Dupuytren's Contracture
Conditions
Brief summary
The objectives of this study are to assess the safety and efficacy of concurrent administration of two injections of AA4500 into the same hand of subjects with multiple Dupuytren's contractures caused by palpable cords.
Detailed description
Methodology/Study Design: This is an open-label, study in men and women with multiple Dupuytren's contractures. Approximately 60 subjects who have at least two Dupuytren's contractures caused by palpable cords in the same hand will be enrolled. After all pre-injection procedures are completed on Day 1, eligible men and women will receive two concurrent injections of AA4500 0.58 mg into the same hand. On Day 2, a finger extension procedure to facilitate cord disruption will be performed in those subjects who do not have spontaneous disruption of their cord(s). Follow-up visits for the evaluation of safety and efficacy will be on Day 8, Day 30, and Day 60. Upon completion of the Day 60 follow-up visit, subjects who require further treatment will have the option to receive three additional open-label treatments according to the XIAFLEX package insert (Appendix C). Subjects may receive up to a total of five injections and individual cords may receive up to a total of three injections.
Interventions
BIOLOGICALAA4500 collagenase clostridium histolyticum
2 concurrent injections (0.58 mg) into 2 cords on the same hand
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
1. Provide written informed consent 2. Be a man or woman ≥ 18 years of age 3. Have a diagnosis of Dupuytren's disease and have at least 2 fixed-flexion contractures on the same hand that are ≥ 20º in PIP and/or MP joints in fingers, other than the thumbs, which are caused by palpable cords suitable for treatment 4. Have a positive table top test defined as the inability to simultaneously place the affected finger(s) and palm flat against a table top 5. Either be using an accepted method of birth control (ie, surgical sterilization; intra uterine contraceptive device; oral contraceptive; diaphragm or condom in combination with contraceptive cream, or jelly or foam) and have negative pregnancy testing before administration of AA4500, if a female of childbearing potential, or be a postmenopausal female (no menses for at least 1 year or hysterectomy) 6. Not have any clinically significant medical history or condition(s) that would, in the opinion of the investigator, substantially increase the risk associated with the subject's participation in the protocol or compromise the scientific objectives of the study 7. Be able to comply with the study visit schedule as specified in the protocol
Exclusion criteria
1. Received surgery (fasciectomy or surgical fasciotomy) and/or needle aponeurotomy/fasciotomy on the selected joints to be treated within 90 days before the first injection of AA4500 2. Has a chronic muscular, neurological, or neuromuscular disorder that affects the hands 3. Has a known systemic allergy to collagenase or any other excipient of AA4500 4. Has received any collagenase treatments (eg, Santyl® ointment and/or XIAFLEX/XIAPEX) within 30 days before injection of AA4500 5. Is currently receiving or plans to receive anticoagulant medication or has received anticoagulant medication (except for ≤ 150 mg aspirin daily and over-the-counter nonsteroidal anti-inflammatory drugs \[NSAIDs\]) within 7 days before injection of AA4500) 6. Has a known recent history of stroke, bleeding, or other medical condition, which in the investigator's opinion would make the subject unsuitable for enrollment in the study 7. Is known to be immunocompromised or human immunodeficiency virus (HIV) positive 8. Has a history of illicit drug abuse or alcoholism within the year before injection of AA4500 9. Received an investigational drug within 30 days before injection of AA4500 10. Is a pregnant or lactating female 11. Has any clinically significant medical history or condition(s), including conditions that affect the hands, that would, in the opinion of the investigator, substantially increase the risk associated with the subject's participation in the protocol or compromise the scientific objectives of the study 12. Has jewelry on the hand to be treated that cannot be removed
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Total Fixed Flexion | 30 days after last injection | Total fixed flexion is defined as the sum of the fixed flexion contractures of the two joints receiving treatment. Change in fixed-flexion contracture is measured in degrees where a decrease of 100% would correspond to a reduction in contracture to 0 degrees |
| Change in Total Range of Motion | 30 days after last injection | The total range of motion is the sum of the range of motion measurements of the two treated joints. Range of motion is defined as difference between full flexion angle and full extension angle expressed in degrees. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Subject Satisfaction With Treatment | 60 days after last injection | At the Day 60 follow-up visit, each subject will be asked to rate his/her satisfaction with treatment as follows: 1. Very Satisfied 2. Quite Satisfied 3. Neither Satisfied nor Dissatisfied 4. Quite Dissatisfied 5. Very Dissatisfied |
| Investigator Assessment of Improvement With Treatment | 60 days after last injection | At the Day 60 follow-up visit, the investigator will determine the degree of improvement in the severity of the subject's treated finger(s) compared with screening as follows: 1. Very Much Improved 2. Much improved 3. Minimally Improved 4. No Change 5. Minimally Worse 6. Much Worse 7. Very Much Worse |
| Clinical Success by Joint Type | 30 days after injection | Clinical success is defined as a reduction in fixed flexion contracture to 5° or less 30 days after injection of AA4500. |
Countries
Australia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AA4500 AA4500 collagenase clostridium histolyticum
AA4500 collagenase clostridium histolyticum: 2 concurrent injections (0.58 mg) into 2 cords on the same hand | 60 |
| Total | 60 |
Baseline characteristics
| Characteristic | AA4500 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 31 Participants |
| Age, Categorical Between 18 and 65 years | 29 Participants |
| Age, Continuous | 63.7 years STANDARD_DEVIATION 10.59 |
| Region of Enrollment Australia | 39 participants |
| Region of Enrollment United States | 21 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 60 / 60 |
| serious Total, serious adverse events | 3 / 60 |
Outcome results
Primary
Change in Total Range of Motion
The total range of motion is the sum of the range of motion measurements of the two treated joints. Range of motion is defined as difference between full flexion angle and full extension angle expressed in degrees.
Time frame: 30 days after last injection
Population: Efficacy analysis is based of the intent-to-treat population (ITT). The population is defined as all enrolled subjects who received two injections of AA4500 and had at least one-post-injection measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AA4500 | Change in Total Range of Motion | 60.4 degrees | Standard Deviation 21.8 |
Primary
Percent Change From Baseline in Total Fixed Flexion
Total fixed flexion is defined as the sum of the fixed flexion contractures of the two joints receiving treatment. Change in fixed-flexion contracture is measured in degrees where a decrease of 100% would correspond to a reduction in contracture to 0 degrees
Time frame: 30 days after last injection
Population: Efficacy analysis is based of the intent-to-treat population (ITT). The population is defined as all enrolled subjects who received two injections of AA4500 and had at least one-post-injection measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AA4500 | Percent Change From Baseline in Total Fixed Flexion | 75.5 percentage of contracture change | Standard Deviation 24.11 |
Secondary
Clinical Success by Joint Type
Clinical success is defined as a reduction in fixed flexion contracture to 5° or less 30 days after injection of AA4500.
Time frame: 30 days after injection
Population: Efficacy analysis is based of the intent-to-treat population (ITT). The population is defined as all enrolled subjects who received two injections of AA4500 and had at least one-post-injection measurement.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AA4500 | Clinical Success by Joint Type | Yes | 57 number of joints |
| AA4500 | Clinical Success by Joint Type | No | 18 number of joints |
| AA4500 PIP | Clinical Success by Joint Type | Yes | 15 number of joints |
| AA4500 PIP | Clinical Success by Joint Type | No | 30 number of joints |
Secondary
Investigator Assessment of Improvement With Treatment
At the Day 60 follow-up visit, the investigator will determine the degree of improvement in the severity of the subject's treated finger(s) compared with screening as follows: 1. Very Much Improved 2. Much improved 3. Minimally Improved 4. No Change 5. Minimally Worse 6. Much Worse 7. Very Much Worse
Time frame: 60 days after last injection
Population: Efficacy analysis is based of the intent-to-treat population (ITT). The population is defined as all enrolled subjects who received two injections of AA4500 and had at least one-post-injection measurement.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AA4500 | Investigator Assessment of Improvement With Treatment | Very much improved | 33 participants |
| AA4500 | Investigator Assessment of Improvement With Treatment | Much improved | 22 participants |
| AA4500 | Investigator Assessment of Improvement With Treatment | Minimally improved | 4 participants |
| AA4500 | Investigator Assessment of Improvement With Treatment | No change | 1 participants |
| AA4500 | Investigator Assessment of Improvement With Treatment | Minimally worse | 0 participants |
| AA4500 | Investigator Assessment of Improvement With Treatment | Much worse | 0 participants |
| AA4500 | Investigator Assessment of Improvement With Treatment | Very much worse | 0 participants |
| AA4500 | Investigator Assessment of Improvement With Treatment | Not done | 0 participants |
Secondary
Subject Satisfaction With Treatment
At the Day 60 follow-up visit, each subject will be asked to rate his/her satisfaction with treatment as follows: 1. Very Satisfied 2. Quite Satisfied 3. Neither Satisfied nor Dissatisfied 4. Quite Dissatisfied 5. Very Dissatisfied
Time frame: 60 days after last injection
Population: Efficacy analysis is based of the intent-to-treat population (ITT). The population is defined as all enrolled subjects who received two injections of AA4500 and had at least one-post-injection measurement.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AA4500 | Subject Satisfaction With Treatment | Very satisfied | 36 participants |
| AA4500 | Subject Satisfaction With Treatment | Quite satisfied | 17 participants |
| AA4500 | Subject Satisfaction With Treatment | Neither satisfied nor dissatisfied | 5 participants |
| AA4500 | Subject Satisfaction With Treatment | Quite dissatisfied | 1 participants |
| AA4500 | Subject Satisfaction With Treatment | Very dissatisfied | 1 participants |
| AA4500 | Subject Satisfaction With Treatment | Not done | 0 participants |