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
Safety and Efficacy of Two Concurrent Injections of AA4500 in Adult Subjects With Multiple Dupuytren's Contractures
Sponsors
Source
Endo Pharmaceuticals
Oversight Info
Has Dmc
No
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.
Overall Status
Completed
Start Date
2012-09-01
Completion Date
2013-07-01
Primary Completion Date
2013-07-01
Phase
Phase 3
Study Type
Interventional
Primary Outcome
Measure |
Time Frame |
|
Percent Change From Baseline in Total Fixed Flexion |
Baseline, Day 31 |
|
Change From Baseline in Total Range of Motion |
Baseline, Day 31 |
Secondary Outcome
Measure |
Time Frame |
|
Clinical Success |
Within 30 days |
|
Clinical Improvement |
Within 30 days |
|
Subject Assessment of Satisfaction With Treatment at Day 31 |
Day 31 |
|
Subject Assessment of Satisfaction With Treatment at Day 61 |
Day 61 |
|
Investigator Assessment of Improvement With Treatment at Day 31 |
Day 31 |
|
Investigator Assessment of Improvement With Treatment at Day 61 |
Day 61 |
|
Change From Baseline for Unité Rhumatologique Des Affections de la Main Scale at Day 31 |
Baseline, Day 31 |
|
Change From Baseline for Unité Rhumatologique Des Affections de la Main Scale at Day 61 |
Baseline, Day 61 |
Enrollment
715
Condition
Intervention
Intervention Type
Biological
Intervention Name
Description
injection (0.58 mg after reconstitution with sterile diluent [0.3 mg/mL calcium chloride dihydrate in 0.9% sodium chloride])
Arm Group Label
XIAFLEX / XIAPEX
Other Name
AA4500 (collagenase clostridium histolyticum)
Eligibility
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
Gender
All
Minimum Age
18 Years
Maximum Age
N/A
Healthy Volunteers
Accepts Healthy Volunteers
Overall Official
Last Name |
Role |
Affiliation |
|
Veronica Urdaneta, MD, MPPH |
Study Director |
Endo Pharmaceuticals |
Location
Facility |
|
HOPE Research Institute Phoenix Arizona 85018 United States |
|
Tucson Orthopaedic Institute Tucson Arizona 85712 United States |
|
CORE Orthopaedic Medical Center Encinitas California 92024 United States |
|
Torrey Pines Medical Group La Jolla California 92037 United States |
|
Brigid Freyne, MD, Inc. Murrieta California 92563 United States |
|
The Hand and Upper Extremity Center Atlanta Georgia 30342 United States |
|
Rockford Orthopedic Associates Rockford Illinois 61107 United States |
|
The Indiana Hand to Shoulder Center Indianapolis Indiana 46260 United States |
|
University of Kansas Medical Center Kansas City Kansas 66160 United States |
|
Christine M. Kleinert Institute for Hand and Microsurgery, Inc. Louisville Kentucky 40202 United States |
|
Lake Cumberland Rheumatology Somerset Kentucky 42503 United States |
|
TRIA Orthopedic Center Minneapolis Minnesota 55431 United States |
|
Missoula Bone and Joint Missoula Montana 59808 United States |
|
Nevada Orthopedic and Spine Center Las Vegas Nevada 89128 United States |
|
Central Jersey Hand Surgery Eatontown New Jersey 07724 United States |
|
Hospital for Special Surgery New York New York 10021 United States |
|
SUNY Stony Brook Setauket New York 11733 United States |
|
UNC School of Medicine Chapel Hill North Carolina 27599 United States |
|
OrthoCarolina Research Institute, Inc. Charlotte North Carolina 28207 United States |
|
Health Research Institute Oklahoma City Oklahoma 73109 United States |
|
The Center for Neurosurgical and Orthopedic Care and Research Bend Oregon 97701 United States |
|
Hand Microsurgery & Reconstructive Orthopaedics Erie Pennsylvania 16507 United States |
|
Alpha Clinical Research, LLC Clarksville Tennessee 37043 United States |
|
Accurate Clinical Research, Inc. Houston Texas 77034 United States |
|
The Arthritis Clinic of Northern Virginia, PA Arlington Virginia 22205 United States |
Location Countries
Country
United States
Verification Date
2017-09-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Responsible Party
Responsible Party Type
Sponsor
Keywords
Has Expanded Access
No
Condition Browse
Number Of Arms
1
Arm Group
Arm Group Label
XIAFLEX / XIAPEX
Arm Group Type
Experimental
Description
AA4500 (collagenase clostridium histolyticum)
Firstreceived Results Date
N/A
Firstreceived Results Disposition Date
N/A
Study Design Info
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)
Study First Submitted
August 27, 2012
Study First Submitted Qc
August 28, 2012
Study First Posted
August 29, 2012
Last Update Submitted
September 7, 2017
Last Update Submitted Qc
September 7, 2017
Last Update Posted
October 5, 2017
Results First Submitted
February 4, 2015
Results First Submitted Qc
February 4, 2015
Results First Posted
February 20, 2015
ClinicalTrials.gov processed this data on August 24, 2018
Conditions
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Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.