Clinical trial NCT02193828: Phase 2a Dose-Ranging Study to Evaluate Safety and Effectiveness of AA4500 in Treatment of Dupuytren's Disease Nodules
Official title: A Phase 2a, Double-blind, Randomized, Placebo-Controlled, Dose-Ranging Study to Evaluate the Safety and Effectiveness of AA4500 in the Treatment of Dupuytren's Disease Nodules
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Dupuytren's Disease
Keywords: Dupuytren's nodules
Lead sponsor: Endo Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2014-07-18
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objectives of this study are to assess the safety and effectiveness of AA4500 in treating palmar Dupuytren's disease nodules.

Detailed description: Approximately 13 sites in the United States and Australia, approximately 90 study subjects.

After all pre-injection procedures are completed on day 1, eligible men and women will be randomized in a 1:1:1 ratio to dose group and then in a 4:1 ratio to treatment group. Study drug will be administered into a palmar nodule located on the selected hand.

AA4500 (collagenase clostridium histolyticum) 3 doses (low, medium, and high) after reconstitution with sterile diluent (0.3 mg/mL calcium chloride dihydrate in 0.9% sodium chloride). Each dose of study drug will be injected into the nodule. The injection will be administered in 3 different volumes according to randomization.

Placebo after reconstitution with sterile diluent (0.3 mg/mL calcium chloride dihydrate in 0.9% sodium chloride). Each dose of study drug will be injected into the nodule. The injection will be administered in 3 different volumes according to randomization.

Follow up visits for the evaluation of safety and efficacy will be required for all subjects on days 8, 29, and 57.

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 one palmar nodule on the selected hand that is:

   1. Palpable
   2. Measures between 0.5 cm and 2.0 cm in length and between 0.5 cm and 2.0 cm in width using hand-held calipers n
   3. Not directly associated with a Dupuytren's cord
4. 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)
5. Be able to comply with the study visit schedule as specified in the protocol

Exclusion Criteria:

1. Received steroid injections (eg, tri-amcinolone acetonide) on the selected nodule within 3 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. Had surgery on the selected hand within 3 months before the screening visit
11. Has jewelry on the hand to be treated that cannot be removed

Primary outcomes:
measure: Percent Change From Baseline in Surface Area and Volume of the Treated Nodule at Day 57 Using Caliper Measurements
timeFrame: Baseline, Day 57
Secondary outcomes:
measure: Percent Change From Baseline in Surface Area and Volume of the Treated Nodule at Day 57 Using Ultrasound
timeFrame: Baseline, Day 57
measure: Change From Baseline in Consistency of the Treated Nodules at Day 57
timeFrame: Baseline, Day 57
measure: Percent Change From Baseline in Hardness of the Treated Nodule at Day 57
timeFrame: Baseline, Day 57
measure: Change From Baseline in Nodular Pain of the Treated Nodule at Day 57
timeFrame: Baseline, Day 57
measure: Investigator Global Assessment of Improvement With Treatment
timeFrame: Day 57
measure: Subject Satisfaction With Treatment
timeFrame: Day 57
measure: Composite Responder Analysis
timeFrame: Day 57
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Tucson Orthopaedic Institute
state: Arizona
city: Encinitas
country: United States
facility: CORE Orthopaedic Medical Center
state: California
city: Greenbrae
country: United States
facility: Marin Endocrine Care & Research, Inc.
state: California
city: Murrieta
country: United States
facility: Brigid Freyne, MD, Inc.
state: California
city: Indianapolis
country: United States
facility: Indiana Hand to Shoulder Center
state: Indiana
city: Stony Brook
country: United States
facility: State University of New York
state: New York
city: Charlotte
country: United States
facility: OrthoCarolina Research Institute, Inc.
state: North Carolina
city: Oklahoma City
country: United States
facility: Orthopedic and Reconstructive Center
state: Oklahoma
city: Altoona
country: United States
facility: Blair Orthopedic Associates, Inc.
state: Pennsylvania
city: Brisbane
country: Australia
facility: Brisbane Hand & Upper Limb Clinic
state: Queensland
city: Kippa Ring
country: Australia
facility: Houston Medical
state: Queensland
Study officials:
affiliation: Endo Pharmaceuticals
name: Veronica Urdaneta, MD MPH
role: STUDY_DIRECTOR
References:
citation: Costas B, Coleman S, Kaufman G, James R, Cohen B, Gaston RG. Efficacy and safety of collagenase clostridium histolyticum for Dupuytren disease nodules: a randomized controlled trial. BMC Musculoskelet Disord. 2017 Aug 30;18(1):374. doi: 10.1186/s12891-017-1713-z.