Phase 4 Master Protocol for Patients Prescribed Prademagene Zamikeracel for the Treatment of Wounds
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).
調査の概要
状態
条件
詳細な説明
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.
Study C is an open-label, non-randomized study in patients who are prescribed gene-corrected cellular sheets (pz-cel) in the post-marketing setting and who are part of a patient population not represented in the VIITAL Clinical Trial (NCT04227106). This study will enable patients with wounds that could benefit from treatment with pz-cel, especially those requiring special access for application of pz-cel, to receive pz-cel. 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 (25-60 days before surgery), at Day -1 (one day prior to 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).
研究の種類
入学 (推定)
段階
- フェーズ 4
連絡先と場所
研究連絡先
- 名前：Angela Iheanacho
- 電話番号：646-813-7166
- メール：aiheanacho@abeonatherapeutics.com
参加基準
適格基準
就学可能な年齢
- 子
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
Study A
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).
Exclusion Criteria
- 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.
Study B
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.
Study C
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：非ランダム化
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：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
|
Non-conforming pz-cel is pz-cel intended for commercial treatment that did not meet commercial release criteria, but had no safety concerns associated with its use.
|
|
他の：Study B
Tissue Collection Study for Patients Undergoing Biopsies for Treatment With Prademagene Zamikeracel (Pz-cel)
|
Additional biopsy samples from patients who are expected to receive treatment with pz-cel in the post-marketing setting.
|
|
実験的：Study C
Post-Marketing Pz-cel Access Study in Dystrophic Epidermolysis Bullosa (DEB) Evaluating Patient Populations Not Represented in the VIITAL Clinical Trial (NCT04227106)
|
This intervention is for patients requiring special access for application of pz-cel.
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Study A - Wound Healing ≥50%
時間枠：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.
|
From Baseline at Week 24 (Month 6)
|
|
Study A - Pain Severity Scale (Wong-Baker FACES)
時間枠：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.
|
At Week 24 (Month 6)
|
|
Study C - Wound Healing ≥50%
時間枠：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.
|
From Baseline at Week 24 (Month 6)
|
|
Study C - Pain Severity Scale (Wong-Baker FACES)
時間枠：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.
|
At Week 24 (Month 6)
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Study A - Wound Healing ≥50%
時間枠：At Week 12 (Month 3)
|
Proportion of RDEB wounds with ≥50% healing at Week 12 (Month 3) as determined by direct Investigator assessment.
|
At Week 12 (Month 3)
|
|
Study A - Wound Healing ≥75%
時間枠：At Weeks 12 (Month 3) and 24 (Month 6)
|
Proportion of RDEB wounds with ≥75% healing at Weeks 12 (Month 3) and 24 (Month 6) as determined by direct Investigator assessment.
|
At Weeks 12 (Month 3) and 24 (Month 6)
|
|
Study A - Wound Healing Complete
時間枠：At Weeks 12 (Month 3) and 24 (Month 6)
|
Proportion of RDEB wounds with complete healing (i.e., re-epithelialization with no drainage or erosion and presence of only minor crusting) at Weeks 12 (Month 3) and 24 (Month 6) as determined by direct Investigator assessment.
|
At Weeks 12 (Month 3) and 24 (Month 6)
|
|
Study A - Pain Severity Scale (Wong-Baker FACES)
時間枠：At Week 12 (Month 3)
|
Pain reduction assessed by the Wong-Baker FACES Pain Rating Scale (for patients ≥6 years of age) at Week 12 (Month 3).
The minimum score value is 0 and the maximum score value is 10, with the higher scores being the worse outcome.
|
At Week 12 (Month 3)
|
|
Study A - Worst Itch Severity Scale
時間枠：At Weeks 12 (Month 3) and 24 (Month 6)
|
Change in scores of Worst Itch Numeric Rating Scale (WI-NRS; for patients ≥6 years of age) assessed at Weeks 12 (Month 3) and 24 (Month 6).
The minimum score value is 0 and the maximum score value is 10, with the higher scores being the worse outcome.
|
At Weeks 12 (Month 3) and 24 (Month 6)
|
|
Study C - Wound Healing ≥50%
時間枠：At Week 12 (Month 3)
|
Proportion of DEB wounds with ≥50% healing at Week 12 (Month 3) as determined by direct Investigator assessment.
|
At Week 12 (Month 3)
|
|
Study C - Wound Healing ≥75%
時間枠：At Weeks 12 (Month 3) and 24 (Month 6)
|
Proportion of DEB wounds with ≥75% healing at Weeks 12 (Month 3) and 24 (Month 6) as determined by direct Investigator assessment.
|
At Weeks 12 (Month 3) and 24 (Month 6)
|
|
Study C - Wound Healing Complete
時間枠：At Weeks 12 (Month 3) and 24 (Month 6)
|
Proportion of DEB wounds with complete healing (i.e., re-epithelialization with no drainage or erosion and presence of only minor crusting) at Weeks 12 (Month 3) and 24 (Month 6) as determined by direct Investigator assessment.
|
At Weeks 12 (Month 3) and 24 (Month 6)
|
|
Study C - Pain Severity Scale (Wong-Baker FACES)
時間枠：At Week 12 (Month 3)
|
Pain reduction assessed by the Wong-Baker FACES Pain Rating Scale (for patients ≥6 years of age) at Week 12 (Month 3).
The minimum score value is 0 and the maximum score value is 10, with the higher scores being the worse outcome.
|
At Week 12 (Month 3)
|
|
Study C - Worst Itch Severity Scale
時間枠：At Weeks 12 (Month 3) and 24 (Month 6)
|
Change in scores of WI-NRS (for patients ≥6 years of age) assessed at Weeks 12 (Month 3) and 24 (Month 6).
The minimum score value is 0 and the maximum score value is 10, with the higher scores being the worse outcome.
|
At Weeks 12 (Month 3) and 24 (Month 6)
|
その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Study A - The number of treatment-related cutaneous malignancies.
時間枠：From enrollment to Week 24
|
The number and incidence of treatment-related cutaneous malignancies.
|
From enrollment to Week 24
|
|
Study A - The number of treatment-emergent adverse events (AEs) and serious adverse events (SAEs)
時間枠：From enrollment to Week 24
|
The number and incidence of treatment-emergent adverse events (AEs) and serious adverse events (SAEs) related to pz-cel.
|
From enrollment to Week 24
|
|
Study A - The number of positive replication-competent retrovirus (RCR) testing results
時間枠：From enrollment to Week 24
|
The number and incidence of positive replication-competent retrovirus (RCR) testing results required for AEs and SAEs where retroviral infection is a consideration.
|
From enrollment to Week 24
|
|
Study A - The number of all treatment-emergent AEs and SAEs.
時間枠：From enrollment to Week 24
|
The number and incidence of all treatment-emergent AEs and SAEs.
|
From enrollment to Week 24
|
|
Study C - The number of treatment-related cutaneous malignancies.
時間枠：From enrollment to Week 24
|
The number and incidence of treatment-related cutaneous malignancies.
|
From enrollment to Week 24
|
|
Study C - The number of treatment-emergent AEs and SAEs
時間枠：From enrollment to Week 24
|
The number and incidence of treatment-emergent AEs and SAEs related to pz-cel.
|
From enrollment to Week 24
|
|
Study C - The number of positive RCR testing results required for AEs and SAEs
時間枠：From enrollment to Week 24
|
The number and incidence of positive RCR testing results required for AEs and SAEs where retroviral infection is a consideration.
|
From enrollment to Week 24
|
|
Study C - The number of all treatment-emergent AEs and SAEs.
時間枠：From enrollment to Week 24
|
The number and incidence of all treatment-emergent AEs and SAEs.
|
From enrollment to Week 24
|
協力者と研究者
スポンサー
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- Pz-cel-CL-402
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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