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Phase 2a Dose-Ranging Study to Evaluate Safety and Effectiveness of AA4500 in Treatment of Dupuytren's Disease Nodules

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ClinicalTrials.gov Identifier: NCT02193828
Recruitment Status : Completed
First Posted : July 18, 2014
Results First Posted : July 7, 2015
Last Update Posted : October 5, 2017
Sponsor:
Information provided by (Responsible Party):
Endo Pharmaceuticals

Brief Summary:
The objectives of this study are to assess the safety and effectiveness of AA4500 in treating palmar Dupuytren's disease nodules.

Condition or disease Intervention/treatment Phase
Dupuytren's Disease Biological: Collagenase clostridium histolyticum Biological: Placebo Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 76 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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
Study Start Date : July 2014
Actual Primary Completion Date : December 2014
Actual Study Completion Date : December 2014

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: AA4500 0.25 mg
Collagenase clostridium histolyticum, single 0.25 mg injection
Biological: Collagenase clostridium histolyticum
Single injection into nodule
Other Names:
  • AA4500
  • XIAFLEX
  • XIAPEX

Experimental: AA4500 0.40 mg
Collagenase clostridium histolyticum, single 0.40 mg injection
Biological: Collagenase clostridium histolyticum
Single injection into nodule
Other Names:
  • AA4500
  • XIAFLEX
  • XIAPEX

Experimental: AA4500 0.60 mg
Collagenase clostridium histolyticum, single 0.60 mg injection
Biological: Collagenase clostridium histolyticum
Single injection into nodule
Other Names:
  • AA4500
  • XIAFLEX
  • XIAPEX

Placebo Comparator: Placebo
Placebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection
Biological: Placebo
Single injection into nodule




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Percent Change From Baseline in Surface Area and Volume of the Treated Nodule at Day 57 Using Ultrasound [ Time Frame: Baseline, Day 57 ]
    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.

  2. Change From Baseline in Consistency of the Treated Nodules at Day 57 [ Time Frame: Baseline, 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.

  3. Percent Change From Baseline in Hardness of the Treated Nodule at Day 57 [ Time Frame: Baseline, 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.

  4. Change From Baseline in Nodular Pain of the Treated Nodule at Day 57 [ Time Frame: Baseline, 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.

  5. Investigator Global Assessment of Improvement With Treatment [ Time Frame: Day 57 ]
    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.

  6. Subject Satisfaction With Treatment [ Time Frame: Day 57 ]
    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.

  7. Composite Responder Analysis [ Time Frame: Day 57 ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Provide a signed and dated informed consent
  2. Be a man or woman ≥ 18 years of age
  3. Have a diagnosis of Dupuytren's disease AND have at least one palmar nodule on the selected hand that is:

    1. Palpable
    2. 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
    3. Not directly associated with a Dupuytren's cord
  4. 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)
  5. Be able to comply with the study visit schedule as specified in the protocol

Exclusion Criteria:

  1. Received steroid injections (eg, tri-amcinolone acetonide) on the selected nodule within 3 months before administration of study drug
  2. Has a chronic muscular, neurological, or neuromuscular disorder that affects the hands
  3. Has a known systemic allergy to collagenase or any other excipient of AA4500
  4. 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
  5. 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
  6. 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
  7. Received an investigational drug within 30 days before injection of study drug
  8. Is pregnant or intends on becoming pregnant during the study or is breastfeeding a child
  9. 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
  10. Had surgery on the selected hand within 3 months before the screening visit
  11. Has jewelry on the hand to be treated that cannot be removed

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02193828


Locations
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United States, Arizona
Tucson Orthopaedic Institute
Tucson, Arizona, United States, 85712
United States, California
CORE Orthopaedic Medical Center
Encinitas, California, United States, 92024
Marin Endocrine Care & Research, Inc.
Greenbrae, California, United States, 94904
Brigid Freyne, MD, Inc.
Murrieta, California, United States, 92563
United States, Indiana
Indiana Hand to Shoulder Center
Indianapolis, Indiana, United States, 46260
United States, New York
State University of New York
Stony Brook, New York, United States, 11794
United States, North Carolina
OrthoCarolina Research Institute, Inc.
Charlotte, North Carolina, United States, 28207
United States, Oklahoma
Orthopedic and Reconstructive Center
Oklahoma City, Oklahoma, United States, 73109
United States, Pennsylvania
Blair Orthopedic Associates, Inc.
Altoona, Pennsylvania, United States, 16602
Australia, Queensland
Brisbane Hand & Upper Limb Clinic
Brisbane, Queensland, Australia, 4000
Houston Medical
Kippa Ring, Queensland, Australia, 4021
Sponsors and Collaborators
Endo Pharmaceuticals
Investigators
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Study Director: Veronica Urdaneta, MD MPH Endo Pharmaceuticals

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Endo Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02193828     History of Changes
Other Study ID Numbers: AUX-CC-750
First Posted: July 18, 2014    Key Record Dates
Results First Posted: July 7, 2015
Last Update Posted: October 5, 2017
Last Verified: September 2017

Keywords provided by Endo Pharmaceuticals:
Dupuytren's nodules

Additional relevant MeSH terms:
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Dupuytren Contracture
Fibroma
Neoplasms, Fibrous Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Contracture
Muscular Diseases
Musculoskeletal Diseases
Connective Tissue Diseases