Trial Outcomes & Findings for Safety and Efficacy of Two Concurrent Injections of AA4500 in Adult Subjects With Multiple Dupuytren's Contractures (NCT NCT01674634)
NCT ID: NCT01674634
Last Updated: 2017-10-05
Results Overview
Percent change from baseline in total fixed flexion = 100 \* (baseline total FFC - day 31 total FFC)/baseline total FFC, where total fixed flexion is defined as the sum of the fixed flexion contracture (FCC) of the 2 joints receiving treatment. Positive percent change from baseline indicates improvement.
COMPLETED
PHASE3
715 participants
Baseline, Day 31
2017-10-05
Participant Flow
Participant milestones
| Measure |
XIAFLEX/XIAPEX
AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand
|
|---|---|
|
Overall Study
STARTED
|
715
|
|
Overall Study
COMPLETED
|
709
|
|
Overall Study
NOT COMPLETED
|
6
|
Reasons for withdrawal
| Measure |
XIAFLEX/XIAPEX
AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
3
|
|
Overall Study
Lost to Follow-up
|
3
|
Baseline Characteristics
Safety and Efficacy of Two Concurrent Injections of AA4500 in Adult Subjects With Multiple Dupuytren's Contractures
Baseline characteristics by cohort
| Measure |
XIAFLEX/XIAPEX
n=715 Participants
AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
348 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
367 Participants
n=5 Participants
|
|
Age, Continuous
|
64.0 years
STANDARD_DEVIATION 9.26 • n=5 Participants
|
|
Sex: Female, Male
Female
|
99 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
616 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
278 participants
n=5 Participants
|
|
Region of Enrollment
Australia
|
196 participants
n=5 Participants
|
|
Region of Enrollment
New Zealand
|
70 participants
n=5 Participants
|
|
Region of Enrollment
Denmark
|
87 participants
n=5 Participants
|
|
Region of Enrollment
Sweden
|
50 participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
34 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Day 31Population: Efficacy analysis was based on the modified intent-to-treat (mITT) population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on contralateral hand. Assessment is based on simultaneously treated joint pairs.
Percent change from baseline in total fixed flexion = 100 \* (baseline total FFC - day 31 total FFC)/baseline total FFC, where total fixed flexion is defined as the sum of the fixed flexion contracture (FCC) of the 2 joints receiving treatment. Positive percent change from baseline indicates improvement.
Outcome measures
| Measure |
XIAFLEX/XIAPEX
n=724 Treated Joint Pairs
AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand
|
XIAFLEX/XIAPEX PIP Joint
AA4500 (collagenase clostridium histolyticum); 0.58 mg injection in the proximal interphalangeal (PIP) joint cord
|
|---|---|---|
|
Percent Change From Baseline in Total Fixed Flexion
|
74.41 percentage of contracture change
Standard Deviation 24.83
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 31Population: Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. Assessment is based on simultaneously treated joint pairs.
The total range of motion (ROM) is the sum of the range of motion measurements of the 2 treated joints. ROM is defined as difference between full flexion angle and full extension expressed in degrees. A positive change from baseline indicates increased (improved) ROM.
Outcome measures
| Measure |
XIAFLEX/XIAPEX
n=724 treated joint pairs
AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand
|
XIAFLEX/XIAPEX PIP Joint
AA4500 (collagenase clostridium histolyticum); 0.58 mg injection in the proximal interphalangeal (PIP) joint cord
|
|---|---|---|
|
Change From Baseline in Total Range of Motion
|
66.6 degrees
Interval 64.3 to 68.9
|
—
|
SECONDARY outcome
Timeframe: Within 30 daysPopulation: Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. This assessment is based on individual treated joints by joint type.
Clinical success is defined as reduction of FFC of a treated joint to within 0-5 degrees of normal within 30 days of injection
Outcome measures
| Measure |
XIAFLEX/XIAPEX
n=896 Treated Joints
AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand
|
XIAFLEX/XIAPEX PIP Joint
n=552 Treated Joints
AA4500 (collagenase clostridium histolyticum); 0.58 mg injection in the proximal interphalangeal (PIP) joint cord
|
|---|---|---|
|
Clinical Success
No
|
317 Joints
|
394 Joints
|
|
Clinical Success
Yes
|
579 Joints
|
158 Joints
|
SECONDARY outcome
Timeframe: Within 30 daysPopulation: Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. This assessment is based on individual treated joints by joint type.
Clinical improvement is defined as a reduction of FFC by 50% or greater of the baseline value within 30 days of injection
Outcome measures
| Measure |
XIAFLEX/XIAPEX
n=896 Treated Joints
AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand
|
XIAFLEX/XIAPEX PIP Joint
n=552 Treated Joints
AA4500 (collagenase clostridium histolyticum); 0.58 mg injection in the proximal interphalangeal (PIP) joint cord
|
|---|---|---|
|
Clinical Improvement
No
|
96 Joints
|
157 Joints
|
|
Clinical Improvement
Yes
|
800 Joints
|
395 Joints
|
SECONDARY outcome
Timeframe: Day 31Population: Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. Assessment is based on simultaneously treated joint pairs.
Subject's were asked to rate satisfaction with treatment at the day 31 follow-up visit
Outcome measures
| Measure |
XIAFLEX/XIAPEX
n=724 Treated Joint Pairs
AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand
|
XIAFLEX/XIAPEX PIP Joint
AA4500 (collagenase clostridium histolyticum); 0.58 mg injection in the proximal interphalangeal (PIP) joint cord
|
|---|---|---|
|
Subject Assessment of Satisfaction With Treatment at Day 31
Very satisfied
|
461 Joint Pairs
|
—
|
|
Subject Assessment of Satisfaction With Treatment at Day 31
Quite satisfied
|
198 Joint Pairs
|
—
|
|
Subject Assessment of Satisfaction With Treatment at Day 31
Neither satisfied nor dissatisfied
|
38 Joint Pairs
|
—
|
|
Subject Assessment of Satisfaction With Treatment at Day 31
Quite dissatisfied
|
9 Joint Pairs
|
—
|
|
Subject Assessment of Satisfaction With Treatment at Day 31
Very dissatisfied
|
6 Joint Pairs
|
—
|
|
Subject Assessment of Satisfaction With Treatment at Day 31
Not done
|
12 Joint Pairs
|
—
|
SECONDARY outcome
Timeframe: Day 61Population: Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. Assessment is based on simultaneously treated joint pairs.
Subject's were asked to rate satisfaction with treatment at the day 61 follow-up visit
Outcome measures
| Measure |
XIAFLEX/XIAPEX
n=724 Treated Joint Pairs
AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand
|
XIAFLEX/XIAPEX PIP Joint
AA4500 (collagenase clostridium histolyticum); 0.58 mg injection in the proximal interphalangeal (PIP) joint cord
|
|---|---|---|
|
Subject Assessment of Satisfaction With Treatment at Day 61
Very satisfied
|
496 Joint Pairs
|
—
|
|
Subject Assessment of Satisfaction With Treatment at Day 61
Quite satisfied
|
167 Joint Pairs
|
—
|
|
Subject Assessment of Satisfaction With Treatment at Day 61
Neither satisfied nor dissatisfied
|
38 Joint Pairs
|
—
|
|
Subject Assessment of Satisfaction With Treatment at Day 61
Quite dissatisfied
|
11 Joint Pairs
|
—
|
|
Subject Assessment of Satisfaction With Treatment at Day 61
Very dissatisfied
|
8 Joint Pairs
|
—
|
|
Subject Assessment of Satisfaction With Treatment at Day 61
Not done
|
4 Joint Pairs
|
—
|
SECONDARY outcome
Timeframe: Day 31Population: Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. Assessment is based on simultaneously treated joint pairs.
Investigator's determined the degree of improvement in the severity of the subject's treated finger(s) compared with screening at the day 31 follow-up visit.
Outcome measures
| Measure |
XIAFLEX/XIAPEX
n=724 Treated Joint Pairs
AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand
|
XIAFLEX/XIAPEX PIP Joint
AA4500 (collagenase clostridium histolyticum); 0.58 mg injection in the proximal interphalangeal (PIP) joint cord
|
|---|---|---|
|
Investigator Assessment of Improvement With Treatment at Day 31
Very much worse
|
0 Joint Pairs
|
—
|
|
Investigator Assessment of Improvement With Treatment at Day 31
Very much improved
|
375 Joint Pairs
|
—
|
|
Investigator Assessment of Improvement With Treatment at Day 31
Much improved
|
271 Joint Pairs
|
—
|
|
Investigator Assessment of Improvement With Treatment at Day 31
Minimally improved
|
51 Joint Pairs
|
—
|
|
Investigator Assessment of Improvement With Treatment at Day 31
No change
|
4 Joint Pairs
|
—
|
|
Investigator Assessment of Improvement With Treatment at Day 31
Minimally worse
|
3 Joint Pairs
|
—
|
|
Investigator Assessment of Improvement With Treatment at Day 31
Much worse
|
0 Joint Pairs
|
—
|
|
Investigator Assessment of Improvement With Treatment at Day 31
Not done
|
20 Joint Pairs
|
—
|
SECONDARY outcome
Timeframe: Day 61Population: Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. Assessment is based on simultaneously treated joint pairs.
Investigator's determined the degree of improvement in the severity of the subject's treated finger(s) compared with screening at the day 61 follow-up visit.
Outcome measures
| Measure |
XIAFLEX/XIAPEX
n=724 Treated Joint Pairs
AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand
|
XIAFLEX/XIAPEX PIP Joint
AA4500 (collagenase clostridium histolyticum); 0.58 mg injection in the proximal interphalangeal (PIP) joint cord
|
|---|---|---|
|
Investigator Assessment of Improvement With Treatment at Day 61
Very much improved
|
382 Joint Pairs
|
—
|
|
Investigator Assessment of Improvement With Treatment at Day 61
Much improved
|
263 Joint Pairs
|
—
|
|
Investigator Assessment of Improvement With Treatment at Day 61
Minimally improved
|
62 Joint Pairs
|
—
|
|
Investigator Assessment of Improvement With Treatment at Day 61
No change
|
7 Joint Pairs
|
—
|
|
Investigator Assessment of Improvement With Treatment at Day 61
Minimally worse
|
2 Joint Pairs
|
—
|
|
Investigator Assessment of Improvement With Treatment at Day 61
Much worse
|
0 Joint Pairs
|
—
|
|
Investigator Assessment of Improvement With Treatment at Day 61
Very much worse
|
0 Joint Pairs
|
—
|
|
Investigator Assessment of Improvement With Treatment at Day 61
Not done
|
8 Joint Pairs
|
—
|
SECONDARY outcome
Timeframe: Baseline, Day 31Population: Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. Assessment is based on simultaneously treated joint pairs.
The Unité Rhumatologique des Affections de la Main (URAM) scale is a patient-reported functional 9-item scale (total score 0-45) developed and validated to assess functional outcome of patients suffering from Dupuytren's disease with higher scores indicating greater difficulty using the hand.The estimated clinically important change of the URAM scale is 2.9 points. A decrease in total URAM score indicates improvement in hand function.
Outcome measures
| Measure |
XIAFLEX/XIAPEX
n=724 Treated Joint Pairs
AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand
|
XIAFLEX/XIAPEX PIP Joint
AA4500 (collagenase clostridium histolyticum); 0.58 mg injection in the proximal interphalangeal (PIP) joint cord
|
|---|---|---|
|
Change From Baseline for Unité Rhumatologique Des Affections de la Main Scale at Day 31
|
-11.3 units on a scale
Standard Deviation 9.19
|
—
|
SECONDARY outcome
Timeframe: Baseline, Day 61Population: Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. Assessment is based on simultaneously treated joint pairs.
The URAM scale is a patient-reported functional 9-item scale (total score 0-45) developed and validated to assess functional outcome of patients suffering from Dupuytren's disease with higher scores indicating greater difficulty using the hand.The estimated clinically important change of the URAM scale is 2.9 points. A decrease in total URAM score indicates improvement in hand function.
Outcome measures
| Measure |
XIAFLEX/XIAPEX
n=724 Treated Joint Pairs
AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand
|
XIAFLEX/XIAPEX PIP Joint
AA4500 (collagenase clostridium histolyticum); 0.58 mg injection in the proximal interphalangeal (PIP) joint cord
|
|---|---|---|
|
Change From Baseline for Unité Rhumatologique Des Affections de la Main Scale at Day 61
|
-12.3 units on a scale
Standard Deviation 9.75
|
—
|
Adverse Events
XIAFLEX/XIAPEX
Serious adverse events
| Measure |
XIAFLEX/XIAPEX
n=715 participants at risk
AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand
|
|---|---|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.14%
1/715 • Number of events 1
|
|
Immune system disorders
Anaphylactic reaction
|
0.14%
1/715 • Number of events 1
|
|
Injury, poisoning and procedural complications
Feeding tube complication
|
0.14%
1/715 • Number of events 1
|
|
Vascular disorders
Arteriosclerosis
|
0.14%
1/715 • Number of events 1
|
|
Nervous system disorders
Myelopathy
|
0.14%
1/715 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Spinal column stenosis
|
0.14%
1/715 • Number of events 1
|
|
Renal and urinary disorders
Haematuria
|
0.14%
1/715 • Number of events 1
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
0.14%
1/715 • Number of events 1
|
|
Infections and infestations
Lymphangitis
|
0.14%
1/715 • Number of events 1
|
|
Infections and infestations
Bronchitis
|
0.14%
1/715 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Emphysema
|
0.14%
1/715 • Number of events 1
|
|
Infections and infestations
Pneumonia
|
0.14%
1/715 • Number of events 1
|
|
Vascular disorders
Deep vein thrombosis
|
0.14%
1/715 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.28%
2/715 • Number of events 2
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
0.14%
1/715 • Number of events 1
|
|
General disorders
Malaise
|
0.14%
1/715 • Number of events 1
|
|
General disorders
oedema peripheral
|
0.14%
1/715 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.14%
1/715 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.14%
1/715 • Number of events 1
|
|
Infections and infestations
Anal abscess
|
0.14%
1/715 • Number of events 1
|
|
Infections and infestations
Cellulitis
|
0.14%
1/715 • Number of events 1
|
|
Injury, poisoning and procedural complications
Tendon rupture
|
0.14%
1/715 • Number of events 1
|
Other adverse events
| Measure |
XIAFLEX/XIAPEX
n=715 participants at risk
AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand
|
|---|---|
|
General disorders
Oedema peripheral
|
77.2%
552/715 • Number of events 626
|
|
Injury, poisoning and procedural complications
Contusion
|
58.7%
420/715 • Number of events 513
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
50.5%
361/715 • Number of events 431
|
|
Injury, poisoning and procedural complications
Laceration
|
25.7%
184/715 • Number of events 192
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
15.0%
107/715 • Number of events 121
|
|
General disorders
Injection site pain
|
14.3%
102/715 • Number of events 109
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
12.9%
92/715 • Number of events 102
|
|
Skin and subcutaneous tissue disorders
Blood blister
|
12.4%
89/715 • Number of events 98
|
|
General disorders
Injection site haematoma
|
8.4%
60/715 • Number of events 61
|
|
General disorders
Axillary pain
|
7.1%
51/715 • Number of events 53
|
|
General disorders
injection site haemorrhage
|
6.3%
45/715 • Number of events 45
|
|
General disorders
Injection site swelling
|
5.9%
42/715 • Number of events 42
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
5.2%
37/715 • Number of events 39
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER