Dystrophic Epidermolysis BullosaPhase 1/2GEM-1NCT03536143
A Phase I/II Study of KB103, a Topical HSV1-COL7, on DEB Patients
A Phase 1/2 study testing Topical beremagene geperpavec in people with Dystrophic Epidermolysis Bullosa, run by Krystal Biotech, Inc. at 1 site in United States.
Trial summary
This study was conducted to assess the safety and efficacy of topical Beremagene Geperpavec (KB103, HSV1-COL7) on DEB patients. Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- 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
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 6 May 2018to 1 Nov 2019
- Phase
- Phase 1/2
- 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 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Clinical diagnosis of the recessive form of dystrophic epidermolysis bullosa (RDEB).
- Age
- Phase 1: 18 years old or older,
- Phase 2a: 5 years old or older,
- Phase 2b: 2 years old or older,
- Phase 2c: 2 years old or older.
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- Willing and able to give consent/assent
- Confirmation of RDEB diagnosis by genetic testing, IF, and IEM
- LH24 antibody negative (non-collagenous [NC] 2domain [NC2-]) and NC1 domain [NC1+]). (This criterion is applicable to the first 2 adults on the study (Phase 1). Subsequent subjects can be NC1+ or NC1-)
- Confirmed RDEB COL7A1 mutations in subject
- Wound that meets the wound size/surface area entry criteria:
- Phase 1: Two wounds up to 10 cm2; 1 randomized to B-VEC and 1 randomized to placebo
- Phase 2a and 2b: At least 3 wounds up to 20 cm2; 2 wounds randomized to B-VEC and 1 randomized to placebo
- Phase 2c: At least 2 wounds up to 50 cm2; at least 1 randomized to B-VEC and 1 randomized to placebo
- Subjects, who are, in the opinion of the investigator, able to understand the study, cooperate with the study procedures, and are willing to return to the clinic for all the required follow-up visits.
Who cannot join
- Medical instability limiting ability to travel to the investigative center
- The presence of medical illness expected to complicate participation and/or compromise the safety of this technique, such as active infection with human immunodeficiency virus (HIV), hepatitis B (as determined by hepatitis B surface antigen screening), or hepatitis C (as determined by detection of hepatitis C antibodies, or positive result of hepatitis C polymerase chain reaction [PCR] analysis)
- Serum antibodies to COL7 demonstrated on enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence microscopy, Western blot, or cell-mediated immunity to enzyme-lined ImmunoSpot® (subjects with negative results within 12 months of screening are eligible)
- Active infection in the area that will undergo administration
- Evidence of systemic infection
- Known allergy to any of the constituents of the product
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- Current evidence or a history of squamous cell carcinoma in the area that will undergo treatment
- Active drug or alcohol addiction
- Hypersensitivity to local anesthesia (lidocaine/prilocaine cream)
- Receipt of chemical or biological study product for the specific treatment of RDEB in the past 3 months
- Specific wounds that have previously been administered investigational gene or cell therapy
- Subjects who have taken systemic antibiotics within 7 days
- Positive pregnancy test or breast-feeding
- Clinically significant abnormalities as determined by the investigator
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I/II Study of KB103, a Non-Integrating, Replication-Incompetent HSV Vector Expressing the Human Collagen VII Protein, for the Treatment of Dystrophic Epidermolysis Bullosa (DEB)
This study was conducted to assess the safety and efficacy of topical Beremagene Geperpavec (KB103, HSV1-COL7) on DEB patients.
Read the detailed description
The primary objectives were the evaluation of safety, through incidence of adverse events associated with the administration of B-VEC as compared to placebo, as well as the demonstration of molecular correction of the disease by establishing the presence of functional COL7 expression and anchoring fibrils (AF) formation post administration of B-VEC. Additional primary objectives were to assess the proportion of wounds with complete wound closure (≥90% reduction from baseline wound surface area) at Week 8, 10, and 12, the duration of wound closure, and the time to wound closure of B-VEC treated wounds as compared with placebo treated wounds.
- Conditions
- Dystrophic Epidermolysis Bullosa
- Being tested
- Topical beremagene geperpavec, Placebo gel
- Keywords
- bullosa, DEB, RDEB, Krystal, epidermolysis, Beremagene, Geperpavec, KB103, HSV-COL7A1
- 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
Also called HSV1-COL7A1, KB103
Topical gel of non-integrating, replication-incompetent HSV-1 expressing the human collagen VII protein
Placebo gelBiological
Placebo gel
| Study group | Role | What they receive |
|---|---|---|
| Topical beremagene geperpavec | Experimental | HSV1-COL7A1 vector (KB103) Receives: Biological: Topical beremagene geperpavec |
| Placebo | Placebo comparator | Placebo Receives: Biological: Placebo gel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects Reported at Least One Adverse Event, Safety Population
Safety assessments included evaluation of medical and medication history, physical / skin examination, vital signs, adverse events, and laboratory evaluations. Due to the 'split-person' intrasubject design, the safety assessments were reported at subject level, but not per intervention.
Measured: baseline to 12 weeks
Number of Adverse Events Reported, Safety Population
Safety assessments included evaluation of medical and medication history, physical / skin examination, vital signs, adverse events, and laboratory evaluations. Due to the 'split-person' intrasubject design, the safety assessments were reported at subject level, but not per intervention.
Measured: baseline to 12 weeks
Complete Wound Closure Responder, ITT Population
One wound is a responder if the reduction from baseline in wound surface is ≥90%.
Measured: from baseline at Weeks 8, 10, and 12
Time to Wound Closure Analysis, ITT Population
Time to wound closure was defined as the time from the first treatment to Complete Wound Closure (≥90% reduction in wound surface area from baseline)
Measured: baseline to complete wound closure
Duration of Wound Closure, ITT Population
Duration of wound closure
Measured: Time from the complete closure to the first reopening of the same wound
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2018
- Study start6 May 2018
- Primary completion1 Nov 2019
- Study completion1 Nov 2019
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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Intrasubject treatment assignment/randomization
- Masking
- None (open label)
- Enrolment
- 12 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
- NCT03536143
- Sponsor's protocol ID
- KB103-001
- Acronym
- GEM-1
- Status last verified
- Nov 2022
- First submitted
- 20 Apr 2018
- Last updated
- 31 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Gurevich I, Agarwal P, Zhang P, Dolorito JA, Oliver S, Liu H, Reitze N, Sarma N, Bagci IS, Sridhar K, Kakarla V, Yenamandra VK, O'Malley M, Prisco M, Tufa SF, Keene DR, South AP, Krishnan SM, Marinkovich MP. In vivo topical gene therapy for recessive dystrophic epidermolysis bullosa: a phase 1 and 2 trial. Nat Med. 2022 Apr;28(4):780-788. doi: 10.1038/s41591-022-01737-y. Epub 2022 Mar 28.
PubMed 35347281
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of KB103, a Non-Integrating, Replication-Incompetent HSV Vector Expressing the Human Collagen VII Protein, for the Treatment of Dystrophic Epidermolysis Bullosa (DEB)
- ClinicalTrials.gov ID
- NCT03536143
- Acronym / sponsor ID
- GEM-1 / KB103-001
- Conditions
- Dystrophic Epidermolysis Bullosa
- Keywords
- bullosa, DEB, RDEB, Krystal, epidermolysis, Beremagene, Geperpavec, KB103
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Krystal Biotech, Inc.Industry (pharma, biotech, devices)
- Study start
- 6 May 2018 (actual)
- Primary completion
- 1 Nov 2019 (actual)
- Study completion
- 1 Nov 2019 (actual)
- First posted
- 24 May 2018 (actual)
- Results
- Posted 31 Jan 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study was conducted to assess the safety and efficacy of topical Beremagene Geperpavec (KB103, HSV1-COL7) on DEB patients.
Detailed description
The primary objectives were the evaluation of safety, through incidence of adverse events associated with the administration of B-VEC as compared to placebo, as well as the demonstration of molecular correction of the disease by establishing the presence of functional COL7 expression and anchoring fibrils (AF) formation post administration of B-VEC. Additional primary objectives were to assess the proportion of wounds with complete wound closure (≥90% reduction from baseline wound surface area) at Week 8, 10, and 12, the duration of wound closure, and the time to wound closure of B-VEC treated wounds as compared with placebo treated wounds.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Intrasubject treatment assignment/randomization
| Arm | Type | Receives |
|---|---|---|
| Topical beremagene geperpavec | Experimental | Biological: Topical beremagene geperpavecHSV1-COL7A1 vector (KB103) |
| Placebo | Placebo comparator | Biological: Placebo gelPlacebo |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (15 listed)
- Clinical diagnosis of the recessive form of dystrophic epidermolysis bullosa (RDEB).
- Age
- Willing and able to give consent/assent
- Confirmation of RDEB diagnosis by genetic testing, IF, and IEM
- LH24 antibody negative (non-collagenous [NC] 2domain [NC2-]) and NC1 domain [NC1+]). (This criterion is applicable to the first 2 adults on the study (Phase 1). Subsequent subjects can be NC1+ or NC1-)
Key exclusion criteria (14 listed)
- Medical instability limiting ability to travel to the investigative center
- The presence of medical illness expected to complicate participation and/or compromise the safety of this technique, such as active infection with human immunodeficiency virus (HIV), hepatitis B (as determined by hepatitis B surface antigen screening), or hepatitis C (as determined by detection of hepatitis C antibodies, or positive result of hepatitis C polymerase chain reaction [PCR] analysis)
- Serum antibodies to COL7 demonstrated on enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence microscopy, Western blot, or cell-mediated immunity to enzyme-lined ImmunoSpot® (subjects with negative results within 12 months of screening are eligible)
- Active infection in the area that will undergo administration
- Evidence of systemic infection
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 geperpavecAlso: HSV1-COL7A1, KB103Topical gel of non-integrating, replication-incompetent HSV-1 expressing the human collagen VII protein | Biological | Topical beremagene geperpavec |
| Placebo gelPlacebo gel | Biological | Placebo |
Primary outcome
Number of Subjects Reported at Least One Adverse Event, Safety Population
Time frame: baseline to 12 weeks
Safety assessments included evaluation of medical and medication history, physical / skin examination, vital signs, adverse events, and laboratory evaluations. Due to the 'split-person' intrasubject design, the safety assessments were reported at subject level, but not per intervention.
Number of Adverse Events Reported, Safety Population
Time frame: baseline to 12 weeks
Safety assessments included evaluation of medical and medication history, physical / skin examination, vital signs, adverse events, and laboratory evaluations. Due to the 'split-person' intrasubject design, the safety assessments were reported at subject level, but not per intervention.
Complete Wound Closure Responder, ITT Population
Time frame: from baseline at Weeks 8, 10, and 12
One wound is a responder if the reduction from baseline in wound surface is ≥90%.
Time to Wound Closure Analysis, ITT Population
Time frame: baseline to complete wound closure
Time to wound closure was defined as the time from the first treatment to Complete Wound Closure (≥90% reduction in wound surface area from baseline)
Duration of Wound Closure, ITT Population
Time frame: Time from the complete closure to the first reopening of the same wound
Duration of wound closure
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 35347281Gurevich I, Agarwal P, Zhang P, Dolorito JA, Oliver S, Liu H, Reitze N, Sarma N, Bagci IS, Sridhar K, Kakarla V, Yenamandra VK, O'Malley M, Prisco M, Tufa SF, Keene DR, South AP, Krishnan SM, Marinkovich MP. In vivo topical gene therapy for recessive dystrophic epidermolysis bullosa: a phase 1 and 2 trial. Nat Med. 2022 Apr;28(4):780-788. doi: 10.1038/s41591-022-01737-y. Epub 2022 Mar 28.
- 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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Topical beremagene geperpavec in people with Dystrophic Epidermolysis Bullosa, run by Krystal Biotech, Inc. at 1 site 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 15 inclusion and 14 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 31 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 31 Jan 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?
Number of Subjects Reported at Least One Adverse Event, Safety Population (time frame: baseline to 12 weeks). The study lists 5 primary outcomes in all. 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 NCT03536143, 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 31 Jan 2023.