Trial Outcomes & Findings for Retreatment of Recurrent Dupuytren's Contractures (NCT NCT01498640)

NCT ID: NCT01498640

Last Updated: 2017-10-05

Results Overview

Clinical success defined as reduction in fixed-flexion contracture to less than or equal to 5 degrees 30 days after the last injection of AA4500

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

52 participants

Primary outcome timeframe

30 days after last injection

Results posted on

2017-10-05

Participant Flow

Participant milestones

Participant milestones
Measure
XIAFLEX/XIAPEX
XIAFLEX/XIAPEX: up to three 0.58 mg injections
Overall Study
STARTED
52
Overall Study
COMPLETED
47
Overall Study
NOT COMPLETED
5

Reasons for withdrawal

Reasons for withdrawal
Measure
XIAFLEX/XIAPEX
XIAFLEX/XIAPEX: up to three 0.58 mg injections
Overall Study
Lost to Follow-up
1
Overall Study
Death
1
Overall Study
Other
3

Baseline Characteristics

Retreatment of Recurrent Dupuytren's Contractures

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
XIAFLEX/XIAPEX
n=52 Participants
XIAFLEX/XIAPEX: up to three 0.58 mg injections
Age, Categorical
<=18 years
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
20 Participants
n=5 Participants
Age, Categorical
>=65 years
32 Participants
n=5 Participants
Age, Continuous
66.5 Years
STANDARD_DEVIATION 9.53 • n=5 Participants
Sex: Female, Male
Female
2 Participants
n=5 Participants
Sex: Female, Male
Male
50 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
52 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
0 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
0 Participants
n=5 Participants
Race (NIH/OMB)
White
52 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
Region of Enrollment
United States
21 participants
n=5 Participants
Region of Enrollment
Australia
21 participants
n=5 Participants
Region of Enrollment
United Kingdom
4 participants
n=5 Participants
Region of Enrollment
Sweden
6 participants
n=5 Participants

PRIMARY outcome

Timeframe: 30 days after last injection

Population: Efficacy assessment based on modified intent-to-treat (mITT) population which includes all enrolled subjects who received at least 1 AA4500 injection to the treated joint and had at least 1 post-injection efficacy measure

Clinical success defined as reduction in fixed-flexion contracture to less than or equal to 5 degrees 30 days after the last injection of AA4500

Outcome measures

Outcome measures
Measure
XIAFLEX/XIAPEX MP Joint
n=31 Participants
Up to 3 injections of collagenase clostridium histolyticum 0.58 mg in the metacarpophalangeal (MP) joint cord
XIAFLEX/XIAPEX PIP Joint
n=20 Participants
Up to 3 injections of collagenase clostridium histolyticum 0.58 mg in the proximal interphalangeal (PIP) joint cord
Clinical Success
64.5 percentage of particpants
Interval 45.37 to 80.77
45.0 percentage of particpants
Interval 23.06 to 68.47

PRIMARY outcome

Timeframe: Baseline and 30 days after last injection

Population: Efficacy assessment based on mITT population which includes all enrolled subjects who received at least 1 AA4500 injection to the treated joint and had at least 1 post-injection efficacy measure

Change in fixed-flection contracture measured in degrees where a decrease of 100% would correspond to a reduction in contracture to 0 degrees

Outcome measures

Outcome measures
Measure
XIAFLEX/XIAPEX MP Joint
n=31 Participants
Up to 3 injections of collagenase clostridium histolyticum 0.58 mg in the metacarpophalangeal (MP) joint cord
XIAFLEX/XIAPEX PIP Joint
n=20 Participants
Up to 3 injections of collagenase clostridium histolyticum 0.58 mg in the proximal interphalangeal (PIP) joint cord
Percent Change From Baseline in Degree of Contracture
83.24 percentage of contracture change
Standard Deviation 24.275
69.10 percentage of contracture change
Standard Deviation 26.776

PRIMARY outcome

Timeframe: Baseline and 30 days after last injection

Population: Efficacy assessment based on mITT population which includes all enrolled subjects who received at least 1 AA4500 injection to the treated joint and had at least 1 post-injection efficacy measure

Range of motion defined as difference between full flexion angle and full extension angle expressed in degrees

Outcome measures

Outcome measures
Measure
XIAFLEX/XIAPEX MP Joint
n=31 Participants
Up to 3 injections of collagenase clostridium histolyticum 0.58 mg in the metacarpophalangeal (MP) joint cord
XIAFLEX/XIAPEX PIP Joint
n=20 Participants
Up to 3 injections of collagenase clostridium histolyticum 0.58 mg in the proximal interphalangeal (PIP) joint cord
Change in Range of Motion
31.4 degrees
Standard Deviation 17.52
26.8 degrees
Standard Deviation 17.39

SECONDARY outcome

Timeframe: 30 days after last injection

Population: Efficacy assessment based on mITT population which includes all enrolled subjects who received at least 1 AA4500 injection to the treated joint and had at least 1 post-injection efficacy measure

Physician global assessment of change (improvement) in subject's Dupuytren's contracture

Outcome measures

Outcome measures
Measure
XIAFLEX/XIAPEX MP Joint
n=31 Participants
Up to 3 injections of collagenase clostridium histolyticum 0.58 mg in the metacarpophalangeal (MP) joint cord
XIAFLEX/XIAPEX PIP Joint
n=20 Participants
Up to 3 injections of collagenase clostridium histolyticum 0.58 mg in the proximal interphalangeal (PIP) joint cord
Physician Global Assessment of Improvement
Very much improved
18 participants
12 participants
Physician Global Assessment of Improvement
Much improved
11 participants
5 participants
Physician Global Assessment of Improvement
Minimally improved
0 participants
2 participants
Physician Global Assessment of Improvement
No change
1 participants
1 participants
Physician Global Assessment of Improvement
Minimally worse
0 participants
0 participants
Physician Global Assessment of Improvement
Much worse
0 participants
0 participants
Physician Global Assessment of Improvement
Very much worse
0 participants
0 participants
Physician Global Assessment of Improvement
Not done
1 participants
0 participants

SECONDARY outcome

Timeframe: 30 days after last injection

Population: Efficacy assessment based on mITT population which includes all enrolled subjects who received at least 1 AA4500 injection to the treated joint and had at least 1 post-injection efficacy measure

Subject global assessment of overall treatment satisfaction

Outcome measures

Outcome measures
Measure
XIAFLEX/XIAPEX MP Joint
n=31 Participants
Up to 3 injections of collagenase clostridium histolyticum 0.58 mg in the metacarpophalangeal (MP) joint cord
XIAFLEX/XIAPEX PIP Joint
n=20 Participants
Up to 3 injections of collagenase clostridium histolyticum 0.58 mg in the proximal interphalangeal (PIP) joint cord
Subject Global Assessment of Satisfaction
Very satisfied
20 participants
10 participants
Subject Global Assessment of Satisfaction
Quite satisfied
9 participants
5 participants
Subject Global Assessment of Satisfaction
Neither satisfied nor dissatisfied
1 participants
2 participants
Subject Global Assessment of Satisfaction
Quite dissatisfied
0 participants
1 participants
Subject Global Assessment of Satisfaction
Very dissatisfied
0 participants
0 participants
Subject Global Assessment of Satisfaction
Not done
1 participants
2 participants

SECONDARY outcome

Timeframe: Day 365

Population: Efficacy assessment based on mITT population which includes all enrolled subjects who received at least 1 AA4500 injection to the treated joint and had at least 1 post-injection efficacy measure; only joints that were successfully treated (reduction in contracture to 5 degrees or less) 30 days after last injection were assessed

Recurrence of contracture in the joint at day 365 that was successfully treated 30 days after last injection assessed. Recurrence was defined as 20 degree or greater increase of contracture of the treated joint at day 365 or medication intervention of the treated joint between the 2 time points.

Outcome measures

Outcome measures
Measure
XIAFLEX/XIAPEX MP Joint
n=29 Joints
Up to 3 injections of collagenase clostridium histolyticum 0.58 mg in the metacarpophalangeal (MP) joint cord
XIAFLEX/XIAPEX PIP Joint
Up to 3 injections of collagenase clostridium histolyticum 0.58 mg in the proximal interphalangeal (PIP) joint cord
Recurrence of Contracture
6 joints

Adverse Events

XIAFLEX/XIAPEX

Serious events: 4 serious events
Other events: 44 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
XIAFLEX/XIAPEX
n=52 participants at risk
XIAFLEX/XIAPEX: up to three 0.58 mg injections
Nervous system disorders
Cerebellar infarction
1.9%
1/52 • Number of events 1 • 1 year
Cardiac disorders
Acute coronary syndrome
1.9%
1/52 • Number of events 1 • 1 year
Cardiac disorders
Acute myocardial infarction
1.9%
1/52 • Number of events 1 • 1 year
General disorders
Chest pain
1.9%
1/52 • Number of events 1 • 1 year
Musculoskeletal and connective tissue disorders
Dupuytren's contracture
1.9%
1/52 • Number of events 1 • 1 year
Infections and infestations
Urosepsis
1.9%
1/52 • Number of events 1 • 1 year

Other adverse events

Other adverse events
Measure
XIAFLEX/XIAPEX
n=52 participants at risk
XIAFLEX/XIAPEX: up to three 0.58 mg injections
General disorders
Oedema peripheral
61.5%
32/52 • Number of events 41 • 1 year
Injury, poisoning and procedural complications
Contusion
44.2%
23/52 • Number of events 28 • 1 year
Musculoskeletal and connective tissue disorders
Pain in extremity
30.8%
16/52 • Number of events 22 • 1 year
General disorders
Injection site pain
19.2%
10/52 • Number of events 14 • 1 year
Skin and subcutaneous tissue disorders
Pruritus
19.2%
10/52 • Number of events 13 • 1 year
General disorders
Injection site haematoma
15.4%
8/52 • Number of events 12 • 1 year
Blood and lymphatic system disorders
Lymphadenopathy
15.4%
8/52 • Number of events 8 • 1 year
Injury, poisoning and procedural complications
Skin laceration
13.5%
7/52 • Number of events 7 • 1 year
General disorders
Injection site pruritus
9.6%
5/52 • Number of events 5 • 1 year
General disorders
Injection site swelling
9.6%
5/52 • Number of events 9 • 1 year
Vascular disorders
Hypertension
5.8%
3/52 • Number of events 3 • 1 year

Additional Information

Clinical Trial Coordinator

Endo Pharmaceuticals, Inc.

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place

Restriction type: OTHER