NCT01263379已完成1 期
A Phase 1/2A Single Center Trial of Gene Transfer for Recessive Dystrophic Epidermolysis Bullosa (RDEB) Using the Drug LZRSE-Col7A1 Engineered Autologous Epidermal Sheets (LEAES)
适应症
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 Wounds by Healing Category Per Investigator Visual Assessment
研究概览
简要总结
This trial will create a skin graft, which the investigators call "LEAES," using the patient's own skin cells that have been genetically engineered in the lab to express a missing protein called type VII collagen. The corrected cells will be transplanted back to the patient.
详细描述
The research project involves gene transfer into keratinocytes, which are the majority of the cells in the outer layer of skin. In this gene transfer trial we plan to biopsy some skin tissue, grow the cells in a skin cell culture (sterile dishes with special fluid that allows cells to grow and multiply) and then infect the cells with a virus that we have genetically engineered to insert the correct type VII collagen gene. The cells should then make type VII collagen.
The process of inserting the correct type VII collagen gene into cells is called "gene transfer." The virus used is called a "retrovirus." The virus is made so that it only delivers the type VII collagen gene and it should not spread to other parts of the body. During the study we will check for growth of the virus.
After cells have received gene transfer, we will grow the cells in culture into a sheet of cells that look like a plastic film. We plan to graft the sheet to wounds. Grafting means we will take cells from the culture and stitch them to the patient's skin.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 13 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinical diagnosis of recessive dystrophic epidermolysis bullosa (RDEB)
- •13 years old or older and willing and able to give assent/consent
- •Confirmation of RDEB diagnosis by immunofluorescence (IF) and electron microscopy (EM)
- •NC1[+] and mAb LH24 antibody staining negative
- •RDEB type VII collagen mutations in subject and carrier parents confirmed
- •At least 100 to 200 cm2 areas of open erosions on the trunk and/or extremities suitable for skin grafting
- •Able to undergo adequate anesthesia to allow grafting procedures to take place.
排除标准
- •Medical instability limiting ability to travel to Stanford University Medical Center
- •The presence of medical illness expected to complicate participation and/or compromise the safety of this technique, such as active infection with HIV, hepatitis B or hepatitis C, as determined by hepatitis B surface antigen screening, detection of hepatitis C antibodies, or positive result of hepatitis C polymerase chain reaction (PCR) analysis.
- •Antibodies to type VII collagen associated antigens
- •Active infection in the area that will undergo grafting
- •Evidence of systemic infection
- •Current evidence or a history of squamous cell carcinoma in the area that will undergo grafting
- •Active drug or alcohol addiction
- •Hypersensitivity to vancomycin or amikacin
- •Receipt of chemical or biological study product for the specific treatment of RDEB in the past six months
- •Positive pregnancy test or breast-feeding
- •Clinically significant abnormalities (Grade 2 or higher on the National Cancer Institute [NCI] toxicity scale) on laboratory tests performed prior to grafting, except for the following specific exclusionary laboratory threshold results, subject to approval or exemption by the EB physician:
- •Albumin < 2.5 g/dL
- •Leukocytes > 20K/uL
- •Hemoglobin < 7.5 g/dL. Low hemoglobin will be treated at the discretion of the investigators and the EB physician.
- •Additional exceptions may be made at the discretion of the investigators and the EB physician.
- •Clinically significant abnormalities (Grade 2 or higher on the NCI toxicity scale) identified through medical history and physical examination on Day 0, with the following exceptions:
- •Anorexia, can enroll up to Grade 4 (inclusive)
- •Constipation, can enroll up to Grade 2 (inclusive)
- •Dysphagia, can enroll up to Grade 4 (inclusive)
- •Keratitis, can enroll up to Grade 4 (inclusive)
- •Bone pain, can enroll up to Grade 2 (inclusive)
- •Additional exceptions may be made at the discretion of the investigators and the EB physician.
结局指标
主要结局
Number of Wounds by Healing Category Per Investigator Visual Assessment
时间窗: 3, 6, 12 and 24 months post grafting
The graft site was clinically evaluated by the investigator with a global score of: 1) 100% to 75% healed, 2) 74% to 50% healed, 3) 49% or less healed with 100% meaning completely healed.
Percentage Surface Area of Wound Healing
时间窗: 3, 6 and 12 months post grafting
Percentage of wound area will be obtained using the Canfield system. Changes in dimensions between visits as well as changes in dimensions from baseline will be recorded. Dimensions of untreated wounded skin will be used for comparison
次要结局
- Number Participants Positive for NC2 Epitope as a Measure of Duration of Type VII Collagen Production(3 months, 6 months, 12 months, 24 months post-grafting)
研究者
研究点 (2)
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相关资讯
FDA to Decide on Abeona's Pz-cel for Recessive Dystrophic Epidermolysis Bullosa by April 29- The FDA is expected to decide on the approval of Abeona Therapeutics' pz-cel (prademagene zamikeracel) for recessive dystrophic epidermolysis bullosa (RDEB) by April 29, 2025.
- Pz-cel is a cell therapy involving genetically engineering a patient's skin cells to produce healthy collagen, addressing the underlying cause of RDEB.
- The FDA's decision is based on data from Phase 1/2a and Phase 3 VIITAL clinical trials, which demonstrated improved wound healing and reduced pain in RDEB patients.
- This marks Abeona's second attempt to gain FDA approval for pz-cel, with the agency previously raising concerns about the therapy's manufacturing process.last yearFDA Accepts Abeona's BLA Resubmission for Pz-Cel in Recessive Dystrophic Epidermolysis Bullosa- The FDA has accepted Abeona Therapeutics' resubmitted Biologics License Application (BLA) for pz-cel, a gene therapy for recessive dystrophic epidermolysis bullosa (RDEB).
- The FDA set a PDUFA target action date of April 29, 2025, for the decision on pz-cel, an autologous, cell-based gene therapy.
- The BLA resubmission addresses Chemistry, Manufacturing, and Controls (CMC) issues raised in a previous Complete Response Letter, with no new clinical data requested.
- Pz-cel has shown significant wound healing and pain reduction in Phase 3 trials, potentially addressing unmet needs for RDEB patients.last yearFDA Accepts Abeona's Gene Therapy BLA Resubmission for Recessive Dystrophic Epidermolysis Bullosa- The FDA has accepted Abeona Therapeutics' resubmitted Biologics License Application (BLA) for prademagene zamikeracel (pz-cel) for treating recessive dystrophic epidermolysis bullosa (RDEB).
- Pz-cel is an autologous cell-based gene therapy designed to deliver the COL7A1 gene to wound sites, promoting collagen VII expression in RDEB patients.
- The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of April 29, 2025, for the completion of its review of the pz-cel application.
- Clinical data from Phase 3 VIITAL study and a Phase 1/2a study support the BLA resubmission, showing safety and efficacy after a single pz-cel administration.last yearFDA Accepts Abeona's BLA Resubmission for Pz-cel in Recessive Dystrophic Epidermolysis Bullosa- The FDA has accepted Abeona Therapeutics' resubmitted Biologics License Application (BLA) for prademagene zamikeracel (pz-cel) to treat recessive dystrophic epidermolysis bullosa (RDEB).
- The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of April 29, 2025, for the decision on pz-cel approval.
- The BLA is supported by positive data from the Phase 3 VIITAL study and Phase 1/2a data, demonstrating sustained wound healing and pain reduction.
- Pz-cel represents a potential differentiated treatment option for RDEB, addressing the significant unmet needs of patients in the US.last yearFDA Accepts Abeona Therapeutics' BLA Resubmission for Prademagene Zamikeracel in RDEB Treatment- The FDA has accepted Abeona Therapeutics' resubmitted Biologics License Application (BLA) for prademagene zamikeracel (pz-cel) for recessive dystrophic epidermolysis bullosa (RDEB).
- Pz-cel, an autologous cell-based gene therapy, aims to address the unmet needs of RDEB patients by providing collagen VII expression at wound sites.
- The BLA is supported by data from the Phase 3 VIITAL study and a Phase 1/2a study with up to 8 years of follow-up, showcasing clinical efficacy and safety.
- The FDA has set a PDUFA target action date of April 29, 2025, with potential for Abeona to receive a Priority Review Voucher upon approval.last year
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