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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase 3b Open-label, Historically-controlled Study to Assess the Safety and Efficacy of Two Concurrent Injections of AA4500 in Adult Subjects With Multiple Dupuytren's Contract

Brief Summary:

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.

Detailed Summary:

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.

Current Primary Outcome:

• Percent Change From Baseline in Total Fixed Flexion [ Time Frame: Baseline, Day 31 ]
  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.
• Change From Baseline in Total Range of Motion [ Time Frame: Baseline, Day 31 ]
  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.

Original Primary Outcome: The actual change and the percent change in degree of flexion [ Time Frame: 30 days after injection of AA4500 ]

Current Secondary Outcome:

• Clinical Success [ Time Frame: Within 30 days ]
  Clinical success is defined as reduction of FFC of a treated joint to within 0-5 degrees of normal within 30 days of injection
• Clinical Improvement [ Time Frame: Within 30 days ]
  Clinical improvement is defined as a reduction of FFC by 50% or greater of the baseline value within 30 days of injection
• Subject Assessment of Satisfaction With Treatment at Day 31 [ Time Frame: Day 31 ]
  Subject's were asked to rate satisfaction with treatment at the day 31 follow-up visit
• Subject Assessment of Satisfaction With Treatment at Day 61 [ Time Frame: Day 61 ]
  Subject's were asked to rate satisfaction with treatment at the day 61 follow-up visit
• Investigator Assessment of Improvement With Treatment at Day 31 [ Time Frame: 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.
• Investigator Assessment of Improvement With Treatment at Day 61 [ Time Frame: 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.
• Change From Baseline for Unité Rhumatologique Des Affections de la Main Scale at Day 31 [ Time Frame: Baseline, 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.
• Change From Baseline for Unité Rhumatologique Des Affections de la Main Scale at Day 61 [ Time Frame: Baseline, 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.

Original Secondary Outcome:

Information By: Endo Pharmaceuticals

Dates:
Date Received: August 27, 2012
Date Started: September 2012
Date Completion:
Last Updated: September 14, 2016
Last Verified: August 2016