Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The objectives of this study are to assess the safety and effectiveness of AA4500 in treating palmar Dupuytren's disease nodules.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AA4500 0.25 mg | Experimental | Collagenase clostridium histolyticum, single 0.25 mg injection |
|
| AA4500 0.40 mg | Experimental | Collagenase clostridium histolyticum, single 0.40 mg injection |
|
| AA4500 0.60 mg | Experimental | Collagenase clostridium histolyticum, single 0.60 mg injection |
|
| Placebo | Placebo Comparator | Placebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Collagenase clostridium histolyticum | Biological | Single injection into nodule |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change From Baseline in Surface Area and Volume of the Treated Nodule at Day 57 Using Ultrasound | Percent change from baseline in surface area and volume of the treated nodule was determined from ultrasound measurements of the length, width, and depth 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. |
Not provided
Inclusion Criteria:
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:
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
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Veronica Urdaneta, MD MPH | Endo USA Inc., a Keenova Therapeutics Company | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Tucson Orthopaedic Institute | Tucson | Arizona | 85712 | United States | ||
| CORE Orthopaedic Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28854973 | Derived | 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. |
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | AA4500 0.60 mg | Collagenase clostridium histolyticum (AA4500), single 0.60 mg injection into the nodule |
| FG001 | AA4500 0.40 mg | Collagenase clostridium histolyticum (AA4500), single 0.40 mg injection into the nodule |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Placebo | Biological | Single injection into nodule |
|
| Baseline, Day 57 |
| Change From Baseline in Consistency of the Treated Nodules at Day 57 | Investigators determined the consistency of the nodule through palpitation using a 5-point scale: 5 = hard (solid), 4 = firm throughout, 3 = moderate firmness, 2 = soft, and 1 = non-palpable. The change scores could range from +4 (greatest worsening in consistency) to -4 (greatest improvement in consistency); a negative change from baseline value reflects improvement from baseline (softening) while a positive value reflects worsening. | Baseline, Day 57 |
| Percent Change From Baseline in Hardness of the Treated Nodule at Day 57 | A durometer was used to assess nodule hardness on a scale of 0 (soft) to 100 (hard). Percent change = 100*(Day 57 hardness - baseline hardness)/baseline hardness. A negative value represents the improvement from baseline (softening) while a positive value represents worsening. | Baseline, Day 57 |
| Change From Baseline in Nodular Pain of the Treated Nodule at Day 57 | After the nodule was squeezed using a dynamometer, subjects were asked to rate the amount of pain they felt on an 11-point visual analog scale (VAS) from 0 (no pain or discomfort) to 10 (extreme pain or discomfort). A negative change from baseline value reflects improvement from baseline (less pain) while a positive value reflects worsening. | Baseline, Day 57 |
| Investigator Global Assessment of Improvement With Treatment | Investigators were asked to determine the degree of improvement in the subject's treated nodule compared with screening on a 7-point scale: 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. | Day 57 |
| Subject Satisfaction With Treatment | Subjects were asked to rate their satisfaction with treatment on a 5-point scale: 1 = very satisfied, 2 = quite satisfied, 3 = neither satisfied nor dissatisfied, 4 = quite dissatisfied, and 5 = very dissatisfied. | Day 57 |
| Composite Responder Analysis | A composite responder is a subject who had an improved assessment [values of 1 (very much improved), 2 (much improved), or 3 (minimally improved)] on the investigator global assessment and had a satisfied assessment [values of 1 (very satisfied) or 2 (quite satisfied)] on the subject assessment. | Day 57 |
| Encinitas |
| California |
| 92024 |
| United States |
| Marin Endocrine Care & Research, Inc. | Greenbrae | California | 94904 | United States |
| Brigid Freyne, MD, Inc. | Murrieta | California | 92563 | United States |
| Indiana Hand to Shoulder Center | Indianapolis | Indiana | 46260 | United States |
| State University of New York | Stony Brook | New York | 11794 | United States |
| OrthoCarolina Research Institute, Inc. | Charlotte | North Carolina | 28207 | United States |
| Orthopedic and Reconstructive Center | Oklahoma City | Oklahoma | 73109 | United States |
| Blair Orthopedic Associates, Inc. | Altoona | Pennsylvania | 16602 | United States |
| Brisbane Hand & Upper Limb Clinic | Brisbane | Queensland | 4000 | Australia |
| Houston Medical | Kippa-Ring | Queensland | 4021 | Australia |
| FG002 | AA4500 0.25 mg | Collagenase clostridium histolyticum (AA4500), single 0.25 mg injection into the nodule |
| FG003 | Placebo | Placebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection into the nodule |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Analysis based on Safety population; all randomized subjects who received an injection of study medication. One subject did not receive study medication.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | AA4500 0.60 mg | Collagenase clostridium histolyticum (AA4500), single 0.60 mg injection into the nodule |
| BG001 | AA4500 0.40 mg | Collagenase clostridium histolyticum (AA4500), single 0.40 mg injection into the nodule |
| BG002 | AA4500 0.25 mg | Collagenase clostridium histolyticum (AA4500), single 0.25 mg injection into the nodule |
| BG003 | Placebo | Placebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection into the nodule |
| BG004 | Total | Total of all reporting groups |
| 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 | Median | Full Range | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | 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 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. | Analysis based on Modified Intent-to-Treat (mITT) population; all randomized subjects who received study medication and had pre- and post-baseline nodule measurements for ultrasound and calipers. Analytical outliers (subjects whose percent change in ultrasound volume was greater than the 75th percentile + 3× the interquartile range) were excluded. | Posted | Mean | Standard Deviation | percentage of change | Baseline, Day 57 |
|
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percent Change From Baseline in Surface Area and Volume of the Treated Nodule at Day 57 Using Ultrasound | Percent change from baseline in surface area and volume of the treated nodule was determined from ultrasound measurements of the length, width, and depth 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. | Analysis based on mITT population; all randomized subjects who received study medication and had pre- and post-baseline nodule measurements for ultrasound and calipers. Analytical outliers (subjects whose percent change in ultrasound volume was greater than the 75th percentile + 3× the interquartile range) were excluded. | Posted | Mean | Standard Deviation | percentage of change | Baseline, Day 57 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Consistency of the Treated Nodules at Day 57 | Investigators determined the consistency of the nodule through palpitation using a 5-point scale: 5 = hard (solid), 4 = firm throughout, 3 = moderate firmness, 2 = soft, and 1 = non-palpable. The change scores could range from +4 (greatest worsening in consistency) to -4 (greatest improvement in consistency); a negative change from baseline value reflects improvement from baseline (softening) while a positive value reflects worsening. | Analysis based on mITT population; all randomized subjects who received an injection of study medication and had pre- and post-baseline nodule measurements for both ultrasound and calipers. Subjects with an incomplete assessment (not done) on Day 57 were excluded. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Day 57 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percent Change From Baseline in Hardness of the Treated Nodule at Day 57 | A durometer was used to assess nodule hardness on a scale of 0 (soft) to 100 (hard). Percent change = 100*(Day 57 hardness - baseline hardness)/baseline hardness. A negative value represents the improvement from baseline (softening) while a positive value represents worsening. | Analysis based on mITT population; all randomized subjects who received an injection of study medication and had pre- and post-baseline nodule measurements for both ultrasound and calipers. Subjects with an incomplete assessment (not done) on Day 57 were excluded. | Posted | Mean | Standard Deviation | percentage of change | Baseline, Day 57 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Nodular Pain of the Treated Nodule at Day 57 | After the nodule was squeezed using a dynamometer, subjects were asked to rate the amount of pain they felt on an 11-point visual analog scale (VAS) from 0 (no pain or discomfort) to 10 (extreme pain or discomfort). A negative change from baseline value reflects improvement from baseline (less pain) while a positive value reflects worsening. | Analysis based on mITT population; all randomized subjects who received an injection of study medication and had pre- and post-baseline nodule measurements for both ultrasound and calipers. Subjects with an incomplete assessment (not done) on Day 57 were excluded. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Day 57 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Investigator Global Assessment of Improvement With Treatment | Investigators were asked to determine the degree of improvement in the subject's treated nodule compared with screening on a 7-point scale: 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. | Analysis based on mITT population; all randomized subjects who received an injection of study medication and had pre- and post-baseline nodule measurements for both ultrasound and calipers. | Posted | Mean | Standard Deviation | units on a scale | Day 57 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Subject Satisfaction With Treatment | Subjects were asked to rate their satisfaction with treatment on a 5-point scale: 1 = very satisfied, 2 = quite satisfied, 3 = neither satisfied nor dissatisfied, 4 = quite dissatisfied, and 5 = very dissatisfied. | Analysis based on mITT population; all randomized subjects who received an injection of study medication and had pre- and post-baseline nodule measurements for both ultrasound and calipers. | Posted | Mean | Standard Deviation | units on a scale | Day 57 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Composite Responder Analysis | A composite responder is a subject who had an improved assessment [values of 1 (very much improved), 2 (much improved), or 3 (minimally improved)] on the investigator global assessment and had a satisfied assessment [values of 1 (very satisfied) or 2 (quite satisfied)] on the subject assessment. | Analysis based on mITT population; all randomized subjects who received an injection of study medication and had pre- and post-baseline nodule measurements for both ultrasound and calipers. | Posted | Number | participants | Day 57 |
|
Adverse events were collected from enrollment through the end of the study (Day 57).
Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | AA4500 0.60 mg | Collagenase clostridium histolyticum (AA4500), single 0.60 mg injection into the nodule | 0 | 18 | 17 | 18 | ||
| EG001 | AA4500 0.40 mg | Collagenase clostridium histolyticum (AA4500), single 0.40 mg injection into the nodule | 0 | 18 | 18 | 18 | ||
| EG002 | AA4500 0.25 mg | Collagenase clostridium histolyticum (AA4500), single 0.25 mg injection into the nodule | 0 | 22 | 21 | 22 | ||
| EG003 | Placebo | Placebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection into the nodule | 0 | 17 | 7 | 17 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA 17.0 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 17.0 | Non-systematic Assessment |
| |
| Axillary pain | General disorders | MedDRA 17.0 | Non-systematic Assessment |
| |
| Injection site bruising | General disorders | MedDRA 17.0 | Non-systematic Assessment |
| |
| Injection site haemorrhage | General disorders | MedDRA 17.0 | Non-systematic Assessment |
| |
| Injection site hypoaesthesia | General disorders | MedDRA 17.0 | Non-systematic Assessment |
| |
| Injection site oedema | General disorders | MedDRA 17.0 | Non-systematic Assessment |
| |
| Injection site pain | General disorders | MedDRA 17.0 | Non-systematic Assessment |
| |
| Injection site pruritus | General disorders | MedDRA 17.0 | Non-systematic Assessment |
| |
| Injection site swelling | General disorders | MedDRA 17.0 | Non-systematic Assessment |
| |
| Local swelling | General disorders | MedDRA 17.0 | Non-systematic Assessment |
| |
| Localised oedema | General disorders | MedDRA 17.0 | Non-systematic Assessment |
| |
| Pain | General disorders | MedDRA 17.0 | Non-systematic Assessment |
| |
| Tenderness | General disorders | MedDRA 17.0 | Non-systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 17.0 | Non-systematic Assessment |
| |
| Injection related reaction | Injury, poisoning and procedural complications | MedDRA 17.0 | Non-systematic Assessment |
| |
| Liver function test abnormal | Investigations | MedDRA 17.0 | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Non-systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Non-systematic Assessment |
| |
| Dupuytren's contracture | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Non-systematic Assessment |
| |
| Joint range of motion decreased | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Non-systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Non-systematic Assessment |
| |
| Pain in jaw | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 17.0 | Non-systematic Assessment |
| |
| Blister | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Non-systematic Assessment |
| |
| Blood blister | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Non-systematic Assessment |
| |
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Non-systematic Assessment |
|
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Trial Coordinator | Endo Pharmaceuticals, Inc. | clinicalsite.inquiries@endo.com |
| ID | Term |
|---|---|
| D004387 | Dupuytren 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 |
| D003286 | Contracture |
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
Not provided
Not provided
| 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 |
Not provided
Not provided
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Australia |
|
| Volume |
|
| <.0001 |
| 2-Sided |
| Superiority or Other |
| For surface area | ANOVA | <.0001 | 2-Sided | Superiority or Other |
| For surface area | ANOVA | .0713 | 2-Sided | Superiority or Other |
| For volume | ANOVA | .0002 | 2-Sided | Superiority or Other |
| For volume | ANOVA | .0001 | 2-Sided | Superiority or Other |
| For volume | ANOVA | .0001 | 2-Sided | Superiority or Other |
| For volume | ANOVA | .0446 | 2-Sided | Superiority or Other |
| OG003 | Placebo | Placebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection into the nodule |
|
|
|
| OG003 | Placebo | Placebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection into the nodule |
|
|
|
| Placebo |
Placebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection into the nodule |
|
|
|
| OG003 |
| Placebo |
Placebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection into the nodule |
|
|
|
Placebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection into the nodule
|
|
|
|
|
|
|
|
|