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The primary objective of this study is to assess the safety of two concurrent injections of AA4500 into the same hand in subjects with multiple Dupuytren's contractures with palpable cords followed 24 to 72 hours later by a finger extension procedure and compare the rate of occurrence of targeted serious adverse events (tendon rupture/ligament injury and anaphylaxis) to historical rates of the same in clinical studies and post-marketing commercial use.
The secondary objective is to evaluate the efficacy of two concurrent injections of AA4500.
Methodology/Study Design: After all pre-injection procedures are completed on Day 1, eligible men and women will receive two concurrent injections AA4500 (AA4500/AA4500) into cord(s) affecting MP and/or PIP joints on the same or different fingers in the selected hand. A finger extension procedure to facilitate cord disruption will be performed (after administration of local anesthesia, if needed) 24 to 72 hours after injection in those subjects who do not have spontaneous disruption of their cord(s).
Follow up visits for the evaluation of safety and efficacy will be required for all subjects 24 to 72 hours after injection, and on Days 15, 31, and 61.
Upon completion of the day 61 follow-up visit (end of study visit), subjects who require additional treatment in the treated hand may receive up to three additional injections of AA4500 according to the XIAFLEX package insert. Subjects may receive up to a total of five injections and individual cords may receive up to a total of three injections. Subjects who require additional treatment will be followed for safety.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| XIAFLEX / XIAPEX | Experimental | AA4500 (collagenase clostridium histolyticum) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| XIAFLEX / XIAPEX | Biological | injection (0.58 mg after reconstitution with sterile diluent [0.3 mg/mL calcium chloride dihydrate in 0.9% sodium chloride]) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change From Baseline in Total Fixed Flexion | Percent change from baseline in total fixed flexion = 100 * (baseline total FFC - day 31 total FFC)/baseline total FFC, where total fixed flexion is defined as the sum of the fixed flexion contracture (FCC) of the 2 joints receiving treatment. Positive percent change from baseline indicates improvement. | Baseline, Day 31 |
| Change From Baseline in Total Range of Motion | The total range of motion (ROM) is the sum of the range of motion measurements of the 2 treated joints. ROM is defined as difference between full flexion angle and full extension expressed in degrees. A positive change from baseline indicates increased (improved) ROM. | Baseline, Day 31 |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical Success | Clinical success is defined as reduction of FFC of a treated joint to within 0-5 degrees of normal within 30 days of injection | Within 30 days |
| Clinical Improvement | Clinical improvement is defined as a reduction of FFC by 50% or greater of the baseline value within 30 days of injection |
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Inclusion Criteria:
Exclusion Criteria:
A subject will be excluded from study participation if he/she:
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| Name | Affiliation | Role |
|---|---|---|
| Veronica Urdaneta, MD, MPPH | Endo USA Inc., a Keenova Therapeutics Company | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| HOPE Research Institute | Phoenix | Arizona | 85018 | United States | ||
| Tucson Orthopaedic Institute |
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| ID | Title | Description |
|---|---|---|
| FG000 | XIAFLEX/XIAPEX | AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Within 30 days |
| Subject Assessment of Satisfaction With Treatment at Day 31 | Subject's were asked to rate satisfaction with treatment at the day 31 follow-up visit | Day 31 |
| Subject Assessment of Satisfaction With Treatment at Day 61 | Subject's were asked to rate satisfaction with treatment at the day 61 follow-up visit | Day 61 |
| Investigator Assessment of Improvement With Treatment at Day 31 | Investigator's determined the degree of improvement in the severity of the subject's treated finger(s) compared with screening at the day 31 follow-up visit. | Day 31 |
| Investigator Assessment of Improvement With Treatment at Day 61 | Investigator's determined the degree of improvement in the severity of the subject's treated finger(s) compared with screening at the day 61 follow-up visit. | Day 61 |
| Change From Baseline for Unité Rhumatologique Des Affections de la Main Scale at Day 31 | The Unité Rhumatologique des Affections de la Main (URAM) scale is a patient-reported functional 9-item scale (total score 0-45) developed and validated to assess functional outcome of patients suffering from Dupuytren's disease with higher scores indicating greater difficulty using the hand.The estimated clinically important change of the URAM scale is 2.9 points. A decrease in total URAM score indicates improvement in hand function. | Baseline, Day 31 |
| Change From Baseline for Unité Rhumatologique Des Affections de la Main Scale at Day 61 | The URAM scale is a patient-reported functional 9-item scale (total score 0-45) developed and validated to assess functional outcome of patients suffering from Dupuytren's disease with higher scores indicating greater difficulty using the hand.The estimated clinically important change of the URAM scale is 2.9 points. A decrease in total URAM score indicates improvement in hand function. | Baseline, Day 61 |
| Tucson |
| Arizona |
| 85712 |
| United States |
| CORE Orthopaedic Medical Center | Encinitas | California | 92024 | United States |
| Torrey Pines Medical Group | La Jolla | California | 92037 | United States |
| Brigid Freyne, MD, Inc. | Murrieta | California | 92563 | United States |
| The Hand and Upper Extremity Center | Atlanta | Georgia | 30342 | United States |
| Rockford Orthopedic Associates | Rockford | Illinois | 61107 | United States |
| The Indiana Hand to Shoulder Center | Indianapolis | Indiana | 46260 | United States |
| University of Kansas Medical Center | Kansas City | Kansas | 66160 | United States |
| Christine M. Kleinert Institute for Hand and Microsurgery, Inc. | Louisville | Kentucky | 40202 | United States |
| Lake Cumberland Rheumatology | Somerset | Kentucky | 42503 | United States |
| TRIA Orthopedic Center | Minneapolis | Minnesota | 55431 | United States |
| Missoula Bone and Joint | Missoula | Montana | 59808 | United States |
| Nevada Orthopedic and Spine Center | Las Vegas | Nevada | 89128 | United States |
| Central Jersey Hand Surgery | Eatontown | New Jersey | 07724 | United States |
| Hospital for Special Surgery | New York | New York | 10021 | United States |
| SUNY Stony Brook | Setauket | New York | 11733 | United States |
| UNC School of Medicine | Chapel Hill | North Carolina | 27599 | United States |
| OrthoCarolina Research Institute, Inc. | Charlotte | North Carolina | 28207 | United States |
| Health Research Institute | Oklahoma City | Oklahoma | 73109 | United States |
| The Center for Neurosurgical and Orthopedic Care and Research | Bend | Oregon | 97701 | United States |
| Hand Microsurgery & Reconstructive Orthopaedics | Erie | Pennsylvania | 16507 | United States |
| Alpha Clinical Research, LLC | Clarksville | Tennessee | 37043 | United States |
| Accurate Clinical Research, Inc. | Houston | Texas | 77034 | United States |
| The Arthritis Clinic of Northern Virginia, PA | Arlington | Virginia | 22205 | United States |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | XIAFLEX/XIAPEX | AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| |||||||||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
| ||||||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| |||||||||||||||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percent Change From Baseline in Total Fixed Flexion | Percent change from baseline in total fixed flexion = 100 * (baseline total FFC - day 31 total FFC)/baseline total FFC, where total fixed flexion is defined as the sum of the fixed flexion contracture (FCC) of the 2 joints receiving treatment. Positive percent change from baseline indicates improvement. | Efficacy analysis was based on the modified intent-to-treat (mITT) population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on contralateral hand. Assessment is based on simultaneously treated joint pairs. | Posted | Mean | Standard Deviation | percentage of contracture change | Baseline, Day 31 | Treated Joint Pairs | Treated Joint Pairs |
|
|
| |||||||||||||||||||||||||
| Primary | Change From Baseline in Total Range of Motion | The total range of motion (ROM) is the sum of the range of motion measurements of the 2 treated joints. ROM is defined as difference between full flexion angle and full extension expressed in degrees. A positive change from baseline indicates increased (improved) ROM. | Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. Assessment is based on simultaneously treated joint pairs. | Posted | Mean | 95% Confidence Interval | degrees | Baseline, Day 31 | treated joint pairs | treated joint pairs |
|
| ||||||||||||||||||||||||||
| Secondary | Clinical Success | Clinical success is defined as reduction of FFC of a treated joint to within 0-5 degrees of normal within 30 days of injection | Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. This assessment is based on individual treated joints by joint type. | Posted | Number | Joints | Within 30 days | Treated Joints | Treated Joints |
|
| |||||||||||||||||||||||||||
| Secondary | Clinical Improvement | Clinical improvement is defined as a reduction of FFC by 50% or greater of the baseline value within 30 days of injection | Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. This assessment is based on individual treated joints by joint type. | Posted | Number | Joints | Within 30 days | Treated Joints | Treated Joints |
|
| |||||||||||||||||||||||||||
| Secondary | Subject Assessment of Satisfaction With Treatment at Day 31 | Subject's were asked to rate satisfaction with treatment at the day 31 follow-up visit | Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. Assessment is based on simultaneously treated joint pairs. | Posted | Number | Joint Pairs | Day 31 | Treated Joint Pairs | Treated Joint Pairs |
|
| |||||||||||||||||||||||||||
| Secondary | Subject Assessment of Satisfaction With Treatment at Day 61 | Subject's were asked to rate satisfaction with treatment at the day 61 follow-up visit | Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. Assessment is based on simultaneously treated joint pairs. | Posted | Number | Joint Pairs | Day 61 | Treated Joint Pairs | Treated Joint Pairs |
|
| |||||||||||||||||||||||||||
| Secondary | Investigator Assessment of Improvement With Treatment at Day 31 | Investigator's determined the degree of improvement in the severity of the subject's treated finger(s) compared with screening at the day 31 follow-up visit. | Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. Assessment is based on simultaneously treated joint pairs. | Posted | Number | Joint Pairs | Day 31 | Treated Joint Pairs | Treated Joint Pairs |
|
| |||||||||||||||||||||||||||
| Secondary | Investigator Assessment of Improvement With Treatment at Day 61 | Investigator's determined the degree of improvement in the severity of the subject's treated finger(s) compared with screening at the day 61 follow-up visit. | Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. Assessment is based on simultaneously treated joint pairs. | Posted | Number | Joint Pairs | Day 61 | Treated Joint Pairs | Treated Joint Pairs |
|
| |||||||||||||||||||||||||||
| Secondary | Change From Baseline for Unité Rhumatologique Des Affections de la Main Scale at Day 31 | The Unité Rhumatologique des Affections de la Main (URAM) scale is a patient-reported functional 9-item scale (total score 0-45) developed and validated to assess functional outcome of patients suffering from Dupuytren's disease with higher scores indicating greater difficulty using the hand.The estimated clinically important change of the URAM scale is 2.9 points. A decrease in total URAM score indicates improvement in hand function. | Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. Assessment is based on simultaneously treated joint pairs. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Day 31 | Treated Joint Pairs | Treated Joint Pairs |
|
| ||||||||||||||||||||||||||
| Secondary | Change From Baseline for Unité Rhumatologique Des Affections de la Main Scale at Day 61 | The URAM scale is a patient-reported functional 9-item scale (total score 0-45) developed and validated to assess functional outcome of patients suffering from Dupuytren's disease with higher scores indicating greater difficulty using the hand.The estimated clinically important change of the URAM scale is 2.9 points. A decrease in total URAM score indicates improvement in hand function. | Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. Assessment is based on simultaneously treated joint pairs. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Day 61 | Treated Joint Pairs | Treated Joint Pairs |
|
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | XIAFLEX/XIAPEX | AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand | 15 | 715 | 680 | 715 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Anaphylactic reaction | Immune system disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Feeding tube complication | Injury, poisoning and procedural complications | MedDRA (15.1) | Non-systematic Assessment | PEG feeding tube obstruction |
|
| Arteriosclerosis | Vascular disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Myelopathy | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Spinal column stenosis | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Post procedural haemorrhage | Injury, poisoning and procedural complications | MedDRA (15.1) | Non-systematic Assessment | Bleeding left hand post procedure |
|
| Lymphangitis | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
| |
| Emphysema | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Malaise | General disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| oedema peripheral | General disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Prostate cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.1) | Non-systematic Assessment |
| |
| Anal abscess | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment | Left lower leg |
|
| Tendon rupture | Injury, poisoning and procedural complications | MedDRA (15.1) | Non-systematic Assessment | Upgraded to an SAE by the sponsor |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Oedema peripheral | General disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA (15.1) | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Laceration | Injury, poisoning and procedural complications | MedDRA (15.1) | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Injection site pain | General disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Blood blister | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Injection site haematoma | General disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Axillary pain | General disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| injection site haemorrhage | General disorders | MedDRA (15.1) | Non-systematic Assessment | injection site ecchymosis |
|
| Injection site swelling | General disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Trial Coordinator | Endo Pharmaceuticals, Inc. | clinicalsite.inquiries@endo.com |
| ID | Term |
|---|---|
| D004387 | Dupuytren Contracture |
| D003286 | Contracture |
| ID | Term |
|---|---|
| D005350 | Fibroma |
| D018218 | Neoplasms, Fibrous Tissue |
| D009372 | Neoplasms, Connective Tissue |
| D018204 | Neoplasms, Connective and Soft Tissue |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D007592 | Joint Diseases |
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| ID | Term |
|---|---|
| D003012 | Microbial Collagenase |
| C570746 | xiapex |
| ID | Term |
|---|---|
| D017364 | Collagenases |
| D008666 | Metalloendopeptidases |
| D010450 | Endopeptidases |
| D010447 | Peptide Hydrolases |
| D006867 | Hydrolases |
| D004798 | Enzymes |
| D045762 | Enzymes and Coenzymes |
| D045726 | Metalloproteases |
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| New Zealand |
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| Denmark |
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| Sweden |
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| United Kingdom |
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| treated joint pairs |
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| Treated Joints |
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| Treated Joints |
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| Treated Joint Pairs |
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| Treated Joint Pairs |
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| Treated Joint Pairs |
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| Treated Joint Pairs |
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| Treated Joint Pairs |
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| Treated Joint Pairs |
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