Multi-centeR, open-label study to EValuate the safety, efficacy, and pharmacokinetics of FIlsuVEz (Oleogel-S10) in Japanese subjects with epidermolysis bullosa (REVIVE)
A study to learn about the safety and efficacy of the drug Oleogel-S10 in Japanese patients with epidermolysis bullosa (REVIVE)
1. Male or female aged >= 21 days
2. Confirmed diagnosis of either JEB or DEB
3. Both biological parents and all 4 grandparents of Japanese descent
4. At least three EB wounds that meet the following criteria at the time of enrollment:
- All are located outside of the anogenital region
- All are distinguishable from any other wounds on the subjects body (separated by a minimum of 5 cm)
Note 1: Patients who satisfy all selection criteria, including inclusion criterion #4, may be considered for study enrollment. Whenever possible, patients with wounds measuring close to 10 cm2 should be considered first for enrollment. The enrollment plan aims to include a minimum of 6 subjects, structured as follows:
- At least one subject with at least one target wound that has been present for a minimum of 21 days but less than 9 months AND is >=10 cm2 in size
- At least two subjects with at least one target wound that has been present for a minimum of 21 days but less than 9 months AND is >=5 cm2 in size
- For the remaining subjects, the three largest wounds will be selected as target wounds, and the largest wound must have been present for at least 21 days but less than 9 months.
Note 2: wound size will be determined by the ARANZ Silhouette system as described in Protocol.
5. A female subject must meet one of the following criteria:
- If of childbearing potential, she must:
a. Have a negative pregnancy test result at Screening and Baseline Visits, AND
b. Agree to use one of the following highly reliable methods of contraception from the day of the informed consent signature until the day after the last Oleogel-S10 application. The following methods are acceptable:
- Placement of an intrauterine device (IUD) or intrauterine releasing system (IUS)
- Combined (both oestrogen and progestogen) hormonal contraception (oral) associated with inhibition of ovulation, supplemented with a barrier method (preferably male condom)
- Bilateral tubal occlusion
- Sexual abstinence, defined as refraining from heterosexual intercourse during the entire study period
- Partner vasectomy, provided that the partner is the sole sexual partner and has received medical verification of the surgical success
Be of non-childbearing potential, defined as one of the following:
- Pre-menarche, OR
- Post-menopausal (12 consecutive months of amenorrhea), OR
- Permanently sterile following hysterectomy, bilateral salpingectomy, or bilateral oophorectomy (supporting evidence required)
6. Subject and or their legal representative has been informed about the study, has read and understood the information provided, and has given written informed consent
7. Subject and or their legal representative is able and willing to follow all study procedures and instructions
1. Hypersensitivity to Oleogel-S10 or any of its excipients
2. Diagnosis of EB subtypes simplex or Kindler EB
3. Receipt of systemic antibiotics for wound-related infections within 7 days prior to enrollment
4. Receipt of systemic or topical (on EB wounds) steroids within 30 days prior to enrollment
Exceptions: Inhaled, ophthalmic, or mucosal applications, such as budesonide suspension for esophageal strictures
5. Receipt of immunosuppressive therapy or cytotoxic chemotherapy within 60 days prior to enrollment
Note: Dupilumab or similar products (e.g. nemolizumab) to manage pruritus are allowed if the subject has been on a stable dose for more than 3 months prior to baseline
6. Receipt of systemic gene therapy for the treatment of inherited EB
7. Receipt of short-acting stem cell therapy (infusion of Muse cells, allogeneic adipocyte-derived MSC sheet (topically applied), TEMCELL (allogeneic MSCs, subcutaneous injection)) within 6 months prior to study enrollment
8. Receipt of topical gene therapy for the treatment of inherited EB (e.g., beremagene geperpavec) within 3 months prior to enrollment
9. Receipt of a JACE skin graft on one of the selected wounds
10. Current and or former malignancy, including skin malignancies such as basal cell carcinoma and squamous cell carcinoma
11. Females: Pregnant or lactating, or of childbearing potential with a fertile male partner and unwilling to use a highly reliable method of contraception from the informed consent signature until study participation ends
12. Enrollment in any other interventional study or treated with any other investigational drug for any disease within 4 weeks prior to enrollment
13. Presence of any factor in the subject and/or legal representative that could interfere with study compliance, such as the ability to attend the scheduled study visits or to properly manage the dressing changes at home
3week old over
No limit
Both
One of two subtypes of inherited epidermolysis bullosa: junctional EB or dystrophic EB
Oleogel-S10 will be administered topically at approximately 1 mm thickness to the EB target wound and to all areas on the subjects body that are affected by EB wounds
Incidence of complete closure of the target wounds within 45 days of treatment
The following will be evaluated from baseline through Day 45 and from baseline through Day 90:
- Proportion of subjects achieving complete closure of at least one target wound
- Proportion of subjects achieving complete closure of a target wound that meets both age and size inclusion criteria
The following will be evaluated on Day 45 and Day 90
- Mean change from baseline in the surface area of each of the 3 target wounds
- Score on the Patient Global Impression of Improvement (PGI-I)
- Score on the Clinician Global Impression of Improvement (CGI-I)
- Mean change from baseline in the frequency of dressing changes
- The incidence of infections in the target wounds
The following will be continually evaluated through Day 90:
- Incidence of complete closure of the target wounds within 90 days of treatment
- Time to first complete closure of any of the 3 target wounds
- Time to first complete closure of a target wound that meets both age and size inclusion criteria
- The maximum severity of infection in the target wounds
Chiesi Farmaceutici S.p.A.
Hokkaido University Hospital Institutional Review Board
Kita 14, Nishi 5, Kita-ku, Sapporo, Hokkaido, Hokkaido
