Phase 4 Master Protocol for Patients Prescribed Prademagene Zamikeracel for the Treatment of Wounds
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 100
- 主要终点
- Study A
研究概览
简要总结
The Master Protocol includes 3 studies (Study A, Study B, and Study C) that will evaluate pz-cel and related processes in the post-marketing setting.
Study A investigates the efficacy and safety of non-conforming pz-cel in patients with Recessive Dystrophic Epidermolysis Bullosa (RDEB).
Study B enables the collection of additional biopsy samples from patients receiving treatment with pz-cel.
Study C assesses the efficacy and safety of pz-cel in patient populations not represented in the VIITAL clinical trial (NCT04227106).
详细描述
The Master Protocol includes 3 studies (Study A, Study B, and Study C) that will evaluate pz-cel (LZRSE-COL7A1 gene-corrected cellular sheets with type VII collagen [C7] expression) and related processes in the post-marketing setting.
Pz-cel is a genetically engineered autologous cell therapy indicated for the treatment of wounds associated with RDEB. Pz-cel is composed of autologous keratinocytes from patients with mutations in the collagen type VII alpha 1 chain (COL7A1) gene, which have been transduced ex vivo with the Moloney leukemia virus-derived retroviral vector (LZRSE)-COL7A1. The gene-corrected cellular sheets express functional C7.
The pz-cel sheets are a one-time surgical application to debrided and cauterized wound beds of the corresponding patients with DEB. The COL7A1 transgene integrates into the host cell genome, resulting in durable expression and secretion of collagen protein, which addresses the underlying mechanism of the disease.
Study A is an open-label, non-randomized study in patients who are expected to receive gene-corrected cellular sheets (pz-cel) for the treatment of RDEB wound sites in the post-marketing setting and whose manufactured patient-specific batch of pz-cel intended for commercial treatment did not meet commercial release criteria, but had no safety concerns associated with its use. This study will allow surgical application of such non-conforming pz-cel when the benefit of application outweighs the risks. All patients will be followed through 24 weeks after treatment and may be eligible for further follow-up after Week 24. Patients will be evaluated at their Screening visit (30 days before surgery), at Day 0 (Surgery day), by phone on Week 4 (Month 1) and by Telehealth or Clinic Visit at Week 12 (Month 3) and Week 24 (Month 6).
Study B is a study to collect additional biopsy samples from patients who are expected to receive treatment with pz-cel in the post-marketing setting. The additional biopsy samples are being collected to support pz-cel product optimization. Patients receiving treatment with pz-cel can consent to have 2 additional 8-mm biopsies for use in the pz-cel assay and process development as well as in the optimization of the pz-cel manufacturing processes. The study will consist of Screening (in-person or via phone and eConsent), a pre-surgery biopsy and an End of Study Phone call 10-14 days after biopsy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Inclusion Criteria
- •Willing and able to provide informed consent/assent; if under the age of 18, guardian(s) is (are) willing and able to provide consent.
- •Patients who are expected to receive pz-cel manufactured as intended for commercial treatment; however, the final manufactured product was non-conforming and therefore did not meet commercial release criteria.
- •All women of childbearing potential should discuss reproductive and breastfeeding plans and precautions with the treating physician in accordance with the considerations for special populations in the United States Prescribing Information (USPI).
排除标准
- •Inability to adequately follow the protocol and ensure the protection of cellular sheet sites, as determined by the Investigator.
- •Hypersensitivity to vancomycin or amikacin.
- •The presence of medical illness expected to complicate participation and/or compromise the safety of this technique, such as, but not limited to, active infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
- •Evidence of systemic infection.
- •Current evidence of squamous cell carcinoma (SCC) in the area that will undergo pz-cel application.
- •Grade 3 clinical event or laboratory abnormality prior to pz-cel treatment, with the exception of abnormalities such as esophageal strictures, anemia, low albumin, and pain/itch, which are expected in patients with severe DEB.
- •Any other circumstance where the Investigator believes that it is not appropriate for the patient to participate in the study.
- •Inclusion Criteria
- •Willing and able to provide informed consent/assent; if under the age of 18, guardian(s) is (are) willing and able to provide consent.
- •Patients who are expected to receive treatment with pz-cel and are receiving a biopsy prior to pz-cel application in the post-marketing setting.
- •Exclusion Criteria
- •1. Any circumstance where the Investigator believes that the patient may not be appropriate for participation in the study.
- •Inclusion Criteria:
- •Willing and able to provide informed consent/assent; if under the age of 18, guardian(s) is (are) willing and able to provide consent.
- •Patients who were prescribed pz-cel for commercial treatment but require special access defined in the protocol for treatment to occur.
- •All women of childbearing potential must have a negative urine pregnancy test and agree to use a reliable birth control method throughout the duration of the study.
- •Exclusion Criteria:
- •Inability to properly follow protocol assessments and protect cellular sheet sites as determined by the Investigator.
- •Currently enrolled in an interventional clinical trial involving an investigational medicinal product to treat DEB or receipt of the investigational therapy within the 3 months prior to pz-cel application.
- •Breastfeeding.
- •The presence of medical illness expected to complicate participation and/or compromise the safety of this technique, such as, but not limited to, active infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
- •Evidence of systemic infection.
- •Current evidence or a history of SCC in the area that will undergo pz-cel application.
- •Active drug or alcohol addiction.
- •Hypersensitivity to vancomycin or amikacin.
- •Grade 3 clinical event or laboratory abnormality prior to pz-cel treatment, with the exception of abnormalities such as esophageal strictures, anemia, low albumin, and pain/itch, which are expected in patients with severe DEB.
- •Any other circumstance where the Investigator believes that it is not appropriate for the patient to participate in the study.
研究组 & 干预措施
Study A
Clinical Evaluation of Prademagene Zamikeracel (Pz-cel) Treatment in Patients With Recessive Dystrophic Epidermolysis Bullosa (RDEB) Who Were Prescribed Pz-cel and Received Non-conforming Pz-cel in the Post-marketing Setting
干预措施: Non-conforming pz-cel surgical application to RDEB wounds (Biological)
Study C
Post-Marketing Pz-cel Access Study in Dystrophic Epidermolysis Bullosa (DEB) Evaluating Patient Populations Not Represented in the VIITAL Clinical Trial (NCT04227106)
干预措施: Pz-cel surgical application to DEB wounds (Biological)
Study B
Tissue Collection Study for Patients Undergoing Biopsies for Treatment With Prademagene Zamikeracel (Pz-cel)
干预措施: Additional biopsies (Procedure)
结局指标
主要结局
Study A
时间窗: From Baseline at Week 24 (Month 6)
Proportion of RDEB wounds with healing ≥50% from Baseline at Week 24 (Month 6) as determined by direct Investigator assessment.
Study A
时间窗: At Week 24 (Month 6)
Pain reduction assessed by the Wong-Baker FACES Pain Rating Scale (for patients ≥6 years of age) at Week 24 (Month 6).
Study C
时间窗: From Baseline at Week 24 (Month 6)
Proportion of wounds with healing ≥50% from Baseline at Week 24 (Month 6) as determined by direct Investigator assessment.
Study C
时间窗: At Week 24 (Month 6)
Pain reduction assessed by Wong-Baker FACES Pain Rating Scale (for patients ≥6 years old) at Week 24 (Month 6).
Study A - Wound Healing ≥50%
时间窗: From Baseline at Week 24 (Month 6)
Proportion of RDEB wounds with healing ≥50% from Baseline at Week 24 (Month 6) as determined by direct Investigator assessment.
Study A - Pain Severity Scale (Wong-Baker FACES)
时间窗: At Week 24 (Month 6)
Pain reduction assessed by the Wong-Baker FACES Pain Rating Scale (for patients ≥6 years of age) at Week 24 (Month 6). The minimum score value is 0 and the maximum score value is 10, with the higher scores being the worse outcome.
Study C - Wound Healing ≥50%
时间窗: From Baseline at Week 24 (Month 6)
Proportion of wounds with healing ≥50% from Baseline at Week 24 (Month 6) as determined by direct Investigator assessment.
Study C - Pain Severity Scale (Wong-Baker FACES)
时间窗: At Week 24 (Month 6)
Pain reduction assessed by Wong-Baker FACES Pain Rating Scale (for patients ≥6 years old) at Week 24 (Month 6). The minimum score value is 0 and the maximum score value is 10, with the higher scores being the worse outcome.
次要结局
- Study A(At Week 12 (Month 3))
- Study A(At Weeks 12 (Month 3) and 24 (Month 6))
- Study C(At Week 12 (Month 3))
- Study C(At Weeks 12 (Month 3) and 24 (Month 6))
- Study A - Wound Healing ≥50%(At Week 12 (Month 3))
- Study A - Wound Healing ≥75%(At Weeks 12 (Month 3) and 24 (Month 6))
- Study A - Wound Healing Complete(At Weeks 12 (Month 3) and 24 (Month 6))
- Study A - Pain Severity Scale (Wong-Baker FACES)(At Week 12 (Month 3))
- Study A - Worst Itch Severity Scale(At Weeks 12 (Month 3) and 24 (Month 6))
- Study C - Wound Healing ≥50%(At Week 12 (Month 3))
- Study C - Wound Healing ≥75%(At Weeks 12 (Month 3) and 24 (Month 6))
- Study C - Wound Healing Complete(At Weeks 12 (Month 3) and 24 (Month 6))
- Study C - Pain Severity Scale (Wong-Baker FACES)(At Week 12 (Month 3))
- Study C - Worst Itch Severity Scale(At Weeks 12 (Month 3) and 24 (Month 6))