Non-US Study of AA4500 (XIAFLEX™, Proposed Name) in the Treatment of Advanced Dupuytren's Disease (CORD-II)

October 26, 2017 updated by: Endo Pharmaceuticals

A Phase 3, Double-Blind, Randomized, Placebo-Controlled Study of the Safety and Efficacy of AA4500 in the Treatment of Subjects With Advanced Dupuytren's Disease Followed by an Open-Label Extension Phase

This 12-month study had two phases: a 90-day double-blind, randomized, placebo-controlled phase and a nine-month open-label extension phase. Before treatment, eligible subjects were stratified by the primary joint type (30 metacarpophalangeal [MP] joints and 30 proximal interphalangeal [PIP] joints) and by severity of the primary joint contracture (ie, up to 50° or >50° for MP joints and up to 40° or >40° for PIP joints) and then randomized in a 2:1 ratio to either AA4500 0.58 mg or placebo. Upon completion of the double-blind phase (ie, 90-day evaluation after the first injection), all subjects were eligible to enter the open-label extension phase of the study in which they were followed for an additional nine months. Subjects who required further treatment because they either did not achieve reduction in contracture to 5° or less, the cord affecting the primary joint received placebo, another cord received less than three injections of AA4500, or they had untreated cords that were affecting other joints had the option to receive up to five additional injections of AA4500 0.58 mg in the open-label extension phase, with individual cords receiving up to three injections of AA4500.

This study was designed to be part of the larger clinical program, for adult patients with Dupuytren's contracture with a palpable cord, where the data from 2 pivotal Placebo-Controlled studies (AUX-CC-857 [NCT00528606] and AUX-CC-859 [NCT00533273]) and 7 non-pivotal studies were evaluated.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
66

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Queensland
      • Auchenflower, Queensland, Australia, 4067
        • Rivercity Research
      • Brisbane, Queensland, Australia, 4000
        • Brisbane Hand & Upper Limb Clinic
      • Caboolture, Queensland, Australia, 4510
        • Caboolture Clinical Research Centre
      • Kippa Ring, Queensland, Australia, 4019
        • Peninsula Clinical Research Centre
    • Tasmania
      • Hobart, Tasmania, Australia, 7000
        • Menzies Reserarch Institute
    • Victoria
      • Malvern, Victoria, Australia, 3144
        • Emeritus Research
    • Western Australia
      • Shenton Park, Western Australia, Australia, 6007
        • Royal Perth Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Subjects with a diagnosis of advanced Dupuytren's disease, with a fixed flexion deformity of at least one finger, other than the thumb, that had a contracture at least 20°, but not greater than 100°, for MP (80° for PIP) joints, caused by a palpable cord.
  • Had a positive "table top test," defined as the inability to simultaneously place the affected finger(s) and palm flat against a table top.
  • Were naive to AA4500 treatment
  • Were judged to be in good health, based upon the results of a medical history, physical examination, and safety laboratory profile.

Exclusion Criteria:

  • Had a chronic muscular, neurological, or neuromuscular disorder that affected the hands.
  • Had received a treatment for advanced Dupuytren's disease, including surgery (fasciectomy or surgical fasciotomy), needle aponeurotomy/fasciotomy, or injection of verapamil and/or interferon on the selected primary joint within 90 days before the first dose of study drug.
  • Had a known recent history of stroke, bleeding, a disease process that affected the hands, or other medical condition, which in the investigator's opinion, would make the subject unsuitable for enrollment in the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo
Biological: collagenase clostridium histolyticum
Subjects could have received up to three injections of AA4500 0.58 mg/placebo into the cord of the affected hand in the double-blind phase. In the open-label extension phase, subjects could have received up to five additional injections of AA4500, with each injection separated by at least 30 days. Individual joints could have received up to a maximum of three AA4500 injections.
Other Names:
  • XIAFLEX®
  • AA4500
Experimental: AA4500 0.58 mg
Biological: collagenase clostridium histolyticum
Subjects could have received up to three injections of AA4500 0.58 mg/placebo into the cord of the affected hand in the double-blind phase. In the open-label extension phase, subjects could have received up to five additional injections of AA4500, with each injection separated by at least 30 days. Individual joints could have received up to a maximum of three AA4500 injections.
Other Names:
  • XIAFLEX®
  • AA4500

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Reduction in Primary Joint Contracture to 5° or Less
Time Frame: Within 30 days after last injection
Successfully treated or clinical success in primary joint defined as reduction in contracture to within 0-5° of normal within 30 days of injection.
Within 30 days after last injection

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Clinical Improvement in Primary Joint After the Last Injection
Time Frame: Baseline, Within 30 days after last injection
Clinical improvement in primary joint defined as ≥50% reduction from baseline in the degree of contracture within 30 days after injection
Baseline, Within 30 days after last injection
Percent Reduction From Baseline Contracture of Primary Joint After the Last Injection
Time Frame: Baseline, Day 30 after last injection
Percent change in degree of contracture of primary joint measured as 100 * (baseline contracture - last available post-injection contracture)/baseline contracture
Baseline, Day 30 after last injection
Change From Baseline Range of Motion in Primary Joint After the Last Injection
Time Frame: Baseline, Day 30 after last injection
Change in degree of range of motion in primary joint measured as last available post-injection range of motion - baseline range of motion
Baseline, Day 30 after last injection
Time to Reach Clinical Success in Primary Joint
Time Frame: Within 30 days after last injection
Clinical success in primary joint defined as reduction in contracture to within 0-5° of normal within 30 days of injection, displayed in post injection time point categories
Within 30 days after last injection
Clinical Success in Primary Joint After the First Injection
Time Frame: Within 30 days after first injection
Clinical success in primary joint defined as reduction in contracture to within 0-5° of normal within 30 days of injection.
Within 30 days after first injection
Clinical Improvement in Primary Joint After the First Injection
Time Frame: Baseline, Within 30 days after first injection
Clinical improvement in primary joint defined as ≥50% reduction from baseline in the degree of contracture within 30 days after injection
Baseline, Within 30 days after first injection
Percent Reduction From Baseline Contracture of Primary Joint After the First Injection
Time Frame: Baseline, Day 30 after first injection
Percent change in degree of contracture of primary joint measured as 100 * (baseline contracture - last available post-injection contracture prior to next injection)/baseline contracture
Baseline, Day 30 after first injection
Change From Baseline Range of Motion in Primary Joint After the First Injection
Time Frame: Baseline, Day 30 after first injection
Change in degree of range of motion in primary joint measured as last available post-injection range of motion prior to the next injection - baseline range of motion
Baseline, Day 30 after first injection
Reduction in Non-primary Joint Contracture to 5° or Less After the Last Injection
Time Frame: Within 30 days after last injection
Successfully treated or clinical success in non-primary joint defined as reduction in contracture to within 0-5° of normal within 30 days of injection.
Within 30 days after last injection
Clinical Improvement in Non-Primary Joint After the Last Injection
Time Frame: Baseline, Within 30 days after last injection
Clinical improvement in non-primary joint defined as ≥50% reduction from baseline in the degree of contracture within 30 days after injection
Baseline, Within 30 days after last injection
Percent Reduction From Baseline Contracture of Non-Primary Joint After the Last Injection
Time Frame: Baseline, Day 30 after last injection
Percent change in degree of contracture of non-primary joint measured as 100 * (baseline contracture - last available post-injection contracture)/baseline contracture
Baseline, Day 30 after last injection
Change From Baseline Range of Motion in Non-Primary Joint After the Last Injection
Time Frame: Baseline, Day 30 after last injection
Change in degree of range of motion in non-primary joint measured as last available post-injection range of motion - baseline range of motion
Baseline, Day 30 after last injection
Time to Reach Clinical Success in Non-Primary Joint
Time Frame: Within 30 days after last injection
Clinical success in non-primary joint defined as reduction in contracture to within 0-5° of normal within 30 days of injection, displayed in post injection time point categories
Within 30 days after last injection
Clinical Success in Non-Primary Joint After the First Injection
Time Frame: Within 30 days after first injection
Clinical success in non-primary joint defined as reduction in contracture to within 0-5° of normal within 30 days of injection.
Within 30 days after first injection
Clinical Improvement in Non-Primary Joint After the First Injection
Time Frame: Baseline, Within 30 days after first injection
Clinical improvement in non-primary joint defined as ≥50% reduction from baseline in the degree of contracture within 30 days after injection
Baseline, Within 30 days after first injection
Percent Reduction From Baseline Contracture of Non-Primary Joint After the First Injection
Time Frame: Baseline, Day 30 after first injection
Percent change in degree of contracture of non-primary joint measured as 100 * (baseline contracture - last available post-injection contracture prior to next injection)/baseline contracture
Baseline, Day 30 after first injection
Change From Baseline Range of Motion in Non-Primary Joint After the First Injection
Time Frame: Baseline, Day 30 after first injection
Change in degree of range of motion in non-primary joint measured as last available post-injection range of motion prior to the next injection - baseline range of motion
Baseline, Day 30 after first injection

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Endo Pharmaceuticals

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Veronica Urdaneta, MD, Endo Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2007

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2008

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2008

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 20, 2007

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 20, 2007

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 21, 2007

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 2, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 26, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • AUX CC 859

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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