Clinical trial NCT01674634: Safety and Efficacy of Two Concurrent Injections of AA4500 in Adult Subjects With Multiple Dupuytren's Contractures
Official title: A Phase 3b Open-label, Historically-controlled Study to Assess the Safety and Efficacy of Two Concurrent Injections of AA4500 in Adult Subjects With Multiple Dupuytren's Contractures With Palpable Cords
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Dupuytren's Contracture
Keywords: XIAFLEX
XIAPEX
Dupuytren's disease
contracture
Lead sponsor: Endo Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2012-08-29
Enrollment: 715
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to assess the safety of two concurrent injections of AA4500 into the same hand in subjects with multiple Dupuytren's contractures with palpable cords followed 24 to 72 hours later by a finger extension procedure and compare the rate of occurrence of targeted serious adverse events (tendon rupture/ligament injury and anaphylaxis) to historical rates of the same in clinical studies and post-marketing commercial use.

The secondary objective is to evaluate the efficacy of two concurrent injections of AA4500.

Detailed description: Methodology/Study Design: After all pre-injection procedures are completed on Day 1, eligible men and women will receive two concurrent injections AA4500 (AA4500/AA4500) into cord(s) affecting MP and/or PIP joints on the same or different fingers in the selected hand. A finger extension procedure to facilitate cord disruption will be performed (after administration of local anesthesia, if needed) 24 to 72 hours after injection 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 required for all subjects 24 to 72 hours after injection, and on Days 15, 31, and 61.

Upon completion of the day 61 follow-up visit (end of study visit), subjects who require additional treatment in the treated hand may receive up to three additional injections of AA4500 according to the XIAFLEX package insert. Subjects may receive up to a total of five injections and individual cords may receive up to a total of three injections. Subjects who require additional treatment will be followed for safety.

Eligibility criteria: Inclusion Criteria:

1. Provide a signed and dated 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 cord(s) 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. Have a negative urine pregnancy test at screening and before injection of study drug and be using a highly effective (ie, \< 1% failure rate) contraception method as judged by the investigator (eg, abstinence, intrauterine device \[IUD\], hormonal \[estrogen/progestin\] contraceptives, or barrier control) for at least one menstrual cycle prior to study enrollment and for the duration of the study or be surgically sterile (if female of childbearing potential); or be a postmenopausal female (no menses for at least 1 year or hysterectomy).
6. Be able to comply with the study visit schedule as specified in the protocol

Exclusion Criteria:

A subject will be excluded from study participation if he/she:

1. Received surgery (fasciectomy or surgical fasciotomy) and/or needle aponeurotomy/fasciotomy on the selected joints to be treated within 6 months before administration of study drug
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 study drug in the hand selected for treatment
5. Is currently receiving or plans to receive anticoagulant medication or has received anticoagulant medication (except for ≤ 150 mg aspirin daily) within 7 days before injection of study drug
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. Received an investigational drug within 30 days before injection of study drug
8. Is pregnant or intends on becoming pregnant during the study or is breastfeeding a child
9. 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
10. Has jewelry on the hand to be treated that cannot be removed

Primary outcomes:
measure: Percent Change From Baseline in Total Fixed Flexion
timeFrame: Baseline, Day 31
measure: Change From Baseline in Total Range of Motion
timeFrame: Baseline, Day 31
Secondary outcomes:
measure: Clinical Success
timeFrame: Within 30 days
measure: Clinical Improvement
timeFrame: Within 30 days
measure: Subject Assessment of Satisfaction With Treatment at Day 31
timeFrame: Day 31
measure: Subject Assessment of Satisfaction With Treatment at Day 61
timeFrame: Day 61
measure: Investigator Assessment of Improvement With Treatment at Day 31
timeFrame: Day 31
measure: Investigator Assessment of Improvement With Treatment at Day 61
timeFrame: Day 61
measure: Change From Baseline for Unité Rhumatologique Des Affections de la Main Scale at Day 31
timeFrame: Baseline, Day 31
measure: Change From Baseline for Unité Rhumatologique Des Affections de la Main Scale at Day 61
timeFrame: Baseline, Day 61
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: HOPE Research Institute
state: Arizona
city: Tucson
country: United States
facility: Tucson Orthopaedic Institute
state: Arizona
city: Encinitas
country: United States
facility: CORE Orthopaedic Medical Center
state: California
city: La Jolla
country: United States
facility: Torrey Pines Medical Group
state: California
city: Murrieta
country: United States
facility: Brigid Freyne, MD, Inc.
state: California
city: Atlanta
country: United States
facility: The Hand and Upper Extremity Center
state: Georgia
city: Rockford
country: United States
facility: Rockford Orthopedic Associates
state: Illinois
city: Indianapolis
country: United States
facility: The Indiana Hand to Shoulder Center
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Louisville
country: United States
facility: Christine M. Kleinert Institute for Hand and Microsurgery, Inc.
state: Kentucky
city: Somerset
country: United States
facility: Lake Cumberland Rheumatology
state: Kentucky
city: Minneapolis
country: United States
facility: TRIA Orthopedic Center
state: Minnesota
city: Missoula
country: United States
facility: Missoula Bone and Joint
state: Montana
city: Las Vegas
country: United States
facility: Nevada Orthopedic and Spine Center
state: Nevada
city: Eatontown
country: United States
facility: Central Jersey Hand Surgery
state: New Jersey
city: New York
country: United States
facility: Hospital for Special Surgery
state: New York
city: Setauket
country: United States
facility: SUNY Stony Brook
state: New York
city: Chapel Hill
country: United States
facility: UNC School of Medicine
state: North Carolina
city: Charlotte
country: United States
facility: OrthoCarolina Research Institute, Inc.
state: North Carolina
city: Oklahoma City
country: United States
facility: Health Research Institute
state: Oklahoma
city: Bend
country: United States
facility: The Center for Neurosurgical and Orthopedic Care and Research
state: Oregon
city: Erie
country: United States
facility: Hand Microsurgery & Reconstructive Orthopaedics
state: Pennsylvania
city: Clarksville
country: United States
facility: Alpha Clinical Research, LLC
state: Tennessee
city: Houston
country: United States
facility: Accurate Clinical Research, Inc.
state: Texas
city: Arlington
country: United States
facility: The Arthritis Clinic of Northern Virginia, PA
state: Virginia
Study officials:
affiliation: Endo Pharmaceuticals
name: Veronica Urdaneta, MD, MPPH
role: STUDY_DIRECTOR
References: