The Objective of This Study is to Compare the Efficacy and Safety of Beremagene Geperpavec (B-VEC) Topical Gel With That of Placebo for the Treatment of Dystrophic Epidermolysis Bullosa (DEB).

• ClinicalTrials.gov Identifier: NCT04491604
• Recruitment Status: Recruiting
• First Posted: July 29, 2020
• Last Update Posted: July 29, 2020
• Sponsor: Krystal Biotech, Inc.
• Information provided by (Responsible Party): Krystal Biotech, Inc.

Study Description

Brief Summary:

To determine whether administration of topical B-VEC improves wound healing as compared to placebo, and to evaluate durability, repeat dosing (Primary Endpoint) and further obtain safety and tolerability data.

Condition or disease	Intervention/treatment	Phase
Dystrophic Epidermolysis Bullosa; Recessive Dystrophic Epidermolysis Bullosa; Dominant Dystrophic Epidermolysis Bullosa	Biological: Topical Beremagene Geperpavec; Other: Placebo	Phase 3

Detailed Description:

Thirty (30) participants with DEB, aged 6 months or older at time of consent are planned for this Phase III study. The trial duration for each subject is about 6 months, with administration occurring once weekly. A Safety Follow-up Visit occurring 30 days from the date of final treatment with the Investigational Product will also occur. Each subject provides at least one pair of primary target wounds, with one wound from each pair being treated with B-VEC and the other wound with placebo. In addition to the primary target wound pair(s), additional wounds (secondary wounds) may be selected to be treated with B-VEC. Throughout the study, participants will complete questionnaires, have images captured of their study wounds, undergo physical exams, have vital signs and safety labs monitored.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: An intra-participant parallel study. Primary wounds will be randomized within the participant, such that one wound receives B-VEC and the other wound will receive placebo. Secondary wounds may be selected to receive B-VEC only.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase III Double Blinded, Placebo-Controlled, Efficacy and Safety Study of Beremagene Geperpavec (B-VEC, Previously "KB103") for the Treatment of Dystrophic Epidermolysis Bullosa (DEB)
• Estimated Study Start Date: August 2020
• Estimated Primary Completion Date: August 2021
• Estimated Study Completion Date: August 2021

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; Matching masked inactive topical gel	Other: Placebo; Matching masked inactive topical gel
Active Comparator: B-VEC-03; Topical gel of non-integrating, replication-incompetent HSV-1 expressing the human collagen VII protein	Biological: Topical Beremagene Geperpavec; Topical gel of non-integrating, replication-incompetent HSV-1 expressing the human collagen VII protein

Outcome Measures

Primary Outcome Measures :

1. Complete wound healing, determined by the Investigator, as compared to baseline in B-VEC treated wounds versus placebo treated. [ Time Frame: 24 weeks post-baseline ]
   The primary outcome measure will look at the proportion of primary wound sites with complete wound healing, determined by the Investigator, as compared to baseline at Week 24.

Secondary Outcome Measures :

1. Complete wound healing, determined by the Investigator, as compared to baseline in B-VEC treated wounds versus placebo treated. [ Time Frame: 12 weeks post-baseline ]
   The secondary outcome measure will look at the proportion of primary wound sites with complete wound healing, determined by the Investigator, as compared to baseline at Week 12.
2. Mean change in pain severity (using either a VAS or FLACC-R Scale) per primary wound site associated with wound dressing changes. [ Time Frame: 24 weeks post-baseline ]
   The secondary outcome measure will look at the mean change in pain severity using a VAS or FLACC-R score, associated with wound dressing change at primary wounds sites at Week 24.
3. Proportion of primary wound sites with ≥75% healing as compared to baseline in B-VEC versus placebo treated, using Canfield photography quantitation. [ Time Frame: 24 weeks post-baseline ]
   The secondary outcome measure will look at the proportion of primary wound sites with ≥75% would healing as compared to baseline at Week 24.

Other Outcome Measures:

1. Relative time to wound closure from baseline. [ Time Frame: 24 weeks post-baseline ]
   The exploratory outcome measure will look at the relative time, during weekly visits, it takes for a wound to close, as determined by the Investigator.
2. Duration of closure, as defined by the time from complete wound closure to the reopening of the primary wounds. [ Time Frame: 24 weeks post-baseline ]
   The exploratory outcome measure will look at the relative time, during weekly visits, it takes for a wound that was determined to be completely closed by the Investigator, to reopen.

Eligibility Criteria

• Ages Eligible for Study: 6 Months and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. The subject or legally appointed and authorized representative must have read, understood and signed an Institutional Review Board/Ethics Committee (IRB/EC) approved Informed Consent or Assent Form and must be able to and willing to follow study procedures and instructions.
2. Age ≥ 6 months and older at the time of Informed Consent.
3. Clinical diagnosis of the Dystrophic Epidermolysis Bullosa.
4. Confirmation of DEB diagnosis (either DDEB or RDEB) by genetic testing including COL7A1.

5. At least two (2) cutaneous wounds meeting the following criteria:

   1. Location: similar in size, located in similar anatomical regions, and have similar appearance
   2. Appearance: clean with adequate granulation tissue, excellent vascularization, and do not appear infected.
6. Subjects and caregivers who, in the opinion of the Investigator, are 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 visits.
7. Male or Female of childbearing potential must use a reliable birth control method throughout the duration of the study and for three (3) months post last dose of B-VEC.
8. Negative pregnancy test at Visit 1 (Week 1), if applicable.

Exclusion Criteria:

1. Medical instability limiting ability to travel to the Investigative Center.
2. Diseases or conditions that could interfere with the assessment of safety and efficacy of the study treatment and compliance of the subject with study visits/procedures, as determined by the Investigator.
3. Current evidence or a history of squamous cell carcinoma in the area that will undergo treatment.
4. Subject's actively receiving chemotherapy or immunotherapy at Visit 1 (Week 1).
5. Active drug or alcohol addiction as determined by the Investigator.
6. Hypersensitivity to local anesthesia (lidocaine/prilocaine cream).
7. Participation in an interventional clinical trial within the past three (3) months (not including BVEC administration).
8. Receipt of a skin graft in the past three (3) months.
9. Pregnant or nursing women.

Contacts and Locations

Contacts

Contact: Brittani Agostini; 412-586-5830; bagostini@krystalbio.com

Locations

United States, California

Mission Dermatology Center; Recruiting

Rancho Santa Margarita, California, United States, 92688

Contact: Guida Pino 949-858-3376 ext 108 gpinto.missionderm@gmail.com

Principal Investigator: Shireen Guide, MD

Stanford University; Recruiting

Stanford, California, United States, 94305

Contact: Sinem Bagci, MD 650-484-6878 isbagci@stanford.edu

Principal Investigator: Peter Marinkovich, MD

United States, Florida

Pediatric Skin Research, LLC; Recruiting

Coral Gables, Florida, United States, 33146

Contact: Edilmary Urdaneta 786-585-5774 coordinator1@pediatricskinresearch.com

Principal Investigator: Mercedes Gonzalez, MD

United States, Illinois

Northwestern University; Recruiting

Chicago, Illinois, United States, 60611

Contact: Lyndsey O'Hara 312-503-5908 lyndsey.dombrowski@northwestern.edu

Principal Investigator: Amy Paller, MD

United States, Ohio

Cincinnati Children's Hospital Medical Center; Not yet recruiting

Cincinnati, Ohio, United States, 45229

United States, Texas

Ascension Seton; Not yet recruiting

Austin, Texas, United States, 78723

Sponsors and Collaborators

Krystal Biotech, Inc.

More Information

Additional Information:

Krystal Biotech, Inc. Patient and Family Advocacy Site 

• Responsible Party: Krystal Biotech, Inc.
• ClinicalTrials.gov Identifier: NCT04491604
• Other Study ID Numbers: GEM-3
• First Posted: July 29, 2020
• Last Update Posted: July 29, 2020
• Last Verified: July 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.:

DEB

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