Collagenase in the Treatment of Dupuytrens Disease

• Sponsor: Stony Brook University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00260429
• Collaborator: Biospecifics Technologies Corp. (Industry), Endo Pharmaceuticals (Industry)
• Enrollment: 38
• Location: 1
• Arms: 2
• Duration (Months): 58
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The purpose of the study is to determine if collagenase will reduce the degree of contracture in the primary joint in subjects with Dupuytren's disease.

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 and AUX-CC-859) and 7 non-pivotal studies were evaluated.

Condition or Disease	Intervention/Treatment	Phase
Dupuytren's Disease	Biological: collagenase clostridium histolyticum	Phase 3

Detailed Description

In a random, placebo controlled, double blind study, collagenase injection therapy will be investigated for it's ability to disrupt the Dupuytren's cord.

Resultant cord disruption may obviate the need for patients to have surgery to correct the finger flexion contractures of Dupuytren's disease.

Study Design

• Study Type: Interventional
• Actual Enrollment: 38 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Double-blind, Randomized Placebo Controlled Study of the Relative Safety and Efficacy of Collagenase Therapy in the Treatment of Residual-type Dupuytren's Disease.
• Study Start Date: Jun 1, 2003
• Actual Primary Completion Date: Aug 1, 2005
• Actual Study Completion Date: Apr 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AA4500 0.58 mg	Biological: collagenase clostridium histolyticum; Subjects could have received up to three injections of AA4500/placebo into the cord of the affected hand. Each injection was separated by at least 30 days. Individual cords may have received up to a maximum of three injections.; Other Names: XIAFLEX® AA4500
Placebo Comparator: placebo	Biological: collagenase clostridium histolyticum; Subjects could have received up to three injections of AA4500/placebo into the cord of the affected hand. Each injection was separated by at least 30 days. Individual cords may have received up to a maximum of three injections.; Other Names: XIAFLEX® AA4500

Outcome Measures

Primary Outcome Measures

1. Primary Outcome Measure is Reduction of Flexion Contracture of the Primary Joint. [30 days after the last injection]

   The Primary Outcome Measure for patients treated with AA4500 is the percentage of 23 joints that were successfully treated where "successfully treated" was defined as reduction in contracture to 5° or less. The Primary Outcome Measure for placebo treated patients is the percentage of 12 joints that were successfully treated where "successfully treated" was defined as reduction in contracture to 5° or less.

Secondary Outcome Measures

1. Percent Reduction From Baseline Contracture After the Last Injection [30 days after last treatment to the primary joint]

2. Percent Change From Baseline Range of Motion After the Last Injection [30 days after last treatment to the primary joint]

3. Time to First Achieve and Maintain Clinical Success After the Last Injection [First evaluation visit on which clinical success is achieved and maintained through the Day 30 evaluation of the primary joint]

4. Clinical Success After the First Injection [30 days after first treatment to the primary joint]

5. Percent Reduction From Baseline Contracture After the First Injection [30 days after first treatment to the primary joint]

6. Change From Baseline Range of Motion After the First Injection [30 days after first treatment to the primary joint]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects were at least 18 years of age, of either sex or any race.

• Subjects had residual Dupuytren's disease with a fixed-flexion deformity of the finger(s) of at least 20 degrees or greater, caused by a palpable cord.

• Subjects had a positive "table-top test" defined as the inability to simultaneously place their affected finger(s) and palm flat against a table top.

• Subjects must have been willing to participate in and complete the study, and comply with its procedures by signing an IRB approved written consent form.

• Subjects must have been able to understand and adhere to the visit schedule. They must have been able to follow study procedures and instructions, and have agreed to report concomitant medications and adverse events accurately and consistently.

• Women of childbearing potential must have agreed to use an acceptable method of birth control or must have been surgically sterilized (hysterectomy or tubal ligation). Women of childbearing age had a urine pregnancy test on Day 0 (day of injection) prior to the injection.

Exclusion Criteria

• Women who were nursing or who were pregnant (as evidenced by a positive urine pregnancy test at the time of enrollment).

• Subjects who had participated in an investigational drug trial within 30 days of enrollment in this study.

• Subjects who had received surgery for Dupuytren's disease within 30 days of enrollment in this study.

• Subjects who had a known allergy to AA4500 or any of the inactive ingredients in the AA4500 injection.

• Subjects who had a known allergy to doxycycline.

• Subjects who had a medical condition that would have made them unsuitable for enrollment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stony Brook University Hospital and Mediacl Center	Stony Brook	New York	United States	11794

Sponsors and Collaborators

• Stony Brook University
• Biospecifics Technologies Corp.
• Endo Pharmaceuticals

Investigators

• Principal Investigator: Lawrence C Hurst, MD, Stony Brook University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• XIAFLEX Prescribing Information

Publications

• Badalamente MA, Hurst LC, Hentz VR. Collagen as a clinical target: nonoperative treatment of Dupuytren's disease. J Hand Surg Am. 2002 Sep;27(5):788-98.

• ClinicalTrials.gov Identifier: NCT00260429
• Other Study ID Numbers: DUPY 303
• First Posted: Dec 1, 2005
• Last Update Posted: Dec 9, 2010
• Last Verified: Nov 1, 2010

• Keywords provided by , ,: Dupuytren's contracture; fixed flexion contracture
• Additional relevant MeSH terms: Dupuytren Contracture

Study Results

Participant Flow

Arm/Group Title	AA4500	Placebo
Arm/Group Description	collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
Period Title: Overall Study
STARTED	23	12
COMPLETED	21	12
NOT COMPLETED	2	0

Baseline Characteristics

Arm/Group Title	AA4500	Placebo	Total
Arm/Group Description	collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints	Total of all reporting groups
Overall Participants	23	12	35
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	16 69.6%	5 41.7%	21 60%
>=65 years	7 30.4%	7 58.3%	14 40%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.1 (7.6)	63.8 (10.0)	61.3 (8.5)
Sex: Female, Male (Count of Participants)
Female	3 13%	4 33.3%	7 20%
Male	20 87%	8 66.7%	28 80%
Region of Enrollment (participants) [Number]
United States	23 100%	12 100%	35 100%

Outcome Measures

1. Primary Outcome

Title	Primary Outcome Measure is Reduction of Flexion Contracture of the Primary Joint.
Description	The Primary Outcome Measure for patients treated with AA4500 is the percentage of 23 joints that were successfully treated where "successfully treated" was defined as reduction in contracture to 5° or less. The Primary Outcome Measure for placebo treated patients is the percentage of 12 joints that were successfully treated where "successfully treated" was defined as reduction in contracture to 5° or less.
Time Frame	30 days after the last injection

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AA4500	Placebo
Arm/Group Description	collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
Measure Participants	23	12
Number [% Joints]	91.3	0

2. Secondary Outcome

Title	Percent Reduction From Baseline Contracture After the Last Injection
Time Frame	30 days after last treatment to the primary joint

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Percent Change From Baseline Range of Motion After the Last Injection
Time Frame	30 days after last treatment to the primary joint

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Time to First Achieve and Maintain Clinical Success After the Last Injection
Time Frame	First evaluation visit on which clinical success is achieved and maintained through the Day 30 evaluation of the primary joint

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Clinical Success After the First Injection
Time Frame	30 days after first treatment to the primary joint

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Percent Reduction From Baseline Contracture After the First Injection
Time Frame	30 days after first treatment to the primary joint

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Change From Baseline Range of Motion After the First Injection
Time Frame	30 days after first treatment to the primary joint

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Adverse Event Reporting Description	This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide & XIAFLEX Prescribing Information (see links above).
Arm/Group Title	AA4500		Placebo
Arm/Group Description	collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
All Cause Mortality
	AA4500		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	AA4500		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/23 (8.7%)		1/15 (6.7%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	0/23 (0%)	0	1/12 (8.3%)	1
Nervous system disorders
Cerebrovascular accident	2/23 (8.7%)	2	0/12 (0%)	0
Other (Not Including Serious) Adverse Events
	AA4500		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/23 (100%)		12/15 (80%)
Blood and lymphatic system disorders
Lymphadenopathy	10/23 (43.5%)		0/15 (0%)
General disorders
Edema peripheral	23/23 (100%)		1/15 (6.7%)
Injection site pain	23/23 (100%)		7/15 (46.7%)
Tenderness	3/23 (13%)		0/15 (0%)
Infections and infestations
Upper respiratory tract infection	2/23 (8.7%)		3/15 (20%)
nasopharyngitis	1/23 (4.3%)		2/15 (13.3%)
Injury, poisoning and procedural complications
Skin laceration	3/23 (13%)		0/15 (0%)
Investigations
Body temperature increased	2/23 (8.7%)		0/15 (0%)
Musculoskeletal and connective tissue disorders
Pain in extremity	3/23 (13%)		0/15 (0%)
Trigger finger	2/23 (8.7%)		0/15 (0%)
Nervous system disorders
Headache	2/23 (8.7%)		0/15 (0%)
Skin and subcutaneous tissue disorders
Ecchymosis	12/23 (52.2%)		0/15 (0%)
Blood blister	10/23 (43.5%)		0/15 (0%)
Pruritus	7/23 (30.4%)		0/15 (0%)
Vascular disorders
Hypertension	1/23 (4.3%)		2/15 (13.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.