Dupuytren's ContracturePhase 3NCT01674634
Safety and Efficacy of Two Concurrent Injections of AA4500 in Adult Subjects With Multiple Dupuytren's Contractures
A Phase 3 study testing XIAFLEX / XIAPEX in people with Dupuytren's Contracture, run by Endo USA Inc., a Keenova Therapeutics Company at 25 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Dupuytren's Contracture
- What is being tested?
- XIAFLEX / XIAPEX
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 715 participants
- Where
- 25 sitesUnited States
- Study dates
- Sep 2012to Jul 2013
- 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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Provide a signed and dated informed consent
- Be a man or woman ≥ 18 years of age
- 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
- Have a positive "table top test" defined as the inability to simultaneously place the affected finger(s) and palm flat against a table top
- 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).
- Be able to comply with the study visit schedule as specified in the protocol
Who cannot join
- A subject will be excluded from study participation if he/she:
- 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
- Has a chronic muscular, neurological, or neuromuscular disorder that affects the hands
- Has a known systemic allergy to collagenase or any other excipient of AA4500
- 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
- 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
Show all 11Show fewer
- 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
- Received an investigational drug within 30 days before injection of study drug
- Is pregnant or intends on becoming pregnant during the study or is breastfeeding a child
- 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
- Has jewelry on the hand to be treated that cannot be removed
Trial locations and contacts
25 sites in 1 country.
25 sites in 1 country
United States25 sites
The Arthritis Clinic of Northern Virginia, PA
Arlington, Virginia, 22205
The Hand and Upper Extremity Center
Atlanta, Georgia, 30342
The Center for Neurosurgical and Orthopedic Care and Research
Bend, Oregon, 97701
UNC School of Medicine
Chapel Hill, North Carolina, 27599
OrthoCarolina Research Institute, Inc.
Charlotte, North Carolina, 28207
Alpha Clinical Research, LLC
Clarksville, Tennessee, 37043
Central Jersey Hand Surgery
Eatontown, New Jersey, 07724
CORE Orthopaedic Medical Center
Encinitas, California, 92024
Hand Microsurgery & Reconstructive Orthopaedics
Erie, Pennsylvania, 16507
Accurate Clinical Research, Inc.
Houston, Texas, 77034
The Indiana Hand to Shoulder Center
Indianapolis, Indiana, 46260
University of Kansas Medical Center
Kansas City, Kansas, 66160
Torrey Pines Medical Group
La Jolla, California, 92037
Nevada Orthopedic and Spine Center
Las Vegas, Nevada, 89128
Christine M. Kleinert Institute for Hand and Microsurgery, Inc.
Louisville, Kentucky, 40202
TRIA Orthopedic Center
Minneapolis, Minnesota, 55431
Missoula Bone and Joint
Missoula, Montana, 59808
Brigid Freyne, MD, Inc.
Murrieta, California, 92563
Hospital for Special Surgery
New York, New York, 10021
Health Research Institute
Oklahoma City, Oklahoma, 73109
HOPE Research Institute
Phoenix, Arizona, 85018
Rockford Orthopedic Associates
Rockford, Illinois, 61107
SUNY Stony Brook
Setauket, New York, 11733
Lake Cumberland Rheumatology
Somerset, Kentucky, 42503
Tucson Orthopaedic Institute
Tucson, Arizona, 85712
About this study
Official title: 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
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.
Read the 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.
- Conditions
- Dupuytren's Contracture
- Being tested
- XIAFLEX / XIAPEX
- Keywords
- XIAFLEX, XIAPEX, Dupuytren's disease, contracture
- Medical subject headings
- Dupuytren Contracture, Contracture
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
XIAFLEX / XIAPEXBiological
Also called AA4500 (collagenase clostridium histolyticum)
injection (0.58 mg after reconstitution with sterile diluent [0.3 mg/mL calcium chloride dihydrate in 0.9% sodium chloride])
| Study group | Role | What they receive |
|---|---|---|
| XIAFLEX / XIAPEX | Experimental | AA4500 (collagenase clostridium histolyticum) Receives: Biological: XIAFLEX / XIAPEX |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change From Baseline in Total Fixed Flexion
Percent change from baseline in total fixed flexion = 100 * (baseline total FFC - day 31 total FFC)/baseline total FFC, where total fixed flexion is defined as the sum of the fixed flexion contracture (FCC) of the 2 joints receiving treatment. Positive percent change from baseline indicates improvement.
Measured: Baseline, Day 31
Change From Baseline in Total Range of Motion
The total range of motion (ROM) is the sum of the range of motion measurements of the 2 treated joints. ROM is defined as difference between full flexion angle and full extension expressed in degrees. A positive change from baseline indicates increased (improved) ROM.
Measured: Baseline, Day 31
Secondary outcomes (8)
Clinical Success
Clinical success is defined as reduction of FFC of a treated joint to within 0-5 degrees of normal within 30 days of injection
Measured: Within 30 days
Clinical Improvement
Clinical improvement is defined as a reduction of FFC by 50% or greater of the baseline value within 30 days of injection
Measured: Within 30 days
Subject Assessment of Satisfaction With Treatment at Day 31
Subject's were asked to rate satisfaction with treatment at the day 31 follow-up visit
Measured: Day 31
Subject Assessment of Satisfaction With Treatment at Day 61
Subject's were asked to rate satisfaction with treatment at the day 61 follow-up visit
Measured: Day 61
Investigator Assessment of Improvement With Treatment at Day 31
Investigator's determined the degree of improvement in the severity of the subject's treated finger(s) compared with screening at the day 31 follow-up visit.
Measured: Day 31
Investigator Assessment of Improvement With Treatment at Day 61
Investigator's determined the degree of improvement in the severity of the subject's treated finger(s) compared with screening at the day 61 follow-up visit.
Measured: Day 61
Change From Baseline for Unité Rhumatologique Des Affections de la Main Scale at Day 31
The Unité Rhumatologique des Affections de la Main (URAM) scale is a patient-reported functional 9-item scale (total score 0-45) developed and validated to assess functional outcome of patients suffering from Dupuytren's disease with higher scores indicating greater difficulty using the hand.The estimated clinically important change of the URAM scale is 2.9 points. A decrease in total URAM score indicates improvement in hand function.
Measured: Baseline, Day 31
Change From Baseline for Unité Rhumatologique Des Affections de la Main Scale at Day 61
The URAM scale is a patient-reported functional 9-item scale (total score 0-45) developed and validated to assess functional outcome of patients suffering from Dupuytren's disease with higher scores indicating greater difficulty using the hand.The estimated clinically important change of the URAM scale is 2.9 points. A decrease in total URAM score indicates improvement in hand function.
Measured: Baseline, Day 61
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2012 (estimated)
- Study startSep 2012
- Primary completionJul 2013
- Study completionJul 2013
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 Dupuytren's ContractureStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 715 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, MPPH, Study director, Endo USA Inc., a Keenova Therapeutics Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01674634
- Sponsor's protocol ID
- AUX-CC-867
- Status last verified
- Sep 2017
- First submitted
- 27 Aug 2012
- Last updated
- 5 Oct 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 5 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01674634
- Acronym / sponsor ID
- AUX-CC-867
- Conditions
- Dupuytren's Contracture
- Keywords
- XIAFLEX, XIAPEX, Dupuytren's disease, contracture
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 715 participants (actual)
- Lead sponsor
- Endo USA Inc., a Keenova Therapeutics CompanyIndustry (pharma, biotech, devices)
- Study start
- Sep 2012
- Primary completion
- Jul 2013 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 29 Aug 2012 (estimated)
- Results
- Posted 20 Feb 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| XIAFLEX / XIAPEX | Experimental | Biological: XIAFLEX / XIAPEXAA4500 (collagenase clostridium histolyticum) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Provide a signed and dated informed consent
- Be a man or woman ≥ 18 years of age
- 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
- Have a positive "table top test" defined as the inability to simultaneously place the affected finger(s) and palm flat against a table top
- 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).
Key exclusion criteria (11 listed)
- 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
- Has a chronic muscular, neurological, or neuromuscular disorder that affects the hands
- Has a known systemic allergy to collagenase or any other excipient of AA4500
- 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
- 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
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 |
|---|---|---|
| XIAFLEX / XIAPEXAlso: AA4500 (collagenase clostridium histolyticum)injection (0.58 mg after reconstitution with sterile diluent [0.3 mg/mL calcium chloride dihydrate in 0.9% sodium chloride]) | Biological | XIAFLEX / XIAPEX |
Primary outcome
Percent Change From Baseline in Total Fixed Flexion
Time frame: Baseline, Day 31
Percent change from baseline in total fixed flexion = 100 * (baseline total FFC - day 31 total FFC)/baseline total FFC, where total fixed flexion is defined as the sum of the fixed flexion contracture (FCC) of the 2 joints receiving treatment. Positive percent change from baseline indicates improvement.
Change From Baseline in Total Range of Motion
Time frame: Baseline, Day 31
The total range of motion (ROM) is the sum of the range of motion measurements of the 2 treated joints. ROM is defined as difference between full flexion angle and full extension expressed in degrees. A positive change from baseline indicates increased (improved) ROM.
8 secondary outcomes
Clinical Success
Time frame: Within 30 days
Clinical Improvement
Time frame: Within 30 days
Subject Assessment of Satisfaction With Treatment at Day 31
Time frame: Day 31
Subject Assessment of Satisfaction With Treatment at Day 61
Time frame: Day 61
Investigator Assessment of Improvement With Treatment at Day 31
Time frame: Day 31
Investigator Assessment of Improvement With Treatment at Day 61
Time frame: Day 61
Change From Baseline for Unité Rhumatologique Des Affections de la Main Scale at Day 31
Time frame: Baseline, Day 31
Change From Baseline for Unité Rhumatologique Des Affections de la Main Scale at Day 61
Time frame: Baseline, Day 61
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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, MPPH study director
Endo USA Inc., a Keenova Therapeutics Company
25 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 XIAFLEX / XIAPEX in people with Dupuytren's Contracture, run by Endo USA Inc., a Keenova Therapeutics Company at 25 sites in United States.
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 6 inclusion and 11 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 5 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in United States. 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. 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 20 Feb 2015). 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?
Percent Change From Baseline in Total Fixed Flexion (time frame: Baseline, Day 31). The study lists 2 primary outcomes in all. 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 5 Oct 2017.