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

Dupuytren's Contracture Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01674634
• Other study ID #: AUX-CC-867
• Status: Completed
• Phase: Phase 3
• First received: August 27, 2012
• Last updated: September 7, 2017
• Start date: September 2012
• Est. completion date: July 2013

Study information

• Verified date: September 2017
• Source: Endo Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 715
• Est. completion date: July 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Contracture
• Dupuytren Contracture
• Dupuytren's Contracture

Intervention

Biological:
• XIAFLEX / XIAPEX
injection (0.58 mg after reconstitution with sterile diluent [0.3 mg/mL calcium chloride dihydrate in 0.9% sodium chloride])

Locations

Country	Name	City	State
United States	The Arthritis Clinic of Northern Virginia, PA	Arlington	Virginia
United States	The Hand and Upper Extremity Center	Atlanta	Georgia
United States	The Center for Neurosurgical and Orthopedic Care and Research	Bend	Oregon
United States	UNC School of Medicine	Chapel Hill	North Carolina
United States	OrthoCarolina Research Institute, Inc.	Charlotte	North Carolina
United States	Alpha Clinical Research, LLC	Clarksville	Tennessee
United States	Central Jersey Hand Surgery	Eatontown	New Jersey
United States	CORE Orthopaedic Medical Center	Encinitas	California
United States	Hand Microsurgery & Reconstructive Orthopaedics	Erie	Pennsylvania
United States	Accurate Clinical Research, Inc.	Houston	Texas
United States	The Indiana Hand to Shoulder Center	Indianapolis	Indiana
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Torrey Pines Medical Group	La Jolla	California
United States	Nevada Orthopedic and Spine Center	Las Vegas	Nevada
United States	Christine M. Kleinert Institute for Hand and Microsurgery, Inc.	Louisville	Kentucky
United States	TRIA Orthopedic Center	Minneapolis	Minnesota
United States	Missoula Bone and Joint	Missoula	Montana
United States	Brigid Freyne, MD, Inc.	Murrieta	California
United States	Hospital for Special Surgery	New York	New York
United States	Health Research Institute	Oklahoma City	Oklahoma
United States	HOPE Research Institute	Phoenix	Arizona
United States	Rockford Orthopedic Associates	Rockford	Illinois
United States	SUNY Stony Brook	Setauket	New York
United States	Lake Cumberland Rheumatology	Somerset	Kentucky
United States	Tucson Orthopaedic Institute	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Endo Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline, Day 31
Primary	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.	Baseline, Day 31
Secondary	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	Within 30 days
Secondary	Clinical Improvement	Clinical improvement is defined as a reduction of FFC by 50% or greater of the baseline value within 30 days of injection	Within 30 days
Secondary	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	Day 31
Secondary	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	Day 61
Secondary	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.	Day 31
Secondary	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.	Day 61
Secondary	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.	Baseline, Day 31
Secondary	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.	Baseline, Day 61