Dupuytren's Contracture
Conditions
Keywords
Assessment of AUX I and/or AUX II in human plasma
Brief summary
A Phase 1, open-label, single-dose pharmacokinetic study in subjects with Dupuytren's contracture conducted at one site in the United States. All subjects received a single dose of AA4500 0.58 mg, which was injected directly into the cord affecting either the metacarpophalangeal (MP) or proximal interphalangeal (PIP) joint. Pharmacokinetic blood samples were collected before dosing, at predetermined time points through the 24 hours after dosing, Day 7, and Day 30. Efficacy and safety assessments were performed up to 30 days after the AA4500 0.58 injection. 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
Single dose of AA4500 0.58 mg into the cord
Sponsors
Endo Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects with a diagnosis of Dupuytren's contracture, 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.
Exclusion criteria
* Had a chronic muscular, neurological, or neuromuscular disorder that affected the hands. * Had received treatment for Dupuytren's contracture within 90 days of the AA4500 injection to the MP or PIP selected, 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 |
|---|---|---|
| Number of Subjects With AUX I and AUX II Detected in Their Blood After a Single Dose of AA4500 | Before dosing, at predetermined time points through the 24 hours after dosing, Day 7, and Day 30 | AUX I and AUX II are the constituent protein collagenases of collagenase clostridium histolyticum (AA4500). Plasma concentrations of AUX I and AUX II were assessed through an enzymye-linked-immunoabsorbent assay (ELISA). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Success | 30 days after treatment to the primary joint | Clinical success defined as a reduction in contracture (ie, flexion deformity) to ≤5° of normal as measured by finger goniometry 30 days after an injection. Last observation carried forward (LOCF) after the injection was used if the status at day 30 could not be determined. |
| Clinical Improvement | 30 days after treatment to the primary joint | Clinical improvement defined as ≥50% reduction from baseline in contracture within 30 days of the injection. LOCF after the injection was used if the status at day 30 could not be determined. |
| Percent Change From Baseline Contracture | Baseline, 30 days after treatment to the primary joint | Change from baseline in the degree of fixed-flexion contracture calculated as 100 times (baseline contracture minus last available post-injection contracture measurement) divided by baseline contracture where a positive change indicates a reduction in the degree of contracture. |
| Change From Baseline Range of Motion | Baseline, 30 days after treatment to the primary joint | Range of motion defined as the difference between the finger extension angle and finger flexion angle expressed in degrees |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AA4500 0.58 mg collagenase clostridium histolyticum 0.58mg injected into either the metacarpophalangeal (MP) or proximal interphalangeal (PIP) joint | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | AA4500 0.58 mg |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age, Continuous | 60.6 years STANDARD_DEVIATION 11.74 |
| Race/Ethnicity, Customized Black or African American | 1 participants |
| Race/Ethnicity, Customized Other | 1 participants |
| Race/Ethnicity, Customized White | 14 participants |
| Region of Enrollment United States | 16 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 16 / 16 |
| serious Total, serious adverse events | 1 / 16 |
Outcome results
Primary
Number of Subjects With AUX I and AUX II Detected in Their Blood After a Single Dose of AA4500
AUX I and AUX II are the constituent protein collagenases of collagenase clostridium histolyticum (AA4500). Plasma concentrations of AUX I and AUX II were assessed through an enzymye-linked-immunoabsorbent assay (ELISA).
Time frame: Before dosing, at predetermined time points through the 24 hours after dosing, Day 7, and Day 30
Population: Pharmacokinetic population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AA4500 0.58 mg | Number of Subjects With AUX I and AUX II Detected in Their Blood After a Single Dose of AA4500 | 0 participants |
Secondary
Change From Baseline Range of Motion
Range of motion defined as the difference between the finger extension angle and finger flexion angle expressed in degrees
Time frame: Baseline, 30 days after treatment to the primary joint
Population: Efficacy assessment based on safety population which included all enrolled subjects who received the AA4500 injection.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AA4500 0.58 mg | Change From Baseline Range of Motion | 39.1 Degrees | Standard Deviation 15.38 |
Secondary
Clinical Improvement
Clinical improvement defined as ≥50% reduction from baseline in contracture within 30 days of the injection. LOCF after the injection was used if the status at day 30 could not be determined.
Time frame: 30 days after treatment to the primary joint
Population: Efficacy assessment based on safety population which included all enrolled subjects who received the AA4500 injection.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AA4500 0.58 mg | Clinical Improvement | 100.0 Percentage of joints |
Secondary
Clinical Success
Clinical success defined as a reduction in contracture (ie, flexion deformity) to ≤5° of normal as measured by finger goniometry 30 days after an injection. Last observation carried forward (LOCF) after the injection was used if the status at day 30 could not be determined.
Time frame: 30 days after treatment to the primary joint
Population: Efficacy assessment based on safety population which included all enrolled subjects who received the AA4500 injection
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AA4500 0.58 mg | Clinical Success | 75.0 Percentage of joints |
Secondary
Percent Change From Baseline Contracture
Change from baseline in the degree of fixed-flexion contracture calculated as 100 times (baseline contracture minus last available post-injection contracture measurement) divided by baseline contracture where a positive change indicates a reduction in the degree of contracture.
Time frame: Baseline, 30 days after treatment to the primary joint
Population: Efficacy assessment based on safety population which included all enrolled subjects who received the AA4500 injection.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AA4500 0.58 mg | Percent Change From Baseline Contracture | 91.6 Percentage of contracture change | Standard Deviation 16.57 |