Ph 3 Efficacy and Safety of B-VEC for the Treatment of DEB (GEM-3)

• ClinicalTrials.gov Identifier: NCT04491604
• Recruitment Status: Completed
• First Posted: July 29, 2020
• Results First Posted: February 17, 2023
• Last Update Posted: February 17, 2023
• 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-one (31) participants with DEB, aged 6 months or older at time of consent were enrolled for this Phase III study. The trial duration for each subject was 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 also occurred. Each subject provided one pair of primary target wounds, with one wound from each pair randomized to be treated with B-VEC and the other wound with placebo. In addition to the primary target wound pair(s), additional wounds (secondary wounds) were selected to be treated with B-VEC. Throughout the study, participants complete questionnaires, had images captured of their study wounds, underwent physical exams, had vital signs and safety labs monitored.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 31 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: An intra-subject parallel study. Primary wounds are randomized within each subject, such that one wound receives B-VEC and the other wound receives placebo. Secondary wounds are selected to receive B-VEC only.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase III Efficacy and Safety Study of Beremagene Geperpavec (B-VEC, Previously "KB103") for the Treatment of Dystrophic Epidermolysis Bullosa (DEB)
• Actual Study Start Date: August 17, 2020
• Actual Primary Completion Date: October 29, 2021
• Actual Study Completion Date: January 14, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: B-VEC; 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
Placebo Comparator: Placebo; Matching masked inactive topical gel	Other: Placebo; Matching masked inactive topical gel

Outcome Measures

Primary Outcome Measures :

1. Primary Wound With Complete Wound Healing (100% Wound Closure) on Weeks 22 and 24 or Weeks 24 and 26 [ Time Frame: 26 weeks post-baseline ]

   The primary wound was defined as a responder wound that met either of the following conditions:

   • Complete wound healing on Week 22 and Week 24, or
   • Complete wound healing on Week 24 and Week 26.

   For subjects with missing primary wound healing data, a multiple imputation approach (10 repliates) was used. The total numbers of primary wounds with complete healing for B-VEC and Placebo presented below were the average of those from the multiple imputation replicates, and therefore, they would not be whole numbers (integers).

Secondary Outcome Measures :

1. Primary Wound With Complete Wound Healing (100% Wound Closure) on Weeks 8 and 10 or Weeks 10 and 12 [ Time Frame: 12 weeks post-baseline ]

   The primary wound was defined as a responder wound that met either of the following conditions:

   • Complete wound healing on Week 8 and Week 10, or
   • Complete wound healing on Week 10 and Week 12.

   For subjects with missing primary wound healing data, a multiple imputation approach (10 repliates) was used. The total numbers of primary wounds with complete healing for B-VEC and Placebo presented below were the average of those from the multiple imputation replicates, and therefore, they would not be whole numbers (integers).

2. Primary Wound Pain Severity (Visual Analog Scale (VAS)) Change for Ages 6 and Above Subjects at Weeks 22, 24, and 26. [ Time Frame: 26 weeks post-baseline ]
   Changes from baseline at Weeks 22, 24, and 26 in primary wound pain severity (visual analog scale (VAS)) for ages 6 and above subjects. The Visual Analog Scale scores from 0 (no pain) to 10 (the worst possible pain). Negative values in changes from baseline mean improvement in pain severity.

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. 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. Subjects 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

Locations

United States, California

Mission Dermatology Center

Rancho Santa Margarita, California, United States, 92688

Stanford University

Stanford, California, United States, 94305

United States, Florida

Pediatric Skin Research, LLC

Coral Gables, Florida, United States, 33146

Sponsors and Collaborators

Krystal Biotech, Inc.

  Study Documents (Full-Text)

Documents provided by Krystal Biotech, Inc.:

Study Protocol  [PDF] April 21, 2021

Statistical Analysis Plan  [PDF] August 25, 2021

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: B-VEC-03
• First Posted: July 29, 2020
• Results First Posted: February 17, 2023
• Last Update Posted: February 17, 2023
• Last Verified: December 2022

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