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.

Tracking Information

• First Submitted Date: July 22, 2020
• First Posted Date: July 29, 2020
• Last Update Posted Date: July 29, 2020
• Estimated Study Start Date: August 2020
• Estimated Primary Completion Date: August 2021 (Final data collection date for primary outcome measure)

Current 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.

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current 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.

• Original Secondary Outcome Measures: Same as current

Current 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.

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: 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).
• 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)
• 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 (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 Type: Interventional
• Study Phase: Phase 3

Study Design

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

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

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 27, 2020): 30
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 2021
• Estimated Primary Completion Date: August 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. 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Months and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04491604
• Other Study ID Numbers: GEM-3
• 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

• Responsible Party: Krystal Biotech, Inc.
• Study Sponsor: Krystal Biotech, Inc.
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Krystal Biotech, Inc.
• Verification Date: July 2020