Advanced Dupuytren's Disease
Conditions
Brief summary
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.
Interventions
BIOLOGICALcollagenase clostridium histolyticum
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.
Sponsors
Endo Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
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 naive to AA4500 treatment * Were judged to be in good health, based upon the results of a medical history, physical examination, and safety laboratory profile.
Exclusion criteria
* Had a chronic muscular, neurological, or neuromuscular disorder that affected the hands. * Had received a treatment for advanced Dupuytren's disease, including surgery (fasciectomy or surgical fasciotomy), needle aponeurotomy/fasciotomy, or injection of verapamil and/or interferon on the selected primary joint within 90 days before the first dose of study drug. * 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 Primary Joint Contracture to 5° or Less | Within 30 days after last injection | Successfully treated or clinical success in primary joint defined as reduction in contracture to within 0-5° of normal within 30 days of injection. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Improvement in Primary Joint After the Last Injection | Baseline, Within 30 days after last injection | Clinical improvement in primary joint defined as ≥50% reduction from baseline in the degree of contracture within 30 days after injection |
| Percent Reduction From Baseline Contracture of Primary Joint After the Last Injection | Baseline, Day 30 after last injection | Percent change in degree of contracture of primary joint measured as 100 \* (baseline contracture - last available post-injection contracture)/baseline contracture |
| Change From Baseline Range of Motion in Primary Joint After the Last Injection | Baseline, Day 30 after last injection | Change in degree of range of motion in primary joint measured as last available post-injection range of motion - baseline range of motion |
| Time to Reach Clinical Success in Primary Joint | Within 30 days after last injection | 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 After the First Injection | Within 30 days after first injection | 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 After the First Injection | Baseline, Within 30 days after first injection | Clinical improvement in primary joint defined as ≥50% reduction from baseline in the degree of contracture within 30 days after injection |
| Change From Baseline Range of Motion in Primary Joint After the First Injection | Baseline, Day 30 after first injection | 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 |
| Reduction in Non-primary Joint Contracture to 5° or Less After the Last Injection | Within 30 days after last injection | 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. |
| Percent Reduction From Baseline Contracture of Primary Joint After the First Injection | Baseline, Day 30 after first 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 |
| Percent Reduction From Baseline Contracture of Non-Primary Joint After the Last Injection | Baseline, Day 30 after last injection | Percent change in degree of contracture of non-primary joint measured as 100 \* (baseline contracture - last available post-injection contracture)/baseline contracture |
| Change From Baseline Range of Motion in Non-Primary Joint After the Last Injection | Baseline, Day 30 after last injection | Change in degree of range of motion in non-primary joint measured as last available post-injection range of motion - baseline range of motion |
| Time to Reach Clinical Success in Non-Primary Joint | Within 30 days after last injection | 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 After the First Injection | Within 30 days after first injection | 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 After the First Injection | Baseline, Within 30 days after first injection | Clinical improvement in non-primary joint defined as ≥50% reduction from baseline in the degree of contracture within 30 days after injection |
| Percent Reduction From Baseline Contracture of Non-Primary Joint After the First Injection | Baseline, Day 30 after first 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 From Baseline Range of Motion in Non-Primary Joint After the First Injection | Baseline, Day 30 after first injection | 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 |
| Clinical Improvement in Non-Primary Joint After the Last Injection | Baseline, Within 30 days after last injection | Clinical improvement in non-primary joint defined as ≥50% reduction from baseline in the degree of contracture within 30 days after injection |
Countries
Australia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AA4500 0.58 mg Collagenase clostridium histolyticum 0.58 mg injected into MP and/or PIP joints | 45 |
| Placebo Placebo (Sucrose and Tris) injection | 21 |
| Total | 66 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-blind | Withdrew consent | 0 | 2 |
| Open-label | Withdrawal by Subject | 6 | 0 |
Baseline characteristics
| Characteristic | AA4500 0.58 mg | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 20 Participants | 12 Participants | 32 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants | 9 Participants | 34 Participants |
| Age, Continuous | 63.0 years STANDARD_DEVIATION 7.8 | 65.5 years STANDARD_DEVIATION 11.1 | 63.8 years STANDARD_DEVIATION 9 |
| Race/Ethnicity, Customized White | 45 participants | 21 participants | 66 participants |
| Region of Enrollment Australia | 45 participants | 21 participants | 66 participants |
| Sex: Female, Male Female | 6 Participants | 4 Participants | 10 Participants |
| Sex: Female, Male Male | 39 Participants | 17 Participants | 56 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 63 / 63 | 10 / 21 |
| serious Total, serious adverse events | 7 / 63 | 1 / 21 |
Outcome results
Primary
Reduction in Primary Joint Contracture to 5° or Less
Successfully treated or clinical success in primary joint 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: Subjects who were randomized and received at least 1 injection
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AA4500 0.58 mg | Reduction in Primary Joint Contracture to 5° or Less | 44.4 Percentage of Joints |
| Placebo | Reduction in Primary Joint Contracture to 5° or Less | 4.8 Percentage of Joints |
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Change From Baseline Range of Motion in Non-Primary Joint After the First Injection
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
Time frame: Baseline, Day 30 after first injection
Population: 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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AA4500 0.58 mg | Change From Baseline Range of Motion in Non-Primary Joint After the First Injection | 20.5 Degrees | Standard Deviation 17.52 |
Secondary
Change From Baseline Range of Motion in Non-Primary Joint After the Last Injection
Change in degree of range of motion in non-primary joint measured as last available post-injection range of motion - baseline range of motion
Time frame: Baseline, Day 30 after last injection
Population: 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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AA4500 0.58 mg | Change From Baseline Range of Motion in Non-Primary Joint After the Last Injection | 25.2 Degrees | Standard Deviation 16.8 |
Secondary
Change From Baseline Range of Motion in Primary Joint After the First Injection
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
Time frame: Baseline, Day 30 after first injection
Population: Subjects who were randomized and received at least 1 injection
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AA4500 0.58 mg | Change From Baseline Range of Motion in Primary Joint After the First Injection | 28.6 Degrees | Standard Deviation 17.41 |
| Placebo | Change From Baseline Range of Motion in Primary Joint After the First Injection | 3.6 Degrees | Standard Deviation 9.51 |
p-value: <0.001ANOVA
Secondary
Change From Baseline Range of Motion in Primary Joint After the Last Injection
Change in degree of range of motion in primary joint measured as last available post-injection range of motion - baseline range of motion
Time frame: Baseline, Day 30 after last injection
Population: Subjects who were randomized and received at least 1 injection
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AA4500 0.58 mg | Change From Baseline Range of Motion in Primary Joint After the Last Injection | 35.4 Degrees | Standard Deviation 17.77 |
| Placebo | Change From Baseline Range of Motion in Primary Joint After the Last Injection | 7.6 Degrees | Standard Deviation 14.88 |
p-value: <0.001ANOVA
Secondary
Clinical Improvement in Non-Primary Joint After the First Injection
Clinical improvement in non-primary joint 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: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AA4500 0.58 mg | Clinical Improvement in Non-Primary Joint After the First Injection | 58.4 Percentage of Joints |
Secondary
Clinical Improvement in Non-Primary Joint After the Last Injection
Clinical improvement in non-primary joint 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: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AA4500 0.58 mg | Clinical Improvement in Non-Primary Joint After the Last Injection | 70.8 Percentage of Joints |
Secondary
Clinical Improvement in Primary Joint After the First Injection
Clinical improvement in primary joint 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: Subjects who were randomized and received at least 1 injection
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AA4500 0.58 mg | Clinical Improvement in Primary Joint After the First Injection | 60.0 Percentage of Joints |
| Placebo | Clinical Improvement in Primary Joint After the First Injection | 4.8 Percentage of Joints |
p-value: <0.0001Cochran-Mantel-Haenszel
Secondary
Clinical Improvement in Primary Joint After the Last Injection
Clinical improvement in primary joint 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: Subjects who were randomized and received at least 1 injection
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AA4500 0.58 mg | Clinical Improvement in Primary Joint After the Last Injection | 77.8 Percentage of Joints |
| Placebo | Clinical Improvement in Primary Joint After the Last Injection | 14.3 Percentage of Joints |
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Clinical Success in Non-Primary Joint After the First Injection
Clinical success in non-primary joint 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: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AA4500 0.58 mg | Clinical Success in Non-Primary Joint After the First Injection | 36.0 Percentage of Joints |
Secondary
Clinical Success in Primary Joint After the First Injection
Clinical success in primary joint 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: Subjects who were randomized and received at least 1 injection
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AA4500 0.58 mg | Clinical Success in Primary Joint After the First Injection | 26.7 Percentage of Joints |
| Placebo | Clinical Success in Primary Joint After the First Injection | 4.8 Percentage of Joints |
p-value: 0.014Cochran-Mantel-Haenszel
Secondary
Percent Reduction From Baseline Contracture of Non-Primary Joint After the First 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
Time frame: Baseline, Day 30 after first injection
Population: 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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AA4500 0.58 mg | Percent Reduction From Baseline Contracture of Non-Primary Joint After the First Injection | 54.7 Percentage of change | Standard Deviation 38.37 |
Secondary
Percent Reduction From Baseline Contracture of Non-Primary Joint After the Last Injection
Percent change in degree of contracture of non-primary joint measured as 100 \* (baseline contracture - last available post-injection contracture)/baseline contracture
Time frame: Baseline, Day 30 after last injection
Population: 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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AA4500 0.58 mg | Percent Reduction From Baseline Contracture of Non-Primary Joint After the Last Injection | 66.4 Percentage of change | Standard Deviation 34.63 |
Secondary
Percent Reduction From Baseline Contracture of Primary Joint After the First 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
Time frame: Baseline, Day 30 after first injection
Population: Subjects who were randomized and received at least 1 injection
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AA4500 0.58 mg | Percent Reduction From Baseline Contracture of Primary Joint After the First Injection | 58.5 Percentage of change | Standard Deviation 31.74 |
| Placebo | Percent Reduction From Baseline Contracture of Primary Joint After the First Injection | 6.0 Percentage of change | Standard Deviation 20.79 |
p-value: <0.001ANOVA
Secondary
Percent Reduction From Baseline Contracture of Primary Joint After the Last Injection
Percent change in degree of contracture of primary joint measured as 100 \* (baseline contracture - last available post-injection contracture)/baseline contracture
Time frame: Baseline, Day 30 after last injection
Population: Subjects who were randomized and received at least 1 injection
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AA4500 0.58 mg | Percent Reduction From Baseline Contracture of Primary Joint After the Last Injection | 70.5 Percentage of change | Standard Deviation 29.21 |
| Placebo | Percent Reduction From Baseline Contracture of Primary Joint After the Last Injection | 13.6 Percentage of change | Standard Deviation 26.1 |
p-value: <0.001ANOVA
Secondary
Reduction in Non-primary Joint Contracture to 5° or Less After the Last Injection
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.
Time frame: Within 30 days after last injection
Population: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AA4500 0.58 mg | Reduction in Non-primary Joint Contracture to 5° or Less After the Last Injection | 53.9 Percentage of Joints |
Secondary
Time to Reach Clinical Success in Non-Primary Joint
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
Time frame: Within 30 days after last injection
Population: 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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AA4500 0.58 mg | Time to Reach Clinical Success in Non-Primary Joint | Injection 1, Day 1 | 6.7 Percentage of Joints |
| AA4500 0.58 mg | Time to Reach Clinical Success in Non-Primary Joint | Injection 1, Day 7 | 18.0 Percentage of Joints |
| AA4500 0.58 mg | Time to Reach Clinical Success in Non-Primary Joint | Injection 1, Day 30 | 11.2 Percentage of Joints |
| AA4500 0.58 mg | Time to Reach Clinical Success in Non-Primary Joint | Injection 2, Day 0 | 0.0 Percentage of Joints |
| AA4500 0.58 mg | Time to Reach Clinical Success in Non-Primary Joint | Injection 2, Day 1 | 9.0 Percentage of Joints |
| AA4500 0.58 mg | Time to Reach Clinical Success in Non-Primary Joint | Injection 2, Day 7 | 2.2 Percentage of Joints |
| AA4500 0.58 mg | Time to Reach Clinical Success in Non-Primary Joint | Injection 2, Day 30 | 4.5 Percentage of Joints |
| AA4500 0.58 mg | Time to Reach Clinical Success in Non-Primary Joint | Injection 3, Day 0 | 0.0 Percentage of Joints |
| AA4500 0.58 mg | Time to Reach Clinical Success in Non-Primary Joint | Injection 3, Day 1 | 0.0 Percentage of Joints |
| AA4500 0.58 mg | Time to Reach Clinical Success in Non-Primary Joint | Injection 3, Day 7 | 0.0 Percentage of Joints |
| AA4500 0.58 mg | Time to Reach Clinical Success in Non-Primary Joint | Injection 3, Day 30 | 2.2 Percentage of Joints |
| AA4500 0.58 mg | Time to Reach Clinical Success in Non-Primary Joint | Did not reach Clinical Success | 46.1 Percentage of Joints |
Secondary
Time to Reach Clinical Success in Primary Joint
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
Time frame: Within 30 days after last injection
Population: Subjects who were randomized and received at least 1 injection
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AA4500 0.58 mg | Time to Reach Clinical Success in Primary Joint | Injection 3, Day 1 | 4.4 Percentage of Joints |
| AA4500 0.58 mg | Time to Reach Clinical Success in Primary Joint | Did not reach Clinical Success | 55.6 Percentage of Joints |
| AA4500 0.58 mg | Time to Reach Clinical Success in Primary Joint | Injection 2, Day 30 | 8.9 Percentage of Joints |
| AA4500 0.58 mg | Time to Reach Clinical Success in Primary Joint | Injection 1, Day 1 | 2.2 Percentage of Joints |
| AA4500 0.58 mg | Time to Reach Clinical Success in Primary Joint | Injection 3, Day 7 | 0.0 Percentage of Joints |
| AA4500 0.58 mg | Time to Reach Clinical Success in Primary Joint | Injection 1, Day 7 | 6.7 Percentage of Joints |
| AA4500 0.58 mg | Time to Reach Clinical Success in Primary Joint | Injection 2, Day 7 | 4.4 Percentage of Joints |
| AA4500 0.58 mg | Time to Reach Clinical Success in Primary Joint | Injection 1, Day 30 | 17.8 Percentage of Joints |
| AA4500 0.58 mg | Time to Reach Clinical Success in Primary Joint | Injection 3, Day 30 | 0.0 Percentage of Joints |
| AA4500 0.58 mg | Time to Reach Clinical Success in Primary Joint | Injection 2, Day 1 | 0.0 Percentage of Joints |
| Placebo | Time to Reach Clinical Success in Primary Joint | Injection 3, Day 30 | 0.0 Percentage of Joints |
| Placebo | Time to Reach Clinical Success in Primary Joint | Injection 2, Day 7 | 0.0 Percentage of Joints |
| Placebo | Time to Reach Clinical Success in Primary Joint | Injection 2, Day 30 | 0.0 Percentage of Joints |
| Placebo | Time to Reach Clinical Success in Primary Joint | Injection 3, Day 1 | 0.0 Percentage of Joints |
| Placebo | Time to Reach Clinical Success in Primary Joint | Injection 3, Day 7 | 0.0 Percentage of Joints |
| Placebo | Time to Reach Clinical Success in Primary Joint | Injection 2, Day 1 | 0.0 Percentage of Joints |
| Placebo | Time to Reach Clinical Success in Primary Joint | Did not reach Clinical Success | 95.2 Percentage of Joints |
| Placebo | Time to Reach Clinical Success in Primary Joint | Injection 1, Day 1 | 0.0 Percentage of Joints |
| Placebo | Time to Reach Clinical Success in Primary Joint | Injection 1, Day 7 | 4.8 Percentage of Joints |
| Placebo | Time to Reach Clinical Success in Primary Joint | Injection 1, Day 30 | 0.0 Percentage of Joints |