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

Primary Purpose

Dupuytren's Disease

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Collagenase clostridium histolyticum
Placebo
Sponsored by
Endo Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Dupuytren's Disease focused on measuring Dupuytren's nodules

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Tucson Orthopaedic Institute
  • CORE Orthopaedic Medical Center
  • Marin Endocrine Care & Research, Inc.
  • Brigid Freyne, MD, Inc.
  • Indiana Hand to Shoulder Center
  • State University of New York
  • OrthoCarolina Research Institute, Inc.
  • Orthopedic and Reconstructive Center
  • Blair Orthopedic Associates, Inc.
  • Brisbane Hand & Upper Limb Clinic
  • Houston Medical

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

AA4500 0.25 mg

AA4500 0.40 mg

AA4500 0.60 mg

Placebo

Arm Description

Collagenase clostridium histolyticum, single 0.25 mg injection

Collagenase clostridium histolyticum, single 0.40 mg injection

Collagenase clostridium histolyticum, single 0.60 mg injection

Placebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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.

Full Information

First Posted
June 19, 2014
Last Updated
September 7, 2017
Sponsor
Endo Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT02193828
Brief Title
Phase 2a Dose-Ranging Study to Evaluate Safety and Effectiveness of AA4500 in Treatment of Dupuytren's Disease Nodules
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 Type
Interventional

2. Study Status

Record Verification Date
September 2017
Overall Recruitment Status
Completed
Study Start Date
July 2014 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
December 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Endo Pharmaceuticals

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dupuytren's Disease
Keywords
Dupuytren's nodules

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
76 (Actual)

8. Arms, Groups, and Interventions

Arm Title
AA4500 0.25 mg
Arm Type
Experimental
Arm Description
Collagenase clostridium histolyticum, single 0.25 mg injection
Arm Title
AA4500 0.40 mg
Arm Type
Experimental
Arm Description
Collagenase clostridium histolyticum, single 0.40 mg injection
Arm Title
AA4500 0.60 mg
Arm Type
Experimental
Arm Description
Collagenase clostridium histolyticum, single 0.60 mg injection
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection
Intervention Type
Biological
Intervention Name(s)
Collagenase clostridium histolyticum
Other Intervention Name(s)
AA4500, XIAFLEX, XIAPEX
Intervention Description
Single injection into nodule
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Single injection into nodule
Primary Outcome Measure Information:
Title
Percent Change From Baseline in Surface Area and Volume of the Treated Nodule at Day 57 Using Caliper Measurements
Description
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.
Time Frame
Baseline, Day 57
Secondary Outcome Measure Information:
Title
Percent Change From Baseline in Surface Area and Volume of the Treated Nodule at Day 57 Using Ultrasound
Description
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.
Time Frame
Baseline, Day 57
Title
Change From Baseline in Consistency of the Treated Nodules at Day 57
Description
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.
Time Frame
Baseline, Day 57
Title
Percent Change From Baseline in Hardness of the Treated Nodule at Day 57
Description
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.
Time Frame
Baseline, Day 57
Title
Change From Baseline in Nodular Pain of the Treated Nodule at Day 57
Description
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.
Time Frame
Baseline, Day 57
Title
Investigator Global Assessment of Improvement With Treatment
Description
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.
Time Frame
Day 57
Title
Subject Satisfaction With Treatment
Description
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.
Time Frame
Day 57
Title
Composite Responder Analysis
Description
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.
Time Frame
Day 57

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Veronica Urdaneta, MD MPH
Organizational Affiliation
Endo Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Tucson Orthopaedic Institute
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85712
Country
United States
Facility Name
CORE Orthopaedic Medical Center
City
Encinitas
State/Province
California
ZIP/Postal Code
92024
Country
United States
Facility Name
Marin Endocrine Care & Research, Inc.
City
Greenbrae
State/Province
California
ZIP/Postal Code
94904
Country
United States
Facility Name
Brigid Freyne, MD, Inc.
City
Murrieta
State/Province
California
ZIP/Postal Code
92563
Country
United States
Facility Name
Indiana Hand to Shoulder Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46260
Country
United States
Facility Name
State University of New York
City
Stony Brook
State/Province
New York
ZIP/Postal Code
11794
Country
United States
Facility Name
OrthoCarolina Research Institute, Inc.
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28207
Country
United States
Facility Name
Orthopedic and Reconstructive Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73109
Country
United States
Facility Name
Blair Orthopedic Associates, Inc.
City
Altoona
State/Province
Pennsylvania
ZIP/Postal Code
16602
Country
United States
Facility Name
Brisbane Hand & Upper Limb Clinic
City
Brisbane
State/Province
Queensland
ZIP/Postal Code
4000
Country
Australia
Facility Name
Houston Medical
City
Kippa Ring
State/Province
Queensland
ZIP/Postal Code
4021
Country
Australia

12. IPD Sharing Statement

Citations:
PubMed Identifier
28854973
Citation
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.
Results Reference
derived

Learn more about this trial

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

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