Dupuytren's Disease
Conditions
Keywords
XIAFLEX, XIAPEX, Dupuytren's disease, contracture
Brief summary
The objectives of this study are to assess the safety and efficacy of AA4500 in the retreatment of recurrent contractures in joints that were effectively treated with AA4500 in a previous Auxilium-sponsored Phase 3 study.
Detailed description
Open-label, Phase 4 study in subjects who are currently participating in the long-term follow-up study (ie, AUX-CC-860) in the United States, Australia, or Europe and who have recurrence of contracture (ie, joint contracture increases by at least 20 degrees compared with the Day 30 value after the last injection in a Phase 3 Auxilium-sponsored study and a palpable cord present) in a joint that was effectively treated (ie, reduction in contracture to 5 degrees or less 30 days after the last injection) with AA4500 in a Phase 3 Auxilium-sponsored study. Subjects who experience recurrence of contracture in one or more effectively treated joints may be enrolled in this retreatment study after the investigator determines subject eligibility and after informed consent has been obtained. The investigator will treat the cord affecting the recurrent joint with up to three injections. Only one recurrent joint will be treated in this study.
Interventions
BIOLOGICALCollagenase clostridium histolyticum
up to three 0.58 mg injections
Sponsors
Endo Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Provide written informed consent 2. Be currently participating in the AUX-CC-860 follow-up study 3. Have at least one joint with all of the following: * The joint was effectively treated (had a correction to 5 degrees or less at the Day 30 evaluation after the last injection of AA4500) in a previous Auxilium Phase 3 study * The effectively treated joint has an increase in contracture of at least 20 degrees compared with the Day 30 value after the last injection of AA4500 in a previous Auxilium Phase 3 study * A palpable cord is present in the joint to be treated 4. Be able to comply with the study visit schedule as specified in the protocol
Exclusion criteria
1. Is a pregnant or lactating female or female intending to become pregnant during the study 2. Has hypersensitivity to AA4500 or any of the AA4500 excipients 3. Is currently receiving or plans to receive anticoagulant medication or has received anticoagulant medication (except for equal to or less than 150 mg aspirin daily and over-the-counter nonsteroidal antiinflammatory drugs \[NSAIDs\]) within 7 days before injection of AA4500
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Success | 30 days after last injection | Clinical success defined as reduction in fixed-flexion contracture to less than or equal to 5 degrees 30 days after the last injection of AA4500 |
| Percent Change From Baseline in Degree of Contracture | Baseline and 30 days after last injection | Change in fixed-flection contracture measured in degrees where a decrease of 100% would correspond to a reduction in contracture to 0 degrees |
| Change in Range of Motion | Baseline and 30 days after last injection | Range of motion defined as difference between full flexion angle and full extension angle expressed in degrees |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Physician Global Assessment of Improvement | 30 days after last injection | Physician global assessment of change (improvement) in subject's Dupuytren's contracture |
| Subject Global Assessment of Satisfaction | 30 days after last injection | Subject global assessment of overall treatment satisfaction |
| Recurrence of Contracture | Day 365 | Recurrence of contracture in the joint at day 365 that was successfully treated 30 days after last injection assessed. Recurrence was defined as 20 degree or greater increase of contracture of the treated joint at day 365 or medication intervention of the treated joint between the 2 time points. |
Countries
Australia, Sweden, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| XIAFLEX/XIAPEX XIAFLEX/XIAPEX: up to three 0.58 mg injections | 52 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Other | 3 |
Baseline characteristics
| Characteristic | XIAFLEX/XIAPEX |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 32 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants |
| Age, Continuous | 66.5 Years STANDARD_DEVIATION 9.53 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 52 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 52 Participants |
| Region of Enrollment Australia | 21 participants |
| Region of Enrollment Sweden | 6 participants |
| Region of Enrollment United Kingdom | 4 participants |
| Region of Enrollment United States | 21 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 44 / 52 |
| serious Total, serious adverse events | 4 / 52 |
Outcome results
Primary
Change in Range of Motion
Range of motion defined as difference between full flexion angle and full extension angle expressed in degrees
Time frame: Baseline and 30 days after last injection
Population: Efficacy assessment based on mITT population which includes all enrolled subjects who received at least 1 AA4500 injection to the treated joint and had at least 1 post-injection efficacy measure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| XIAFLEX/XIAPEX MP Joint | Change in Range of Motion | 31.4 degrees | Standard Deviation 17.52 |
| XIAFLEX/XIAPEX PIP Joint | Change in Range of Motion | 26.8 degrees | Standard Deviation 17.39 |
Primary
Clinical Success
Clinical success defined as reduction in fixed-flexion contracture to less than or equal to 5 degrees 30 days after the last injection of AA4500
Time frame: 30 days after last injection
Population: Efficacy assessment based on modified intent-to-treat (mITT) population which includes all enrolled subjects who received at least 1 AA4500 injection to the treated joint and had at least 1 post-injection efficacy measure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| XIAFLEX/XIAPEX MP Joint | Clinical Success | 64.5 percentage of particpants |
| XIAFLEX/XIAPEX PIP Joint | Clinical Success | 45.0 percentage of particpants |
Primary
Percent Change From Baseline in Degree of Contracture
Change in fixed-flection contracture measured in degrees where a decrease of 100% would correspond to a reduction in contracture to 0 degrees
Time frame: Baseline and 30 days after last injection
Population: Efficacy assessment based on mITT population which includes all enrolled subjects who received at least 1 AA4500 injection to the treated joint and had at least 1 post-injection efficacy measure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| XIAFLEX/XIAPEX MP Joint | Percent Change From Baseline in Degree of Contracture | 83.24 percentage of contracture change | Standard Deviation 24.275 |
| XIAFLEX/XIAPEX PIP Joint | Percent Change From Baseline in Degree of Contracture | 69.10 percentage of contracture change | Standard Deviation 26.776 |
Secondary
Physician Global Assessment of Improvement
Physician global assessment of change (improvement) in subject's Dupuytren's contracture
Time frame: 30 days after last injection
Population: Efficacy assessment based on mITT population which includes all enrolled subjects who received at least 1 AA4500 injection to the treated joint and had at least 1 post-injection efficacy measure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| XIAFLEX/XIAPEX MP Joint | Physician Global Assessment of Improvement | Not done | 1 participants |
| XIAFLEX/XIAPEX MP Joint | Physician Global Assessment of Improvement | No change | 1 participants |
| XIAFLEX/XIAPEX MP Joint | Physician Global Assessment of Improvement | Much improved | 11 participants |
| XIAFLEX/XIAPEX MP Joint | Physician Global Assessment of Improvement | Minimally worse | 0 participants |
| XIAFLEX/XIAPEX MP Joint | Physician Global Assessment of Improvement | Very much improved | 18 participants |
| XIAFLEX/XIAPEX MP Joint | Physician Global Assessment of Improvement | Much worse | 0 participants |
| XIAFLEX/XIAPEX MP Joint | Physician Global Assessment of Improvement | Minimally improved | 0 participants |
| XIAFLEX/XIAPEX MP Joint | Physician Global Assessment of Improvement | Very much worse | 0 participants |
| XIAFLEX/XIAPEX PIP Joint | Physician Global Assessment of Improvement | Minimally improved | 2 participants |
| XIAFLEX/XIAPEX PIP Joint | Physician Global Assessment of Improvement | Very much worse | 0 participants |
| XIAFLEX/XIAPEX PIP Joint | Physician Global Assessment of Improvement | Very much improved | 12 participants |
| XIAFLEX/XIAPEX PIP Joint | Physician Global Assessment of Improvement | Much improved | 5 participants |
| XIAFLEX/XIAPEX PIP Joint | Physician Global Assessment of Improvement | Not done | 0 participants |
| XIAFLEX/XIAPEX PIP Joint | Physician Global Assessment of Improvement | No change | 1 participants |
| XIAFLEX/XIAPEX PIP Joint | Physician Global Assessment of Improvement | Minimally worse | 0 participants |
| XIAFLEX/XIAPEX PIP Joint | Physician Global Assessment of Improvement | Much worse | 0 participants |
Secondary
Recurrence of Contracture
Recurrence of contracture in the joint at day 365 that was successfully treated 30 days after last injection assessed. Recurrence was defined as 20 degree or greater increase of contracture of the treated joint at day 365 or medication intervention of the treated joint between the 2 time points.
Time frame: Day 365
Population: Efficacy assessment based on mITT population which includes all enrolled subjects who received at least 1 AA4500 injection to the treated joint and had at least 1 post-injection efficacy measure; only joints that were successfully treated (reduction in contracture to 5 degrees or less) 30 days after last injection were assessed
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| XIAFLEX/XIAPEX MP Joint | Recurrence of Contracture | 6 joints |
Secondary
Subject Global Assessment of Satisfaction
Subject global assessment of overall treatment satisfaction
Time frame: 30 days after last injection
Population: Efficacy assessment based on mITT population which includes all enrolled subjects who received at least 1 AA4500 injection to the treated joint and had at least 1 post-injection efficacy measure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| XIAFLEX/XIAPEX MP Joint | Subject Global Assessment of Satisfaction | Very satisfied | 20 participants |
| XIAFLEX/XIAPEX MP Joint | Subject Global Assessment of Satisfaction | Quite satisfied | 9 participants |
| XIAFLEX/XIAPEX MP Joint | Subject Global Assessment of Satisfaction | Neither satisfied nor dissatisfied | 1 participants |
| XIAFLEX/XIAPEX MP Joint | Subject Global Assessment of Satisfaction | Quite dissatisfied | 0 participants |
| XIAFLEX/XIAPEX MP Joint | Subject Global Assessment of Satisfaction | Very dissatisfied | 0 participants |
| XIAFLEX/XIAPEX MP Joint | Subject Global Assessment of Satisfaction | Not done | 1 participants |
| XIAFLEX/XIAPEX PIP Joint | Subject Global Assessment of Satisfaction | Very dissatisfied | 0 participants |
| XIAFLEX/XIAPEX PIP Joint | Subject Global Assessment of Satisfaction | Very satisfied | 10 participants |
| XIAFLEX/XIAPEX PIP Joint | Subject Global Assessment of Satisfaction | Quite dissatisfied | 1 participants |
| XIAFLEX/XIAPEX PIP Joint | Subject Global Assessment of Satisfaction | Quite satisfied | 5 participants |
| XIAFLEX/XIAPEX PIP Joint | Subject Global Assessment of Satisfaction | Not done | 2 participants |
| XIAFLEX/XIAPEX PIP Joint | Subject Global Assessment of Satisfaction | Neither satisfied nor dissatisfied | 2 participants |