Advanced Dupuytren's Disease
Conditions
Brief summary
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.
Interventions
BIOLOGICALAA4500
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.
Sponsors
Endo Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects with a diagnosis of advanced Dupuytren's disease, with a fixed flexion deformity of at least one finger, other than the thumb, that had a contracture at least 20°, but not greater than 100° for MP (80° for PIP) joints, caused by a palpable cord. * Had a positive table top test, defined as the inability to simultaneously place the affected finger(s) and palm flat against a table top. * Were naïve to AA4500 treatment or had received only one or two injections of AA4500 for the treatment of advanced Dupuytren's disease in AUX-CC-857 ((NCT00528606). * Were judged to be in good health. * Must have participated in protocol AUX-CC-857 (NCT00528606).
Exclusion criteria
* Had a chronic muscular, neurological, or neuromuscular disorder that affected the hands. * Had received treatment for advanced Dupuytren's disease within 90 days of enrollment on the joint selected for the initial injection of AA4500, including surgery (fasciectomy or surgical fasciotomy), needle aponeurotomy/fasciotomy, or injection of verapamil and/or interferon. * Had a known recent history of stroke, bleeding, a disease process that affected the hands, or other medical condition, which in the investigator's opinion, would make the subject unsuitable for enrollment in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reduction in Contracture to 5° or Less | Within 30 days after last injection | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Reduction From Baseline Contracture After the Last Injection | Baseline, Day 30 after last injection | Percent change in degree of contracture in non-primary joints measured as 100 \* (baseline contracture - last available post-injection contracture)/baseline contracture. |
| Change From Baseline Range of Motion After the Last Injection | Baseline, Day 30 after last injection | Change in degree of range of motion in non-primary joints measured as last available post-injection range of motion - baseline range of motion |
| Time to Reach Clinical Success | Within 30 days after last injection | 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 Improvement After the Last Injection | Baseline, within 30 days after last injection | Clinical improvement in non-primary joints defined as ≥50% reduction from baseline in the degree of contracture within 30 days after injection |
| Clinical Improvement After the First Injection | Baseline, within 30 days after first injection | Clinical improvement in non-primary joints defined as ≥50% reduction from baseline in the degree of contracture within 30 days after injection |
| Percent Reduction From Baseline Contracture After the First Injection | Baseline, Day 30 after first injection | Percent change in degree of contracture in non-primary joints measured as 100 \* (baseline contracture - last available post-injection contracture)/baseline contracture. |
| Change From Baseline Range of Motion After the First Injection | Baseline, Day 30 after first injection | 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 After the First Injection | Within 30 days after first injection | Clinical success in non-primary joints defined as reduction in contracture to within 0-5° of normal within 30 days of injection. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AA4500 0.58 mg Collagenase clostridium histolyticum 0.58 mg injected into MP and/or PIP joints | 286 |
| Total | 286 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Administrative reason | 2 |
| Overall Study | Lost to Follow-up | 13 |
| Overall Study | Other | 12 |
| Overall Study | Withdrew consent | 2 |
Baseline characteristics
| Characteristic | AA4500 0.58 mg |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 120 Participants |
| Age, Categorical Between 18 and 65 years | 166 Participants |
| Age, Continuous | 62.7 years STANDARD_DEVIATION 9.5 |
| Race/Ethnicity, Customized Hispanic | 1 participants |
| Race/Ethnicity, Customized White | 285 participants |
| Region of Enrollment United States | 286 participants |
| Sex: Female, Male Female | 60 Participants |
| Sex: Female, Male Male | 226 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 171 / 286 |
| serious Total, serious adverse events | 9 / 286 |
Outcome results
Primary
Reduction in Contracture to 5° or Less
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AA4500 0.58 mg | Reduction in Contracture to 5° or Less | 41.9 Percentage of joints |
Secondary
Change From Baseline Range of Motion After the First Injection
Change in degree of range of motion in non-primary joints measured as last available post-injection range of motion - baseline range of motion
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AA4500 0.58 mg | Change From Baseline Range of Motion After the First Injection | 20 Degrees | Standard Deviation 19.46 |
Secondary
Change From Baseline Range of Motion After the Last Injection
Change in degree of range of motion in non-primary joints measured as last available post-injection range of motion - baseline range of motion
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AA4500 0.58 mg | Change From Baseline Range of Motion After the Last Injection | 24.0 Degrees | Standard Deviation 20.83 |
Secondary
Clinical Improvement After the First Injection
Clinical improvement in non-primary joints defined as ≥50% reduction from baseline in the degree of contracture within 30 days after injection
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AA4500 0.58 mg | Clinical Improvement After the First Injection | 56.3 Percentage of Joints |
Secondary
Clinical Improvement After the Last Injection
Clinical improvement in non-primary joints defined as ≥50% reduction from baseline in the degree of contracture within 30 days after injection
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AA4500 0.58 mg | Clinical Improvement After the Last Injection | 65.0 Percentage of joints |
Secondary
Clinical Success After the First Injection
Clinical success in non-primary joints defined as reduction in contracture to within 0-5° of normal within 30 days of injection.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AA4500 0.58 mg | Clinical Success After the First Injection | 34.1 Percentage of Joints |
Secondary
Percent Reduction From Baseline Contracture After the First Injection
Percent change in degree of contracture in non-primary joints measured as 100 \* (baseline contracture - last available post-injection contracture)/baseline contracture.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AA4500 0.58 mg | Percent Reduction From Baseline Contracture After the First Injection | 53.9 Percentage of change | Standard Deviation 38.64 |
Secondary
Percent Reduction From Baseline Contracture After the Last Injection
Percent change in degree of contracture in non-primary joints measured as 100 \* (baseline contracture - last available post-injection contracture)/baseline contracture.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AA4500 0.58 mg | Percent Reduction From Baseline Contracture After the Last Injection | 60.8 Percentage of change | Standard Deviation 39 |
Secondary
Time to Reach Clinical Success
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
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AA4500 0.58 mg | Time to Reach Clinical Success | Injection 1, Day 1 | 12.5 Percentage of Joints |
| AA4500 0.58 mg | Time to Reach Clinical Success | Injection 1, Day 7 | 15.9 Percentage of Joints |
| AA4500 0.58 mg | Time to Reach Clinical Success | Injection 2, Day 0 | 0.0 Percentage of Joints |
| AA4500 0.58 mg | Time to Reach Clinical Success | Injection 2, Day 1 | 2.2 Percentage of Joints |
| AA4500 0.58 mg | Time to Reach Clinical Success | Injection 2, Day 7 | 1.3 Percentage of Joints |
| AA4500 0.58 mg | Time to Reach Clinical Success | Injection 2, Day 30 | 1.9 Percentage of Joints |
| AA4500 0.58 mg | Time to Reach Clinical Success | Injection 3, Day 0 | 0.0 Percentage of Joints |
| AA4500 0.58 mg | Time to Reach Clinical Success | Injection 3, Day 1 | 1.3 Percentage of Joints |
| AA4500 0.58 mg | Time to Reach Clinical Success | Injection 3, Day 7 | 0.6 Percentage of Joints |
| AA4500 0.58 mg | Time to Reach Clinical Success | Injection 3, Day 30 | 0.3 Percentage of Joints |
| AA4500 0.58 mg | Time to Reach Clinical Success | Did not reach Clinical Success | 58.1 Percentage of Joints |
| AA4500 0.58 mg | Time to Reach Clinical Success | Injection 1, Day 30 | 5.9 Percentage of Joints |