Safety and Efficacy Study of AA4500 (XIAFLEX™, Proposed Name) in the Treatment of Advanced Dupuytren's Disease

A Phase 3, Open-Label Study of the Safety and Efficacy of AA4500 in the Treatment of Subjects With Advanced Dupuytren's Disease

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00528840

Acronym

JOINT-I

Enrollment

201

Registered

2007-09-12

Start date

2007-10-31

Completion date

2008-10-31

Last updated

2017-12-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Advanced Dupuytren's Disease

Brief summary

This was a Phase 3, 9-month, open-label study conducted in the United States. Subjects with a diagnosis of advanced Dupuytren's disease in a metacarpophalangeal (MP) or proximal interphalangeal (PIP) joint that resulted in a fixed flexion deformity of at least one finger, other than the thumb, that was at least 20° as measured by finger goniometry and was suitable for evaluation and injection were enrolled. 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 (NCT00528606) and AUX-CC-859 (NCT00533273)) and 7 non-pivotal studies were evaluated.

Interventions

BIOLOGICALcollagenase clostridium histolyticum

Up to five injections of AA4500 into cord(s) of the affected hand(s). Each injection was separated by at least 30 days.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Subjects with a diagnosis of advanced Dupuytren's disease, with a fixed flexion deformity of at least one finger, other than the thumb, that had a contracture at least 20°, but not greater than 100° for MP (80° for PIP) joints, caused by a palpable cord. * Had a positive table top test, defined as the inability to simultaneously place the affected finger(s) and palm flat against a table top. * Were naïve to AA4500 treatment or had received one or two injections of AA4500 for the treatment of advanced Dupuytren's disease in Auxilium Studies AUX-CC-851, AUX-CC-853, or AUX-CC-855. * Were judged to be in good health.

Exclusion criteria

* Had a chronic muscular, neurological, or neuromuscular disorder that affected the hands. * Had received treatment for advanced Dupuytren's disease within 90 days of enrollment on the joint selected for the initial injection of AA4500, including surgery (fasciectomy or surgical fasciotomy), needle aponeurotomy/fasciotomy, or injection of verapamil and/or interferon. * Had a known recent history of stroke, bleeding, a disease process that affected the hands, or other medical condition, which in the investigator's opinion, would make the subject unsuitable for enrollment in the study.

Design outcomes

Primary

Measure	Time frame	Description
Reduction in Contracture to 5° or Less	Within 30 days after the last injection	The Primary Outcome Measure is the percentage of joints that were successfully treated where successfully treated was defined as reduction in contracture to within 0-5 degrees of normal within 30 days of injection

Secondary

Measure	Time frame	Description
Percent Reduction From Baseline Contracture After the Last Injection	Baseline, within 30 days after last injection	Percent change in degree of contracture measured as 100\*(baseline contracture -last available post-injection contracture)/baseline contracture)
Change From Baseline Range of Motion After the Last Injection	Baseline, 30 days after last injection	Change in degree of range of motion measured as last available post-injection range of motion - baseline range of motion.
Time to Reach Clinical Success	First evaluation visit on which clinical success is achieved through the Day 30 evaluation	Clinical success is defined as reduction in contracture to within 0-5 degrees of normal within 30 days of injection, displayed in post-injection timepoint categories.
Clinical Improvement After the Last Injection	Baseline; within 30 days after last injection	Clinical Improvement is defined as \>=50% percent reduction from baseline in degree of contracture within 30 days after injection.
Clinical Improvement After the First Injection	Baseline; within 30 days after first injection	Clinical Improvement is defined as \>=50% reduction from baseline in the degree of contracture within 30 days after the first injection
Percent Reduction From Baseline Contracture After the First Injection	Baseline; within 30 days after first injection	Percent change in degree of contracture is measured as 100\* (baseline contracture- last available post-injection contracture)/baseline contracture.
Change From Baseline Range of Motion After the First Injection	Baseline; within 30 days after first injection	Change in degree of range of motion measured as last available post-injection range of motion-baseline range of motion.
Clinical Success After the First Injection	Within 30 days after first injection	Clinical Success is defined as reduction in contracture to within 0-5 degrees of normal within 30 days of injection.

Countries

United States

Participant flow

Participants by arm

Arm	Count
AA4500 0.58 mg collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints	201
Total	201

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Administrative Reasons	1
Overall Study	Adverse Event	1
Overall Study	Death	2
Overall Study	Lost to Follow-up	10
Overall Study	Other	2
Overall Study	Withdrawal by Subject	17

Baseline characteristics

Characteristic	AA4500 0.58 mg
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	106 Participants
Age, Categorical Between 18 and 65 years	95 Participants
Age, Continuous	64.7 years STANDARD_DEVIATION 9.86
Race/Ethnicity, Customized White	201 participants
Region of Enrollment United States	201 participants
Sex: Female, Male Female	37 Participants
Sex: Female, Male Male	164 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	197 / 201
serious Total, serious adverse events	11 / 201

Outcome results

Primary

Reduction in Contracture to 5° or Less

The Primary Outcome Measure is the percentage of joints that were successfully treated where successfully treated was defined as reduction in contracture to within 0-5 degrees of normal within 30 days of injection

Time frame: Within 30 days after the last injection