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.

Tracking Information

• First Submitted Date: July 22, 2020
• First Posted Date: July 29, 2020
• Results First Submitted Date: December 8, 2022
• Results First Posted Date: February 17, 2023
• Last Update Posted Date: February 17, 2023
• Actual Study Start Date: August 17, 2020
• Actual Primary Completion Date: October 29, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 25, 2023)

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).

Original Primary Outcome Measures (submitted: July 27, 2020)

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.

Current Secondary Outcome Measures (submitted: January 25, 2023)

• 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).
• 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.

Original Secondary Outcome Measures (submitted: July 27, 2020)

• 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.
• 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.
• 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.

• Current Other Pre-specified Outcome Measures: Not Provided

Original Other Pre-specified Outcome Measures (submitted: July 27, 2020)

• 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.
• 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.

Descriptive Information

• Brief Title: Ph 3 Efficacy and Safety of B-VEC for the Treatment of DEB
• Official Title: A Phase III Efficacy and Safety Study of Beremagene Geperpavec (B-VEC, Previously "KB103") for the Treatment of Dystrophic Epidermolysis Bullosa (DEB)
• 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.
• 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 Type: Interventional
• Study Phase: Phase 3

Study Design

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

Condition

• Dystrophic Epidermolysis Bullosa
• Recessive Dystrophic Epidermolysis Bullosa
• Dominant Dystrophic Epidermolysis Bullosa

Intervention

• Biological: Topical Beremagene Geperpavec
  Topical gel of non-integrating, replication-incompetent HSV-1 expressing the human collagen VII protein
• Other: Placebo
  Matching masked inactive topical gel

Study Arms

• Experimental: B-VEC
  Topical gel of non-integrating, replication-incompetent HSV-1 expressing the human collagen VII protein
  Intervention: Biological: Topical Beremagene Geperpavec
• Placebo Comparator: Placebo
  Matching masked inactive topical gel
  Intervention: Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 27, 2021): 31
• Original Estimated Enrollment (submitted: July 27, 2020): 30
• Actual Study Completion Date: January 14, 2022
• Actual Primary Completion Date: October 29, 2021 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Months and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04491604
• Other Study ID Numbers: B-VEC-03
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Krystal Biotech, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Krystal Biotech, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Krystal Biotech, Inc.
• Verification Date: December 2022