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

Primary Purpose

Dupuytren's Contracture

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
XIAFLEX / XIAPEX
Sponsored by
Endo Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Dupuytren's Contracture focused on measuring XIAFLEX, XIAPEX, Dupuytren's disease, contracture

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • HOPE Research Institute
  • Tucson Orthopaedic Institute
  • CORE Orthopaedic Medical Center
  • Torrey Pines Medical Group
  • Brigid Freyne, MD, Inc.
  • The Hand and Upper Extremity Center
  • Rockford Orthopedic Associates
  • The Indiana Hand to Shoulder Center
  • University of Kansas Medical Center
  • Christine M. Kleinert Institute for Hand and Microsurgery, Inc.
  • Lake Cumberland Rheumatology
  • TRIA Orthopedic Center
  • Missoula Bone and Joint
  • Nevada Orthopedic and Spine Center
  • Central Jersey Hand Surgery
  • Hospital for Special Surgery
  • SUNY Stony Brook
  • UNC School of Medicine
  • OrthoCarolina Research Institute, Inc.
  • Health Research Institute
  • The Center for Neurosurgical and Orthopedic Care and Research
  • Hand Microsurgery & Reconstructive Orthopaedics
  • Alpha Clinical Research, LLC
  • Accurate Clinical Research, Inc.
  • The Arthritis Clinic of Northern Virginia, PA

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

XIAFLEX / XIAPEX

Arm Description

AA4500 (collagenase clostridium histolyticum)

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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
Clinical Improvement
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
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
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
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
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
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
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.

Full Information

First Posted
August 27, 2012
Last Updated
September 7, 2017
Sponsor
Endo Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01674634
Brief Title
Safety and Efficacy of Two Concurrent Injections of AA4500 in Adult Subjects With Multiple Dupuytren's Contractures
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2017
Overall Recruitment Status
Completed
Study Start Date
September 2012 (undefined)
Primary Completion Date
July 2013 (Actual)
Study Completion Date
July 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Endo Pharmaceuticals

4. Oversight

Data Monitoring Committee
No

5. Study Description

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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dupuytren's Contracture
Keywords
XIAFLEX, XIAPEX, Dupuytren's disease, contracture

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
715 (Actual)

8. Arms, Groups, and Interventions

Arm Title
XIAFLEX / XIAPEX
Arm Type
Experimental
Arm Description
AA4500 (collagenase clostridium histolyticum)
Intervention Type
Biological
Intervention Name(s)
XIAFLEX / XIAPEX
Other Intervention Name(s)
AA4500 (collagenase clostridium histolyticum)
Intervention Description
injection (0.58 mg after reconstitution with sterile diluent [0.3 mg/mL calcium chloride dihydrate in 0.9% sodium chloride])
Primary Outcome Measure Information:
Title
Percent Change From Baseline in Total Fixed Flexion
Description
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
Title
Change From Baseline in Total Range of Motion
Description
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
Secondary Outcome Measure Information:
Title
Clinical Success
Description
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
Title
Clinical Improvement
Description
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
Title
Subject Assessment of Satisfaction With Treatment at Day 31
Description
Subject's were asked to rate satisfaction with treatment at the day 31 follow-up visit
Time Frame
Day 31
Title
Subject Assessment of Satisfaction With Treatment at Day 61
Description
Subject's were asked to rate satisfaction with treatment at the day 61 follow-up visit
Time Frame
Day 61
Title
Investigator Assessment of Improvement With Treatment at Day 31
Description
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
Title
Investigator Assessment of Improvement With Treatment at Day 61
Description
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
Title
Change From Baseline for Unité Rhumatologique Des Affections de la Main Scale at Day 31
Description
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
Title
Change From Baseline for Unité Rhumatologique Des Affections de la Main Scale at Day 61
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Provide a signed and dated informed consent Be a man or woman ≥ 18 years of age 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 Have a positive "table top test" defined as the inability to simultaneously place the affected finger(s) and palm flat against a table top 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). 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: 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 Has a chronic muscular, neurological, or neuromuscular disorder that affects the hands Has a known systemic allergy to collagenase or any other excipient of AA4500 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 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 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 Received an investigational drug within 30 days before injection of study drug Is pregnant or intends on becoming pregnant during the study or is breastfeeding a child 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 Has jewelry on the hand to be treated that cannot be removed
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Veronica Urdaneta, MD, MPPH
Organizational Affiliation
Endo Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
HOPE Research Institute
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85018
Country
United States
Facility Name
Tucson Orthopaedic Institute
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85712
Country
United States
Facility Name
CORE Orthopaedic Medical Center
City
Encinitas
State/Province
California
ZIP/Postal Code
92024
Country
United States
Facility Name
Torrey Pines Medical Group
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
Brigid Freyne, MD, Inc.
City
Murrieta
State/Province
California
ZIP/Postal Code
92563
Country
United States
Facility Name
The Hand and Upper Extremity Center
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
Rockford Orthopedic Associates
City
Rockford
State/Province
Illinois
ZIP/Postal Code
61107
Country
United States
Facility Name
The Indiana Hand to Shoulder Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46260
Country
United States
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Christine M. Kleinert Institute for Hand and Microsurgery, Inc.
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Lake Cumberland Rheumatology
City
Somerset
State/Province
Kentucky
ZIP/Postal Code
42503
Country
United States
Facility Name
TRIA Orthopedic Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55431
Country
United States
Facility Name
Missoula Bone and Joint
City
Missoula
State/Province
Montana
ZIP/Postal Code
59808
Country
United States
Facility Name
Nevada Orthopedic and Spine Center
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89128
Country
United States
Facility Name
Central Jersey Hand Surgery
City
Eatontown
State/Province
New Jersey
ZIP/Postal Code
07724
Country
United States
Facility Name
Hospital for Special Surgery
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
SUNY Stony Brook
City
Setauket
State/Province
New York
ZIP/Postal Code
11733
Country
United States
Facility Name
UNC School of Medicine
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
OrthoCarolina Research Institute, Inc.
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28207
Country
United States
Facility Name
Health Research Institute
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73109
Country
United States
Facility Name
The Center for Neurosurgical and Orthopedic Care and Research
City
Bend
State/Province
Oregon
ZIP/Postal Code
97701
Country
United States
Facility Name
Hand Microsurgery & Reconstructive Orthopaedics
City
Erie
State/Province
Pennsylvania
ZIP/Postal Code
16507
Country
United States
Facility Name
Alpha Clinical Research, LLC
City
Clarksville
State/Province
Tennessee
ZIP/Postal Code
37043
Country
United States
Facility Name
Accurate Clinical Research, Inc.
City
Houston
State/Province
Texas
ZIP/Postal Code
77034
Country
United States
Facility Name
The Arthritis Clinic of Northern Virginia, PA
City
Arlington
State/Province
Virginia
ZIP/Postal Code
22205
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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