Advanced Dupuytren's DiseasePhase 3CORD-IINCT00533273
Non-US Study of AA4500 (XIAFLEX™, Proposed Name) in the Treatment of Advanced Dupuytren's Disease
A Phase 3 study testing collagenase clostridium histolyticum in people with Advanced Dupuytren's Disease, run by Endo USA Inc., a Keenova Therapeutics Company at 7 sites in Australia.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Dupuytren's Disease
- What is being tested?
- collagenase clostridium histolyticum
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 66 participants
- Where
- 7 sitesAustralia
- Study dates
- Aug 2007to Sep 2008
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
Australia7 sites
Rivercity Research
Auchenflower, Queensland, 4067
Brisbane Hand & Upper Limb Clinic
Brisbane, Queensland, 4000
Caboolture Clinical Research Centre
Caboolture, Queensland, 4510
Menzies Reserarch Institute
Hobart, Tasmania, 7000
Peninsula Clinical Research Centre
Kippa-Ring, Queensland, 4019
Emeritus Research
Malvern, Victoria, 3144
Royal Perth Hospital
Shenton Park, Western Australia, 6007
About this study
Official 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
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.
- Conditions
- Advanced Dupuytren's Disease
- Being tested
- collagenase clostridium histolyticum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
collagenase clostridium histolyticumBiological
Also called XIAFLEX®, AA4500
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.
| Study group | Role | What they receive |
|---|---|---|
| AA4500 0.58 mg | Experimental | Not described Receives: Biological: collagenase clostridium histolyticum |
| Placebo | Placebo comparator | Not described Receives: Biological: collagenase clostridium histolyticum |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reduction in Primary Joint Contracture to 5° or Less
Successfully treated or clinical success in primary joint defined as reduction in contracture to within 0-5° of normal within 30 days of injection.
Measured: Within 30 days after last injection
Secondary outcomes (17)
Clinical Improvement in Primary Joint After the Last Injection
Clinical improvement in primary joint defined as ≥50% reduction from baseline in the degree of contracture within 30 days after injection
Measured: Baseline, Within 30 days after last injection
Percent Reduction From Baseline Contracture of Primary Joint After the Last Injection
Percent change in degree of contracture of primary joint measured as 100 * (baseline contracture - last available post-injection contracture)/baseline contracture
Measured: Baseline, Day 30 after last injection
Change From Baseline Range of Motion in Primary Joint After the 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
Measured: Baseline, Day 30 after last injection
Time to Reach Clinical Success in Primary Joint
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
Measured: Within 30 days after last injection
Clinical Success in Primary Joint After the First Injection
Clinical success in primary joint defined as reduction in contracture to within 0-5° of normal within 30 days of injection.
Measured: Within 30 days after first injection
Clinical Improvement in Primary Joint After the First Injection
Clinical improvement in primary joint defined as ≥50% reduction from baseline in the degree of contracture within 30 days after injection
Measured: Baseline, Within 30 days after first injection
Percent Reduction From Baseline Contracture of Primary Joint After the 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
Measured: Baseline, Day 30 after first injection
Change From Baseline Range of Motion in Primary Joint After the 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
Measured: Baseline, Day 30 after first injection
Reduction in Non-primary Joint Contracture to 5° or Less After the 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.
Measured: Within 30 days after last injection
Clinical Improvement in Non-Primary Joint After the Last Injection
Clinical improvement in non-primary joint defined as ≥50% reduction from baseline in the degree of contracture within 30 days after injection
Measured: Baseline, Within 30 days after last injection
Percent Reduction From Baseline Contracture of Non-Primary Joint After the Last Injection
Percent change in degree of contracture of non-primary joint measured as 100 * (baseline contracture - last available post-injection contracture)/baseline contracture
Measured: Baseline, Day 30 after last injection
Change From Baseline Range of Motion in Non-Primary Joint After the 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
Measured: Baseline, Day 30 after last injection
Time to Reach Clinical Success in Non-Primary Joint
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
Measured: Within 30 days after last injection
Clinical Success in Non-Primary Joint After the First Injection
Clinical success in non-primary joint defined as reduction in contracture to within 0-5° of normal within 30 days of injection.
Measured: Within 30 days after first injection
Clinical Improvement in Non-Primary Joint After the First Injection
Clinical improvement in non-primary joint defined as ≥50% reduction from baseline in the degree of contracture within 30 days after injection
Measured: Baseline, Within 30 days after first injection
Percent Reduction From Baseline Contracture of Non-Primary Joint After the 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
Measured: Baseline, Day 30 after first injection
Change From Baseline Range of Motion in Non-Primary Joint After the 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
Measured: Baseline, Day 30 after first injection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2007 (estimated)
- Study startAug 2007
- Primary completionSep 2008
- Study completionSep 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Advanced Dupuytren's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- Endo USA Inc., a Keenova Therapeutics Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Veronica Urdaneta, MD, Study director, Endo USA Inc., a Keenova Therapeutics Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00533273
- Sponsor's protocol ID
- AUX CC 859
- Acronym
- CORD-II
- Status last verified
- Oct 2017
- First submitted
- 20 Sep 2007
- Last updated
- 2 Dec 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT00533273
- Acronym / sponsor ID
- CORD-II / AUX CC 859
- Conditions
- Advanced Dupuytren's Disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- Endo USA Inc., a Keenova Therapeutics CompanyIndustry (pharma, biotech, devices)
- Study start
- Aug 2007 (actual)
- Primary completion
- Sep 2008 (actual)
- Study completion
- Sep 2008 (actual)
- First posted
- 21 Sep 2007 (estimated)
- Results
- Posted 22 Oct 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AA4500 0.58 mg | Experimental | Biological: collagenase clostridium histolyticum |
| Placebo | Placebo comparator | Biological: collagenase clostridium histolyticum |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| collagenase clostridium histolyticumAlso: XIAFLEX®, AA4500Subjects 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. | Biological | AA4500 0.58 mg, Placebo |
Primary outcome
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.
17 secondary outcomes
Clinical Improvement in Primary Joint After the Last Injection
Time frame: 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
Change From Baseline Range of Motion in Primary Joint After the Last Injection
Time frame: 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 After the First Injection
Time frame: Within 30 days after first injection
Clinical Improvement in Primary Joint After the First Injection
Time frame: 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
Change From Baseline Range of Motion in Primary Joint After the First Injection
Time frame: 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
Clinical Improvement in Non-Primary Joint After the Last Injection
Time frame: 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
Change From Baseline Range of Motion in Non-Primary Joint After the Last Injection
Time frame: 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 After the First Injection
Time frame: 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
Percent Reduction From Baseline Contracture of Non-Primary Joint After the First Injection
Time frame: 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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- XIAFLEX Prescribing InformationLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Veronica Urdaneta, MD study director
Endo USA Inc., a Keenova Therapeutics Company
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing collagenase clostridium histolyticum in people with Advanced Dupuytren's Disease, run by Endo USA Inc., a Keenova Therapeutics Company at 7 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Oct 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Reduction in Primary Joint Contracture to 5° or Less (time frame: Within 30 days after last injection). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2017.