The objectives of this study are to assess the safety and effectiveness of AA4500 in treating palmar Dupuytren's disease nodules.
Approximately 13 sites in the United States and Australia, approximately 90 study subjects. After all pre-injection procedures are completed on day 1, eligible men and women will be randomized in a 1:1:1 ratio to dose group and then in a 4:1 ratio to treatment group. Study drug will be administered into a palmar nodule located on the selected hand. AA4500 (collagenase clostridium histolyticum) 3 doses (low, medium, and high) after reconstitution with sterile diluent (0.3 mg/mL calcium chloride dihydrate in 0.9% sodium chloride). Each dose of study drug will be injected into the nodule. The injection will be administered in 3 different volumes according to randomization. Placebo after reconstitution with sterile diluent (0.3 mg/mL calcium chloride dihydrate in 0.9% sodium chloride). Each dose of study drug will be injected into the nodule. The injection will be administered in 3 different volumes according to randomization. Follow up visits for the evaluation of safety and efficacy will be required for all subjects on days 8, 29, and 57.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
76
Single injection into nodule
Single injection into nodule
Tucson Orthopaedic Institute
Tucson, Arizona, United States
CORE Orthopaedic Medical Center
Encinitas, California, United States
Marin Endocrine Care & Research, Inc.
Greenbrae, California, United States
Percent Change From Baseline in Surface Area and Volume of the Treated Nodule at Day 57 Using Caliper Measurements
Percent change from baseline in surface area and volume of the treated nodule was determined from hand-held caliper measurements of the length and width of the nodule. Percent change = 100\*(Day 57 area \[or volume\] - baseline area \[or volume\])/baseline area \[or volume\]. A negative value represents the improvement from baseline (decreased size) while a positive value represents worsening.
Time frame: Baseline, Day 57
Percent Change From Baseline in Surface Area and Volume of the Treated Nodule at Day 57 Using Ultrasound
Percent change from baseline in surface area and volume of the treated nodule was determined from ultrasound measurements of the length, width, and depth of the nodule. Percent change = 100\*(Day 57 area \[or volume\] - baseline area \[or volume\])/baseline area \[or volume\]. A negative value represents the improvement from baseline (decreased size) while a positive value represents worsening.
Time frame: Baseline, Day 57
Change From Baseline in Consistency of the Treated Nodules at Day 57
Investigators determined the consistency of the nodule through palpitation using a 5-point scale: 5 = hard (solid), 4 = firm throughout, 3 = moderate firmness, 2 = soft, and 1 = non-palpable. The change scores could range from +4 (greatest worsening in consistency) to -4 (greatest improvement in consistency); a negative change from baseline value reflects improvement from baseline (softening) while a positive value reflects worsening.
Time frame: Baseline, Day 57
Percent Change From Baseline in Hardness of the Treated Nodule at Day 57
A durometer was used to assess nodule hardness on a scale of 0 (soft) to 100 (hard). Percent change = 100\*(Day 57 hardness - baseline hardness)/baseline hardness. A negative value represents the improvement from baseline (softening) while a positive value represents worsening.
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Brigid Freyne, MD, Inc.
Murrieta, California, United States
Indiana Hand to Shoulder Center
Indianapolis, Indiana, United States
State University of New York
Stony Brook, New York, United States
OrthoCarolina Research Institute, Inc.
Charlotte, North Carolina, United States
Orthopedic and Reconstructive Center
Oklahoma City, Oklahoma, United States
Blair Orthopedic Associates, Inc.
Altoona, Pennsylvania, United States
Brisbane Hand & Upper Limb Clinic
Brisbane, Queensland, Australia
...and 1 more locations
Time frame: Baseline, Day 57
Change From Baseline in Nodular Pain of the Treated Nodule at Day 57
After the nodule was squeezed using a dynamometer, subjects were asked to rate the amount of pain they felt on an 11-point visual analog scale (VAS) from 0 (no pain or discomfort) to 10 (extreme pain or discomfort). A negative change from baseline value reflects improvement from baseline (less pain) while a positive value reflects worsening.
Time frame: Baseline, Day 57
Investigator Global Assessment of Improvement With Treatment
Investigators were asked to determine the degree of improvement in the subject's treated nodule compared with screening on a 7-point scale: 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse.
Time frame: Day 57
Subject Satisfaction With Treatment
Subjects were asked to rate their satisfaction with treatment on a 5-point scale: 1 = very satisfied, 2 = quite satisfied, 3 = neither satisfied nor dissatisfied, 4 = quite dissatisfied, and 5 = very dissatisfied.
Time frame: Day 57
Composite Responder Analysis
A composite responder is a subject who had an improved assessment \[values of 1 (very much improved), 2 (much improved), or 3 (minimally improved)\] on the investigator global assessment and had a satisfied assessment \[values of 1 (very satisfied) or 2 (quite satisfied)\] on the subject assessment.
Time frame: Day 57