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Trial registered on ANZCTR


Registration number
ACTRN12607000216415
Ethics application status
Not yet submitted
Date submitted
16/04/2007
Date registered
20/04/2007
Date last updated
21/01/2008
Type of registration
Prospectively registered

Titles & IDs
Public title
A Placebo Controlled Study of the Safety and Efficacy of AA4500 in the Treatment of Subjects With Dupuytren’s Contracture Followed by an Open-Label Extension Phase
Scientific title
A Phase 3, Double-Blind, Randomized, Placebo Controlled Study of the Safety and Efficacy of AA4500 in the Treatment of Subjects With Dupuytren’s Contracture Followed by an Open-Label Extension Phase
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Dupuytren's contracture 1744 0
Condition category
Condition code
Musculoskeletal 1835 1835 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Double blind phase:

0.58mg of Clostridial collagenase (AA4500) or placebo will be injected directly into the Dupuytren's cord. 30 days after this first injection, if no response is seen or if the first cord responds and the patient has an additional Dupuytren's cord to be treated, a second dose of AA4500 or placebo will be injected directly either into the initially injected Dupuytren's cord or into the second Dupuytren's cord as appropriate. In the double blind phase a maximum of 3 AA4500/placebo injections will be given, each 30 days apart.

Open label phase:

0.58mg of Clostridial collagenase (AA4500) will be injected directly into the Dupuytren's cord. 30 days after the first open label injection, if no response is seen or if the previously injected cord responds and the patient has an additional Dupuytren's cord to be treated, a second dose of open label AA4500 will be injected directly either into the initially injected Dupuytren's cord or into the second Dupuytren's cord as appropriate. In the open label phase a maximum of 5 injections will be given, 30 days apart.

Hence, a subject can receive up to 8 injections (3 in the double blind phase, 5 in the open label phase), but if they only have 1 Dupuytren's cord to treat and respond to the first injection they will not proceed with any further injections and will enter the follow-up phase of the study.

Follow-up phase:
Subjects will be reviewed at 3, 6, 9 and 12 months after the first injection. At these visits the study objectives will be reviewed.
Intervention code [1] 1704 0
Treatment: Drugs
Comparator / control treatment
Double blind phase:

Placebo will be injected directly into the Dupuytren's cord. 30 days after this first injection, if no response is seen or if the first cord responds and the patient has an additional Dupuytren's cord to be treated, a second dose of placebo will be injected directly either into the initially injected Dupuytren's cord or into the second Dupuytren's cord as appropriate. In the double blind phase a maximum of 3 AA4500/placebo injections will be given, each 30 days apart.
Control group
Placebo

Outcomes
Primary outcome [1] 2568 0
To evaluate the safety of up to 3 injections of AA4500 as compared to placebo in reducing the degree of contracture (flexion deformity) of the primary joint of subjects with Dupuytren’s contracture. The primary joint can be either metacarpophalangeal (MP) or proximal interphalangeal (PIP).

Assessment of safety: adverse events; vital signs; grip strength of treated hand.
Timepoint [1] 2568 0
At baseline, immediately before each injection and day 1, day 7 and day 30 after each injection of AA4500. Plus during the follow-up phase at 3 months, 6 months, 9 months and 12 months after the initial injection of AA4500.
Primary outcome [2] 2569 0
To evaluate the safety of up to 3 injections of AA4500 as compared to placebo in reducing the degree of contracture (flexion deformity) of the primary joint of subjects with Dupuytren’s contracture. The primary joint can be either metacarpophalangeal (MP) or proximal interphalangeal (PIP).

Assessment of safety: clinical laboratory tests
Timepoint [2] 2569 0
At baseline and day 30 after each injection of AA4500. Plus during the follow-up phase at 12 months after the initial injection of AA4500.
Primary outcome [3] 2570 0
To evaluate the safety of up to 3 injections of AA4500 as compared to placebo in reducing the degree of contracture (flexion deformity) of the primary joint of subjects with Dupuytren’s contracture. The primary joint can be either metacarpophalangeal (MP) or proximal interphalangeal (PIP).

Assessment of safety: level of antibodies against collagenase formed
Timepoint [3] 2570 0
Immediately before each injection and day 30 after each injection of AA4500. Plus during the follow-up phase at 3 months, 6 months, 9 months and 12 months after the initial injection of AA4500.
Primary outcome [4] 2571 0
To evaluate the efficacy of up to 3 injections of AA4500 as compared to placebo in reducing the degree of contracture (flexion deformity) of the primary joint of subjects with Dupuytren’s contracture. The primary joint can be either metacarpophalangeal (MP) or proximal interphalangeal (PIP).

Assessment of efficacy: The change in the degree of contracture of the joint affected by the treated Dupuytren's cord, measured by digital goniometry.
Timepoint [4] 2571 0
At aseline, immediately before each injection and day 1, day 7 and day 30 after each injection of AA4500. Plus during the follow-up phase at 3 months, 6 months, 9 months and 12 months after the initial injection of AA4500.
Secondary outcome [1] 4423 0
Key secondary outcome/s: To evaluate the efficacy and safety of up to 3 injections of AA4500 as compared to placebo in reducing the degree of contracture (flexion deformity) in multiple joints (MP and PIP) of subjects with Dupuytren's contracture.
To evaluate the recurrence rate in joints that were successfully treated during the 12-month study period.
Secondary Outcome Name: safety
Timepoint [1] 4423 0
Secondary outcome [2] 4424 0
Assessment of safety: adverse events; vital signs; grip strength of treated hand
Timepoint [2] 4424 0
Baseline, immediately before each injection and day 1, day 7 and day 30 after each injection of AA4500. Plus during the follow-up phase at 3 months, 6 months, 9 months and 12 months after the initial injection of AA4500.
Secondary outcome [3] 4425 0
Assessment of safety: clinical laboratory tests
Timepoint [3] 4425 0
Baseline and day 30 after each injection of AA4500. Plus during the follow-up phase at 12 months after the initial injection of AA4500.
Secondary outcome [4] 4426 0
Assessment of safety: level of antibodies against collagenase formed
Timepoint [4] 4426 0
immediately before each injection and day 30 after each injection of AA4500. Plus during the follow-up phase at 3 months, 6 months, 9 months and 12 months after the initial injection of AA4500.
Secondary outcome [5] 4427 0
Secondary Outcome Name: efficacy
Timepoint [5] 4427 0
Secondary outcome [6] 4428 0
Assessment of efficacy: The change in the degree of contracture of the joint affected by the treated Dupuytren's cord, measured by digital goniometry.
Timepoint [6] 4428 0
Baseline, immediately before each injection and day 1, day 7 and day 30 after each injection of AA4500. Plus during the follow-up phase at 3 months, 6 months, 9 months and 12 months after the initial injection of AA4500.
Secondary outcome [7] 4429 0
Secondary Outcome Name: recurrence rate
Timepoint [7] 4429 0
Secondary outcome [8] 4430 0
Assessment of recurrence rate: The change in the degree of contracture of the joint affected by the treated Dupuytren's cord.
Timepoint [8] 4430 0
Baseline, immediately before each injection and 30 days after each injection of AA4500 and at 3 months, 6 months, 9 months and 12 months after the initial injection of AA4500.

Eligibility
Key inclusion criteria
1. Subject has a diagnosis of Dupuytren’s contracture with a fixed flexion deformity of the finger(s) of at least 20° or no greater than 100° for MP (80° for PIP) contracture, caused by a palpable cord. 2. Subject has a positive “table top test” defined as the inability to simultaneously place the affected finger(s) and palm flat against a table top. 3. Subject is judged to be in good health, based upon the results of a medical history, physical examination, and safety laboratory profile. 4. Subject voluntarily signs and dates an informed consent agreement approved by the Institutional Review Board/Independent Ethics Committee (IRB/IEC). 5. Female subjects of child bearing potential must use an acceptable method of birth control or be surgically sterilized or be a post menopausal female (ie, no menses for at least 1 year). A pregnancy test will be performed prior to enrollment in the study.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Female subjects who are nursing or pregnant, or plan to become pregnant during the treatment phase.2. Subject has received an investigational drug within 30 days prior to the first dose of study drug.3. Subject has received a treatment on the selected primary joint(s), within 90 days of enrollment in the study, for Dupuytren’s contracture including surgery (fasciectomy or surgical fasciotomy), needle aponeurotomy/fasciotomy, or injection of verapamil and/or interferon.4. Subject has a known allergy to collagenase or any other excipient of AA4500.5. Subject has received doxycycline or doxycycline derivative during the 14 days prior to the first dose of study drug.6. Subject has received any collagenase treatments within 30 days.7. Subject is receiving anticoagulant medication or has received anticoagulant medication (except for aspirin = 150 mg daily) within 7 days of enrollment in this study.8. Subject 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Blinded treatment generated by Interactive Voice Recognition System (IVRS). Patients are randomised to active or placebo in a 2:1 ratio.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Stratified allocation using computerised sequence generation. Subjects will be stratified by the primary joint type (30 subjects with metacarpophalangeal (MP) and 30 subjects with proximal interphalangeal (PIP)) and by the severity of the primary joint contracture (=50 degrees or =50 degrees for MP joint and =40 degrees or =40 degrees for PIP joint).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
The following people are blinded in the study: the people receiving the treatment/s (subjects), the people administering the treatment/s (therapist or clinician) and the people assessing the outcomes (assessor).
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/07/2007
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment outside Australia
Country [1] 513 0
United Kingdom
State/province [1] 513 0

Funding & Sponsors
Funding source category [1] 1985 0
Commercial sector/Industry
Name [1] 1985 0
Auxilium Pharmaceuticals, Inc.
Country [1] 1985 0
Primary sponsor type
Commercial sector/Industry
Name
Auxilium Pharmaceuticals, Inc.
Address
Country
United States of America
Secondary sponsor category [1] 1797 0
Commercial sector/Industry
Name [1] 1797 0
Novotech (Australia) Pty Ltd
Address [1] 1797 0
Country [1] 1797 0
Australia

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 3684 0
Emeritus Research
Ethics committee address [1] 3684 0
291 Wattletree Road, Malvern, VIC 3144
Ethics committee country [1] 3684 0
Australia
Date submitted for ethics approval [1] 3684 0
Approval date [1] 3684 0
Ethics approval number [1] 3684 0
Ethics committee name [2] 3685 0
Peninsula Clinical Research Centre
Ethics committee address [2] 3685 0
Suite 10 & 11, Cnr George & Florence Street, Kippa Ring, QLD 4019
Ethics committee country [2] 3685 0
Australia
Date submitted for ethics approval [2] 3685 0
Approval date [2] 3685 0
Ethics approval number [2] 3685 0
Ethics committee name [3] 3686 0
Rivercity Private Hospital, Rivercity Research, Rivercity Private Hospital
Ethics committee address [3] 3686 0
401 Milton Road, Auchenflower, QLD 4067
Ethics committee country [3] 3686 0
Australia
Date submitted for ethics approval [3] 3686 0
Approval date [3] 3686 0
Ethics approval number [3] 3686 0
Ethics committee name [4] 3687 0
Caboolture Clinical Research Centre, Caboolture Clinical Research Centre
Ethics committee address [4] 3687 0
17 Hasking St, Caboolture, QLD 4510
Ethics committee country [4] 3687 0
Australia
Date submitted for ethics approval [4] 3687 0
Approval date [4] 3687 0
Ethics approval number [4] 3687 0
Ethics committee name [5] 3688 0
Brisbane Hand & Upper Limb Clinic
Ethics committee address [5] 3688 0
9/259 Wickham Terrace, Brisbane, QLD 4001
Ethics committee country [5] 3688 0
Australia
Date submitted for ethics approval [5] 3688 0
Approval date [5] 3688 0
Ethics approval number [5] 3688 0
Ethics committee name [6] 3689 0
Menzies Research Institute
Ethics committee address [6] 3689 0
199 Macquarie Street, Hobart, Tasmania 7000
Ethics committee country [6] 3689 0
Australia
Date submitted for ethics approval [6] 3689 0
Approval date [6] 3689 0
Ethics approval number [6] 3689 0

Summary
Brief summary
The purpose of the study is to test whether injections of AA4500 are safe and will dissolve the cord of tissue causing the bending of the finger(s) due to Dupuytren's disease.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 27807 0
Address 27807 0
Country 27807 0
Phone 27807 0
Fax 27807 0
Email 27807 0
Contact person for public queries
Name 10893 0
Kerin Singleton
Address 10893 0
Novotech (Australia) Pty Ltd
Level 3, 19 Harris Street
Pyrmont
NSW 2009
Country 10893 0
Australia
Phone 10893 0
+61 2 95189600
Fax 10893 0
+61 2 95189390
Email 10893 0
[email protected]
Contact person for scientific queries
Name 1821 0
Nigel Jones
Address 1821 0
Auxilium UK Limited
Orchard Lea
Winkfield Lane
Windsor
Berks
SL4 4RU
Country 1821 0
United Kingdom
Phone 1821 0
+44 (0)1443 421707
Fax 1821 0
+44 (0)1443 433044
Email 1821 0
[email protected]

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