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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Endo Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01674634
First received: August 27, 2012
Last updated: June 12, 2015
Last verified: June 2015
  Purpose

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.


Condition Intervention Phase
Dupuytren's Contracture
Biological: XIAFLEX / XIAPEX
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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 Contractures With Palpable Cords

Resource links provided by NLM:


Further study details as provided by Endo Pharmaceuticals:

Primary Outcome Measures:
  • Percent Change From Baseline in Total Fixed Flexion [ Time Frame: Baseline, Day 31 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Clinical Success [ Time Frame: Within 30 days ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 715
Study Start Date: September 2012
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: XIAFLEX / XIAPEX
AA4500 (collagenase clostridium histolyticum)
Biological: XIAFLEX / XIAPEX
injection (0.58 mg after reconstitution with sterile diluent [0.3 mg/mL calcium chloride dihydrate in 0.9% sodium chloride])
Other Name: AA4500 (collagenase clostridium histolyticum)

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Provide a signed and dated informed consent
  2. Be a man or woman ≥ 18 years of age
  3. Have a diagnosis of Dupuytren's disease and have at least 2 fixed-flexion contractures on the same hand that are ≥ 20º in PIP and/or MP joints in fingers, other than the thumbs, which are caused by palpable cord(s) suitable for treatment
  4. Have a positive "table top test" defined as the inability to simultaneously place the affected finger(s) and palm flat against a table top
  5. Have a negative urine pregnancy test at screening and before injection of study drug and be using a highly effective (ie, < 1% failure rate) contraception method as judged by the investigator (eg, abstinence, intrauterine device [IUD], hormonal [estrogen/progestin] contraceptives, or barrier control) for at least one menstrual cycle prior to study enrollment and for the duration of the study or be surgically sterile (if female of childbearing potential); or be a postmenopausal female (no menses for at least 1 year or hysterectomy).
  6. Be able to comply with the study visit schedule as specified in the protocol

Exclusion Criteria:

A subject will be excluded from study participation if he/she:

  1. Received surgery (fasciectomy or surgical fasciotomy) and/or needle aponeurotomy/fasciotomy on the selected joints to be treated within 6 months before administration of study drug
  2. Has a chronic muscular, neurological, or neuromuscular disorder that affects the hands
  3. Has a known systemic allergy to collagenase or any other excipient of AA4500
  4. Has received any collagenase treatments (eg, Santyl® ointment and/or XIAFLEX®/XIAPEX®) within 30 days before injection of study drug in the hand selected for treatment
  5. Is currently receiving or plans to receive anticoagulant medication or has received anticoagulant medication (except for ≤ 150 mg aspirin daily) within 7 days before injection of study drug
  6. Has a known recent history of stroke, bleeding, or other medical condition, which in the investigator's opinion would make the subject unsuitable for enrollment in the study
  7. Received an investigational drug within 30 days before injection of study drug
  8. Is pregnant or intends on becoming pregnant during the study or is breastfeeding a child
  9. Has any clinically significant medical history or condition(s), including conditions that affect the hands, that would, in the opinion of the investigator, substantially increase the risk associated with the subject's participation in the protocol or compromise the scientific objectives of the study
  10. Has jewelry on the hand to be treated that cannot be removed
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01674634

  Show 25 Study Locations
Sponsors and Collaborators
Endo Pharmaceuticals
Investigators
Study Director: Veronica Urdaneta, MD, MPPH Endo Pharmaceuticals
  More Information

No publications provided

Responsible Party: Endo Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01674634     History of Changes
Other Study ID Numbers: AUX-CC-867
Study First Received: August 27, 2012
Results First Received: February 4, 2015
Last Updated: June 12, 2015
Health Authority: United States: Food and Drug Administration
European Union: European Medicines Agency
Australia: Department of Health and Ageing Therapeutic Goods Administration
New Zealand: Medsafe

Keywords provided by Endo Pharmaceuticals:
XIAFLEX
XIAPEX
Dupuytren's disease
contracture

Additional relevant MeSH terms:
Contracture
Dupuytren Contracture
Connective Tissue Diseases
Joint Diseases
Muscular Diseases
Musculoskeletal Diseases

ClinicalTrials.gov processed this record on July 30, 2015