Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
COLLAGENASE CLOSTRIDIUM HISTOLYTICUM · 6 trials · 7 indications
Aesthetic appearance improvement for each treatment area (buttocks or thighs) was assessed by a blinded central assessment, using a 5-point Likert scale with scores ranging from -1 to 3. Aesthetic improvement was scored as worse (-1), stayed the same (0), improved (1), much improved (2) and very much improved (3). The assessor evaluated the image at Day 22 in comparison with baseline and recorded the Likert score. Aesthetic appearance Likert scale scores were analyzed using linear mixed model with treatment arm, study visit, interaction of treatment arm and study visit as fixed effects. This model was fitted using the response for the average of left and right of treatment area (that is, average of left buttock and right buttock or average of left thigh and right thigh).
Aesthetic appearance improvement for each treatment area (buttocks or thighs) was assessed by a blinded central assessment, using a 5-point Likert scale with scores ranging from -1 to 3. Aesthetic improvement was scored as worse (-1), stayed the same (0), improved (1), much improved (2) and very much improved (3). The assessor evaluated the image at Day 43 in comparison with baseline and recorded the Likert score. Aesthetic appearance Likert scale scores were analyzed using linear mixed model with treatment arm, study visit, interaction of treatment arm and study visit as fixed effects. This model was fitted using the response for the average of left and right of treatment area (that is, average of left buttock and right buttock or average of left thigh and right thigh).
Aesthetic appearance improvement for each treatment area (buttocks or thighs) was assessed by a blinded central assessment, using a 5-point Likert scale with scores ranging from -1 to 3. Aesthetic improvement was scored as worse (-1), stayed the same (0), improved (1), much improved (2) and very much improved (3). The assessor evaluated the image at Day 71 in comparison with baseline and recorded the Likert score. Aesthetic appearance Likert scale scores were analyzed using linear mixed model with treatment arm, study visit, interaction of treatment arm and study visit as fixed effects. This model was fitted using the response for the average of left and right of treatment area (that is, average of left buttock and right buttock or average of left thigh and right thigh).
Dimple depth depression for each treatment area was assessed by the Investigator using the Hexsel Cellulite Severity Scale (B). Dimple Depth Depression of Hexsel Cellulite Severity Scale (B) was assessed and graded as: no depression (0), superficial depressions (1), medium depth depressions (2) and deep depressions (3). A negative change in Hexsel CSS (B) from baseline indicated an improvement in depression depth. Change from Baseline in dimple depth depression of Hexsel Cellulite Severity Scale (B) was analyzed using linear mixed model with treatment arm, study visits, interaction of treatment arm and study visit as fixed effect. This model was fitted using the response for the average of left and right of treatment areas (that is, average of left buttock and right buttock; average of left thigh and right thigh)
Dimple depth depression for each treatment area was assessed by the Investigator using the Hexsel Cellulite Severity Scale (B). Dimple Depth Depression of Hexsel Cellulite Severity Scale (B) was assessed and graded as: no depression (0), superficial depressions (1), medium depth depressions (2) and deep depressions (3). A negative change in Hexsel CSS (B) from baseline indicated an improvement in depression depth. Change from Baseline in dimple depth depression of Hexsel Cellulite Severity Scale (B) was analyzed using linear mixed model with treatment arm, study visits, interaction of treatment arm and study visit as fixed effect. This model was fitted using the response for the average of left and right of treatment areas (that is, average of left buttock and right buttock; average of left thigh and right thigh)
Dimple depth depression for each treatment area was assessed by the Investigator using the Hexsel Cellulite Severity Scale (B). Dimple Depth Depression of Hexsel Cellulite Severity Scale (B) was assessed and graded as: no depression (0), superficial depressions (1), medium depth depressions (2) and deep depressions (3). A negative change in Hexsel CSS (B) from baseline indicated an improvement in depression depth. Change from Baseline in dimple depth depression of Hexsel Cellulite Severity Scale (B) was analyzed using linear mixed model with treatment arm, study visits, interaction of treatment arm and study visit as fixed effect. This model was fitted using the response for the average of left and right of treatment areas (that is, average of left buttock and right buttock; average of left thigh and right thigh)
Percentage of composite responders defined as subjects with an improvement from baseline of at least 2-levels of severity on each, the Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) and Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS), at Day 71 in the ITT population. The CR-PCSS is a photonumeric scale that was used by the Investigator to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). The PR-PCSS is a photonumeric scale that was used by the subjects to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). A 2-level improvement on each scale for example would represent a change from a 4 (severe) to a 2 (mild). In order to be considered a responder a subject needs to have at least a 2-level improvement on both scales.
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.
Active range of motion (AROM) measurement using a goniometer to assess forward flexion in the affected shoulder
| Arm | Type | Description |
|---|---|---|
| Group 1: CCH High Dose | EXPERIMENTAL | Participants will receive a high dose of CCH on Day 1. |
| Group 2: CCH Low Dose | EXPERIMENTAL | Participants will receive a low dose of CCH on Day 1. |
| Group 3: Placebo | PLACEBO_COMPARATOR | Participants will receive matching placebo on Day 1. |
| Treatment I: CCH Shallow Injection, 3 Aliquots | ACTIVE_COMPARATOR | In Treatment I, CCH will be injected subcutaneously while the participant lies in a prone position. Each injection will consist of a single skin injection of study drug administered as three 0.1 milliliters (mL) aliquots (for a total injection volume of 0.3 mL). During each treatment visit, 8 syringes (4 syringes per treatment area) will be prepared for dosing. Each syringe will contain 0.9 mL of CCH (3 injections in each syringe). Dose per participant per treatment visit = up to 1.68 milligrams (mg) of CCH (0.84 mg in each treatment area). |
| Treatment II: CCH Shallow Injection, 1 Aliquot | ACTIVE_COMPARATOR | In Treatment II, CCH will be injected subcutaneously while the participant is in a prone position. Each injection will consist of a single skin injection of study drug administered as a single shallow injection of a 0.3 mL aliquot. During each treatment visit, 8 syringes (4 syringes per treatment area) will be prepared for dosing. Each syringe will contain 0.9 mL of CCH (3 injections in each syringe). Dose per participant per treatment visit = up to 1.68 mg of CCH (0.84 mg in each treatment area). |
| Treatment III: CCH Deep Injection, 1 Aliquot | ACTIVE_COMPARATOR | In Treatment III, CCH will be injected subcutaneously while the participant is in a prone position. Each injection will consist of a single skin injection of study drug administered as a single deep injection of a 0.3 mL study drug aliquot. During each treatment visit, 8 syringes (4 syringes per treatment area) will be prepared for dosing. Each syringe will contain 0.9 mL of CCH (3 injections in each syringe). Dose per participant per treatment visit = up to 1.68 mg of CCH (0.84 mg in each treatment area). |
| Treatment IV: CCH Deep and Shallow Injections, 5 Aliquots | ACTIVE_COMPARATOR | In Treatment IV, CCH will be injected subcutaneously while the participant lies in a prone position. Each injection will consist of a single skin injection of study drug administered as five 0.3 mL (for a total injection volume of 1.5 mL). During each treatment visit, 24 syringes (12 syringes per treatment area) will be prepared for dosing. Each syringe will contain 1.5 mL of CCH (5 aliquots of 0.3 mL, for each injection, in each syringe). Dose per participant per treatment visit = up to 1.68 mg of CCH (0.84 mg in each treatment area). |
| Treatment V: CCH Shallow Injections, 4 Aliquots | ACTIVE_COMPARATOR | In Treatment V, CCH will be injected subcutaneously while the participant lies in a prone position. Each injection will receive a single skin injection of study drug administered as four 0.3 mL aliquots (for a total injection volume of 1.2 mL). During each treatment visit, 24 syringes (12 syringes per treatment area) will be prepared for dosing. Each syringe will contain 1.2 mL of CCH (4 aliquots of 0.3 mL each). Dose per participant per treatment visit = up to 1.68 mg of CCH (0.84 mg in each treatment area). |
| EN3835 Active | EXPERIMENTAL | EN3835 0.84 mg (Collagenase Clostridium Histolyticum). Each subject can receive up to three treatment sessions. Each treatment session will be separated by approximately 21 days. |
| EN3835 Placebo | PLACEBO_COMPARATOR | Placebo |
| 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 |
| Collagenase Clostridium Histolyticum | EXPERIMENTAL | Up to 3 injections of .58 mg/1 mL of collagenase clostridium histolyticum (CCH), minimum of 21 days apart and home shoulder exercise. |
| AA4500 0.0029 mg in 1 mL | EXPERIMENTAL | - |
| AA4500 0.0145 mg in 5 mL | EXPERIMENTAL | - |
| AA4500 0.0145 mg in 1 mL | EXPERIMENTAL | - |
| AA4500 0.0435 mg in 5 mL | EXPERIMENTAL | - |
| AA4500 0.0435 mg in 1 mL | EXPERIMENTAL | - |
| AA4500 0.116 mg in 5 mL | EXPERIMENTAL | - |
| AA4500 0.116 mg in 1 mL | EXPERIMENTAL | - |
| AA4500 0.232 mg in 5 mL | EXPERIMENTAL | - |
| AA4500 at 0.232 in 1 mL | EXPERIMENTAL | - |
| AA4500 0.464 mg in 5 mL | EXPERIMENTAL | - |
| AA4500 0.464 mg in 1 mL | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Collagenase Clostridium Histolyticum (CCH) | BIOLOGICAL | Biologic: Intrafascial injection |
| Placebo | BIOLOGICAL | Intrafascial injection |
| COLLAGENASE CLOSTRIDIUM HISTOLYTICUM | BIOLOGICAL | Injectable intervention |
| Placebo Comparator | BIOLOGICAL | - |
Key Inclusion Criteria: * Have no significant medical history or examination findings related to the foot to be treated, which in the investigator's opinion, would make the participant unsuitable for study intervention administration. * Have a diagnosis of plantar fasciitis for ≥6 months, which has...
COLLAGENASE CLOSTRIDIUM HISTOLYTICUM is an investigational drug being studied for Edematous Fibrosclerotic Panniculopathy (commonly known as cellulite), Plantar Fasciitis, Edematous Skin, Adhesive Capsulitis, and Dupuytren's Disease. It is in Phase 2 clinical development for these conditions.
COLLAGENASE CLOSTRIDIUM HISTOLYTICUM is being developed by BrainsWay Ltd., a company traded under the ticker BWAY. The drug is in Phase 2 clinical development for multiple indications including cellulite and plantar fasciitis.
COLLAGENASE CLOSTRIDIUM HISTOLYTICUM is in Phase 2 clinical development. It is investigational and not yet approved by regulatory authorities. Clinical trials have been completed for conditions such as Edematous Fibrosclerotic Panniculopathy and Plantar Fasciitis.
COLLAGENASE CLOSTRIDIUM HISTOLYTICUM has completed several clinical trials. NCT01518907 studied its safety and effectiveness for cellulite. NCT02724644 and NCT03632993 also evaluated it for cellulite and edematous skin. NCT06169319 assessed it for plantar fasciitis. All trials were conducted in the United States.
COLLAGENASE CLOSTRIDIUM HISTOLYTICUM is also known by the names AA4500 and EN3835 in clinical trials. NCT01518907 used AA4500, while NCT02724644 used EN3835, both for treating Edematous Fibrosclerotic Panniculopathy, commonly called cellulite.