Trial Outcomes & Findings for A Pharmacokinetic Study of AA4500 (XIAFLEX™, Proposed Name) in Subjects With Dupuytren's Contracture (NCT NCT00528931)

Last Updated: 2017-10-05

Results Overview

AUX I and AUX II are the constituent protein collagenases of collagenase clostridium histolyticum (AA4500). Plasma concentrations of AUX I and AUX II were assessed through an enzymye-linked-immunoabsorbent assay (ELISA).

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

16 participants

Primary outcome timeframe

Before dosing, at predetermined time points through the 24 hours after dosing, Day 7, and Day 30

Results posted on

2017-10-05

Participant Flow

Participant milestones

Participant milestones
Measure	AA4500 0.58 mg collagenase clostridium histolyticum 0.58mg injected into either the metacarpophalangeal (MP) or proximal interphalangeal (PIP) joint
Overall Study STARTED	16
Overall Study COMPLETED	15
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	AA4500 0.58 mg collagenase clostridium histolyticum 0.58mg injected into either the metacarpophalangeal (MP) or proximal interphalangeal (PIP) joint
Overall Study Lost to Follow-up	1

Baseline Characteristics

A Pharmacokinetic Study of AA4500 (XIAFLEX™, Proposed Name) in Subjects With Dupuytren's Contracture

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AA4500 0.58 mg n=16 Participants collagenase clostridium histolyticum 0.58mg injected into either the metacarpophalangeal (MP) or proximal interphalangeal (PIP) joint
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	12 Participants n=5 Participants
Age, Categorical >=65 years	4 Participants n=5 Participants
Age, Continuous	60.6 years STANDARD_DEVIATION 11.74 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 participants n=5 Participants
Race/Ethnicity, Customized White	14 participants n=5 Participants
Race/Ethnicity, Customized Other	1 participants n=5 Participants
Region of Enrollment United States	16 participants n=5 Participants

PRIMARY outcome

Timeframe: Before dosing, at predetermined time points through the 24 hours after dosing, Day 7, and Day 30

Population: Pharmacokinetic population

Outcome measures

Outcome measures
Measure	AA4500 0.58 mg n=16 Participants collagenase clostridium histolyticum 0.58mg injected into either the metacarpophalangeal (MP) or proximal interphalangeal (PIP) joint
Number of Subjects With AUX I and AUX II Detected in Their Blood After a Single Dose of AA4500	0 participants

SECONDARY outcome

Timeframe: 30 days after treatment to the primary joint

Population: Efficacy assessment based on safety population which included all enrolled subjects who received the AA4500 injection

Clinical success defined as a reduction in contracture (ie, flexion deformity) to ≤5° of normal as measured by finger goniometry 30 days after an injection. Last observation carried forward (LOCF) after the injection was used if the status at day 30 could not be determined.

Outcome measures

Outcome measures
Measure	AA4500 0.58 mg n=16 Joints collagenase clostridium histolyticum 0.58mg injected into either the metacarpophalangeal (MP) or proximal interphalangeal (PIP) joint
Clinical Success	75.0 Percentage of joints

SECONDARY outcome

Timeframe: 30 days after treatment to the primary joint

Population: Efficacy assessment based on safety population which included all enrolled subjects who received the AA4500 injection.

Clinical improvement defined as ≥50% reduction from baseline in contracture within 30 days of the injection. LOCF after the injection was used if the status at day 30 could not be determined.

Outcome measures

Outcome measures
Measure	AA4500 0.58 mg n=16 Joints collagenase clostridium histolyticum 0.58mg injected into either the metacarpophalangeal (MP) or proximal interphalangeal (PIP) joint
Clinical Improvement	100.0 Percentage of joints

SECONDARY outcome

Timeframe: Baseline, 30 days after treatment to the primary joint

Population: Efficacy assessment based on safety population which included all enrolled subjects who received the AA4500 injection.

Change from baseline in the degree of fixed-flexion contracture calculated as 100 times (baseline contracture minus last available post-injection contracture measurement) divided by baseline contracture where a positive change indicates a reduction in the degree of contracture.

Outcome measures

Outcome measures
Measure	AA4500 0.58 mg n=16 Joints collagenase clostridium histolyticum 0.58mg injected into either the metacarpophalangeal (MP) or proximal interphalangeal (PIP) joint
Percent Change From Baseline Contracture	91.6 Percentage of contracture change Standard Deviation 16.57

SECONDARY outcome

Timeframe: Baseline, 30 days after treatment to the primary joint

Population: Efficacy assessment based on safety population which included all enrolled subjects who received the AA4500 injection.

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

Outcome measures

Outcome measures
Measure	AA4500 0.58 mg n=16 Joints collagenase clostridium histolyticum 0.58mg injected into either the metacarpophalangeal (MP) or proximal interphalangeal (PIP) joint
Change From Baseline Range of Motion	39.1 Degrees Standard Deviation 15.38

Adverse Events

AA4500 0.58 mg

Serious events: 1 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	AA4500 0.58 mg n=16 participants at risk collagenase clostridium histolyticum 0.58mg injected into either the metacarpophalangeal (MP) or proximal interphalangeal (PIP) joint
Injury, poisoning and procedural complications Tendon rupture	6.2% 1/16 • Number of events 1 • From the time that the first dose of study drug was administered until 30 days elapsed following discontinuation of study drug administration. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).

Other adverse events

Other adverse events
Measure	AA4500 0.58 mg n=16 participants at risk collagenase clostridium histolyticum 0.58mg injected into either the metacarpophalangeal (MP) or proximal interphalangeal (PIP) joint
Skin and subcutaneous tissue disorders Blister	6.2% 1/16 • Number of events 1 • From the time that the first dose of study drug was administered until 30 days elapsed following discontinuation of study drug administration. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).
Investigations Blood urine present	6.2% 1/16 • Number of events 1 • From the time that the first dose of study drug was administered until 30 days elapsed following discontinuation of study drug administration. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).
Nervous system disorders Burning sensation	6.2% 1/16 • Number of events 1 • From the time that the first dose of study drug was administered until 30 days elapsed following discontinuation of study drug administration. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).
Injury, poisoning and procedural complications Contusion	6.2% 1/16 • Number of events 1 • From the time that the first dose of study drug was administered until 30 days elapsed following discontinuation of study drug administration. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).
Gastrointestinal disorders Food poisoning	6.2% 1/16 • Number of events 1 • From the time that the first dose of study drug was administered until 30 days elapsed following discontinuation of study drug administration. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).
Vascular disorders Hypertension	12.5% 2/16 • Number of events 2 • From the time that the first dose of study drug was administered until 30 days elapsed following discontinuation of study drug administration. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).
General disorders Injection site haemorrhage	93.8% 15/16 • Number of events 15 • From the time that the first dose of study drug was administered until 30 days elapsed following discontinuation of study drug administration. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).
General disorders Injection site oedema	6.2% 1/16 • Number of events 1 • From the time that the first dose of study drug was administered until 30 days elapsed following discontinuation of study drug administration. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).
General disorders Injection site pain	81.2% 13/16 • Number of events 13 • From the time that the first dose of study drug was administered until 30 days elapsed following discontinuation of study drug administration. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).
General disorders Injection site swelling	87.5% 14/16 • Number of events 14 • From the time that the first dose of study drug was administered until 30 days elapsed following discontinuation of study drug administration. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).
Blood and lymphatic system disorders Lymphadenopathy	6.2% 1/16 • Number of events 1 • From the time that the first dose of study drug was administered until 30 days elapsed following discontinuation of study drug administration. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).
General disorders Oedema peripheral	6.2% 1/16 • Number of events 1 • From the time that the first dose of study drug was administered until 30 days elapsed following discontinuation of study drug administration. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).
General disorders Pain	6.2% 1/16 • Number of events 1 • From the time that the first dose of study drug was administered until 30 days elapsed following discontinuation of study drug administration. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).
Musculoskeletal and connective tissue disorders Pain in extremity	6.2% 1/16 • Number of events 1 • From the time that the first dose of study drug was administered until 30 days elapsed following discontinuation of study drug administration. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).
Nervous system disorders Paraesthesia	12.5% 2/16 • Number of events 2 • From the time that the first dose of study drug was administered until 30 days elapsed following discontinuation of study drug administration. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).
Injury, poisoning and procedural complications Skin laceration	6.2% 1/16 • Number of events 1 • From the time that the first dose of study drug was administered until 30 days elapsed following discontinuation of study drug administration. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above).

Additional Information

Clinical Trial Coordinator

Endo Pharmaceuticals, Inc.

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Auxilium Pharmaceuticals, Inc. agreements may vary with individual investigators but will not prohibit any investigator from publishing. Auxilium supports the publication of results from all centers of a multicenter trial but requests that reports based on single site data not preceed the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER