自家 CRISPR-Cas12b 編集造血幹細胞の安全性と有効性の評価
輸血依存性βサラセミア患者における自家CRISPR-Cas12b編集造血幹細胞の有効性と安全性を評価する研究
This is a single-arm, open, single-injection exploratory clinical study with two transfusion-dependent β thalassemia (β-TDT) participants planned to enroll.
調査の概要
詳細な説明
Through CRISPR-Cas 12b editing tool with independent intellectual property rights of Chinese Academy of Sciences, HBG1/2 promoter was edited to reactivate gamma-globin and induce fetal hemoglobin (HbF) expression. This leads to a subsequent reduction in ineffective red blood cell production (due to a reduction in the uncompounded alpha-globin chain) and improved red blood cell survival (due to reduced hemolysis), ultimately improving the sequelae of anemia and reducing the need for transfusion. Safety and efficacy will be evaluated continuously throughout the study, follow-up was up to 24 months. After the end of this trial, participants who received the infusion of autologous CRISPR-Cas12b edited hematopoietic stem cells (VGB-Ex01) will be invited to participate in the long-term follow-up study to complete the 15-year follow-up plan.
研究の種類
入学 (実際)
段階
- 適用できない
連絡先と場所
研究場所
-
-
Tianjin Municipality
-
Tianjin、Tianjin Municipality、中国
- Regenerative Medicine Center
-
-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- Age 3-35 years old (inclusive), male or female;
- The subject and/or his/her legally recognized representative/parent/guardian fully understands the study and all information related to the study and has signed the informed consent form;
- Clinical diagnosis of transfusion-dependent β-thalassemia (TDT) with a blood transfusion record within 2 years (inclusive) prior to screening showing a history of ≥ 10 units (U)/kg/year (or ≥ 100 mL/kg/year) or ≥ 8 times/year of suspended RBC transfusions in at least 1 consecutive 12-month period;
- Karnofsky score (for subjects aged ≥ 16 years) or Lansky score (for subjects aged < 16 years) of ≥ 80;
- Subjects in stable disease state who are eligible for hematopoietic stem cell transplantation as per investigator's judgment;
- Access to diagnosis and treatment records issued by medical professional institutions within 2 years prior to screening, including the records of blood transfusions, hematology, serum chemistry, and other examinations;
- Willing and able to comply with study procedures, with good compliance, and willing to receive and complete the follow-up study with a duration of at least 2 years;
- Subjects of childbearing potential (including female subjects of childbearing potential and male subjects whose partners are of childbearing potential) must use effective contraception within 12 months of treatment.
Exclusion Criteria:
- Diagnosis of associated α-thalassemia: > 1 alpha chain deletion or alpha gene functional defect;
- Have available HLA-fully matched donors and acceptable for allogeneic hematopoietic stem cell transplantation;
- Irregular antibody or platelet antibody positive;
- Prior allogeneic bone marrow transplantation or gene therapy;
- Subjects with clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator at screening, including but not limited to those with positive etiology of human immunodeficiency virus (HIV-1/2), human cytomegalovirus (HCMV-DNA), Epstein-Barr virus (EBV-DNA), or Treponema pallidum antibody (TP-Ab), or with previous hepatitis B or C infection;
- Subjects with an injury of major organs
- Contraindications for hematopoietic stem cell collection and poor collection efficiency judged by the investigator;
- Contraindications to the clinical investigational product and its excipients, G-CSF (hematopoietic stem cell mobilization), plerixafor (hematopoietic stem cell mobilization), busulfan (myeloablation), and other drugs;
- Participation within 3 months prior to screening or current participation in another interventional clinical study;
- History or family history of malignancy or myeloproliferative disorder;
- History of uncontrollable epilepsy, mental disorder, or other psychiatric disorders;
- Abuse of psychoactive substance, drug, or alcohol within 6 months prior to enrollment;
- Pregnant or breastfeeding females;
- Other diseases or reasons that interfere with study procedures;
- Any other conditions that the investigator deems unsuitable for the subject's participation 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：なし
- 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：VGB-Ex01
Each subject will accept one dose of VGB-Ex01. |
CRISPR-Cas12b editing hematopoietic stem cells |
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 |
|---|---|---|
|
Incidence of adverse events and serious adverse events
時間枠：Baseline up to 24 months
|
An adverse event is any untoward medical occurrence in a clinical investigation/participant administered a product; the event will not need to have a causal relationship with the treatment. A serious adverse event is any untoward medical occurrence at any dose that resulted in death; life threatening;require inpatient hospitalization or prolongation of existing hospitalization; result in persistent or significant disability/incapacity; result in congenital anomaly/birth defect. |
Baseline up to 24 months
|
|
Number of subjects with neutrophil implantation ≤ 42 days
時間枠：Baseline up to 42 days
|
Neutrophil implantation was defined as 3 consecutive days with 3 tests for ANC≥500/μL. |
Baseline up to 42 days
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Number of subjects transfusion independence (TI) for at least 6 months after transfusion
時間枠：Baseline up to 6 months
|
TI defined as Hb≥9g/dL without red blood cell infusion |
Baseline up to 6 months
|
|
Number of subjects transfusion independence (TI) for at least 12 months after transfusion
時間枠：Baseline up to 12 months
|
TI defined as Hb≥9g/dL without red blood cell infusion |
Baseline up to 12 months
|
|
Fetal hemoglobin (HbF) concentration
時間枠：Baseline up to 24 months
|
Changes in HbF concentration from baseline after transfusion |
Baseline up to 24 months
|
|
Total hemoglobin (Hb) concentration
時間枠：Baseline up to 24 months
|
Changes in Hb concentration compared with baseline after transfusion |
Baseline up to 24 months
|
|
The proportion of circulating red blood cells
時間枠：Baseline up to 24 months
|
Changes in the proportion of circulating red blood cells expressing fetal hemoglobin compared to baseline |
Baseline up to 24 months
|
協力者と研究者
捜査官
- 主任研究者：Jun Shi, PhD、Institute of Hematology & Blood Diseases Hospital, China
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
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
- IIT2023048
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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