Administration of Two Injections for Multiple Dupuytren's Contractures

• ClinicalTrials.gov Identifier: NCT01407068
• Recruitment Status: Completed
• First Posted: August 1, 2011
• Results First Posted: February 20, 2015
• Last Update Posted: October 5, 2017
• Sponsor: Endo Pharmaceuticals
• Information provided by (Responsible Party): Endo Pharmaceuticals

Study Description

Brief Summary:

The objectives of this study are to assess the safety and efficacy of concurrent administration of two injections of AA4500 into the same hand of subjects with multiple Dupuytren's contractures caused by palpable cords.

Condition or disease	Intervention/treatment	Phase
Dupuytren's Contracture	Biological: AA4500 collagenase clostridium histolyticum	Phase 3

Detailed Description:

Methodology/Study Design:

This is an open-label, study in men and women with multiple Dupuytren's contractures. Approximately 60 subjects who have at least two Dupuytren's contractures caused by palpable cords in the same hand will be enrolled.

After all pre-injection procedures are completed on Day 1, eligible men and women will receive two concurrent injections of AA4500 0.58 mg into the same hand. On Day 2, a finger extension procedure to facilitate cord disruption will be performed 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 on Day 8, Day 30, and Day 60.

Upon completion of the Day 60 follow-up visit, subjects who require further treatment will have the option to receive three additional open-label treatments according to the XIAFLEX package insert (Appendix C). Subjects may receive up to a total of five injections and individual cords may receive up to a total of three injections.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 60 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label Study to Assess the Safety and Efficacy of Concurrent Administration of Two Injections of AA4500 0.58 mg Into the Same Hand of Subjects With Multiple Dupuytren's Contractures
• Study Start Date: September 2011
• Actual Primary Completion Date: February 2012
• Actual Study Completion Date: February 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: AA4500; AA4500 collagenase clostridium histolyticum	Biological: AA4500 collagenase clostridium histolyticum; 2 concurrent injections (0.58 mg) into 2 cords on the same hand; Other Names: Xiaflex; Xiapex

Outcome Measures

Primary Outcome Measures :

1. Percent Change From Baseline in Total Fixed Flexion [ Time Frame: 30 days after last injection ]
   Total fixed flexion is defined as the sum of the fixed flexion contractures of the two joints receiving treatment. Change in fixed-flexion contracture is measured in degrees where a decrease of 100% would correspond to a reduction in contracture to 0 degrees
2. Change in Total Range of Motion [ Time Frame: 30 days after last injection ]
   The total range of motion is the sum of the range of motion measurements of the two treated joints. Range of motion is defined as difference between full flexion angle and full extension angle expressed in degrees.

Secondary Outcome Measures :

1. Subject Satisfaction With Treatment [ Time Frame: 60 days after last injection ]

   At the Day 60 follow-up visit, each subject will be asked to rate his/her satisfaction with treatment as follows:

   1. Very Satisfied
   2. Quite Satisfied
   3. Neither Satisfied nor Dissatisfied
   4. Quite Dissatisfied
   5. Very Dissatisfied
2. Investigator Assessment of Improvement With Treatment [ Time Frame: 60 days after last injection ]

   At the Day 60 follow-up visit, the investigator will determine the degree of improvement in the severity of the subject's treated finger(s) compared with screening as follows:

   1. Very Much Improved
   2. Much improved
   3. Minimally Improved
   4. No Change
   5. Minimally Worse
   6. Much Worse
   7. Very Much Worse
3. Clinical Success by Joint Type [ Time Frame: 30 days after injection ]
   Clinical success is defined as a reduction in fixed flexion contracture to 5° or less 30 days after injection of AA4500.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Provide written 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 cords 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. Either be using an accepted method of birth control (ie, surgical sterilization; intra uterine contraceptive device; oral contraceptive; diaphragm or condom in combination with contraceptive cream, or jelly or foam) and have negative pregnancy testing before administration of AA4500, if a female of childbearing potential, or be a postmenopausal female (no menses for at least 1 year or hysterectomy)
6. Not have any clinically significant medical history or condition(s) 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
7. Be able to comply with the study visit schedule as specified in the protocol

Exclusion Criteria:

1. Received surgery (fasciectomy or surgical fasciotomy) and/or needle aponeurotomy/fasciotomy on the selected joints to be treated within 90 days before the first injection of AA4500
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 AA4500
5. Is currently receiving or plans to receive anticoagulant medication or has received anticoagulant medication (except for ≤ 150 mg aspirin daily and over-the-counter nonsteroidal anti-inflammatory drugs [NSAIDs]) within 7 days before injection of AA4500)
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. Is known to be immunocompromised or human immunodeficiency virus (HIV) positive
8. Has a history of illicit drug abuse or alcoholism within the year before injection of AA4500
9. Received an investigational drug within 30 days before injection of AA4500
10. Is a pregnant or lactating female
11. 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
12. Has jewelry on the hand to be treated that cannot be removed

Contacts and Locations

Locations

United States, Arizona

Tucson Orthopaedic Institute

Tucson, Arizona, United States, 85712

United States, Indiana

The Indiana Hand Center

Indianapolis, Indiana, United States, 46260

United States, New York

Department of Orthopaedics SUNY-Stony Brook

Stony Brook, New York, United States, 11794

United States, Oklahoma

Health Research Institute

Oklahoma City, Oklahoma, United States, 73109

Australia

AusTrials

Auchenflower, Australia, QLD 4067

AusTrials

Auchenflower, Australia, QLD4066

AusTrials

Kippa Ring, Australia, QLD 4020

Emeritus Research

Malvern, Australia, VIC 3144

Sponsors and Collaborators

Endo Pharmaceuticals

Investigators

• Study Director: Veronica Urdaneta, MD, MPPH; Endo Pharmaceuticals

More Information

• Responsible Party: Endo Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01407068
• Other Study ID Numbers: AUX-CC-864
• First Posted: August 1, 2011
• Results First Posted: February 20, 2015
• Last Update Posted: October 5, 2017
• Last Verified: September 2017

Additional relevant MeSH terms:

Dupuytren Contracture; Contracture; Joint Diseases; Musculoskeletal Diseases; Muscular Diseases; Fibroma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Connective Tissue Diseases