Topical Beremagene Geperpavec (KB103) Gene Therapy to Restore Functional Collagen VII for the Treatment of Dystrophic Epidermolysis Bullosa (GEM-1)

• ClinicalTrials.gov Identifier: NCT03536143
• Recruitment Status: Active, not recruiting
• First Posted: May 24, 2018
• Last Update Posted: March 13, 2020
• Sponsor: Krystal Biotech, Inc.
• Information provided by (Responsible Party): Krystal Biotech, Inc.

Study Description

Brief Summary:

This study is being conducted to determine if topical Beremagene Geperpavec (KB103, HSV1-COL7) can safely and effectively promote healing of DEB patient wounds (primary endpoint) and to assess change from baseline in Investigator Global Assessments and Patient Reported Outcomes (secondary endpoint).

Condition or disease	Intervention/treatment	Phase
Dystrophic Epidermolysis Bullosa	Biological: Topical beremagene geperpavec	Phase 2

Detailed Description:

Four subjects are planned for the Phase II portion of this study: 2 adults and 2 subjects age 5 and older. Subjects are enrolled upon obtaining consent and meeting entry criteria. Three wounds are selected per subject; two will receive bercolagene telserpavec and one will receive placebo. Administrations occur daily on Days 1 through 5, and again on Days 30, 60, and 90 if there is visible wound at the original administration site. Throughout the study wounds will imaged and biopsied for safety and efficacy analyses. Subjects will be on-trial for approximately 6 months: 3 months of on-site visits followed by a 3-month at-home imaging period.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 4 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Beremagene Geperpavec (KB103), a Non-Integrating, Replication-Incompetent Herpes Simplex Virus 1 (HSV-1) Vector Expressing the Human Collagen VII (COL7) Protein, for the Treatment of Dystrophic Epidermolysis Bullosa (DEB)
• Actual Study Start Date: May 7, 2018
• Actual Primary Completion Date: February 1, 2020
• Estimated Study Completion Date: March 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Topical beremagene geperpavec; HSV1-COL7A1 vector (KB103)	Biological: Topical beremagene geperpavec; Topical gel of non-integrating, replication-incompetent HSV-1 expressing the human collagen VII protein; Other Names: HSV1-COL7A1; KB103

Outcome Measures

Primary Outcome Measures :

1. Wound Closure [ Time Frame: 24 weeks post treatment ]
   Change of wound surface area relative to baseline and placebo, time to wound closure relative to placebo, and duration of wound closure relative to placebo.

Secondary Outcome Measures :

1. Investigator's Global Assessment [ Time Frame: 12 weeks post treatment ]
   Change from baseline in the Investigator's Global Assessment score
2. Patient Reported Outcomes [ Time Frame: 12 weeks post treatment ]
   Change from baseline in PRO scales of severity and pain
3. Presence of collagen VII [ Time Frame: 12 weeks post treatment ]
   Level of collagen VII in KB103-administered skin as measured by immunofluorescence.
4. Presence of anchoring fibrils [ Time Frame: 12 weeks post treatment ]
   Presence of anchoring fibrils as measured by immunoelectron microscopy

Eligibility Criteria

• Ages Eligible for Study: 5 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Clinical diagnosis of the recessive form of dystrophic epidermolysis bullosa.

• Age

  1. 2 subjects: 18 years old or older,
  2. 2 subjects: 5 years old or older.
• At least one wound that is between 10 and 20 cm2 in wound area.
• Subjects, who are, in the opinion of the Investigator, able to understand the study, co-operate with the study procedures and are willing to return to the clinic for all the required follow-up visit

Exclusion Criteria:

• The presence of medical illness expected to complicate participation
• Serum antibodies to type collagen VII
• Active infection in the area that will undergo injection.
• Evidence of systemic infection.
• Current evidence or a history of squamous cell carcinoma in the area that will undergo treatment.

Contacts and Locations

Locations

United States, California

Stanford University

Stanford, California, United States, 94305

Sponsors and Collaborators

Krystal Biotech, Inc.

More Information

• Responsible Party: Krystal Biotech, Inc.
• ClinicalTrials.gov Identifier: NCT03536143
• Other Study ID Numbers: KB103-001
• First Posted: May 24, 2018
• Last Update Posted: March 13, 2020
• Last Verified: March 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Krystal Biotech, Inc.:

bullosa; DEB; RDEB; Krystal; epidermolysis; Beremagene; Geperpavec; KB103; HSV-COL7A1

Additional relevant MeSH terms:

Epidermolysis Bullosa; Epidermolysis Bullosa Dystrophica; Skin Abnormalities; Congenital Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Skin Diseases; Skin Diseases, Vesiculobullous; Collagen Diseases; Connective Tissue Diseases