E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10013872 |
E.1.2 | Term | Dupuytren's contracture |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The main objective of the study is to evaluate the safety and efficacy of up to five injections of AA4500 0.58mg (maximum three injections per joint) in reducing the degree of contracture (fixed flexion deformity) in joints of subjects with Dupuytren's Contracture. Clinical success of the treatment will be defined as a reduction in the joint contracture to 0 - 5 degrees of normal measured by digital goniometry. |
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E.2.2 | Secondary objectives of the trial |
Additional secondary objectives of the trial include clinical improvement (defined as 50% reduction in contracture); percentage reduction in contracture from baseline; percent improvement in range of motion of the affected finger(s) from baseline; time to reach clinical success or clinical improvement following last injection. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects must meet all of the following criteria to enter the study: 1. Subject is at least 18 years of age. 2. Subjects must have a diagnosis of Dupuytren’s contracture with a fixed-flexion (ie, ≥ 20º but ≤ 80º for PIP joint; ≥ 20º but ≤ 100º for MP joint) deformity of at least one finger, other than the thumb, that is caused by a palpable cord. 3. Subject must have a positive “table top test” defined as the inability to simultaneously place the affected finger(s) and palm flat against a table top. 4. Subject is naïve to AA4500 treatment or has received one or two injections of AA4500 for the treatment of Dupuytren’s contracture in Auxilium studies AUX CC 851, AUX-CC-853, or AUX-CC-855. 5. Subject is judged to be in good health, based upon the results of a medical history, physical examination, and safety laboratory profile. 6. Subject voluntarily signs and dates an informed consent agreement approved by the Institutional Review Board/Independent Ethics Committee (IRB/IEC). 7. Female subjects of child bearing potential must use an acceptable method of birth control or be surgically sterilized or be a post menopausal female (ie, no menses for at least 1 year). A pregnancy test will be performed prior to enrollment in the study.
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E.4 | Principal exclusion criteria |
Subjects will be excluded from study participation for the following reasons: 1. Female subjects who are nursing or pregnant, or plan to become pregnant during the treatment phase. 2. Subject has a chronic muscular, neurological, or neuromuscular disorder that affects the hands. 3. Subject has received an investigational drug within 30 days prior to the first dose of study drug. 4. Subject has received treatment for Dupuytren’s contracture within 90 days of enrollment on the joint selected for the initial injection of AA4500. Treatment for Dupuytren’s contracture include surgery (fasciectomy or surgical fasciotomy), needle aponeurotomy/fasciotomy, or injection of verapamil and/or interferon. 5. Subject has a known allergy to collagenase or any other excipient of AA4500. 6. Subject has received doxycycline or doxycycline derivative during the 14 days prior to the first dose of study drug. 7. Subject has received any collagenase treatments within 30 days. 8. Subject is receiving anticoagulant medication or has received anticoagulant medication (except for aspirin ≤ 150 mg daily) within 7 days before the first injection. 9. Subject has a known recent history of stroke, bleeding, a disease process that affects the hands, or other medical condition which in the investigator’s opinion would make the subject unsuitable for enrollment in the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
The efficacy endpoint is the reduction in contracture (flexion deformity) of each treated joint. A clinical success is defined as a reduction in contracture to within 0˚ 5˚ of normal measured by digital goniometry at the visit 30 days after the injection for each treated joint. If the Day 30 visit is missing, the last evaluation (LOCF) completed post-injection (Day 1 or Day 7) will be used to determine clinical success. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of study is when the last subject completes the (last) Month 9 follow-up visit. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |