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

NCT ID: NCT01674634

Last Updated: 2017-10-05

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

715 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-09-30

Study Completion Date

2013-07-31

Brief Summary

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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

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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.

Conditions

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Dupuytren's Contracture

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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XIAFLEX / XIAPEX

AA4500 (collagenase clostridium histolyticum)

Group Type EXPERIMENTAL

XIAFLEX / XIAPEX

Intervention Type BIOLOGICAL

injection (0.58 mg after reconstitution with sterile diluent \[0.3 mg/mL calcium chloride dihydrate in 0.9% sodium chloride\])

Interventions

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XIAFLEX / XIAPEX

injection (0.58 mg after reconstitution with sterile diluent \[0.3 mg/mL calcium chloride dihydrate in 0.9% sodium chloride\])

Intervention Type BIOLOGICAL

Other Intervention Names

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AA4500 (collagenase clostridium histolyticum)

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Endo Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Veronica Urdaneta, MD, MPPH

Role: STUDY_DIRECTOR

Endo Pharmaceuticals

Locations

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HOPE Research Institute

Phoenix, Arizona, United States

Site Status

Tucson Orthopaedic Institute

Tucson, Arizona, United States

Site Status

CORE Orthopaedic Medical Center

Encinitas, California, United States

Site Status

Torrey Pines Medical Group

La Jolla, California, United States

Site Status

Brigid Freyne, MD, Inc.

Murrieta, California, United States

Site Status

The Hand and Upper Extremity Center

Atlanta, Georgia, United States

Site Status

Rockford Orthopedic Associates

Rockford, Illinois, United States

Site Status

The Indiana Hand to Shoulder Center

Indianapolis, Indiana, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

Christine M. Kleinert Institute for Hand and Microsurgery, Inc.

Louisville, Kentucky, United States

Site Status

Lake Cumberland Rheumatology

Somerset, Kentucky, United States

Site Status

TRIA Orthopedic Center

Minneapolis, Minnesota, United States

Site Status

Missoula Bone and Joint

Missoula, Montana, United States

Site Status

Nevada Orthopedic and Spine Center

Las Vegas, Nevada, United States

Site Status

Central Jersey Hand Surgery

Eatontown, New Jersey, United States

Site Status

Hospital for Special Surgery

New York, New York, United States

Site Status

SUNY Stony Brook

Setauket, New York, United States

Site Status

UNC School of Medicine

Chapel Hill, North Carolina, United States

Site Status

OrthoCarolina Research Institute, Inc.

Charlotte, North Carolina, United States

Site Status

Health Research Institute

Oklahoma City, Oklahoma, United States

Site Status

The Center for Neurosurgical and Orthopedic Care and Research

Bend, Oregon, United States

Site Status

Hand Microsurgery & Reconstructive Orthopaedics

Erie, Pennsylvania, United States

Site Status

Alpha Clinical Research, LLC

Clarksville, Tennessee, United States

Site Status

Accurate Clinical Research, Inc.

Houston, Texas, United States

Site Status

The Arthritis Clinic of Northern Virginia, PA

Arlington, Virginia, United States

Site Status

Countries

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United States

Other Identifiers

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AUX-CC-867

Identifier Type: -

Identifier Source: org_study_id