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Open Label Extension Protocol (Japan):Assess the Efficacy and Safety of Beremagene Geperpavec (B-VEC, previously KB103) for the Treatment of Japanese Patients with Dystrophic Epidermolysis Bullosa (DEB)

Open Label Extension Protocol (Japan):Assess the Efficacy and Safety of Beremagene Geperpavec (B-VEC, previously KB103) for the Treatment of Japanese Patients with Dystrophic Epidermolysis Bullosa (DEB)

5

The mean age of subjects was 36.2 years (range 12.8 to 68.6); two subjects were pediatric (18 years or younger). The majority of subjects were female (80.0%). All subjects were of Japanese descent and had RDEB. The Primary Wounds ranged in size from 1 cm^2 to 20 cm^2.

The Japan OLE study began enrollment in September 2023 and had a duration of 52 weeks. In total, five subjects were enrolled, four of which completed the study (one subject withdrew consent after Week 8 due to challenges associated with following guidelines regarding wound dressing disposal). In this open-label, single-arm study, conducted at two sites in Japan, topical B-VEC was applied weekly per the participant's weekly maximum dose (4.0x10^9 PFU/week).

Only treatment-emergent adverse events (TEAEs) were collected. - Weekly treatment with B-VEC for 52 weeks was well tolerated by Japanese subjects with no treatment discontinuations and no development of clinically significant immunologic reactions, anti-drug antibodies, or manifestations of active HSV-1 infection being observed. - Four subjects reported 10 TEAEs in total. All TEAEs were mild or moderate in severity and all were reported as not related to IP. - No SAEs were reported. - No clinically significant changes in laboratory values or vital signs were observed. - Together, the safety results are consistent with the results of the Phase 3 study of B-VEC, indicating there is no apparent difference in safety for Japanese subjects after treatment spanning 52.

Treatment with B-VEC resulted in complete wound closure of 100% of Primary Wounds at Month 6, the primary efficacy endpoint. - Complete wound healing of the Primary Wound was also observed at Month 3, the secondary efficacy endpoint, with 100% of wounds showing complete closure. - Of the Primary Wounds assessed for complete closure, 3/4 (75%) showed durable closure at 9 and 12 months, an exploratory measure of efficacy. - Skindex-29 scores trended towards improvement regarding symptoms and functioning aspects of DEB on skin-specific quality of life from baseline to Week 52, while scores for emotions were unchanged. - For EQ-5D-5L, from baseline to Week 52, two subjects reported improvements (one in Usual Activities and one in both Self-Care and Usual Activities), but the majority of responses reported no change in condition across all five domains. There were three responses of worsening, two for Anxiety and one for Mobility. Generally, the small number of subjects limits the conclusions that can be drawn. EQ VAS scores were similarly inconsistent from baseline to Week 52. - Change in pain severity of the Primary Wound during dressing changes, assessed by VAS, was favorable and decreased from baseline to Weeks 22, 24, and 26; subjects reported no pain at all assessed post-dose timepoints. - TSQM-9 scores were generally high (>65) at Week 26 for Effectiveness, Convenience, and Global Satisfaction, indicating high treatment satisfaction with B-VEC. Scores were slightly lower in all three domains by Week 52, but remained >55. - Together, the efficacy results from this analysis are consistent with the results of the Phase 3 study of B-VEC, indicating there is no apparent difference in efficacy for Japanese subjects undergoing treatment spanning 52 weeks.

JP OLE study was initiated with the intention of expanding on the results of the P3 study conducted in US in Japanese DEB subjects, thereby confirming no significant differences in treatment response arise from varying ethnic backgrounds. Its primary and secondary efficacy endpoint were met. PRO measures were consistent with wound healing. B-VEC was well tolerated, with no new safety signals identified. Overall, these results demonstrate a favorable benefit-risk profile for B-VEC in Japanese DEB subjects.

Mar. 31, 2025

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2053230075

Chien David

Krystal Biotech, Inc.

2100 Wharton St. Suite 701 Pittsburgh, PA, United States

dchien@krystalbio.com

Kanmuri Kazuhiro

Ascent Development Services, Inc.

Shibuya SOLASTA 3F, 1-21-1, Dogenzaka, Shibuya-ku, Tokyo, Japan 150-0043

+81-3-4590-9005

kazuhiro.kanmuri@pharmalex.com

Complete

Sept. 15, 2023

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1. Willing and able to give consent/assent
2. Clinical diagnosis of epidermolysis bullosa
3. Confirmation of diagnosis (either DDEB or RDEB) by genetic testing including COL7A1
4. Age: 2 months of age and older at the time of informed consent/assent
5. Women of childbearing age must be willing to use reliable birth control method throughout the treatment duration and for 3 months following the last treatment application.
6. At least one Primary Wound, also meeting the following criteria
- Appearance: clean with adequate granulation tissue, excellent vascularization, and do not appear infected

1. Diseases or conditions that could interfere with the assessment of safety of the study treatment and compliance of the participant with study visits or procedures, as determined by the Investigator
2. Pregnant or nursing women
3. Active infection in the area that will undergo administration, that the Investigator believes will negatively impact the B-VEC application
4. Known allergy to any of the constituents of the product
5. Concurrent skin transplant or mesh skin grafting to the primary wound.
6. Participation in an interventional gene therapy clinical trial within the past three (3) months
7. Current evidence or a history of squamous cell carcinoma in the area that will undergo treatment.
8. Participant's actively receiving chemotherapy or immunosuppressive therapy at Week 1.
9. Active drug or alcohol addiction as determined by the Investigator.

Both

Dystrophic Epidermolysis Bullosa

Participants 3 years or older will receive 1 Unit (~10^9 PFU (+- 0.5 log)) (Weekly Maximum Dose 5.0 x10^9 PFU) of topical administration of B-VEC (mixture of B-VEC and Hydroxypropyl Methylcellulose Excipient Gel). Patients greater than or equal to 2 months to less than 3 years will topically receive half of the volume (Weekly Maximum Dose 2.5 x10^9 PFU) that participants 3 years and older will receive.
PFU = plaque forming units

To evaluate wound healing at 6 months, defined as complete closure of the Primary Wound following treatment with Beremagene Geperpavec (B-VEC).

- To evaluate wound healing at 3 months, defined as complete closure of the Primary Wound following treatment with B-VEC.
- To evaluate safety and tolerability of B-VEC, based on the incidence, severity, and relatedness of AEs and SAEs.
- To evaluate safety and tolerability of B-VEC based on changes from baseline in clinical laboratory test results.

July. 18, 2023

July. 18, 2023

United States