Musculoskeletal Diseases

All Conditions

Skin and Connective Tissue Diseases

Nervous System Diseases

Neoplasms

Joint Diseases

Connective Tissue Diseases

Contracture

Muscular Diseases

Dupuytren Contracture

Fibroma

Neoplasms, Fibrous Tissue

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Veronica Urdaneta, MD

The purpose of study AUX-CC-860 is to assess the durability of response of the AA4500 treatment regimen. This study will also evaluate long-term safety and progression of disease in joints.

Phase 3 non-treatment study in which Year 2 to Year 5 year follow-up of subjects who received AA4500 in the 9-month open-label studies (AUX-CC-854 and AUX-CC-856) or the 12-month double-blind with open-label extension studies (AUX-CC-857/AUX-CC-858 and AUX-CC-859). After completion of one of the above mentioned studies, subjects are enrolled and followed once a calendar year for 4 consecutive years with at least 6 months between consecutive visits.

Longterm Observational Study in Subjects Treated With AA4500 in AUX-CC-854, 856, 857, 858 & 859

CORDLESS- Collagenase Optimal Reduction of Dupuytren's - Long-term Evaluation of Success Study

Endo Pharmaceuticals

Up to five injections of AA4500 into cord(s) of the affected hand(s). Each injection was separated by at least 30 days.

collagenase clostridium histolyticum

This was a Phase 3, 9-month, open-label study conducted in the United States. Subjects with a diagnosis of advanced Dupuytren's disease in a metacarpophalangeal (MP) or proximal interphalangeal (PIP) joint that resulted in a fixed flexion deformity of at least one finger, other than the thumb, that was at least 20° as measured by finger goniometry and was suitable for evaluation and injection were enrolled.

This study was designed to be part of the larger clinical program, for adult patients with Dupuytren's contracture with a palpable cord, where the data from 2 pivotal Placebo-Controlled studies (AUX-CC-857 (NCT00528606) and AUX-CC-859 (NCT00533273)) and 7 non-pivotal studies were evaluated.

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

A Phase 3, Open-Label Study of the Safety and Efficacy of AA4500 in the Treatment of Subjects With Advanced Dupuytren's Disease

The Primary Outcome Measure is the percentage of joints that were successfully treated where "successfully treated" was defined as reduction in contracture to within 0-5 degrees of normal within 30 days of injection

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

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

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

Clinical success is defined as reduction in contracture to within 0-5 degrees of normal within 30 days of injection, displayed in post-injection timepoint categories.

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

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

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

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

This study was designed to be part of the larger clinical program, for adult patients with Dupuytren's contracture with a palpable cord, where the data from 2 pivotal Placebo-Controlled studies (AUX-CC-857 and AUX-CC-859) and 7 non-pivotal studies were evaluated.

collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints

AA4500 0.58 mg

Age, Categorical

Age, Continuous

Sex: Female, Male

White

Race/Ethnicity, Customized

United States

Region of Enrollment

Clinical Trial Coordinator

Intent to treat population (ITT) defined as all subjects who received at least one injection.

Reduction in Contracture to 5° or Less

Clinical Improvement After the Last Injection

Percent Reduction From Baseline Contracture After the Last Injection

Change From Baseline Range of Motion After the Last Injection

Injection 1, Day 1

Injection 1, Day 7

Injection 1, Day 30

Injection 2, Day 0

Injection 2, Day 1

Injection 2, Day 7

Injection 2, Day 30

Injection 3, Day 0

Injection 3, Day 1

Injection 3, Day 7

Injection 3, Day 30

Injection 3, Day 90

Did not reach clinical success

Time to Reach Clinical Success

Clinical Success After the First Injection

Clinical Improvement After the First Injection

Percent Reduction From Baseline Contracture After the First Injection

Change From Baseline Range of Motion After the First Injection

Overall Study

Subjects may have received up to five injections of AA4500 0.58 mg into the cords of the affected hand, with each injection separated by at least 30 days. Individual cords may have received up to a maximum of three AA4500 injections.

AA4500

Study AUX-CC-858 was an open-label continuation of the double-blind Study AUX-CC-857 (NCT00528606). Subjects who complete the Day 90 visit after their initial injection in Study AUX-CC-857 (NCT00528606) entered into Study AUX-CC-858. Subjects who required further treatment in Study AUX-CC-858, either because their treated metacarpophalangeal and/or proximal interphalangeal (PIP) joints did not have a reduction in contracture to 5° or less, the cord affecting that joint received less than three injections of AA4500, or they had other eligible cords that received no treatment in AUX-CC-857 (NCT00528606), had the option to receive up to five injections of AA4500 in this extension study. Subjects requiring further treatment were followed for efficacy and safety on Days 1, 7, and 30 after each injection, with injections separated by four weeks. Follow-up visits for the determination of efficacy and safety were conducted on Day 90, Month 6, and Month 9.

This study was designed to be part of the larger clinical program, for adult patients with Dupuytren's contracture with a palpable cord, where the data from 2 pivotal Placebo-Controlled studies (AUX-CC-857 (NCT00528606) and AUX-CC-859 (NCT00533273)) and 7 non-pivotal studies were evaluated.

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

A Phase 3, Open-Label Extension Study of the Safety and Efficacy of AA4500 in the Treatment of Subjects With Advanced Dupuytren's Disease

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.

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

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

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

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

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

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)

Collagenase clostridium histolyticum 0.58 mg injected into MP and/or PIP joints

Hispanic

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.

Did not reach Clinical Success

Collagenase clostridium histolyticum 0.58 mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints

Subjects could have received up to three injections of AA4500 0.58 mg/placebo into the cord of the affected hand in the double-blind phase. In the open-label extension phase, subjects could have received up to five additional injections of AA4500, with each injection separated by at least 30 days. Individual joints could have received up to a maximum of three AA4500 injections.

This 12-month study had two phases: a 90-day double-blind, randomized, placebo-controlled phase and a nine-month open-label extension phase. Before treatment, eligible subjects were stratified by the primary joint type (30 metacarpophalangeal \[MP\] joints and 30 proximal interphalangeal \[PIP\] joints) and by severity of the primary joint contracture (ie, up to 50° or \>50° for MP joints and up to 40° or \>40° for PIP joints) and then randomized in a 2:1 ratio to either AA4500 0.58 mg or placebo. Upon completion of the double-blind phase (ie, 90-day evaluation after the first injection), all subjects were eligible to enter the open-label extension phase of the study in which they were followed for an additional nine months. Subjects who required further treatment because they either did not achieve reduction in contracture to 5° or less, the cord affecting the primary joint received placebo, another cord received less than three injections of AA4500, or they had untreated cords that were affecting other joints had the option to receive up to five additional injections of AA4500 0.58 mg in the open-label extension phase, with individual cords receiving up to three injections of AA4500.

This study was designed to be part of the larger clinical program, for adult patients with Dupuytren's contracture with a palpable cord, where the data from 2 pivotal Placebo-Controlled studies (AUX-CC-857 \[NCT00528606\] and AUX-CC-859 \[NCT00533273\]) and 7 non-pivotal studies were evaluated.

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

A Phase 3, Double-Blind, Randomized, Placebo-Controlled Study of the Safety and Efficacy of AA4500 in the Treatment of Subjects With Advanced Dupuytren's Disease Followed by an Open-Label Extension Phase

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

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

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

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

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

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

Percent change in degree of contracture of primary joint measured as 100 \* (baseline contracture - last available post-injection contracture prior to next injection)/baseline contracture

Change in degree of range of motion in primary joint measured as last available post-injection range of motion prior to the next injection - baseline range of motion

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

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

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

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

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

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

Percent change in degree of contracture of non-primary joint measured as 100 \* (baseline contracture - last available post-injection contracture prior to next injection)/baseline contracture

Change in degree of range of motion in non-primary joint measured as last available post-injection range of motion prior to the next injection - baseline range of motion

Placebo injection is comprised of sucrose and Tris

Placebo

Total

Australia

Subjects who were randomized and received at least 1 injection

Reduction in Primary Joint Contracture to 5° or Less

Clinical Improvement in Primary Joint After the Last Injection

Percent Reduction From Baseline Contracture of Primary Joint After the Last Injection

Change From Baseline Range of Motion in Primary Joint After the Last Injection

Time to Reach Clinical Success in Primary Joint

Clinical Success in Primary Joint After the First Injection

Clinical Improvement in Primary Joint After the First Injection

Percent Reduction From Baseline Contracture of Primary Joint After the First Injection

Change From Baseline Range of Motion in Primary Joint After the First Injection

Includes evaluable non-primary joints treated with AA4500 with baseline fixed flexion contracture \>5° and at least 1 post-injection contracture measurement in subjects who received at least 1 non-primary joint injection in either study period

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Longterm Observational Study in Subjects Treated With AA4500 in AUX-CC-854, 856, 857, 858 & 859	NCT00954746	Dupuytren's Dis...		18 Years -	Endo Pharmaceuticals
Safety and Efficacy Study of AA4500 (XIAFLEX™, Proposed Name) in the Treatment of Advanced Dupuytren's Disease	NCT00528840	Advanced Dupuyt...	collagenase clo...	18 Years -	Endo Pharmaceuticals
Safety and Efficacy Study of AA4500 (XIAFLEX™, Proposed Name) in the Treatment of Advanced Dupuytren's Disease	NCT00528840	Advanced Dupuyt...	collagenase clo...	18 Years -	Endo Pharmaceuticals
AA4500 (XIAFLEX™, Proposed Name) in the Treatment of Advanced Dupuytren's Disease	NCT00528424	Advanced Dupuyt...	AA4500	18 Years -	Endo Pharmaceuticals
Non-US Study of AA4500 (XIAFLEX™, Proposed Name) in the Treatment of Advanced Dupuytren's Disease	NCT00533273	Advanced Dupuyt...	collagenase clo...	18 Years -	Endo Pharmaceuticals
Longterm Observational Study in Subjects Treated With AA4500 in AUX-CC-854, 856, 857, 858 & 859	NCT00954746	Dupuytren's Dis...		18 Years -	Endo Pharmaceuticals
Safety and Efficacy Study of AA4500 (XIAFLEX™, Proposed Name) in the Treatment of Advanced Dupuytren's Disease	NCT00528840	Advanced Dupuyt...	collagenase clo...	18 Years -	Endo Pharmaceuticals
Longterm Observational Study in Subjects Treated With AA4500 in AUX-CC-854, 856, 857, 858 & 859	NCT00954746	Dupuytren's Dis...		18 Years -	Endo Pharmaceuticals
AA4500 (XIAFLEX™, Proposed Name) in the Treatment of Advanced Dupuytren's Disease	NCT00528424	Advanced Dupuyt...	AA4500	18 Years -	Endo Pharmaceuticals

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