Dystrophic Epidermolysis BullosaPhase 3GEM-3NCT04491604
Ph 3 Efficacy and Safety of B-VEC for the Treatment of DEB
A Phase 3 study testing Topical Beremagene Geperpavec in people with Dystrophic Epidermolysis Bullosa and Recessive Dystrophic Epidermolysis Bullosa, run by Krystal Biotech, Inc. at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 months and older
- Conditions the study is for
- Dystrophic Epidermolysis Bullosa, Recessive Dystrophic Epidermolysis Bullosa, Dominant Dystrophic Epidermolysis Bullosa
- What is being tested?
- Topical Beremagene Geperpavec
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 31 participants
- Where
- 3 sitesUnited States
- Study dates
- 17 Aug 2020to 14 Jan 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
- Age ≥ 6 months and older at the time of Informed Consent.
- Clinical diagnosis of the Dystrophic Epidermolysis Bullosa.
- Confirmation of DEB diagnosis (either DDEB or RDEB) by genetic testing including COL7A1.
- Two (2) cutaneous wounds meeting the following criteria:
- Location: similar in size, located in similar anatomical regions, and have similar appearance
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- Appearance: clean with adequate granulation tissue, excellent vascularization, and do not appear infected.
- 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.
- 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.
- Negative pregnancy test at Visit 1 (Week 1), if applicable.
Who cannot join
- Medical instability limiting ability to travel to the Investigative Center.
- 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.
- Current evidence or a history of squamous cell carcinoma in the area that will undergo treatment.
- Subjects actively receiving chemotherapy or immunotherapy at Visit 1 (Week 1).
- Active drug or alcohol addiction as determined by the Investigator.
- Hypersensitivity to local anesthesia (lidocaine/prilocaine cream).
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- Participation in an interventional clinical trial within the past three (3) months (not including BVEC administration).
- Receipt of a skin graft in the past three (3) months.
- Pregnant or nursing women.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Pediatric Skin Research, LLC
Coral Gables, Florida, 33146
Mission Dermatology Center
Rancho Santa Margarita, California, 92688
Stanford University
Stanford, California, 94305
About this study
Official title: A Phase III Efficacy and Safety Study of Beremagene Geperpavec (B-VEC, Previously "KB103") for the Treatment of Dystrophic Epidermolysis Bullosa (DEB)
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.
Read the 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.
- Conditions
- Dystrophic Epidermolysis Bullosa, Recessive Dystrophic Epidermolysis Bullosa, Dominant Dystrophic Epidermolysis Bullosa
- Being tested
- Topical Beremagene Geperpavec, Placebo
- Keywords
- DEB
- Medical subject headings
- Epidermolysis Bullosa Dystrophica
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Topical Beremagene GeperpavecBiological
Topical gel of non-integrating, replication-incompetent HSV-1 expressing the human collagen VII protein
PlaceboOther
Matching masked inactive topical gel
| Study group | Role | What they receive |
|---|---|---|
| B-VEC | Experimental | Topical gel of non-integrating, replication-incompetent HSV-1 expressing the human collagen VII protein Receives: Biological: Topical Beremagene Geperpavec |
| Placebo | Placebo comparator | Matching masked inactive topical gel Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary Wound With Complete Wound Healing (100% Wound Closure) on Weeks 22 and 24 or Weeks 24 and 26
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).
Measured: 26 weeks post-baseline
Secondary outcomes (2)
Primary Wound With Complete Wound Healing (100% Wound Closure) on Weeks 8 and 10 or Weeks 10 and 12
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).
Measured: 12 weeks post-baseline
Primary Wound Pain Severity (Visual Analog Scale (VAS)) Change for Ages 6 and Above Subjects at Weeks 22, 24, and 26.
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.
Measured: 26 weeks post-baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2020
- Study start17 Aug 2020
- Primary completion29 Oct 2021
- Study completion14 Jan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Dystrophic Epidermolysis BullosaStudies of the same condition, open and under way.
- More trials run by Krystal Biotech, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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 blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Krystal Biotech, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04491604
- Sponsor's protocol ID
- B-VEC-03
- Acronym
- GEM-3
- Status last verified
- Dec 2022
- First submitted
- 22 Jul 2020
- Last updated
- 17 Feb 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Guide SV, Gonzalez ME, Bagci IS, Agostini B, Chen H, Feeney G, Steimer M, Kapadia B, Sridhar K, Quesada Sanchez L, Gonzalez F, Van Ligten M, Parry TJ, Chitra S, Kammerman LA, Krishnan S, Marinkovich MP. Trial of Beremagene Geperpavec (B-VEC) for Dystrophic Epidermolysis Bullosa. N Engl J Med. 2022 Dec 15;387(24):2211-2219. doi: 10.1056/NEJMoa2206663.
PubMed 36516090
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Efficacy and Safety Study of Beremagene Geperpavec (B-VEC, Previously "KB103") for the Treatment of Dystrophic Epidermolysis Bullosa (DEB)
- ClinicalTrials.gov ID
- NCT04491604
- Acronym / sponsor ID
- GEM-3 / B-VEC-03
- Conditions
- Dystrophic Epidermolysis Bullosa, Recessive Dystrophic Epidermolysis Bullosa, Dominant Dystrophic Epidermolysis Bullosa
- Keywords
- DEB
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Krystal Biotech, Inc.Industry (pharma, biotech, devices)
- Study start
- 17 Aug 2020 (actual)
- Primary completion
- 29 Oct 2021 (actual)
- Study completion
- 14 Jan 2022 (actual)
- First posted
- 29 Jul 2020 (actual)
- Results
- Posted 17 Feb 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| B-VEC | Experimental | Biological: Topical Beremagene GeperpavecTopical gel of non-integrating, replication-incompetent HSV-1 expressing the human collagen VII protein |
| Placebo | Placebo comparator | Other: PlaceboMatching masked inactive topical gel |
Who may qualify
- Ages
- 6 months and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
- Age ≥ 6 months and older at the time of Informed Consent.
- Clinical diagnosis of the Dystrophic Epidermolysis Bullosa.
- Confirmation of DEB diagnosis (either DDEB or RDEB) by genetic testing including COL7A1.
- Two (2) cutaneous wounds meeting the following criteria:
Key exclusion criteria (9 listed)
- Medical instability limiting ability to travel to the Investigative Center.
- 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.
- Current evidence or a history of squamous cell carcinoma in the area that will undergo treatment.
- Subjects actively receiving chemotherapy or immunotherapy at Visit 1 (Week 1).
- Active drug or alcohol addiction as determined by the Investigator.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Topical Beremagene GeperpavecTopical gel of non-integrating, replication-incompetent HSV-1 expressing the human collagen VII protein | Biological | B-VEC |
| PlaceboMatching masked inactive topical gel | Other | Placebo |
Primary outcome
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).
2 secondary outcomes
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36516090Guide SV, Gonzalez ME, Bagci IS, Agostini B, Chen H, Feeney G, Steimer M, Kapadia B, Sridhar K, Quesada Sanchez L, Gonzalez F, Van Ligten M, Parry TJ, Chitra S, Kammerman LA, Krishnan S, Marinkovich MP. Trial of Beremagene Geperpavec (B-VEC) for Dystrophic Epidermolysis Bullosa. N Engl J Med. 2022 Dec 15;387(24):2211-2219. doi: 10.1056/NEJMoa2206663.
- Krystal Biotech, Inc. Patient and Family Advocacy SiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Topical Beremagene Geperpavec in people with Dystrophic Epidermolysis Bullosa and Recessive Dystrophic Epidermolysis Bullosa, run by Krystal Biotech, Inc. at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04491604, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2023.