Phase 2a Dose-Ranging Study to Evaluate Safety and Effectiveness of AA4500 in Treatment of Dupuytren's Disease Nodules

NCT02193828 | Completed Phase 2 Results

• 1 other identifier: AUX-CC-750
• Study Type: interventional
• Target: 76
• Locations: 2 countries
• Sites: 11

Brief Summary

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

Conditions

Dupuytren's Disease

Keywords

Dupuytren's nodules

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline in Surface Area and Volume of the Treated Nodule at Day 57 Using Caliper Measurements

  Percent change from baseline in surface area and volume of the treated nodule was determined from hand-held caliper measurements of the length and width of the nodule. Percent change = 100\*(Day 57 area \[or volume\] - baseline area \[or volume\])/baseline area \[or volume\]. A negative value represents the improvement from baseline (decreased size) while a positive value represents worsening.

  Baseline, Day 57

Secondary Outcomes (7)

• Percent Change From Baseline in Surface Area and Volume of the Treated Nodule at Day 57 Using Ultrasound

  Baseline, Day 57

• Change From Baseline in Consistency of the Treated Nodules at Day 57

  Baseline, Day 57

• Percent Change From Baseline in Hardness of the Treated Nodule at Day 57

  Baseline, Day 57

• Change From Baseline in Nodular Pain of the Treated Nodule at Day 57

  Baseline, Day 57

• Investigator Global Assessment of Improvement With Treatment

  Day 57

Study Arms (4)

AA4500 0.25 mg

EXPERIMENTAL

Collagenase clostridium histolyticum, single 0.25 mg injection

Biological: Collagenase clostridium histolyticum

AA4500 0.40 mg

EXPERIMENTAL

Collagenase clostridium histolyticum, single 0.40 mg injection

Biological: Collagenase clostridium histolyticum

AA4500 0.60 mg

EXPERIMENTAL

Collagenase clostridium histolyticum, single 0.60 mg injection

Biological: Collagenase clostridium histolyticum

Placebo

PLACEBO COMPARATOR

Placebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection

Biological: Placebo

Interventions

Collagenase clostridium histolyticum BIOLOGICAL

Single injection into nodule

Also known as: AA4500, XIAFLEX, XIAPEX

AA4500 0.25 mg; AA4500 0.40 mg; AA4500 0.60 mg

Placebo BIOLOGICAL

Single injection into nodule

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide a signed and dated informed consent
• Be a man or woman ≥ 18 years of age
• Have a diagnosis of Dupuytren's disease AND have at least one palmar nodule on the selected hand that is:
• Palpable
• 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
• Not directly associated with a Dupuytren's cord
• 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)
• Be able to comply with the study visit schedule as specified in the protocol

You may not qualify if:

• Received steroid injections (eg, tri-amcinolone acetonide) on the selected nodule within 3 months before administration of study drug
• Has a chronic muscular, neurological, or neuromuscular disorder that affects the hands
• Has a known systemic allergy to collagenase or any other excipient of AA4500
• 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
• 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
• 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
• Received an investigational drug within 30 days before injection of study drug
• Is pregnant or intends on becoming pregnant during the study or is breastfeeding a child
• 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
• Had surgery on the selected hand within 3 months before the screening visit
• Has jewelry on the hand to be treated that cannot be removed

Sponsors & Collaborators

• Endo Pharmaceuticals: lead

Study Sites (11)

Tucson Orthopaedic Institute

Tucson, Arizona, 85712, United States

Location

CORE Orthopaedic Medical Center

Encinitas, California, 92024, United States

Location

Marin Endocrine Care & Research, Inc.

Greenbrae, California, 94904, United States

Location

Brigid Freyne, MD, Inc.

Murrieta, California, 92563, United States

Location

Indiana Hand to Shoulder Center

Indianapolis, Indiana, 46260, United States

Location

State University of New York

Stony Brook, New York, 11794, United States

Location

OrthoCarolina Research Institute, Inc.

Charlotte, North Carolina, 28207, United States

Location

Orthopedic and Reconstructive Center

Oklahoma City, Oklahoma, 73109, United States

Location

Blair Orthopedic Associates, Inc.

Altoona, Pennsylvania, 16602, United States

Location

Brisbane Hand & Upper Limb Clinic

Brisbane, Queensland, 4000, Australia

Location

Houston Medical

Kippa-Ring, Queensland, 4021, Australia

Location

Related Publications (1)

• 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.

  PMID: 28854973 DERIVED

MeSH Terms

Conditions

Dupuytren Contracture

Interventions

Microbial Collagenase; xiapex

Condition Hierarchy (Ancestors)

Fibroma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Contracture; Muscular Diseases; Musculoskeletal Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Collagenases; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases

Results Point of Contact

• Title: Clinical Trial Coordinator
• Organization: Endo Pharmaceuticals, Inc.

clinicalsite.inquiries@endo.com

Study Officials

• Veronica Urdaneta, MD MPH

  Endo Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2014
• First Posted: July 18, 2014
• Study Start: July 1, 2014
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: October 5, 2017
• Results First Posted: July 7, 2015

Record last verified: 2017-09

Locations

US (9); AU (2)