Characteristics of Subcutaneous Tissue
Conditions
Brief summary
To evaluate the histopathology of subcutaneous tissue isolated after single or multiple Collagenase Clostridium Histolyticum (CCH) injection techniques in adult female participants undergoing abdominoplasty.
Interventions
DRUGCollagenase Clostridium Histolyticum Single Injection Technique
CCH was injected subcutaneously using a single injection technique. Dose per each administration was 0.07 mg.
DRUGCollagenase Clostridium Histolyticum Multiple Injection Technique
CCH was injected subcutaneously using a multiple injection technique. Dose per each administration was 0.0653 mg.
Sponsors
Endo Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Be adequately informed and understand the nature and risks of the study and be able to provide consent. 2. Be undergoing planned elective abdominoplasty. 3. Be willing to have their tissue donated for evaluation. 4. Be judged to be in good health. 5. Have a negative pregnancy test. 6. Be willing and able to cooperate with the requirements of the study.
Exclusion criteria
1. Is from a vulnerable population, as defined by the US Code of Federal Regulations (CFR) Title 45, Part 46, Section 46.111(b) and other local and national regulations, including but not limited to, employees (temporary, part-time, full time, etc) or a family member of the research staff conducting the study, or of the sponsor, or of the contract research organization, or of the Institutional Review Board (IRB)/Independent Ethics Committee (IEC). 2. Has systemic conditions (coagulation disorders, malignancy, keloidal scar, abnormal wound healing) that restricts study participation. 3. Has local (in the areas to be treated) conditions (thrombosis, vascular disorder, active infection/inflammation, active cutaneous alteration, tattoo/mole) that restricts study participation. 4. Required use of anticoagulant or antiplatelet medication (except ≤ 150 mg aspirin daily) before or during participation in the trial. 5. Past history of any abdominal surgery, including but not limited to: liposuction, caesarean section, appendectomy, cholecystectomy, or umbilical hernia repair. 6. Has used or intends to use any local applications/therapies/injections/procedures that restricts study participation. 7. Is presently nursing or providing breast milk in any manner. 8. Intends to become pregnant during the study. 9. Intends to initiate an intensive sport or exercise program regimen during the study. 10. Intends to use any tanning spray or tanning booths during the study. 11. Has received any investigational drug or treatment within 30 days prior to first injection of study drug. 12. Has a known systemic allergy to collagenase or any other excipient of study drug. 13. Has received any collagenase treatment at any time prior to treatment in this study. 14. Any other condition(s) that, in the investigator's opinion, might indicate the subject to be unsuitable for the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Histologic Change in a Tissue Specimen That Was Injected With CCH | Up to collection of the excised abdominal tissue on Day 0 (day of abdominoplasty) | Tissue specimens isolated from participants undergoing an abdominoplasty procedure were observed for histopathological structure changes of tissues post treatment with CCH. The number of participants with a histologic change (as determined by the pathologist) in tissue dosed with CCH relative to control tissue (tissue not dosed with CCH) is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Histologic Change in a Tissue Specimen After 2 CCH Dose Injections Relative to a Tissue Specimen After 1 CCH Dose Injection | Up to collection of the excised abdominal tissue on Day 0 (day of abdominoplasty) | Tissue specimens isolated from participants undergoing an abdominoplasty procedure were observed for histopathological structure changes of tissues post treatment with CCH. The number of participants with a histologic change (as determined by the pathologist) in a tissue specimen injected with 2 CCH dose injections (Treatment Area 1) relative to 1 CCH dose injection (Treatment Area 2) is reported. |
| Number of Participants With Anti-AUX-I and Anti-AUX-II Anti-Drug Antibodies (ADAs) After CCH Treatment | End of Study (Day 28) | Serum samples were analyzed for anti-AUX-I clostridial class I collagenase of ADAs and anti-AUX-II Clostridial class II collagenase of ADAs. The number of participants who developed anti-AUX-I and anti-AUX-II ADAs (positive ADA result) are reported. |
| Number of Participants With Anti-AUX-I and Anti-AUX-II Neutralizing Antibodies (NAbs) After CCH Treatment | End of Study (Day 28) | Serum samples were analyzed for anti-AUX-I and Anti-AUX-II Nabs. The number of participants who developed anti-AUX-I and Anti-AUX-II NAbs (positive NAb results) are reported. Neutralizing antibodies were only tested from ADA positive participants. |
Countries
United States
Participant flow
Pre-assignment details
Participants were divided among 6 different cohorts based on injection technique and respective dosing days. Two participants (Group 4 multiple injection technique) were not included in the Evaluable Population when their surgeries were delayed due to the effects of COVID-19 restrictions.
Participants by arm
| Arm | Count |
|---|---|
| CCH Subcutaneous Injection Participants were administered 0.07 mg CCH using a single injection technique or 0.0653 mg CCH using a multiple injection technique. | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | CCH Subcutaneous Injection |
|---|---|
| Age, Continuous | 44.1 years STANDARD_DEVIATION 10.55 |
| BMI | 26.24 kg/m^2 STANDARD_DEVIATION 4.46 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 164.47 cm STANDARD_DEVIATION 7.265 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 0 Participants |
| Weight | 71.31 Kg STANDARD_DEVIATION 16.275 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 1 | 0 / 1 | 0 / 4 | 0 / 1 | 0 / 1 |
| other Total, other adverse events | 2 / 2 | 1 / 1 | 1 / 1 | 4 / 4 | 1 / 1 | 1 / 1 |
| serious Total, serious adverse events | 0 / 2 | 0 / 1 | 0 / 1 | 0 / 4 | 0 / 1 | 0 / 1 |
Outcome results
Primary
Number of Participants With a Histologic Change in a Tissue Specimen That Was Injected With CCH
Tissue specimens isolated from participants undergoing an abdominoplasty procedure were observed for histopathological structure changes of tissues post treatment with CCH. The number of participants with a histologic change (as determined by the pathologist) in tissue dosed with CCH relative to control tissue (tissue not dosed with CCH) is reported.
Time frame: Up to collection of the excised abdominal tissue on Day 0 (day of abdominoplasty)
Population: Evaluable Population: All participants who received at least 1 injection of study drug, underwent abdominoplasty within the protocol specified timelines, and had a histopathology and immunohistochemistry report.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1: CCH Single Injection Technique | Number of Participants With a Histologic Change in a Tissue Specimen That Was Injected With CCH | 2 Participants |
| Group 2: CCH Single Injection Technique | Number of Participants With a Histologic Change in a Tissue Specimen That Was Injected With CCH | 1 Participants |
| Group 3: CCH Single Injection Technique | Number of Participants With a Histologic Change in a Tissue Specimen That Was Injected With CCH | 1 Participants |
| Group 4: CCH Multiple Injection Technique | Number of Participants With a Histologic Change in a Tissue Specimen That Was Injected With CCH | 2 Participants |
| Group 5: CCH Multiple Injection Technique | Number of Participants With a Histologic Change in a Tissue Specimen That Was Injected With CCH | 1 Participants |
| Group 6: CCH Multiple Injection Technique | Number of Participants With a Histologic Change in a Tissue Specimen That Was Injected With CCH | 1 Participants |
Secondary
Number of Participants With a Histologic Change in a Tissue Specimen After 2 CCH Dose Injections Relative to a Tissue Specimen After 1 CCH Dose Injection
Tissue specimens isolated from participants undergoing an abdominoplasty procedure were observed for histopathological structure changes of tissues post treatment with CCH. The number of participants with a histologic change (as determined by the pathologist) in a tissue specimen injected with 2 CCH dose injections (Treatment Area 1) relative to 1 CCH dose injection (Treatment Area 2) is reported.
Time frame: Up to collection of the excised abdominal tissue on Day 0 (day of abdominoplasty)
Population: Evaluable Population: All participants who received at least 1 injection of study drug, underwent abdominoplasty within the protocol specified timelines, and had a histopathology and immunohistochemistry report.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1: CCH Single Injection Technique | Number of Participants With a Histologic Change in a Tissue Specimen After 2 CCH Dose Injections Relative to a Tissue Specimen After 1 CCH Dose Injection | 2 Participants |
| Group 2: CCH Single Injection Technique | Number of Participants With a Histologic Change in a Tissue Specimen After 2 CCH Dose Injections Relative to a Tissue Specimen After 1 CCH Dose Injection | 1 Participants |
| Group 3: CCH Single Injection Technique | Number of Participants With a Histologic Change in a Tissue Specimen After 2 CCH Dose Injections Relative to a Tissue Specimen After 1 CCH Dose Injection | 1 Participants |
| Group 4: CCH Multiple Injection Technique | Number of Participants With a Histologic Change in a Tissue Specimen After 2 CCH Dose Injections Relative to a Tissue Specimen After 1 CCH Dose Injection | 2 Participants |
| Group 5: CCH Multiple Injection Technique | Number of Participants With a Histologic Change in a Tissue Specimen After 2 CCH Dose Injections Relative to a Tissue Specimen After 1 CCH Dose Injection | 1 Participants |
| Group 6: CCH Multiple Injection Technique | Number of Participants With a Histologic Change in a Tissue Specimen After 2 CCH Dose Injections Relative to a Tissue Specimen After 1 CCH Dose Injection | 1 Participants |
Secondary
Number of Participants With Anti-AUX-I and Anti-AUX-II Anti-Drug Antibodies (ADAs) After CCH Treatment
Serum samples were analyzed for anti-AUX-I clostridial class I collagenase of ADAs and anti-AUX-II Clostridial class II collagenase of ADAs. The number of participants who developed anti-AUX-I and anti-AUX-II ADAs (positive ADA result) are reported.
Time frame: End of Study (Day 28)
Population: Safety Population: All participants who received at least 1 injection of study drug irrespective of the timing window of abdominoplasty. ADA data is reported as overall population instead of individual groups due to the small number of participants per arm and to protect PII of the participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1: CCH Single Injection Technique | Number of Participants With Anti-AUX-I and Anti-AUX-II Anti-Drug Antibodies (ADAs) After CCH Treatment | Anti-AUX-I ADAs | 9 Participants |
| Group 1: CCH Single Injection Technique | Number of Participants With Anti-AUX-I and Anti-AUX-II Anti-Drug Antibodies (ADAs) After CCH Treatment | Anti-AUX-II ADAs | 5 Participants |
Secondary
Number of Participants With Anti-AUX-I and Anti-AUX-II Neutralizing Antibodies (NAbs) After CCH Treatment
Serum samples were analyzed for anti-AUX-I and Anti-AUX-II Nabs. The number of participants who developed anti-AUX-I and Anti-AUX-II NAbs (positive NAb results) are reported. Neutralizing antibodies were only tested from ADA positive participants.
Time frame: End of Study (Day 28)
Population: All participants who received at least 1 injection of study drug and were positive for ADAs. NAb data is reported as overall analysis population instead of individual groups due to the small number of participants per arm and to protect PII of the participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1: CCH Single Injection Technique | Number of Participants With Anti-AUX-I and Anti-AUX-II Neutralizing Antibodies (NAbs) After CCH Treatment | Anti-AUX-I NAbs | 7 Participants |
| Group 1: CCH Single Injection Technique | Number of Participants With Anti-AUX-I and Anti-AUX-II Neutralizing Antibodies (NAbs) After CCH Treatment | Anti-AUX-II NAbs | 3 Participants |