Dupuytren's Disease
Conditions
Keywords
Dupuytren's contracture, fixed flexion contracture
Brief summary
The purpose of the study is to determine if collagenase will reduce the degree of contracture in the primary joint in subjects with Dupuytren's disease. 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.
Detailed description
In a random, placebo controlled, double blind study, collagenase injection therapy will be investigated for it's ability to disrupt the Dupuytren's cord. Resultant cord disruption may obviate the need for patients to have surgery to correct the finger flexion contractures of Dupuytren's disease.
Interventions
BIOLOGICALcollagenase clostridium histolyticum
Subjects could have received up to three injections of AA4500/placebo into the cord of the affected hand. Each injection was separated by at least 30 days. Individual cords may have received up to a maximum of three injections.
Sponsors
Biospecifics Technologies Corp.
Endo Pharmaceuticals
Stony Brook University
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects were at least 18 years of age, of either sex or any race. * Subjects had residual Dupuytren's disease with a fixed-flexion deformity of the finger(s) of at least 20 degrees or greater, caused by a palpable cord. * Subjects had a positive table-top test defined as the inability to simultaneously place their affected finger(s) and palm flat against a table top. * Subjects must have been willing to participate in and complete the study, and comply with its procedures by signing an IRB approved written consent form. * Subjects must have been able to understand and adhere to the visit schedule. They must have been able to follow study procedures and instructions, and have agreed to report concomitant medications and adverse events accurately and consistently. * Women of childbearing potential must have agreed to use an acceptable method of birth control or must have been surgically sterilized (hysterectomy or tubal ligation). Women of childbearing age had a urine pregnancy test on Day 0 (day of injection) prior to the injection.
Exclusion criteria
* Women who were nursing or who were pregnant (as evidenced by a positive urine pregnancy test at the time of enrollment). * Subjects who had participated in an investigational drug trial within 30 days of enrollment in this study. * Subjects who had received surgery for Dupuytren's disease within 30 days of enrollment in this study. * Subjects who had a known allergy to AA4500 or any of the inactive ingredients in the AA4500 injection. * Subjects who had a known allergy to doxycycline. * Subjects who had a medical condition that would have made them unsuitable for enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Outcome Measure is Reduction of Flexion Contracture of the Primary Joint. | 30 days after the last injection | The Primary Outcome Measure for patients treated with AA4500 is the percentage of 23 joints that were successfully treated where successfully treated was defined as reduction in contracture to 5° or less. The Primary Outcome Measure for placebo treated patients is the percentage of 12 joints that were successfully treated where successfully treated was defined as reduction in contracture to 5° or less. |
Secondary
| Measure | Time frame |
|---|---|
| Percent Reduction From Baseline Contracture After the Last Injection | 30 days after last treatment to the primary joint |
| Percent Change From Baseline Range of Motion After the Last Injection | 30 days after last treatment to the primary joint |
| Time to First Achieve and Maintain Clinical Success After the Last Injection | First evaluation visit on which clinical success is achieved and maintained through the Day 30 evaluation of the primary joint |
| Clinical Success After the First Injection | 30 days after first treatment to the primary joint |
| Percent Reduction From Baseline Contracture After the First Injection | 30 days after first treatment to the primary joint |
| Change From Baseline Range of Motion After the First Injection | 30 days after first treatment to the primary joint |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AA4500 collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints | 23 |
| Placebo | 12 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | failure to follow appointments | 1 | 0 |
| Overall Study | scheduled hand surgery | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | AA4500 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 7 Participants | 14 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 16 Participants | 21 Participants |
| Age Continuous | 63.8 years STANDARD_DEVIATION 10 | 60.1 years STANDARD_DEVIATION 7.6 | 61.3 years STANDARD_DEVIATION 8.5 |
| Region of Enrollment United States | 12 participants | 23 participants | 35 participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Male | 8 Participants | 20 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 23 / 23 | 12 / 15 |
| serious Total, serious adverse events | 2 / 23 | 1 / 15 |
Outcome results
Primary
Primary Outcome Measure is Reduction of Flexion Contracture of the Primary Joint.
The Primary Outcome Measure for patients treated with AA4500 is the percentage of 23 joints that were successfully treated where successfully treated was defined as reduction in contracture to 5° or less. The Primary Outcome Measure for placebo treated patients is the percentage of 12 joints that were successfully treated where successfully treated was defined as reduction in contracture to 5° or less.
Time frame: 30 days after the last injection
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AA4500 | Primary Outcome Measure is Reduction of Flexion Contracture of the Primary Joint. | 91.3 % Joints |
| Placebo | Primary Outcome Measure is Reduction of Flexion Contracture of the Primary Joint. | 0 % Joints |
Secondary
Change From Baseline Range of Motion After the First Injection
Time frame: 30 days after first treatment to the primary joint
Secondary
Clinical Success After the First Injection
Time frame: 30 days after first treatment to the primary joint
Secondary
Percent Change From Baseline Range of Motion After the Last Injection
Time frame: 30 days after last treatment to the primary joint
Secondary
Percent Reduction From Baseline Contracture After the First Injection
Time frame: 30 days after first treatment to the primary joint
Secondary
Percent Reduction From Baseline Contracture After the Last Injection
Time frame: 30 days after last treatment to the primary joint
Secondary
Time to First Achieve and Maintain Clinical Success After the Last Injection
Time frame: First evaluation visit on which clinical success is achieved and maintained through the Day 30 evaluation of the primary joint