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

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)

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Dystrophic Epidermolysis Bullosa
• Intervention / Treatment: Biological: Topical beremagene geperpavec

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 Type: Interventional
• Enrollment (Anticipated): 4
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Wound Closure	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.	24 weeks post treatment

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Krystal Biotech, Inc.

Publications and helpful links

General Publications

• Gurevich I, Agarwal P, Zhang P, Dolorito JA, Oliver S, Liu H, Reitze N, Sarma N, Bagci IS, Sridhar K, Kakarla V, Yenamandra VK, O'Malley M, Prisco M, Tufa SF, Keene DR, South AP, Krishnan SM, Marinkovich MP. In vivo topical gene therapy for recessive dystrophic epidermolysis bullosa: a phase 1 and 2 trial. Nat Med. 2022 Apr;28(4):780-788. doi: 10.1038/s41591-022-01737-y. Epub 2022 Mar 28.

Study record dates

Study Major Dates

• Study Start (Actual): May 7, 2018
• Primary Completion (Actual): February 1, 2020
• Study Completion (Anticipated): March 1, 2024

Study Registration Dates

• First Submitted: April 20, 2018
• First Submitted That Met QC Criteria: May 14, 2018
• First Posted (Actual): May 24, 2018

Study Record Updates

• Last Update Posted (Actual): September 13, 2021
• Last Update Submitted That Met QC Criteria: September 10, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: DEB; RDEB; bullosa; Krystal; epidermolysis; Beremagene; Geperpavec; KB103; HSV-COL7A1
• Additional Relevant MeSH Terms: Skin Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Connective Tissue Diseases; Skin Diseases, Genetic; Skin Diseases, Vesiculobullous; Skin Abnormalities; Collagen Diseases; Epidermolysis Bullosa; Epidermolysis Bullosa Dystrophica
• Other Study ID Numbers: KB103-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No