Epidermolysis Bullosa
Conditions
Keywords
Amicus Therapeutics, Scioderm, Inc., Simplex, Recessive Dystrophic, Junctional non-Herlitz, Epidermolysis Bullosa, SD-101 6%, SD-101-6.0, Allantoin 6%, Zorblisa
Brief summary
The study aimed to assess the long-term safety of topical use of Zorblisa (SD-101-6.0) in participants with Epidermolysis Bullosa (EB).
Detailed description
This was an open label, multi-center extension study to assess the long-term safety of topically applied SD-101-6.0 in participants with simplex, recessive dystrophic, and junctional non-Herlitz EB. SD-101-6.0 was applied topically once a day to the entire body. The planned duration of treatment with SD-101-6.0 for Study SD-006 was up to 48 months, with a safety follow-up period of 30 days; however, the study was terminated early by the sponsor. The maximum study duration completed by at least 1 participant, treatment and safety follow-up, was 37 months. Participants who successfully completed Study SD-005 had the option to rollover into Study SD-006. The screening/baseline visit (Visit 1) occurred at Visit 5 (approximately 90 days from baseline) of Study SD-005. The Body Surface Area (BSA) assessments of lesional skin and wound burden performed at Visit 5 (approximately 90 days from baseline) for Study SD-005 were utilized as the baseline assessments for Study SD-006. Participants returned for follow-up visits at Month 1 then every 3 months. At each visit, assessments included BSA of lesional skin and wound burden. For target wounds that are not closed by the end of Study SD-005, the ARANZ picture and calculation of target wound area at the final visit for Study SD-005 was used as the baseline area size of the target wound for Study SD-006. These unhealed target wounds from Study SD-005 were assessed via ARANZ SilhouetteStar™ at each subsequent scheduled visit until the target wound was documented as closed. Closed wounds were assessed for scarring.
Interventions
DRUGSD-101-6.0 cream
SD-101 is a white, crystalline powder that is formulated within an odorless, soft, white cream base. SD-101-6.0 cream contains allantoin, a diureide glyoxylic acid, at a concentration of 6% and other excipients.
Sponsors
Amicus Therapeutics
Scioderm, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Months to No maximum
Healthy volunteers
No
Inclusion criteria
* Informed Consent Form signed by the participant or participant's legal representative; if the participant was under the age of 18 but capable of providing assent, signed assent from the participant. * Participant (or caretaker) must have been willing to comply with all protocol requirements. * Participants who completed the SD-005 study (on study drug at Visit 5, approximately 90 days from baseline).
Exclusion criteria
* Participants who did not meet the entry criteria outlined above. * Pregnancy or breastfeeding during the study. (A urine pregnancy test was performed at the final visit for Study SD-005 for female participants of childbearing potential and repeated at screening/baseline visit of Study SD-006 if these visits did not occur on the same day). * Female participants of childbearing potential who were not abstinent or not practicing a medically acceptable method of contraception.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number Of Participants With Treatment Emergent Adverse Events (TEAEs) | From baseline to 30 days after last application of study drug (up to a maximum of 37 months) | TEAEs were defined as adverse events that started or worsened on or after baseline visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline In Body Surface Area Index (BSAI) Of Lesional Skin Up To Month 30 | Baseline, up to Month 30 | Lesional skin was defined as areas that contained any of the following: blisters, erosions, ulcerations, scabbing, bullae, or eschars, as well as areas that were weeping, sloughing, oozing, crusted, or denuded. The percentage, ranging from 0% to 100%, of affected body surface area (BSA) was recorded for each defined body region (that is, head/neck, upper limbs, trunk \[includes groin\], and lower limbs), multiplied by the weighting factor, then summed for all body regions to calculate the BSAI that would range from 0% to 100%. The BSA for lesional skin was to be assessed by the same study physician on each visit for a particular participant. The mean change from baseline in BSAI was assessed every 3 months. Only participants with data available for analysis at each time point are presented. |
| Change From Baseline In BSAI Of Total Body Wound Burden Up To Month 30 | Baseline, up to Month 30 | A wound was defined as an open area on the skin (that is, epidermal covering disrupted). Total body wound burden was calculated using BSAI; the percentage, ranging from 0% to 100%, of affected BSA was recorded for each defined body region (that is, head/neck, upper limbs, trunk \[includes groin\], and lower limbs), multiplied by the weighting factor, then summed for all body regions to calculate the BSAI that would range from 0% to 100%. The BSAI for total body wound burden was to be assessed by the same study physician at each visit for a particular participant. The mean change from baseline in total body wound burden was assessed every 3 months. Only participants with data available for analysis at each time point are presented. |
Countries
Australia, Austria, France, Germany, Israel, Lithuania, Netherlands, Poland, Serbia, Spain, United Kingdom, United States
Participant flow
Recruitment details
152 participants with epidermolysis bullosa (EB) were enrolled between 9 June 2015 and 5 July 2017 in this open-label, multi-center extension study. All enrolled participants had previously completed Study SD-005 (NCT02384460).
Pre-assignment details
Analysis groups were defined based on prior treatment in Study SD-005: 77 participants who received placebo were allocated to the 'Placebo to Zorblisa™ (SD-101-6.0)' group and 75 participants who received SD-101-6.0 were allocated to the 'SD-101-6.0 to SD-101-6.0' group. All participants received SD-101-6.0 upon enrolling in Study SD-006.
Participants by arm
| Arm | Count |
|---|---|
| SD-101-6.0 to SD-101-6.0 Participants who received SD-101-6.0 in Study SD-005 continued to receive SD-101-6.0 in this open label extension study. SD-101-6.0 was applied topically once a day to the entire body. | 75 |
| Placebo to SD-101-6.0 Participants who received placebo in Study SD-005 received SD-101-6.0 in this open-label extension study. SD-101-6.0 was applied topically once a day to the entire body. | 77 |
| Total | 152 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 3 |
| Overall Study | Lost to Follow-up | 3 | 2 |
| Overall Study | Protocol Deviation | 1 | 0 |
| Overall Study | Study Terminated By Sponsor | 36 | 43 |
| Overall Study | Withdrawal by Subject | 34 | 29 |
Baseline characteristics
| Characteristic | Total | SD-101-6.0 to SD-101-6.0 | Placebo to SD-101-6.0 |
|---|---|---|---|
| Age, Continuous | 14.27 years STANDARD_DEVIATION 13.447 | 14.18 years STANDARD_DEVIATION 13.381 | 14.36 years STANDARD_DEVIATION 13.599 |
| EB Type Junctional Non-Herlitz | 27 Participants | 13 Participants | 14 Participants |
| EB Type Recessive Dystrophic | 109 Participants | 53 Participants | 56 Participants |
| EB Type Simplex | 16 Participants | 9 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants | 5 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 127 Participants | 67 Participants | 60 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 7 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 10 Participants | 3 Participants | 7 Participants |
| Race/Ethnicity, Customized Black or African-American | 7 Participants | 4 Participants | 3 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Unknown | 5 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized White/Caucasian | 128 Participants | 65 Participants | 63 Participants |
| Sex: Female, Male Female | 73 Participants | 28 Participants | 45 Participants |
| Sex: Female, Male Male | 79 Participants | 47 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 75 | 0 / 77 |
| other Total, other adverse events | 44 / 75 | 51 / 77 |
| serious Total, serious adverse events | 11 / 75 | 14 / 77 |
Outcome results
Primary
Number Of Participants With Treatment Emergent Adverse Events (TEAEs)
TEAEs were defined as adverse events that started or worsened on or after baseline visit.
Time frame: From baseline to 30 days after last application of study drug (up to a maximum of 37 months)
Population: Safety Population: all participants who applied/were administered the study drug at least once.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SD-101-6.0 to SD-101-6.0 | Number Of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE | 51 Participants |
| SD-101-6.0 to SD-101-6.0 | Number Of Participants With Treatment Emergent Adverse Events (TEAEs) | Any Fatal TEAE | 0 Participants |
| SD-101-6.0 to SD-101-6.0 | Number Of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE Related To Study Drug | 8 Participants |
| SD-101-6.0 to SD-101-6.0 | Number Of Participants With Treatment Emergent Adverse Events (TEAEs) | Any Serious TEAE | 11 Participants |
| SD-101-6.0 to SD-101-6.0 | Number Of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE Leading To Discontinuation | 2 Participants |
| Placebo to SD-101-6.0 | Number Of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE Leading To Discontinuation | 3 Participants |
| Placebo to SD-101-6.0 | Number Of Participants With Treatment Emergent Adverse Events (TEAEs) | Any Fatal TEAE | 0 Participants |
| Placebo to SD-101-6.0 | Number Of Participants With Treatment Emergent Adverse Events (TEAEs) | Any Serious TEAE | 14 Participants |
| Placebo to SD-101-6.0 | Number Of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE | 58 Participants |
| Placebo to SD-101-6.0 | Number Of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE Related To Study Drug | 17 Participants |
Secondary
Change From Baseline In Body Surface Area Index (BSAI) Of Lesional Skin Up To Month 30
Lesional skin was defined as areas that contained any of the following: blisters, erosions, ulcerations, scabbing, bullae, or eschars, as well as areas that were weeping, sloughing, oozing, crusted, or denuded. The percentage, ranging from 0% to 100%, of affected body surface area (BSA) was recorded for each defined body region (that is, head/neck, upper limbs, trunk \[includes groin\], and lower limbs), multiplied by the weighting factor, then summed for all body regions to calculate the BSAI that would range from 0% to 100%. The BSA for lesional skin was to be assessed by the same study physician on each visit for a particular participant. The mean change from baseline in BSAI was assessed every 3 months. Only participants with data available for analysis at each time point are presented.
Time frame: Baseline, up to Month 30
Population: Intent-to-treat (ITT) population: all participants who rolled over from Study SD-005 and had data available for analysis at each specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SD-101-6.0 to SD-101-6.0 | Change From Baseline In Body Surface Area Index (BSAI) Of Lesional Skin Up To Month 30 | Month 1 | -0.76 Percentage of BSAI | Standard Deviation 4.185 |
| SD-101-6.0 to SD-101-6.0 | Change From Baseline In Body Surface Area Index (BSAI) Of Lesional Skin Up To Month 30 | Month 3 | -1.87 Percentage of BSAI | Standard Deviation 5.999 |
| SD-101-6.0 to SD-101-6.0 | Change From Baseline In Body Surface Area Index (BSAI) Of Lesional Skin Up To Month 30 | Month 6 | -1.77 Percentage of BSAI | Standard Deviation 6.015 |
| SD-101-6.0 to SD-101-6.0 | Change From Baseline In Body Surface Area Index (BSAI) Of Lesional Skin Up To Month 30 | Month 9 | -2.48 Percentage of BSAI | Standard Deviation 9.436 |
| SD-101-6.0 to SD-101-6.0 | Change From Baseline In Body Surface Area Index (BSAI) Of Lesional Skin Up To Month 30 | Month 15 | -1.90 Percentage of BSAI | Standard Deviation 7.337 |
| SD-101-6.0 to SD-101-6.0 | Change From Baseline In Body Surface Area Index (BSAI) Of Lesional Skin Up To Month 30 | Month 18 | -2.46 Percentage of BSAI | Standard Deviation 5.275 |
| SD-101-6.0 to SD-101-6.0 | Change From Baseline In Body Surface Area Index (BSAI) Of Lesional Skin Up To Month 30 | Month 21 | -3.06 Percentage of BSAI | Standard Deviation 5.869 |
| SD-101-6.0 to SD-101-6.0 | Change From Baseline In Body Surface Area Index (BSAI) Of Lesional Skin Up To Month 30 | Month 24 | -1.63 Percentage of BSAI | Standard Deviation 5.647 |
| SD-101-6.0 to SD-101-6.0 | Change From Baseline In Body Surface Area Index (BSAI) Of Lesional Skin Up To Month 30 | Month 27 | -1.87 Percentage of BSAI | Standard Deviation 4.405 |
| SD-101-6.0 to SD-101-6.0 | Change From Baseline In Body Surface Area Index (BSAI) Of Lesional Skin Up To Month 30 | Month 30 | -2.77 Percentage of BSAI | Standard Deviation 5.465 |
| SD-101-6.0 to SD-101-6.0 | Change From Baseline In Body Surface Area Index (BSAI) Of Lesional Skin Up To Month 30 | Month 12 | -3.35 Percentage of BSAI | Standard Deviation 9.566 |
| Placebo to SD-101-6.0 | Change From Baseline In Body Surface Area Index (BSAI) Of Lesional Skin Up To Month 30 | Month 30 | 3.37 Percentage of BSAI | Standard Deviation 10.706 |
| Placebo to SD-101-6.0 | Change From Baseline In Body Surface Area Index (BSAI) Of Lesional Skin Up To Month 30 | Month 1 | -0.54 Percentage of BSAI | Standard Deviation 5.398 |
| Placebo to SD-101-6.0 | Change From Baseline In Body Surface Area Index (BSAI) Of Lesional Skin Up To Month 30 | Month 21 | -1.58 Percentage of BSAI | Standard Deviation 10.442 |
| Placebo to SD-101-6.0 | Change From Baseline In Body Surface Area Index (BSAI) Of Lesional Skin Up To Month 30 | Month 3 | -1.21 Percentage of BSAI | Standard Deviation 6.457 |
| Placebo to SD-101-6.0 | Change From Baseline In Body Surface Area Index (BSAI) Of Lesional Skin Up To Month 30 | Month 6 | -1.35 Percentage of BSAI | Standard Deviation 6.813 |
| Placebo to SD-101-6.0 | Change From Baseline In Body Surface Area Index (BSAI) Of Lesional Skin Up To Month 30 | Month 24 | -0.64 Percentage of BSAI | Standard Deviation 5.981 |
| Placebo to SD-101-6.0 | Change From Baseline In Body Surface Area Index (BSAI) Of Lesional Skin Up To Month 30 | Month 9 | 0.31 Percentage of BSAI | Standard Deviation 10.117 |
| Placebo to SD-101-6.0 | Change From Baseline In Body Surface Area Index (BSAI) Of Lesional Skin Up To Month 30 | Month 12 | 0.44 Percentage of BSAI | Standard Deviation 10.327 |
| Placebo to SD-101-6.0 | Change From Baseline In Body Surface Area Index (BSAI) Of Lesional Skin Up To Month 30 | Month 27 | -0.16 Percentage of BSAI | Standard Deviation 6.514 |
| Placebo to SD-101-6.0 | Change From Baseline In Body Surface Area Index (BSAI) Of Lesional Skin Up To Month 30 | Month 15 | 2.15 Percentage of BSAI | Standard Deviation 12.546 |
| Placebo to SD-101-6.0 | Change From Baseline In Body Surface Area Index (BSAI) Of Lesional Skin Up To Month 30 | Month 18 | -4.24 Percentage of BSAI | Standard Deviation 8.207 |
Secondary
Change From Baseline In BSAI Of Total Body Wound Burden Up To Month 30
A wound was defined as an open area on the skin (that is, epidermal covering disrupted). Total body wound burden was calculated using BSAI; the percentage, ranging from 0% to 100%, of affected BSA was recorded for each defined body region (that is, head/neck, upper limbs, trunk \[includes groin\], and lower limbs), multiplied by the weighting factor, then summed for all body regions to calculate the BSAI that would range from 0% to 100%. The BSAI for total body wound burden was to be assessed by the same study physician at each visit for a particular participant. The mean change from baseline in total body wound burden was assessed every 3 months. Only participants with data available for analysis at each time point are presented.
Time frame: Baseline, up to Month 30
Population: Intent-to-treat (ITT) population: all participants who rolled over from Study SD-005 and had data available for analysis at each specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SD-101-6.0 to SD-101-6.0 | Change From Baseline In BSAI Of Total Body Wound Burden Up To Month 30 | Month 30 | -1.55 Percentage of BSAI | Standard Deviation 2.883 |
| SD-101-6.0 to SD-101-6.0 | Change From Baseline In BSAI Of Total Body Wound Burden Up To Month 30 | Month 1 | -1.75 Percentage of BSAI | Standard Deviation 4.891 |
| SD-101-6.0 to SD-101-6.0 | Change From Baseline In BSAI Of Total Body Wound Burden Up To Month 30 | Month 3 | -1.52 Percentage of BSAI | Standard Deviation 5.343 |
| SD-101-6.0 to SD-101-6.0 | Change From Baseline In BSAI Of Total Body Wound Burden Up To Month 30 | Month 6 | -1.54 Percentage of BSAI | Standard Deviation 4.322 |
| SD-101-6.0 to SD-101-6.0 | Change From Baseline In BSAI Of Total Body Wound Burden Up To Month 30 | Month 9 | -1.82 Percentage of BSAI | Standard Deviation 6.083 |
| SD-101-6.0 to SD-101-6.0 | Change From Baseline In BSAI Of Total Body Wound Burden Up To Month 30 | Month 12 | -1.38 Percentage of BSAI | Standard Deviation 5.497 |
| SD-101-6.0 to SD-101-6.0 | Change From Baseline In BSAI Of Total Body Wound Burden Up To Month 30 | Month 15 | -0.15 Percentage of BSAI | Standard Deviation 4.511 |
| SD-101-6.0 to SD-101-6.0 | Change From Baseline In BSAI Of Total Body Wound Burden Up To Month 30 | Month 18 | -1.12 Percentage of BSAI | Standard Deviation 3.053 |
| SD-101-6.0 to SD-101-6.0 | Change From Baseline In BSAI Of Total Body Wound Burden Up To Month 30 | Month 21 | -1.44 Percentage of BSAI | Standard Deviation 3.15 |
| SD-101-6.0 to SD-101-6.0 | Change From Baseline In BSAI Of Total Body Wound Burden Up To Month 30 | Month 24 | -0.68 Percentage of BSAI | Standard Deviation 3.89 |
| SD-101-6.0 to SD-101-6.0 | Change From Baseline In BSAI Of Total Body Wound Burden Up To Month 30 | Month 27 | -0.43 Percentage of BSAI | Standard Deviation 2.924 |
| Placebo to SD-101-6.0 | Change From Baseline In BSAI Of Total Body Wound Burden Up To Month 30 | Month 27 | 0.31 Percentage of BSAI | Standard Deviation 3.615 |
| Placebo to SD-101-6.0 | Change From Baseline In BSAI Of Total Body Wound Burden Up To Month 30 | Month 15 | 0.26 Percentage of BSAI | Standard Deviation 3.03 |
| Placebo to SD-101-6.0 | Change From Baseline In BSAI Of Total Body Wound Burden Up To Month 30 | Month 1 | 0.07 Percentage of BSAI | Standard Deviation 4.044 |
| Placebo to SD-101-6.0 | Change From Baseline In BSAI Of Total Body Wound Burden Up To Month 30 | Month 24 | -0.01 Percentage of BSAI | Standard Deviation 2.898 |
| Placebo to SD-101-6.0 | Change From Baseline In BSAI Of Total Body Wound Burden Up To Month 30 | Month 3 | -0.80 Percentage of BSAI | Standard Deviation 3.001 |
| Placebo to SD-101-6.0 | Change From Baseline In BSAI Of Total Body Wound Burden Up To Month 30 | Month 18 | -1.31 Percentage of BSAI | Standard Deviation 4.665 |
| Placebo to SD-101-6.0 | Change From Baseline In BSAI Of Total Body Wound Burden Up To Month 30 | Month 6 | -0.48 Percentage of BSAI | Standard Deviation 3.595 |
| Placebo to SD-101-6.0 | Change From Baseline In BSAI Of Total Body Wound Burden Up To Month 30 | Month 30 | 1.69 Percentage of BSAI | Standard Deviation 5.933 |
| Placebo to SD-101-6.0 | Change From Baseline In BSAI Of Total Body Wound Burden Up To Month 30 | Month 9 | -0.42 Percentage of BSAI | Standard Deviation 3.586 |
| Placebo to SD-101-6.0 | Change From Baseline In BSAI Of Total Body Wound Burden Up To Month 30 | Month 21 | -0.28 Percentage of BSAI | Standard Deviation 5.507 |
| Placebo to SD-101-6.0 | Change From Baseline In BSAI Of Total Body Wound Burden Up To Month 30 | Month 12 | -0.13 Percentage of BSAI | Standard Deviation 3.211 |