2024-518368-10-00尚未招募1/2 期
Phase I/II ex vivo gene therapy clinical trial for RDEB using autologous skin equivalent grafts genetically corrected with a COL7A1-encoding SIN retroviral vector
Institut National De La Sante Et De La Recherche Medicale1 个研究点 分布在 1 个国家目标入组 3 人开始时间: 2025年1月29日最近更新:
试验速览
- 阶段
- 1/2 期
- 状态
- 尚未招募
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Adverse events (AEs), Serious Adverse Events (SAEs), Adverse Reactions (ARs) and Serious Adverse Reactions (SARs) at each visit over a 12-months period after grafting and at each visit during a long term follow-up period of 5 years in total.
研究概览
简要总结
The primary objective of this phase I/II clinical trial is to evaluate the safety of grafting SIN RV-mediated COL7A1 gene-modified autologous SE in adults with RDEB at M1, M2, M3, M6, M12 after grafting. This evaluation will be continued during a reglementary 5-year follow up at M18, M24, M30, M36, M42, M48, M54, and M60.
研究设计
- 分配方式
- Not Applicable
- 主要目的
- Ebgraft Trial
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •1.≥ 18 year-old
- •2.Clinical and molecular diagnosis of RDEB with confirmed bi-allelic COL7A1 mutations
- •3.Significantly reduced staining of C7 on skin biopsy, measured by immunofluorescence microscopy (IF)
- •4.A reduced number of or morphologically abnormal anchoring fibrils confirmed by TEM
- •5.Presence of non-collagenous-1 domain (NC-1) of C7 on skin biopsy, measured by immunofluorescence microscopy (IF) and/or Western blot analysis
- •6.Presence of ≥100cm2 of blistered and/or erosive skin areas including chronic wounds suitable for skin grafting
- •7.Ability to undergo anaesthesia for grafting procedures
- •8.Subjects aged ≥ 18years, willing and able to give informed consent
排除标准
- •1.Recipients of other investigational medicinal products within 6 months prior to enrolment into this study
- •2.Past medical history of biopsy proven skin malignancy
- •3.Immunotherapy including oral corticosteroids (Prednisolone >1mg/kg) for more than one week (intranasal and topical preparations are permitted) or chemotherapy within 60 days of enrolment into this study
- •4.Known allergy to any of the constituents of the investigational medicinal product (IMP) including Penicillin
- •5.Subjects with BOTH: •positive serum antibodies to C7 confirmed by ELISA and •positive IIF with binding to the base of salt split skin and/or •positive Western blot
- •6.Positive results for HIV, Hepatitis BsAg, Hepatitis BcAb, Hepatitis C IgG, HTLV1&2 or Syphilis serology
- •7.Clinically significant medical, psychological or laboratory abnormalities limiting the ability of the subject to travel to the trial site(s) and to undergo grafting and follow-up procedures, as determined by the Investigator
- •8.Absence of adequate social support
- •9.Subjects who are pregnant, breast-feeding or of child-bearing potential who are neither abstinent nor practicing an acceptable means of contraception when this is in line with the usual and preferred lifestyle of the subject, as determined by the Investigator, for the duration of the trial
结局指标
主要结局
Adverse events (AEs), Serious Adverse Events (SAEs), Adverse Reactions (ARs) and Serious Adverse Reactions (SARs) at each visit over a 12-months period after grafting and at each visit during a long term follow-up period of 5 years in total.
Adverse events (AEs), Serious Adverse Events (SAEs), Adverse Reactions (ARs) and Serious Adverse Reactions (SARs) at each visit over a 12-months period after grafting and at each visit during a long term follow-up period of 5 years in total.
次要结局
- Skin biopsy analysis of grafted skin at, M3, M6, M12, M24, M36, M48 and M60 after grafting compared to baseline for: a)C7 protein expression by immunofluorescence microscopy (IF) b)Morphology of anchoring fibrils (Wetzels et al.) at the dermal-epidermal junction (DEJ) by transmission electron microscopy (TEM)
- Serum analysis at M1, M6, M12, M18, M24, M30, M36, M42, M48, M54 and M60 after grafting compared to baseline for: a)Detection of anti-C7 antibodies by enzyme-linked immunosorbent assay (ELISA) (against the entire C7 molecule) indirect immunofluorescence (IIF) and/or Western blot (WB) b)Detection of T-cell responses to the full length C7 by enzyme-linked immunosorbent spot (ELISPOT) assay
- Clinical assessment at M1, M2, M3, M6, M12, M18, M24, M30, M36, M42, M48, M54 and M60 after grafting compared to baseline for: a)The scar quality measured by the Vancouver Scar Scale (VSS) b)Changes in blister numbers over the grafted skin c)Changes in the clinical appearance of grafted skin through clinical photographs at each visit d)Changes in pruritus measured by the Leuven Itch Scale (LIS) e)Changes in Quality of Life Score measured by the QOLEB
研究者
Alain Hovnanian
Scientific
Institut National De La Sante Et De La Recherche Medicale
研究点 (1)
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