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

NCT ID: NCT02193828

Last Updated: 2017-10-05

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

76 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-07-31

Study Completion Date

2014-12-31

Brief Summary

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

Detailed Description

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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.

Conditions

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Dupuytren's Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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AA4500 0.25 mg

Collagenase clostridium histolyticum, single 0.25 mg injection

Group Type EXPERIMENTAL

Collagenase clostridium histolyticum

Intervention Type BIOLOGICAL

Single injection into nodule

AA4500 0.40 mg

Collagenase clostridium histolyticum, single 0.40 mg injection

Group Type EXPERIMENTAL

Collagenase clostridium histolyticum

Intervention Type BIOLOGICAL

Single injection into nodule

AA4500 0.60 mg

Collagenase clostridium histolyticum, single 0.60 mg injection

Group Type EXPERIMENTAL

Collagenase clostridium histolyticum

Intervention Type BIOLOGICAL

Single injection into nodule

Placebo

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type BIOLOGICAL

Single injection into nodule

Interventions

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Collagenase clostridium histolyticum

Single injection into nodule

Intervention Type BIOLOGICAL

Placebo

Single injection into nodule

Intervention Type BIOLOGICAL

Other Intervention Names

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AA4500 XIAFLEX XIAPEX

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Endo Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Veronica Urdaneta, MD MPH

Role: STUDY_DIRECTOR

Endo Pharmaceuticals

Locations

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Tucson Orthopaedic Institute

Tucson, Arizona, United States

Site Status

CORE Orthopaedic Medical Center

Encinitas, California, United States

Site Status

Marin Endocrine Care & Research, Inc.

Greenbrae, California, United States

Site Status

Brigid Freyne, MD, Inc.

Murrieta, California, United States

Site Status

Indiana Hand to Shoulder Center

Indianapolis, Indiana, United States

Site Status

State University of New York

Stony Brook, New York, United States

Site Status

OrthoCarolina Research Institute, Inc.

Charlotte, North Carolina, United States

Site Status

Orthopedic and Reconstructive Center

Oklahoma City, Oklahoma, United States

Site Status

Blair Orthopedic Associates, Inc.

Altoona, Pennsylvania, United States

Site Status

Brisbane Hand & Upper Limb Clinic

Brisbane, Queensland, Australia

Site Status

Houston Medical

Kippa-Ring, Queensland, Australia

Site Status

Countries

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United States Australia

References

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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.

Reference Type DERIVED
PMID: 28854973 (View on PubMed)

Other Identifiers

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AUX-CC-750

Identifier Type: -

Identifier Source: org_study_id