The primary objective of this study is to assess the safety of two concurrent injections of AA4500 into the same hand in subjects with multiple Dupuytren's contractures with palpable cords followed 24 to 72 hours later by a finger extension procedure and compare the rate of occurrence of targeted serious adverse events (tendon rupture/ligament injury and anaphylaxis) to historical rates of the same in clinical studies and post-marketing commercial use. The secondary objective is to evaluate the efficacy of two concurrent injections of AA4500.
Methodology/Study Design: After all pre-injection procedures are completed on Day 1, eligible men and women will receive two concurrent injections AA4500 (AA4500/AA4500) into cord(s) affecting MP and/or PIP joints on the same or different fingers in the selected hand. A finger extension procedure to facilitate cord disruption will be performed (after administration of local anesthesia, if needed) 24 to 72 hours after injection 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 required for all subjects 24 to 72 hours after injection, and on Days 15, 31, and 61. Upon completion of the day 61 follow-up visit (end of study visit), subjects who require additional treatment in the treated hand may receive up to three additional injections of AA4500 according to the XIAFLEX package insert. Subjects may receive up to a total of five injections and individual cords may receive up to a total of three injections. Subjects who require additional treatment will be followed for safety.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
715
injection (0.58 mg after reconstitution with sterile diluent \[0.3 mg/mL calcium chloride dihydrate in 0.9% sodium chloride\])
HOPE Research Institute
Phoenix, Arizona, United States
Tucson Orthopaedic Institute
Tucson, Arizona, United States
CORE Orthopaedic Medical Center
Encinitas, California, United States
Torrey Pines Medical Group
La Jolla, California, United States
Brigid Freyne, MD, Inc.
Murrieta, California, United States
The Hand and Upper Extremity Center
Atlanta, Georgia, United States
Rockford Orthopedic Associates
Rockford, Illinois, United States
The Indiana Hand to Shoulder Center
Indianapolis, Indiana, United States
University of Kansas Medical Center
Kansas City, Kansas, United States
Christine M. Kleinert Institute for Hand and Microsurgery, Inc.
Louisville, Kentucky, United States
...and 15 more locations
Percent Change From Baseline in Total Fixed Flexion
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
Change From Baseline in Total Range of Motion
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
Clinical Success
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
Clinical Improvement
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
Subject Assessment of Satisfaction With Treatment at Day 31
Subject's were asked to rate satisfaction with treatment at the day 31 follow-up visit
Time frame: Day 31
Subject Assessment of Satisfaction With Treatment at Day 61
Subject's were asked to rate satisfaction with treatment at the day 61 follow-up visit
Time frame: Day 61
Investigator Assessment of Improvement With Treatment at Day 31
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
Investigator Assessment of Improvement With Treatment at Day 61
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
Change From Baseline for Unité Rhumatologique Des Affections de la Main Scale at Day 31
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
Change From Baseline for Unité Rhumatologique Des Affections de la Main Scale at Day 61
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
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