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Collagenase Option for Reduction of Dupuytren's Contracture in Japan (CORD-J)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01588353
Recruitment Status : Completed
First Posted : April 30, 2012
Results First Posted : February 14, 2017
Last Update Posted : March 21, 2017
Sponsor:
Information provided by (Responsible Party):
Asahi Kasei Pharma Corporation

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Dupuytren's Contracture
Intervention Drug: Collagenase Clostridium Histolyticum
Enrollment 104
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.
Pre-assignment Details  
Arm/Group Title AK160 0.58 mg Step1 AK160 0.58 mg Step 2 AK160 0.58 mg Step3
Hide Arm/Group Description

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.

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.

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.

Period Title: Step1
Started 6 0 0
Completed 6 0 0
Not Completed 0 0 0
Period Title: Step2
Started 0 71 0
Completed 0 70 0
Not Completed 0 1 0
Reason Not Completed
Withdrawal by Subject             0             1             0
Period Title: Step3
Started 0 0 25
Completed 0 0 23
Not Completed 0 0 2
Reason Not Completed
Adverse Event             0             0             2
Arm/Group Title AK160 0.58 mg Step 1 AK160 0.58 mg Step 2 AK160 0.58 mg Step3 Total
Hide Arm/Group Description

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.

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.

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.

Total of all reporting groups
Overall Number of Baseline Participants 6 71 25 102
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 71 participants 25 participants 102 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
2
  33.3%
22
  31.0%
2
   8.0%
26
  25.5%
>=65 years
4
  66.7%
49
  69.0%
23
  92.0%
76
  74.5%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 6 participants 71 participants 25 participants 102 participants
69  (8.3) 68  (8.4) 71  (5.9) 68.7  (8.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 71 participants 25 participants 102 participants
Female
1
  16.7%
6
   8.5%
3
  12.0%
10
   9.8%
Male
5
  83.3%
65
  91.5%
22
  88.0%
92
  90.2%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Japan Number Analyzed 6 participants 71 participants 25 participants 102 participants
6 71 25 102
1.Primary Outcome
Title The Percentage of Participants That Were Successfully Treated With a "Successful Reduction in Contracture to 5°or Less"
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The primary efficacy analysis population was the full analysis set (FAS) comprising subjects treated with study drug in Steps 1 and 2.
Arm/Group Title AK160 0.58 mg Step 1-2
Hide Arm/Group Description:
collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
Overall Number of Participants Analyzed 77
Measure Type: Number
Unit of Measure: % Participants
86
2.Secondary Outcome
Title Clinical Improvement After the Last Injection
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The secondary efficacy analysis population was the full analysis set (FAS) comprising subjects treated with study drug in Steps 1 and 2.
Arm/Group Title Primary MP Joints Primary PIP Joints Total
Hide Arm/Group Description:
collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) joints
collagenase clostridium histolyticum 0.58mg injected into proximal interphalangeal (PIP) joints
collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) or proximal interphalangeal (PIP) joints
Overall Number of Participants Analyzed 47 30 77
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: % Participants
100
(92.5 to 100.0)
90.0
(73.5 to 97.9)
96.1
(89.0 to 99.2)
3.Secondary Outcome
Title Percent Reduction From Baseline Contracture After the Last Injection
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The secondary efficacy analysis population was the full analysis set (FAS) comprising subjects treated with study drug in Steps 1 and 2.
Arm/Group Title Primary MP Joints Primary PIP Joints Total
Hide Arm/Group Description:
collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) joints
collagenase clostridium histolyticum 0.58mg injected into proximal interphalangeal (PIP) joints
collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) or proximal interphalangeal (PIP) joints
Overall Number of Participants Analyzed 47 30 77
Mean (Standard Deviation)
Unit of Measure: % of change from baseline
97.08  (7.791) 82.48  (24.674) 91.39  (17.900)
4.Secondary Outcome
Title Change From Baseline Range of Motion After the Last Injection
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The secondary efficacy analysis population was the full analysis set (FAS) comprising subjects treated with study drug in Steps 1 and 2.
Arm/Group Title Primary MP Joints Primary PIP Joints Total
Hide Arm/Group Description:
collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) joints
collagenase clostridium histolyticum 0.58mg injected into proximal interphalangeal (PIP) joints
collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) or proximal interphalangeal (PIP) joints
Overall Number of Participants Analyzed 47 30 77
Mean (Standard Deviation)
Unit of Measure: Degrees
41.6  (18.91) 33.3  (17.73) 38.4  (18.79)
5.Secondary Outcome
Title Time to First Achieve and Maintain Clinical Success After the Last Injection
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The secondary efficacy analysis population was the full analysis set (FAS) comprising subjects treated with study drug in Steps 1 and 2.
Arm/Group Title Primary MP Joints Primary PIP Joints Total
Hide Arm/Group Description:
collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) joints
collagenase clostridium histolyticum 0.58mg injected into proximal interphalangeal (PIP) joints
collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) or proximal interphalangeal (PIP) joints
Overall Number of Participants Analyzed 47 30 77
Median (Inter-Quartile Range)
Unit of Measure: Days
1.0
(1.0 to 28.0)
7.0
(1.0 to 92.0)
1.0
(1.0 to 30.0)
Time Frame Adverse events were investigated from the day of the first injection of the study drug until 360 days after the first injection of the study drug.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title AK160 0.58 mg Step 1-3
Hide Arm/Group Description Collagenase Clostridium Histolyticum: AK160 (Collagenase Clostridium Histolyticum) 0.58 mg
All-Cause Mortality
AK160 0.58 mg Step 1-3
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
AK160 0.58 mg Step 1-3
Affected / at Risk (%)
Total   14/102 (13.73%) 
Blood and lymphatic system disorders   
Idiopathic thrombocytopenic purpura 1 [1]  1/102 (0.98%) 
Cardiac disorders   
Myocardial infarction 1 [1]  1/102 (0.98%) 
Eye disorders   
Cataract 1 [1]  3/102 (2.94%) 
Gastrointestinal disorders   
Duodenal ulcer perforation 1 [1]  1/102 (0.98%) 
Intestinal obstruction 1 [1]  1/102 (0.98%) 
Hepatobiliary disorders   
Bile duct stone 1 [1]  1/102 (0.98%) 
Infections and infestations   
Infectious pleural effusion 1 [1]  1/102 (0.98%) 
Musculoskeletal and connective tissue disorders   
Spondylolysis 1 [1]  1/102 (0.98%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Gastric cancer 1 [1]  1/102 (0.98%) 
Colon cancer 1 [1]  1/102 (0.98%) 
Lung neoplasm malignant 1 [1]  1/102 (0.98%) 
Nervous system disorders   
Subarachnoid haemorrhage 1 [1]  1/102 (0.98%) 
Respiratory, thoracic and mediastinal disorders   
Pneumothorax 1 [1]  1/102 (0.98%) 
1
Term from vocabulary, MedDRA (16.1)
[1]
All were determined by investigators to be not related to the study drug.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5.0%
AK160 0.58 mg Step 1-3
Affected / at Risk (%)
Total   100/102 (98.04%) 
Blood and lymphatic system disorders   
Lymphadenitis  6/102 (5.88%) 
General disorders   
Injection site pain  78/102 (76.47%) 
Injection site bruising  46/102 (45.10%) 
Injection site swelling  35/102 (34.31%) 
Injection site laceration  16/102 (15.69%) 
Injection site oedema  12/102 (11.76%) 
Injection site haematoma  11/102 (10.78%) 
Local swelling  9/102 (8.82%) 
Injection site pruritus  6/102 (5.88%) 
Infections and infestations   
Nasopharyngitis  16/102 (15.69%) 
Injury, poisoning and procedural complications   
Contusion  30/102 (29.41%) 
Laceration  9/102 (8.82%) 
Investigations   
Glucose urine present  6/102 (5.88%) 
Skin and subcutaneous tissue disorders   
Haemorrhage subcutaneous  6/102 (5.88%) 
1
Term from vocabulary, MedDRA (16.1)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Asahi Kasei Pharma Corporation agreements may vary with individual facilities but will not prohibit any investigator from publishing. Asahikasei supports the publication of results from all centers of a multicenter trial but requests that reports based on single site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Name/Title: Norihiro Tateishi, Manager
Organization: XIA Project, Pharmaceuticals Sales Division, Asahi Kasei Pharma Corporation
Phone: +81-3-3296-3641
Responsible Party: Asahi Kasei Pharma Corporation
ClinicalTrials.gov Identifier: NCT01588353     History of Changes
Other Study ID Numbers: AK160-III-1
First Submitted: April 27, 2012
First Posted: April 30, 2012
Results First Submitted: July 3, 2016
Results First Posted: February 14, 2017
Last Update Posted: March 21, 2017