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)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- Number of Subjects Reported at Least One Adverse Event, Safety Population
研究概览
简要总结
This study was conducted to assess the safety and efficacy of topical Beremagene Geperpavec (KB103, HSV1-COL7) on DEB patients.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinical diagnosis of the recessive form of dystrophic epidermolysis bullosa (RDEB).
- •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.
排除标准
- •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
结局指标
主要结局
Number of Subjects Reported at Least One Adverse Event, Safety Population
时间窗: 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
时间窗: from baseline at Weeks 8, 10, and 12
One wound is a responder if the reduction from baseline in wound surface is ≥90%.
Number of Adverse Events Reported, Safety Population
时间窗: 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.
Time to Wound Closure Analysis, ITT Population
时间窗: 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
时间窗: Time from the complete closure to the first reopening of the same wound
Duration of wound closure
次要结局
未报告次要终点