A Phase I/II Study of KB103, a Topical HSV1-COL7, on DEB Patients

Study Overview
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Brief Summary
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This study was conducted to assess the safety and efficacy of topical Beremagene Geperpavec (KB103, HSV1-COL7) on DEB patients.

Detailed Description
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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.

Official Title
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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)

Conditions
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Dystrophic Epidermolysis Bullosa

Intervention / Treatment
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* Biological: Topical beremagene geperpavec
* Biological: Placebo gel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. 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. Exclusion Criteria: 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 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

Ages Eligible for Study
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Minimum Age: 2 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Intrasubject treatment assignment/randomization
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Topical beremagene geperpavec<br>HSV1-COL7A1 vector (KB103) | Biological: Topical beremagene geperpavec<br>* Topical gel of non-integrating, replication-incompetent HSV-1 expressing the human collagen VII protein<br>* Other names: KB103;|
| Placebo Comparator: Placebo<br>Placebo | Biological: Placebo gel<br>* Placebo gel<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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%. | 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) | baseline to complete wound closure | 
| Duration of Wound Closure, ITT Population | Duration of wound closure | Time from the complete closure to the first reopening of the same wound | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bullosa, DEB, RDEB, Krystal, epidermolysis, Beremagene, Geperpavec, KB103, HSV-COL7A1