Dupuytren's DiseasePhase 2NCT02193828
Phase 2a Dose-Ranging Study to Evaluate Safety and Effectiveness of AA4500 in Treatment of Dupuytren's Disease Nodules
A Phase 2 study testing Collagenase clostridium histolyticum in people with Dupuytren's Disease, run by Endo USA Inc., a Keenova Therapeutics Company at 11 sites in 2 countries.
Trial summary
The objectives of this study are to assess the safety and effectiveness of AA4500 in treating palmar Dupuytren's disease nodules. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- 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
- 76 participants
- Where
- 11 sitesin 2 countries
- Study dates
- Jul 2014to Dec 2014
- Phase
- Phase 2
- 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
- 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 one palmar nodule on the selected hand that is:
- Palpable
- Measures between 0.5 cm and 2.0 cm in length and between 0.5 cm and 2.0 cm in width using hand-held calipers n
- Not directly associated with a Dupuytren's cord
- 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
- Received steroid injections (eg, tri-amcinolone acetonide) on the selected nodule within 3 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
- 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
Show all 11Show fewer
- 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
- Had surgery on the selected hand within 3 months before the screening visit
- Has jewelry on the hand to be treated that cannot be removed
Trial locations and contacts
11 sites in 2 countries.
11 sites in 2 countries
United States9 sites
Blair Orthopedic Associates, Inc.
Altoona, Pennsylvania, 16602
OrthoCarolina Research Institute, Inc.
Charlotte, North Carolina, 28207
CORE Orthopaedic Medical Center
Encinitas, California, 92024
Marin Endocrine Care & Research, Inc.
Greenbrae, California, 94904
Indiana Hand to Shoulder Center
Indianapolis, Indiana, 46260
Brigid Freyne, MD, Inc.
Murrieta, California, 92563
Orthopedic and Reconstructive Center
Oklahoma City, Oklahoma, 73109
State University of New York
Stony Brook, New York, 11794
Tucson Orthopaedic Institute
Tucson, Arizona, 85712
Australia2 sites
Brisbane Hand & Upper Limb Clinic
Brisbane, Queensland, 4000
Houston Medical
Kippa-Ring, Queensland, 4021
About this study
Official title: A Phase 2a, Double-blind, Randomized, Placebo-Controlled, Dose-Ranging Study to Evaluate the Safety and Effectiveness of AA4500 in the Treatment of Dupuytren's Disease Nodules
The objectives of this study are to assess the safety and effectiveness of AA4500 in treating palmar Dupuytren's disease nodules.
Read the detailed description
Approximately 13 sites in the United States and Australia, approximately 90 study subjects.
After all pre-injection procedures are completed on day 1, eligible men and women will be randomized in a 1:1:1 ratio to dose group and then in a 4:1 ratio to treatment group. Study drug will be administered into a palmar nodule located on the selected hand.
AA4500 (collagenase clostridium histolyticum) 3 doses (low, medium, and high) after reconstitution with sterile diluent (0.3 mg/mL calcium chloride dihydrate in 0.9% sodium chloride). Each dose of study drug will be injected into the nodule. The injection will be administered in 3 different volumes according to randomization.
Placebo after reconstitution with sterile diluent (0.3 mg/mL calcium chloride dihydrate in 0.9% sodium chloride). Each dose of study drug will be injected into the nodule. The injection will be administered in 3 different volumes according to randomization.
Follow up visits for the evaluation of safety and efficacy will be required for all subjects on days 8, 29, and 57.
- Conditions
- Dupuytren's Disease
- Being tested
- Collagenase clostridium histolyticum, Placebo
- Keywords
- Dupuytren's nodules
- Medical subject headings
- Dupuytren Contracture
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Collagenase clostridium histolyticumBiological
Also called AA4500, XIAFLEX, XIAPEX
Single injection into nodule
PlaceboBiological
Single injection into nodule
| Study group | Role | What they receive |
|---|---|---|
| AA4500 0.25 mg | Experimental | Collagenase clostridium histolyticum, single 0.25 mg injection Receives: Biological: Collagenase clostridium histolyticum |
| AA4500 0.40 mg | Experimental | Collagenase clostridium histolyticum, single 0.40 mg injection Receives: Biological: Collagenase clostridium histolyticum |
| AA4500 0.60 mg | Experimental | Collagenase clostridium histolyticum, single 0.60 mg injection Receives: Biological: Collagenase clostridium histolyticum |
| Placebo | Placebo comparator | Placebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change From Baseline in Surface Area and Volume of the Treated Nodule at Day 57 Using Caliper Measurements
Percent change from baseline in surface area and volume of the treated nodule was determined from hand-held caliper measurements of the length and width of the nodule. Percent change = 100*(Day 57 area [or volume] - baseline area [or volume])/baseline area [or volume]. A negative value represents the improvement from baseline (decreased size) while a positive value represents worsening.
Measured: Baseline, Day 57
Secondary outcomes (7)
Percent Change From Baseline in Surface Area and Volume of the Treated Nodule at Day 57 Using Ultrasound
Percent change from baseline in surface area and volume of the treated nodule was determined from ultrasound measurements of the length, width, and depth of the nodule. Percent change = 100*(Day 57 area [or volume] - baseline area [or volume])/baseline area [or volume]. A negative value represents the improvement from baseline (decreased size) while a positive value represents worsening.
Measured: Baseline, Day 57
Change From Baseline in Consistency of the Treated Nodules at Day 57
Investigators determined the consistency of the nodule through palpitation using a 5-point scale: 5 = hard (solid), 4 = firm throughout, 3 = moderate firmness, 2 = soft, and 1 = non-palpable. The change scores could range from +4 (greatest worsening in consistency) to -4 (greatest improvement in consistency); a negative change from baseline value reflects improvement from baseline (softening) while a positive value reflects worsening.
Measured: Baseline, Day 57
Percent Change From Baseline in Hardness of the Treated Nodule at Day 57
A durometer was used to assess nodule hardness on a scale of 0 (soft) to 100 (hard). Percent change = 100*(Day 57 hardness - baseline hardness)/baseline hardness. A negative value represents the improvement from baseline (softening) while a positive value represents worsening.
Measured: Baseline, Day 57
Change From Baseline in Nodular Pain of the Treated Nodule at Day 57
After the nodule was squeezed using a dynamometer, subjects were asked to rate the amount of pain they felt on an 11-point visual analog scale (VAS) from 0 (no pain or discomfort) to 10 (extreme pain or discomfort). A negative change from baseline value reflects improvement from baseline (less pain) while a positive value reflects worsening.
Measured: Baseline, Day 57
Investigator Global Assessment of Improvement With Treatment
Investigators were asked to determine the degree of improvement in the subject's treated nodule compared with screening on a 7-point scale: 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse.
Measured: Day 57
Subject Satisfaction With Treatment
Subjects were asked to rate their satisfaction with treatment on a 5-point scale: 1 = very satisfied, 2 = quite satisfied, 3 = neither satisfied nor dissatisfied, 4 = quite dissatisfied, and 5 = very dissatisfied.
Measured: Day 57
Composite Responder Analysis
A composite responder is a subject who had an improved assessment [values of 1 (very much improved), 2 (much improved), or 3 (minimally improved)] on the investigator global assessment and had a satisfied assessment [values of 1 (very satisfied) or 2 (quite satisfied)] on the subject assessment.
Measured: Day 57
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2014 (estimated)
- Study startJul 2014
- Primary completionDec 2014
- Study completionDec 2014
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 76 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 MPH, Study director, Endo USA Inc., a Keenova Therapeutics Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02193828
- Sponsor's protocol ID
- AUX-CC-750
- Status last verified
- Sep 2017
- First submitted
- 19 Jun 2014
- Last updated
- 5 Oct 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Costas B, Coleman S, Kaufman G, James R, Cohen B, Gaston RG. Efficacy and safety of collagenase clostridium histolyticum for Dupuytren disease nodules: a randomized controlled trial. BMC Musculoskelet Disord. 2017 Aug 30;18(1):374. doi: 10.1186/s12891-017-1713-z.
PubMed 28854973
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 2a, Double-blind, Randomized, Placebo-Controlled, Dose-Ranging Study to Evaluate the Safety and Effectiveness of AA4500 in the Treatment of Dupuytren's Disease Nodules
- ClinicalTrials.gov ID
- NCT02193828
- Acronym / sponsor ID
- AUX-CC-750
- Conditions
- Dupuytren's Disease
- Keywords
- Dupuytren's nodules
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 76 participants (actual)
- Lead sponsor
- Endo USA Inc., a Keenova Therapeutics CompanyIndustry (pharma, biotech, devices)
- Study start
- Jul 2014
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 18 Jul 2014 (estimated)
- Results
- Posted 7 Jul 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objectives of this study are to assess the safety and effectiveness of AA4500 in treating palmar Dupuytren's disease nodules.
Detailed description
Approximately 13 sites in the United States and Australia, approximately 90 study subjects.
After all pre-injection procedures are completed on day 1, eligible men and women will be randomized in a 1:1:1 ratio to dose group and then in a 4:1 ratio to treatment group. Study drug will be administered into a palmar nodule located on the selected hand.
AA4500 (collagenase clostridium histolyticum) 3 doses (low, medium, and high) after reconstitution with sterile diluent (0.3 mg/mL calcium chloride dihydrate in 0.9% sodium chloride). Each dose of study drug will be injected into the nodule. The injection will be administered in 3 different volumes according to randomization.
Placebo after reconstitution with sterile diluent (0.3 mg/mL calcium chloride dihydrate in 0.9% sodium chloride). Each dose of study drug will be injected into the nodule. The injection will be administered in 3 different volumes according to randomization.
Follow up visits for the evaluation of safety and efficacy will be required for all subjects on days 8, 29, and 57.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| AA4500 0.25 mg | Experimental | Biological: Collagenase clostridium histolyticumCollagenase clostridium histolyticum, single 0.25 mg injection |
| AA4500 0.40 mg | Experimental | Biological: Collagenase clostridium histolyticumCollagenase clostridium histolyticum, single 0.40 mg injection |
| AA4500 0.60 mg | Experimental | Biological: Collagenase clostridium histolyticumCollagenase clostridium histolyticum, single 0.60 mg injection |
| Placebo | Placebo comparator | Biological: PlaceboPlacebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 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 one palmar nodule on the selected hand that is:
- 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
Key exclusion criteria (11 listed)
- Received steroid injections (eg, tri-amcinolone acetonide) on the selected nodule within 3 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 |
|---|---|---|
| Collagenase clostridium histolyticumAlso: AA4500, XIAFLEX, XIAPEXSingle injection into nodule | Biological | AA4500 0.25 mg, AA4500 0.40 mg, AA4500 0.60 mg |
| PlaceboSingle injection into nodule | Biological | Placebo |
Primary outcome
Percent Change From Baseline in Surface Area and Volume of the Treated Nodule at Day 57 Using Caliper Measurements
Time frame: Baseline, Day 57
Percent change from baseline in surface area and volume of the treated nodule was determined from hand-held caliper measurements of the length and width of the nodule. Percent change = 100*(Day 57 area [or volume] - baseline area [or volume])/baseline area [or volume]. A negative value represents the improvement from baseline (decreased size) while a positive value represents worsening.
7 secondary outcomes
Percent Change From Baseline in Surface Area and Volume of the Treated Nodule at Day 57 Using Ultrasound
Time frame: Baseline, Day 57
Change From Baseline in Consistency of the Treated Nodules at Day 57
Time frame: Baseline, Day 57
Percent Change From Baseline in Hardness of the Treated Nodule at Day 57
Time frame: Baseline, Day 57
Change From Baseline in Nodular Pain of the Treated Nodule at Day 57
Time frame: Baseline, Day 57
Investigator Global Assessment of Improvement With Treatment
Time frame: Day 57
Subject Satisfaction With Treatment
Time frame: Day 57
Composite Responder Analysis
Time frame: Day 57
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.
- Derived from this study: PubMed 28854973Costas B, Coleman S, Kaufman G, James R, Cohen B, Gaston RG. Efficacy and safety of collagenase clostridium histolyticum for Dupuytren disease nodules: a randomized controlled trial. BMC Musculoskelet Disord. 2017 Aug 30;18(1):374. doi: 10.1186/s12891-017-1713-z.
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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 MPH study director
Endo USA Inc., a Keenova Therapeutics Company
11 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Collagenase clostridium histolyticum in people with Dupuytren's Disease, run by Endo USA Inc., a Keenova Therapeutics Company at 11 sites in 2 countries.
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 8 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 11 sites in United States, 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 7 Jul 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 Surface Area and Volume of the Treated Nodule at Day 57 Using Caliper Measurements (time frame: Baseline, Day 57). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02193828, which also lists 1 linked publication.
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.