Epidermolysis Bullosa
Conditions
Keywords
Amicus Therapeutics, Scioderm, Inc., Recessive Dystrophic, Junctional non-Herlitz, Epidermolysis Bullosa, Simplex, SD-101 6%, SD-101-6.0, Allantoin 6%, Zorblisa
Brief summary
The purpose of this study was to assess the continued safety of topical use of SD-101 cream (6%) in participants with Epidermolysis Bullosa (EB). Funding Source: FDA Office of Orphan Products Development
Detailed description
This was an open-label extension study to assess the continued safety of topically applied SD-101 dermal cream (6%) in participants with Simplex, Recessive Dystrophic, and Junctional non-Herlitz EB. SD-101 dermal cream (6%) was applied topically, once a day to the entire body for the duration of the study. Participants who successfully completed the entire SD-003 study (NCT02014376) had the option to roll over into the SD-004 study (NCT02090283). The baseline visit occurred at the final visit date for the SD-003 study. The body surface area (BSA) coverage of blisters and lesions assessment made at the final SD-003 study visit were used as the baseline information at the baseline visit for the SD-004 study. Participants returned to the study site for the following 13 visits (36 months) to have BSA assessed. BSA was assessed at all subsequent scheduled study center visits. Scheduled study center visits occurred every 6 months after Month 36 (Month 42, 48, and so on). After completion of Month 36, the next participant visit (Month 39) was a phone call from the site to the participant. Telephone visits occurred every 6 months thereafter (Month 45, 51, and so on) and included assessment of adverse events and concomitant medications only. For female participants of childbearing potential, a urine pregnancy test was performed at Month 6 and every 6 months up to and including the final study visit.
Interventions
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
Food and Drug Administration (FDA)
Scioderm, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Months to No maximum
Healthy volunteers
No
Inclusion criteria
* Informed consent form signed by the participant or participant's legal representative; if the participant is under the age of 18 but capable of providing assent, signed assent from the participant. * Participant (or caretaker) must be willing to comply with all protocol requirements. * Participant must have successfully completed the SD-003 study.
Exclusion criteria
* Participants who do not meet the inclusion criteria. * Pregnancy or breastfeeding during the study. A urine pregnancy test will be performed at the final visit for SD-003 for female participants of childbearing potential. * Females of childbearing potential who are not abstinent and 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 54 months) | Treatment-emergent adverse events were defined as adverse events that started or worsened on or after baseline visit, which occurred at the final visit date for the SD-003 study. A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline In Body Surface Area Index (BSAI) Of Lesional Skin At Month 24 | Baseline, Month 24 | 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, and then summed for all body regions to calculate the BSAI. 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 (final visit from the SD-003 study) in BSAI was assessed every 3 months. Only participants with data available for analysis at the specified time point are presented. |
Countries
United States
Participant flow
Recruitment details
42 participants with epidermolysis bullosa (EB) were enrolled in this open-label, multi-center extension study. All enrolled participants had previously completed Study SD-003 (NCT02014376).
Pre-assignment details
Analysis groups were defined based on prior treatment in Study SD-003: those who received placebo were allocated to the 'Placebo to SD-101-6.0' group, those who received SD-101-3.0 were allocated to the 'SD-101-3.0 to SD-101-6.0' group, and those who received SD-101-6.0 were allocated to the 'SD-101-6.0 to SD-101-6.0' group.
Participants by arm
| Arm | Count |
|---|---|
| Placebo to SD-101-6.0 Participants who received placebo in Study SD-003 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. | 17 |
| SD-101-3.0 to SD-101-6.0 Participants who received SD-101-3.0 in Study SD-003 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. | 15 |
| SD-101-6.0 to SD-101-6.0 Participants who received SD-101-6.0 in Study SD-003 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. | 10 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 0 |
| Overall Study | Lost to Follow-up | 2 | 2 | 3 |
| Overall Study | Protocol Violation | 2 | 0 | 0 |
| Overall Study | Sponsor Terminated Study | 6 | 6 | 1 |
| Overall Study | Withdrawal by Subject | 6 | 6 | 6 |
Baseline characteristics
| Characteristic | Total | SD-101-6.0 to SD-101-6.0 | SD-101-3.0 to SD-101-6.0 | Placebo to SD-101-6.0 |
|---|---|---|---|---|
| Age, Continuous | 12.11 years STANDARD_DEVIATION 11.945 | 8.10 years STANDARD_DEVIATION 4.795 | 15.70 years STANDARD_DEVIATION 15.928 | 11.29 years STANDARD_DEVIATION 10.385 |
| EB Subtype Junctional non-Herlitz | 7 Participants | 1 Participants | 3 Participants | 3 Participants |
| EB Subtype Recessive Dystrophic | 24 Participants | 6 Participants | 8 Participants | 10 Participants |
| EB Subtype Simplex | 11 Participants | 3 Participants | 4 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 3 Participants | 6 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants | 7 Participants | 9 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Black or African-American | 3 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race White/Caucasian | 38 Participants | 7 Participants | 15 Participants | 16 Participants |
| Sex: Female, Male Female | 18 Participants | 5 Participants | 8 Participants | 5 Participants |
| Sex: Female, Male Male | 24 Participants | 5 Participants | 7 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 15 | 0 / 10 |
| other Total, other adverse events | 13 / 17 | 13 / 15 | 5 / 10 |
| serious Total, serious adverse events | 4 / 17 | 2 / 15 | 0 / 10 |
Outcome results
Primary
Number Of Participants With Treatment-Emergent Adverse Events (TEAEs)
Treatment-emergent adverse events were defined as adverse events that started or worsened on or after baseline visit, which occurred at the final visit date for the SD-003 study. A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.
Time frame: From baseline to 30 days after last application of study drug (up to a maximum of 54 months)
Population: Safety: All participants who successfully rolled over into the SD-004 study from the SD-003 study and applied/were administered at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo to SD-101-6.0 | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | Serious TEAE | 4 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 TEAE | 13 Participants |
| Placebo to SD-101-6.0 | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE Related to Study Drug | 1 Participants |
| Placebo to SD-101-6.0 | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE Leading to Discontinuation | 1 Participants |
| SD-101-3.0 to SD-101-6.0 | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any Fatal TEAE | 0 Participants |
| SD-101-3.0 to SD-101-6.0 | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE | 14 Participants |
| SD-101-3.0 to SD-101-6.0 | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE Related to Study Drug | 1 Participants |
| SD-101-3.0 to SD-101-6.0 | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | Serious TEAE | 2 Participants |
| SD-101-3.0 to SD-101-6.0 | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE Leading to Discontinuation | 1 Participants |
| SD-101-6.0 to SD-101-6.0 | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE Leading to Discontinuation | 0 Participants |
| SD-101-6.0 to SD-101-6.0 | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | Serious TEAE | 0 Participants |
| SD-101-6.0 to SD-101-6.0 | Number Of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE | 5 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 | 0 Participants |
Secondary
Change From Baseline In Body Surface Area Index (BSAI) Of Lesional Skin At Month 24
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, and then summed for all body regions to calculate the BSAI. 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 (final visit from the SD-003 study) in BSAI was assessed every 3 months. Only participants with data available for analysis at the specified time point are presented.
Time frame: Baseline, Month 24
Population: Intent to Treat: All participants who successfully rolled over into the SD-004 study from the SD-003 study and applied/were administered at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo to SD-101-6.0 | Change From Baseline In Body Surface Area Index (BSAI) Of Lesional Skin At Month 24 | 1.99 percentage of BSAI | Standard Deviation 6.728 |
| SD-101-3.0 to SD-101-6.0 | Change From Baseline In Body Surface Area Index (BSAI) Of Lesional Skin At Month 24 | -3.73 percentage of BSAI | Standard Deviation 6.152 |
| SD-101-6.0 to SD-101-6.0 | Change From Baseline In Body Surface Area Index (BSAI) Of Lesional Skin At Month 24 | -9.50 percentage of BSAI | Standard Deviation 21.248 |