Administration of Two Injections for Multiple Dupuytren's Contractures

Methodology/Study Design:

This is an open-label, study in men and women with multiple Dupuytren's contractures.
Approximately 60 subjects who have at least two Dupuytren's contractures caused by palpable
cords in the same hand will be enrolled.

After all pre-injection procedures are completed on Day 1, eligible men and women will
receive two concurrent injections of AA4500 0.58 mg into the same hand. On Day 2, a finger
extension procedure to facilitate cord disruption will be performed in those subjects who do
not have spontaneous disruption of their cord(s). Follow-up visits for the evaluation of
safety and efficacy will be on Day 8, Day 30, and Day 60.

Upon completion of the Day 60 follow-up visit, subjects who require further treatment will
have the option to receive three additional open-label treatments according to the XIAFLEX
package insert (Appendix C). Subjects may receive up to a total of five injections and
individual cords may receive up to a total of three injections.

Inclusion Criteria:

1. Provide written informed consent

2. Be a man or woman ≥ 18 years of age

3. Have a diagnosis of Dupuytren's disease and have at least 2 fixed-flexion contractures
on the same hand that are ≥ 20º in PIP and/or MP joints in fingers, other than the
thumbs, which are caused by palpable cords suitable for treatment

4. Have a positive "table top test" defined as the inability to simultaneously place the
affected finger(s) and palm flat against a table top

5. Either be using an accepted method of birth control (ie, surgical sterilization; intra
uterine contraceptive device; oral contraceptive; diaphragm or condom in combination
with contraceptive cream, or jelly or foam) and have negative pregnancy testing before
administration of AA4500, if a female of childbearing potential, or be a
postmenopausal female (no menses for at least 1 year or hysterectomy)

6. Not have any clinically significant medical history or condition(s) 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

7. Be able to comply with the study visit schedule as specified in the protocol

Exclusion Criteria:

1. Received surgery (fasciectomy or surgical fasciotomy) and/or needle
aponeurotomy/fasciotomy on the selected joints to be treated within 90 days before the
first injection of AA4500

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 AA4500

5. Is currently receiving or plans to receive anticoagulant medication or has received
anticoagulant medication (except for ≤ 150 mg aspirin daily and over-the-counter
nonsteroidal anti-inflammatory drugs [NSAIDs]) within 7 days before injection of
AA4500)

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. Is known to be immunocompromised or human immunodeficiency virus (HIV) positive

8. Has a history of illicit drug abuse or alcoholism within the year before injection of
AA4500

9. Received an investigational drug within 30 days before injection of AA4500

10. Is a pregnant or lactating female

11. 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

12. Has jewelry on the hand to be treated that cannot be removed