percentage of Joints
Time to Reach Clinical Success Injection 1, Day 7	15.9 Percentage of Joints
Time to Reach Clinical Success Injection 1, Day 30	5.9 Percentage of Joints
Time to Reach Clinical Success Injection 2, Day 0	0.0 Percentage of Joints
Time to Reach Clinical Success Injection 2, Day 1	2.2 Percentage of Joints
Time to Reach Clinical Success Injection 2, Day 7	1.3 Percentage of Joints
Time to Reach Clinical Success Injection 2, Day 30	1.9 Percentage of Joints
Time to Reach Clinical Success Injection 3, Day 0	0.0 Percentage of Joints
Time to Reach Clinical Success Injection 3, Day 1	1.3 Percentage of Joints
Time to Reach Clinical Success Injection 3, Day 7	0.6 Percentage of Joints
Time to Reach Clinical Success Injection 3, Day 30	0.3 Percentage of Joints
Time to Reach Clinical Success Did not reach Clinical Success	58.1 Percentage of Joints

SECONDARY outcome

Timeframe: Within 30 days after first injection

Population: Evaluable non-primary joints treated with AA4500 with baseline fixed flexion contracture \>5° and at least 1 post-injection contracture measurement. For the purpose of analysis, 13 subjects with non-primary joints treated with AA4500 in double-blind study AUX-CC-857 are included in overall number of participants.

Clinical success in non-primary joints defined as reduction in contracture to within 0-5° of normal within 30 days of injection.

Outcome measures

Outcome measures
Measure	AA4500 0.58 mg n=320 Joints Collagenase clostridium histolyticum 0.58 mg injected into MP and/or PIP joints
Clinical Success After the First Injection	34.1 Percentage of Joints

SECONDARY outcome

Timeframe: Baseline, within 30 days after first injection

Population: Evaluable non-primary joints treated with AA4500 with baseline fixed flexion contracture \>5° and at least 1 post-injection contracture measurement. For the purpose of analysis, 13 subjects with non-primary joints treated with AA4500 in double-blind study AUX-CC-857 are included in overall number of participants.

Clinical improvement in non-primary joints defined as ≥50% reduction from baseline in the degree of contracture within 30 days after injection

Outcome measures

Outcome measures
Measure	AA4500 0.58 mg n=320 Joints Collagenase clostridium histolyticum 0.58 mg injected into MP and/or PIP joints
Clinical Improvement After the First Injection	56.3 Percentage of Joints

SECONDARY outcome

Timeframe: Baseline, Day 30 after first injection

Population: Evaluable non-primary joints treated with AA4500 with baseline fixed flexion contracture \>5° and at least 1 post-injection contracture measurement. For the purpose of analysis, 13 subjects with non-primary joints treated with AA4500 in double-blind study AUX-CC-857 are included in overall number of participants.

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

Outcome measures

Outcome measures
Measure	AA4500 0.58 mg n=320 Joints Collagenase clostridium histolyticum 0.58 mg injected into MP and/or PIP joints
Percent Reduction From Baseline Contracture After the First Injection	53.9 Percentage of change Standard Deviation 38.64

SECONDARY outcome

Timeframe: Baseline, Day 30 after first injection

Population: Evaluable non-primary joints treated with AA4500 with baseline fixed flexion contracture \>5° and at least 1 post-injection contracture measurement. For the purpose of analysis, 13 subjects with non-primary joints treated with AA4500 in double-blind study AUX-CC-857 are included in overall number of participants.

Change in degree of range of motion in non-primary joints measured as last available post-injection range of motion - baseline range of motion

Outcome measures

Outcome measures
Measure	AA4500 0.58 mg n=320 Joints Collagenase clostridium histolyticum 0.58 mg injected into MP and/or PIP joints
Change From Baseline Range of Motion After the First Injection	20 Degrees Standard Deviation 19.46

Adverse Events

AA4500 0.58 mg

Serious events: 9 serious events

Other events: 171 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	AA4500 0.58 mg n=286 participants at risk collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
Gastrointestinal disorders Abdominal pain	0.35% 1/286 • Number of events 1 • From the time of study drug administration until 30 days after completion of or discharge from the 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 Acute myocardial infarction	0.35% 1/286 • Number of events 1 • From the time of study drug administration until 30 days after completion of or discharge from the 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 Asthenia	0.35% 1/286 • Number of events 1 • From the time of study drug administration until 30 days after completion of or discharge from the 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)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic myeloid leukaemia	0.35% 1/286 • Number of events 1 • From the time of study drug administration until 30 days after completion of or discharge from the 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 Clostridial infection	0.35% 1/286 • Number of events 1 • From the time of study drug administration until 30 days after completion of or discharge from the 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 Finger deformity	0.35% 1/286 • Number of events 1 • From the time of study drug administration until 30 days after completion of or discharge from the 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)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Meningioma	0.35% 1/286 • Number of events 1 • From the time of study drug administration until 30 days after completion of or discharge from the 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)
Gastrointestinal disorders Nausea	0.35% 1/286 • Number of events 1 • From the time of study drug administration until 30 days after completion of or discharge from the 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 Nephrolithiasis	0.35% 1/286 • Number of events 1 • From the time of study drug administration until 30 days after completion of or discharge from the 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)
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.35% 1/286 • Number of events 2 • From the time of study drug administration until 30 days after completion of or discharge from the 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 Syncope	0.35% 1/286 • Number of events 1 • From the time of study drug administration until 30 days after completion of or discharge from the 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

Other adverse events
Measure	AA4500 0.58 mg n=286 participants at risk collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
Skin and subcutaneous tissue disorders Blood blister	7.3% 21/286 • Number of events 22 • From the time of study drug administration until 30 days after completion of or discharge from the 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	33.2% 95/286 • Number of events 205 • From the time of study drug administration until 30 days after completion of or discharge from the 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 Dupuytren's contracture	5.2% 15/286 • Number of events 15 • From the time of study drug administration until 30 days after completion of or discharge from the 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	13.6% 39/286 • Number of events 67 • From the time of study drug administration until 30 days after completion of or discharge from the 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	18.2% 52/286 • Number of events 95 • From the time of study drug administration until 30 days after completion of or discharge from the 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	16.4% 47/286 • Number of events 74 • From the time of study drug administration until 30 days after completion of or discharge from the 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	5.2% 15/286 • Number of events 26 • From the time of study drug administration until 30 days after completion of or discharge from the 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	11.9% 34/286 • Number of events 56 • From the time of study drug administration until 30 days after completion of or discharge from the 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	47.6% 136/286 • Number of events 386 • From the time of study drug administration until 30 days after completion of or discharge from the 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 Pain	5.2% 15/286 • Number of events 27 • From the time of study drug administration until 30 days after completion of or discharge from the 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	23.1% 66/286 • Number of events 98 • From the time of study drug administration until 30 days after completion of or discharge from the 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	11.5% 33/286 • Number of events 51 • From the time of study drug administration until 30 days after completion of or discharge from the 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	8.4% 24/286 • Number of events 30 • From the time of study drug administration until 30 days after completion of or discharge from the 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	15.0% 43/286 • Number of events 75 • From the time of study drug administration until 30 days after completion of or discharge from the 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)

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 precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER