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Safety and Efficacy of Two Concurrent Injections of AA4500 in Adult Subjects With Multiple Dupuytren's Contractures

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ClinicalTrials.gov Identifier: NCT01674634
Recruitment Status : Completed
First Posted : August 29, 2012
Results First Posted : February 20, 2015
Last Update Posted : October 5, 2017
Sponsor:
Information provided by (Responsible Party):
Endo Pharmaceuticals

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Dupuytren's Contracture
Intervention Biological: XIAFLEX / XIAPEX
Enrollment 715
Recruitment Details  
Pre-assignment Details  
Arm/Group Title XIAFLEX/XIAPEX
Hide Arm/Group Description AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand
Period Title: Overall Study
Started 715
Completed 709
Not Completed 6
Reason Not Completed
Withdrawal by Subject             3
Lost to Follow-up             3
Arm/Group Title XIAFLEX/XIAPEX
Hide Arm/Group Description AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand
Overall Number of Baseline Participants 715
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 715 participants
<=18 years
0
   0.0%
Between 18 and 65 years
348
  48.7%
>=65 years
367
  51.3%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 715 participants
64.0  (9.26)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 715 participants
Female
99
  13.8%
Male
616
  86.2%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 715 participants
United States 278
Australia 196
New Zealand 70
Denmark 87
Sweden 50
United Kingdom 34
1.Primary Outcome
Title Percent Change From Baseline in Total Fixed Flexion
Hide Description Percent change from baseline in total fixed flexion = 100 * (baseline total FFC - day 31 total FFC)/baseline total FFC, where total fixed flexion is defined as the sum of the fixed flexion contracture (FCC) of the 2 joints receiving treatment. Positive percent change from baseline indicates improvement.
Time Frame Baseline, Day 31
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy analysis was based on the modified intent-to-treat (mITT) population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on contralateral hand. Assessment is based on simultaneously treated joint pairs.
Arm/Group Title XIAFLEX/XIAPEX
Hide Arm/Group Description:
AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand
Overall Number of Participants Analyzed 714
Overall Number of Units Analyzed
Type of Units Analyzed: Treated Joint Pairs
724
Mean (Standard Deviation)
Unit of Measure: percentage of contracture change
74.41  (24.83)
2.Primary Outcome
Title Change From Baseline in Total Range of Motion
Hide Description The total range of motion (ROM) is the sum of the range of motion measurements of the 2 treated joints. ROM is defined as difference between full flexion angle and full extension expressed in degrees. A positive change from baseline indicates increased (improved) ROM.
Time Frame Baseline, Day 31
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. Assessment is based on simultaneously treated joint pairs.
Arm/Group Title XIAFLEX/XIAPEX
Hide Arm/Group Description:
AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand
Overall Number of Participants Analyzed 714
Overall Number of Units Analyzed
Type of Units Analyzed: Treated joint pairs
724
Mean (95% Confidence Interval)
Unit of Measure: degrees
66.6
(64.3 to 68.9)
3.Secondary Outcome
Title Clinical Success
Hide Description Clinical success is defined as reduction of FFC of a treated joint to within 0-5 degrees of normal within 30 days of injection
Time Frame Within 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. This assessment is based on individual treated joints by joint type.
Arm/Group Title XIAFLEX/XIAPEX MP Joint XIAFLEX/XIAPEX PIP Joint
Hide Arm/Group Description:
AA4500 (collagenase clostridium histolyticum); 0.58 mg injection in the metacarpophalangeal (MP) joint cord
AA4500 (collagenase clostridium histolyticum); 0.58 mg injection in the proximal interphalangeal (PIP) joint cord
Overall Number of Participants Analyzed 714 714
Overall Number of Units Analyzed
Type of Units Analyzed: Treated Joints
896 552
Measure Type: Number
Unit of Measure: Joints
No 317 394
Yes 579 158
4.Secondary Outcome
Title Clinical Improvement
Hide Description Clinical improvement is defined as a reduction of FFC by 50% or greater of the baseline value within 30 days of injection
Time Frame Within 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. This assessment is based on individual treated joints by joint type.
Arm/Group Title XIAFLEX/XIAPEX MP Joint XIAFLEX/XIAPEX PIP Joint
Hide Arm/Group Description:
AA4500 (collagenase clostridium histolyticum); 0.58 mg injection in the MP joint cord
AA4500 (collagenase clostridium histolyticum); 0.58 mg injection in the PIP joint cord
Overall Number of Participants Analyzed 714 714
Overall Number of Units Analyzed
Type of Units Analyzed: Treated Joints
896 552
Measure Type: Number
Unit of Measure: Joints
No 96 157
Yes 800 395
5.Secondary Outcome
Title Subject Assessment of Satisfaction With Treatment at Day 31
Hide Description Subject's were asked to rate satisfaction with treatment at the day 31 follow-up visit
Time Frame Day 31
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. Assessment is based on simultaneously treated joint pairs.
Arm/Group Title XIAFLEX/XIAPEX
Hide Arm/Group Description:
AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand
Overall Number of Participants Analyzed 714
Overall Number of Units Analyzed
Type of Units Analyzed: Treated Joint Pairs
724
Measure Type: Number
Unit of Measure: Joint Pairs
Very satisfied 461
Quite satisfied 198
Neither satisfied nor dissatisfied 38
Quite dissatisfied 9
Very dissatisfied 6
Not done 12
6.Secondary Outcome
Title Subject Assessment of Satisfaction With Treatment at Day 61
Hide Description Subject's were asked to rate satisfaction with treatment at the day 61 follow-up visit
Time Frame Day 61
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. Assessment is based on simultaneously treated joint pairs.
Arm/Group Title XIAFLEX/XIAPEX
Hide Arm/Group Description:
AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand
Overall Number of Participants Analyzed 714
Overall Number of Units Analyzed
Type of Units Analyzed: Treated Joint Pairs
724
Measure Type: Number
Unit of Measure: Joint Pairs
Very satisfied 496
Quite satisfied 167
Neither satisfied nor dissatisfied 38
Quite dissatisfied 11
Very dissatisfied 8
Not done 4
7.Secondary Outcome
Title Investigator Assessment of Improvement With Treatment at Day 31
Hide Description Investigator's determined the degree of improvement in the severity of the subject’s treated finger(s) compared with screening at the day 31 follow-up visit.
Time Frame Day 31
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. Assessment is based on simultaneously treated joint pairs.
Arm/Group Title XIAFLEX/XIAPEX
Hide Arm/Group Description:
AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand
Overall Number of Participants Analyzed 714
Overall Number of Units Analyzed
Type of Units Analyzed: Treated Joint Pairs
724
Measure Type: Number
Unit of Measure: Joint Pairs
Very much improved 375
Much improved 271
Minimally improved 51
No change 4
Minimally worse 3
Much worse 0
Very much worse 0
Not done 20
8.Secondary Outcome
Title Investigator Assessment of Improvement With Treatment at Day 61
Hide Description Investigator's determined the degree of improvement in the severity of the subject’s treated finger(s) compared with screening at the day 61 follow-up visit.
Time Frame Day 61
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. Assessment is based on simultaneously treated joint pairs.
Arm/Group Title XIAFLEX/XIAPEX
Hide Arm/Group Description:
AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand
Overall Number of Participants Analyzed 714
Overall Number of Units Analyzed
Type of Units Analyzed: Treated Joint Pairs
724
Measure Type: Number
Unit of Measure: Joint Pairs
Very much improved 382
Much improved 263
Minimally improved 62
No change 7
Minimally worse 2
Much worse 0
Very much worse 0
Not done 8
9.Secondary Outcome
Title Change From Baseline for Unité Rhumatologique Des Affections de la Main Scale at Day 31
Hide Description The Unité Rhumatologique des Affections de la Main (URAM) scale is a patient-reported functional 9-item scale (total score 0-45) developed and validated to assess functional outcome of patients suffering from Dupuytren's disease with higher scores indicating greater difficulty using the hand.The estimated clinically important change of the URAM scale is 2.9 points. A decrease in total URAM score indicates improvement in hand function.
Time Frame Baseline, Day 31
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. Assessment is based on simultaneously treated joint pairs.
Arm/Group Title XIAFLEX/XIAPEX
Hide Arm/Group Description:
AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand
Overall Number of Participants Analyzed 714
Overall Number of Units Analyzed
Type of Units Analyzed: Treated Joint Pairs
724
Mean (Standard Deviation)
Unit of Measure: units on a scale
-11.3  (9.19)
10.Secondary Outcome
Title Change From Baseline for Unité Rhumatologique Des Affections de la Main Scale at Day 61
Hide Description The URAM scale is a patient-reported functional 9-item scale (total score 0-45) developed and validated to assess functional outcome of patients suffering from Dupuytren's disease with higher scores indicating greater difficulty using the hand.The estimated clinically important change of the URAM scale is 2.9 points. A decrease in total URAM score indicates improvement in hand function.
Time Frame Baseline, Day 61
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. Assessment is based on simultaneously treated joint pairs.
Arm/Group Title XIAFLEX/XIAPEX
Hide Arm/Group Description:
AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand
Overall Number of Participants Analyzed 714
Overall Number of Units Analyzed
Type of Units Analyzed: Treated Joint Pairs
724
Mean (Standard Deviation)
Unit of Measure: units on a scale
-12.3  (9.75)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title XIAFLEX/XIAPEX
Hide Arm/Group Description AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand
All-Cause Mortality
XIAFLEX/XIAPEX
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
XIAFLEX/XIAPEX
Affected / at Risk (%) # Events
Total   15/715 (2.10%)    
Blood and lymphatic system disorders   
Lymphadenopathy * 1  1/715 (0.14%)  1
General disorders   
Malaise * 1  1/715 (0.14%)  1
oedema peripheral * 1  1/715 (0.14%)  1
Immune system disorders   
Anaphylactic reaction * 1  1/715 (0.14%)  1
Infections and infestations   
Lymphangitis * 1  1/715 (0.14%)  1
Bronchitis * 1  1/715 (0.14%)  1
Pneumonia * 1  1/715 (0.14%)  1
Anal abscess * 1  1/715 (0.14%)  1
Cellulitis * 1 [1]  1/715 (0.14%)  1
Injury, poisoning and procedural complications   
Feeding tube complication * 1 [2]  1/715 (0.14%)  1
Post procedural haemorrhage * 1 [3]  1/715 (0.14%)  1
Tendon rupture * 1 [4]  1/715 (0.14%)  1
Metabolism and nutrition disorders   
Hypokalaemia * 1  1/715 (0.14%)  1
Musculoskeletal and connective tissue disorders   
Spinal column stenosis * 1  1/715 (0.14%)  1
Pain in extremity * 1  1/715 (0.14%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Prostate cancer * 1  1/715 (0.14%)  1
Nervous system disorders   
Myelopathy * 1  1/715 (0.14%)  1
Renal and urinary disorders   
Haematuria * 1  1/715 (0.14%)  1
Respiratory, thoracic and mediastinal disorders   
Emphysema * 1  1/715 (0.14%)  1
Pulmonary embolism * 1  2/715 (0.28%)  2
Vascular disorders   
Arteriosclerosis * 1  1/715 (0.14%)  1
Deep vein thrombosis * 1  1/715 (0.14%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (15.1)
[1]
Left lower leg
[2]
PEG feeding tube obstruction
[3]
Bleeding left hand post procedure
[4]
Upgraded to an SAE by the sponsor
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
XIAFLEX/XIAPEX
Affected / at Risk (%) # Events
Total   680/715 (95.10%)    
Blood and lymphatic system disorders   
Lymphadenopathy * 1  92/715 (12.87%)  102
General disorders   
Oedema peripheral * 1  552/715 (77.20%)  626
Injection site pain * 1  102/715 (14.27%)  109
Injection site haematoma * 1  60/715 (8.39%)  61
Axillary pain * 1  51/715 (7.13%)  53
injection site haemorrhage * 1 [1]  45/715 (6.29%)  45
Injection site swelling * 1  42/715 (5.87%)  42
Injury, poisoning and procedural complications   
Contusion * 1  420/715 (58.74%)  513
Laceration * 1  184/715 (25.73%)  192
Musculoskeletal and connective tissue disorders   
Pain in extremity * 1  361/715 (50.49%)  431
Skin and subcutaneous tissue disorders   
Pruritus * 1  107/715 (14.97%)  121
Blood blister * 1  89/715 (12.45%)  98
Ecchymosis * 1  37/715 (5.17%)  39
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (15.1)
[1]
injection site ecchymosis
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.
 
Results Point of Contact
Name/Title: Clinical Trial Coordinator
Organization: Endo Pharmaceuticals, Inc.
Responsible Party: Endo Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01674634     History of Changes
Other Study ID Numbers: AUX-CC-867
First Submitted: August 27, 2012
First Posted: August 29, 2012
Results First Submitted: February 4, 2015
Results First Posted: February 20, 2015
Last Update Posted: October 5, 2017