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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00533273




Registration number
NCT00533273
Ethics application status
Date submitted
20/09/2007
Date registered
21/09/2007
Date last updated
2/12/2017

Titles & IDs
Public title
Non-US Study of AA4500 (XIAFLEX™, Proposed Name) in the Treatment of Advanced Dupuytren's Disease
Scientific title
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
Secondary ID [1] 0 0
AUX CC 859
Universal Trial Number (UTN)
Trial acronym
CORD-II
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Dupuytren's Disease 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - collagenase clostridium histolyticum

Experimental: AA4500 0.58 mg -

Placebo comparator: Placebo -


Treatment: Other: 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.
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Reduction in Primary Joint Contracture to 5° or Less
Timepoint [1] 0 0
Within 30 days after last injection
Secondary outcome [1] 0 0
Clinical Improvement in Primary Joint After the Last Injection
Timepoint [1] 0 0
Baseline, Within 30 days after last injection
Secondary outcome [2] 0 0
Percent Reduction From Baseline Contracture of Primary Joint After the Last Injection
Timepoint [2] 0 0
Baseline, Day 30 after last injection
Secondary outcome [3] 0 0
Change From Baseline Range of Motion in Primary Joint After the Last Injection
Timepoint [3] 0 0
Baseline, Day 30 after last injection
Secondary outcome [4] 0 0
Time to Reach Clinical Success in Primary Joint
Timepoint [4] 0 0
Within 30 days after last injection
Secondary outcome [5] 0 0
Clinical Success in Primary Joint After the First Injection
Timepoint [5] 0 0
Within 30 days after first injection
Secondary outcome [6] 0 0
Clinical Improvement in Primary Joint After the First Injection
Timepoint [6] 0 0
Baseline, Within 30 days after first injection
Secondary outcome [7] 0 0
Percent Reduction From Baseline Contracture of Primary Joint After the First Injection
Timepoint [7] 0 0
Baseline, Day 30 after first injection
Secondary outcome [8] 0 0
Change From Baseline Range of Motion in Primary Joint After the First Injection
Timepoint [8] 0 0
Baseline, Day 30 after first injection
Secondary outcome [9] 0 0
Reduction in Non-primary Joint Contracture to 5° or Less After the Last Injection
Timepoint [9] 0 0
Within 30 days after last injection
Secondary outcome [10] 0 0
Clinical Improvement in Non-Primary Joint After the Last Injection
Timepoint [10] 0 0
Baseline, Within 30 days after last injection
Secondary outcome [11] 0 0
Percent Reduction From Baseline Contracture of Non-Primary Joint After the Last Injection
Timepoint [11] 0 0
Baseline, Day 30 after last injection
Secondary outcome [12] 0 0
Change From Baseline Range of Motion in Non-Primary Joint After the Last Injection
Timepoint [12] 0 0
Baseline, Day 30 after last injection
Secondary outcome [13] 0 0
Time to Reach Clinical Success in Non-Primary Joint
Timepoint [13] 0 0
Within 30 days after last injection
Secondary outcome [14] 0 0
Clinical Success in Non-Primary Joint After the First Injection
Timepoint [14] 0 0
Within 30 days after first injection
Secondary outcome [15] 0 0
Clinical Improvement in Non-Primary Joint After the First Injection
Timepoint [15] 0 0
Baseline, Within 30 days after first injection
Secondary outcome [16] 0 0
Percent Reduction From Baseline Contracture of Non-Primary Joint After the First Injection
Timepoint [16] 0 0
Baseline, Day 30 after first injection
Secondary outcome [17] 0 0
Change From Baseline Range of Motion in Non-Primary Joint After the First Injection
Timepoint [17] 0 0
Baseline, Day 30 after first injection

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/08/2007
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/09/2008
Sample size
Target
Accrual to date
Final
66
Recruitment in Australia
Recruitment state(s)
QLD,TAS,VIC,WA
Recruitment hospital [1] 0 0
Rivercity Research - Auchenflower
Recruitment hospital [2] 0 0
Brisbane Hand & Upper Limb Clinic - Brisbane
Recruitment hospital [3] 0 0
Caboolture Clinical Research Centre - Caboolture
Recruitment hospital [4] 0 0
Peninsula Clinical Research Centre - Kippa Ring
Recruitment hospital [5] 0 0
Menzies Reserarch Institute - Hobart
Recruitment hospital [6] 0 0
Emeritus Research - Malvern
Recruitment hospital [7] 0 0
Royal Perth Hospital - Shenton Park
Recruitment postcode(s) [1] 0 0
4067 - Auchenflower
Recruitment postcode(s) [2] 0 0
4000 - Brisbane
Recruitment postcode(s) [3] 0 0
4510 - Caboolture
Recruitment postcode(s) [4] 0 0
4019 - Kippa Ring
Recruitment postcode(s) [5] 0 0
7000 - Hobart
Recruitment postcode(s) [6] 0 0
3144 - Malvern
Recruitment postcode(s) [7] 0 0
6007 - Shenton Park

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Endo Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00533273
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Veronica Urdaneta, MD
Address 0 0
Endo Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00533273