E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Dystrophic Epidermolysis Bullosa |
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E.1.1.1 | Medical condition in easily understood language |
Dystrophic epidermolysis bullosa (DEB) is a group of heritable skin diseases characterized by skin fragility, blister formation, milia, and scarring. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10014989 |
E.1.2 | Term | Epidermolysis bullosa |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objectives were the evaluation of safety, through incidence of adverse events associated with the administration of KB103, 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 KB103. |
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E.2.2 | Secondary objectives of the trial |
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 kB103 treated wounds as compared with placebo treated wounds. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Clinical diagnosis of the recessive form of dystrophic epidermolysis bullosa (RDEB). • Age a. Phase 1: 18 years old or older, b. Phase 2a: 5 years old or older, c. Phase 2b: 2 years old or older, d. 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: a. Phase 1: Two wounds up to 10 cm2; 1 randomized to B-VEC and 1 randomized to placebo b. Phase 2a and 2b: At least 3 wounds up to 20 cm2; 2 wounds randomized to B-VEC and 1 randomized to placebo c. 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, andare willing to return to the clinic for all the required follow-up visits |
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E.4 | Principal 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Number of Subjects Reported at Least One Adverse Event, Safety Population 2. Number of Adverse Events Reported, Safety Population
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. baseline to 12 weeks post-baseline 2. baseline to 12 weeks post-baseline |
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E.5.2 | Secondary end point(s) |
1. Complete Wound Closure Responder, ITT Population 2. Time to Wound Closure Analysis, ITT Population 3. Duration of Wound Closure, ITT Population |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. from baseline to Weeks 8, 10, and 12 2. baseline to complete wound closure 3. from the complete closure to the first reopening of the same wound |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
Will this trial be conducted at a single site globally?
| Yes |
E.8.4 | Will this trial be conducted at multiple sites globally? | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 12 |
E.8.9.2 | In all countries concerned by the trial days | 0 |