Dupuytren's Contracture
Conditions
Keywords
AK160, collagenase clostridium histolyticum
Brief summary
To investigate the efficacy and safety of AK160 in patients with Dupuytren's Contracture. To determine plasma concentration after the first injection of AK160 in patients with Dupuytren's Contracture.
Interventions
DRUGCollagenase Clostridium Histolyticum
AK160 (Collagenase Clostridium Histolyticum) 0.58 mg
Sponsors
Asahi Kasei Pharma Corporation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* At least 20 years old when written informed consent is obtained. * Having a diagnosis of Dupuytren's contracture and flexion contracture due to palpable cord in at least 1 non-thumb finger (20° to 100° in MP joint and 20° to 80° in PIP joint). * Positive tabletop test result (i.e., cannot simultaneously place affected finger and palm on a table). * Voluntary written informed consent is obtained.
Exclusion criteria
Patients meeting any of the following criteria will be excluded: * Is pregnant, may be pregnant, wishes to become or could become pregnant during the study (i.e., unless acceptable contraception is used, the patient has been sterilized, or the patient is postmenopausal \[no menstrual period for at least 12 months without any other medical cause\]), or is breastfeeding. * Has a coexisting chronic disease of the hand that could impact assessment (muscular disease, neurological disease, neuromuscular disease). * Has received another investigational product 30 or fewer days before first injection of the investigational product. * Has undergone aponeurectomy, aponeurotomy, needle aponeurotomy/fasciotomy, verapamil/interferon injection, or another Dupuytren's Contracture treatment of the primary joint 90 or fewer days before first injection of the investigational product. * Is allergic to collagenase or any of the excipients of AK160. * Has taken tetracycline derivative such as minocycline and doxycycline 14 or fewer days before first injection of the investigational product. * Has received a collagenase product 30 or fewer days before first injection of the investigational product. * Is currently taking or has taken, 7 or fewer days before first injection of the investigational product, an anticoagulant or antiplatelet drug (other than ≤150 mg/day of aspirin). * Has suffered a recent stroke, hemorrhage, or other disease affecting the hands. * Has a serious disease unsuited for the study. * Receiving treatment for a malignancy. * History of drug or alcohol addiction within the past 5 years or history of drug or alcohol abuse within the past year. * Has received previously the investigational product (AK160, AA4500, XIAFLEX®, or XIAPEX®). * Otherwise found ineligible as a subject by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Participants That Were Successfully Treated With a Successful Reduction in Contracture to 5°or Less | 30 days after the last injection | The Primary Outcome Measure for participants who were enrolled at Step1 through Step2 and treated with AK160 is the percentage of 77 participants that were successfully treated where successfully treated was defined as reduction in the contracture of the first treated joint to 5° or less. The injection was allowed up to 3 times. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Improvement After the Last Injection | 30 days after the last injection | The Secondary Outcome Measure for participants who were enrolled at Step1 through Step2 and treated with AK160 is the percentage of 77 participants that were clinically improved where clinically improved was defined as reduction in the contracture of the first treated joint by 50% or more from the baseline. The injection was allowed up to 3 times. |
| Percent Reduction From Baseline Contracture After the Last Injection | 30 days after last treatment | The Secondary Outcome Measure for participants who were enrolled at Step1 through Step2 and treated with AK160 is the mean percent decrease from baseline degree of contracture in primary joints after the last injection. The injection was allowed up to 3 times. |
| Change From Baseline Range of Motion After the Last Injection | 30 days after last treatment | The Secondary Outcome Measure for participants who were enrolled at Step1 through Step2 and treated with AK160 is the change from baseline range of motion in primary joints after the last injection. The injection was allowed up to 3 times. |
| 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 each injections, assessed up to 3 months | The Secondary Outcome Measure for participants who were enrolled at Step1 through Step2 and treated with AK160 is the time to first achieve and maintain clinical success after the last injection where clinical success was defined as reduction in the contracture of the first treated joint to 5° or less. The injection was allowed up to 3 times. |
Countries
Japan
Participant flow
Recruitment details
104 patients were enrolled, and 102 received AK160. This study proceeded stepwise from Step1 through Step3. First, 6 patients were enrolled in Step1 at the selected study centers, thereafter, 71 and 25 patients were enrolled in Steps2 and3 respectively at all centers. The primary endpoint was determined in 77 participants enrolled in Steps1 and 2.
Participants by arm
| Arm | Count |
|---|---|
| AK160 0.58 mg Step 1 This arm consisting of participants enrolled in step 1 was used to confirm the efficacy and satety of the drug 30 days after the first dose before starting step 2.
And also this arm was used to determine the efficacy of the drug with participants enrolled in step 2 and to determine the safety with participants enrolled in steps 2 and 3.
Collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal(PIP) joints. Collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints. | 6 |
| AK160 0.58 mg Step 2 This arm consisting of participants enrolled in step 2 was used to determine the efficacy of the drug with participants enrolled in step 1 and to determine the safety with participants enrolled in steps 1 and 3.
Collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal(PIP) joints. Collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints. | 71 |
| AK160 0.58 mg Step3 The participants in step 3 were added until the number of injected joints by joint type became up to 50 or more in steps1 through 3.
This arm was mainly used to determine the safety of the drug with participants enrolled in steps 1 and 2.
Collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal(PIP) joints. Collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints. | 25 |
| Total | 102 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Step2 | Withdrawal by Subject | 0 | 1 | 0 |
| Step3 | Adverse Event | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | AK160 0.58 mg Step 1 | AK160 0.58 mg Step 2 | AK160 0.58 mg Step3 | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 49 Participants | 23 Participants | 76 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 22 Participants | 2 Participants | 26 Participants |
| Age, Continuous | 69 years STANDARD_DEVIATION 8.3 | 68 years STANDARD_DEVIATION 8.4 | 71 years STANDARD_DEVIATION 5.9 | 68.7 years STANDARD_DEVIATION 8 |
| Region of Enrollment Japan | 6 participants | 71 participants | 25 participants | 102 participants |
| Sex: Female, Male Female | 1 Participants | 6 Participants | 3 Participants | 10 Participants |
| Sex: Female, Male Male | 5 Participants | 65 Participants | 22 Participants | 92 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 100 / 102 |
| serious Total, serious adverse events | 14 / 102 |
Outcome results
Primary
The Percentage of Participants That Were Successfully Treated With a Successful Reduction in Contracture to 5°or Less
The Primary Outcome Measure for participants who were enrolled at Step1 through Step2 and treated with AK160 is the percentage of 77 participants that were successfully treated where successfully treated was defined as reduction in the contracture of the first treated joint to 5° or less. The injection was allowed up to 3 times.
Time frame: 30 days after the last injection
Population: The primary efficacy analysis population was the full analysis set (FAS) comprising subjects treated with study drug in Steps 1 and 2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AK160 0.58 mg Step 1-2 | The Percentage of Participants That Were Successfully Treated With a Successful Reduction in Contracture to 5°or Less | 86 % Participants |
Secondary
Change From Baseline Range of Motion After the Last Injection
The Secondary Outcome Measure for participants who were enrolled at Step1 through Step2 and treated with AK160 is the change from baseline range of motion in primary joints after the last injection. The injection was allowed up to 3 times.
Time frame: 30 days after last treatment
Population: The secondary efficacy analysis population was the full analysis set (FAS) comprising subjects treated with study drug in Steps 1 and 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AK160 0.58 mg Step 1-2 | Change From Baseline Range of Motion After the Last Injection | 41.6 Degrees | Standard Deviation 18.91 |
| Primary PIP Joints | Change From Baseline Range of Motion After the Last Injection | 33.3 Degrees | Standard Deviation 17.73 |
| Total | Change From Baseline Range of Motion After the Last Injection | 38.4 Degrees | Standard Deviation 18.79 |
Secondary
Clinical Improvement After the Last Injection
The Secondary Outcome Measure for participants who were enrolled at Step1 through Step2 and treated with AK160 is the percentage of 77 participants that were clinically improved where clinically improved was defined as reduction in the contracture of the first treated joint by 50% or more from the baseline. The injection was allowed up to 3 times.
Time frame: 30 days after the last injection
Population: The secondary efficacy analysis population was the full analysis set (FAS) comprising subjects treated with study drug in Steps 1 and 2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AK160 0.58 mg Step 1-2 | Clinical Improvement After the Last Injection | 100 % Participants |
| Primary PIP Joints | Clinical Improvement After the Last Injection | 90.0 % Participants |
| Total | Clinical Improvement After the Last Injection | 96.1 % Participants |
Secondary
Percent Reduction From Baseline Contracture After the Last Injection
The Secondary Outcome Measure for participants who were enrolled at Step1 through Step2 and treated with AK160 is the mean percent decrease from baseline degree of contracture in primary joints after the last injection. The injection was allowed up to 3 times.
Time frame: 30 days after last treatment
Population: The secondary efficacy analysis population was the full analysis set (FAS) comprising subjects treated with study drug in Steps 1 and 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AK160 0.58 mg Step 1-2 | Percent Reduction From Baseline Contracture After the Last Injection | 97.08 % of change from baseline | Standard Deviation 7.791 |
| Primary PIP Joints | Percent Reduction From Baseline Contracture After the Last Injection | 82.48 % of change from baseline | Standard Deviation 24.674 |
| Total | Percent Reduction From Baseline Contracture After the Last Injection | 91.39 % of change from baseline | Standard Deviation 17.9 |
Secondary
Time to First Achieve and Maintain Clinical Success After the Last Injection
The Secondary Outcome Measure for participants who were enrolled at Step1 through Step2 and treated with AK160 is the time to first achieve and maintain clinical success after the last injection where clinical success was defined as reduction in the contracture of the first treated joint to 5° or less. The injection was allowed up to 3 times.
Time frame: First evaluation visit on which clinical success is achieved and maintained through the Day 30 evaluation of each injections, assessed up to 3 months
Population: The secondary efficacy analysis population was the full analysis set (FAS) comprising subjects treated with study drug in Steps 1 and 2.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AK160 0.58 mg Step 1-2 | Time to First Achieve and Maintain Clinical Success After the Last Injection | 1.0 Days |
| Primary PIP Joints | Time to First Achieve and Maintain Clinical Success After the Last Injection | 7.0 Days |
| Total | Time to First Achieve and Maintain Clinical Success After the Last Injection | 1.0 Days |