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

Endo Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Dupuytren's Disease

Treatments: Biological: Collagenase clostridium histolyticum; Biological: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02193828

AUX-CC-750

Details and patient eligibility

About

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

Full 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.

Enrollment: 76 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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76 participants in 4 patient groups, including a placebo group

AA4500 0.25 mg

Experimental group

Description:

Collagenase clostridium histolyticum, single 0.25 mg injection

Treatment:

Biological: Collagenase clostridium histolyticum

AA4500 0.40 mg

Experimental group

Description:

Collagenase clostridium histolyticum, single 0.40 mg injection

Treatment:

Biological: Collagenase clostridium histolyticum

AA4500 0.60 mg

Experimental group

Description:

Collagenase clostridium histolyticum, single 0.60 mg injection

Treatment:

Biological: Collagenase clostridium histolyticum

Placebo

Placebo Comparator group

Description:

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

Treatment:

Biological: Placebo