A Phase 2 Clinical Trial to Evaluate the Efficacy of the Infusion of Autologous CD34+ Cells Transduced With a Lentiviral Vector Carrying the Codon Optimized Red Cell Pyruvate Kinase (coRPK) Gene in Subjects With Pyruvate Kinase Deficiency

Rocket Pharmaceuticals Inc.4 个研究点分布在 2 个国家目标入组 10 人2026年4月1日

适应症Pyruvate Kinase Deficiency

干预措施RP-L301

概览

阶段: 2 期
干预措施: RP-L301
疾病 / 适应症: Pyruvate Kinase Deficiency
发起方: Rocket Pharmaceuticals Inc.
入组人数: 10
试验地点: 4
主要终点: Improvement in Anemia
状态: 暂停
最后更新: 16天前

概览研究者入排标准研究组 & 干预措施结局指标研究点相似试验

概览

简要总结

This is an open-label Phase II trial to evaluate the efficacy of a hematopoietic cell-based gene therapy for patients with Pyruvate Kinase Deficiency (PKD).

详细描述

Autologous hematopoietic stem cells from mobilized peripheral blood will be transduced ex vivo (outside the body) with a lentiviral vector carrying a correct copy of the deficient PKLR (Pyruvate Kinase L/R) gene. The corrected stem cells will be infused intravenously back into the patient to correct the hematological manifestations of the disease.

注册库

clinicaltrials.gov

开始日期

2026年4月1日

结束日期

2029年1月1日

最后更新

16天前

研究类型

Interventional

研究设计

Single Group

性别

All

研究者

发起方

Rocket Pharmaceuticals Inc.

责任方

Sponsor

入排标准

入选标准

•Pyruvate Kinase Deficiency (PKD) diagnosis with a confirmed PK-LR mutation
•Significant anemia defined as:
•Hemoglobin (Hb) levels \<9.5 g/dL documented during 2 or more assessments in the 12 months prior to screening and either:
•at least 6 Red Blood Cell (RBC) transfusion episodes over the 12- month period prior to screening or
•at least 3 Red Blood Cell (RBC) transfusion episodes each year for 2 years prior to screening; or
•Hemoglobin (Hb) levels \<8.5 g/dL irrespective of transfusions (documented during 2 or more assessments during the prior 2 years); or
•Hemoglobin (Hb) levels \<10.0 g/dL irrespective of transfusions (documented during 2 or more assessments during the prior 2 years) and the presence of either:
•Fatigue or energy-related symptoms limiting activities of daily living (The National Cancer Institute Common Terminology Criteria for Adverse Events v 5.0 (NCI CTCAE v5.0 grade 3)); or
•Fatigue or energy-related symptoms limiting activities of daily living (The National Cancer Institute Common Terminology Criteria for Adverse Events v 5.0 (NCI CTCAE v5.0 grade 2)) not responsive to available medical therapy; or
•Icterus limiting social interactions, education or work activities and not responsive to available medical therapy;

排除标准

•Availability of detailed medical records, including accurate transfusion history and blood count assessments, for the prior 2 years
•Willing and able to read and correctly understand the patient information sheet and provide consent (or informed assent for minors) regarding study participation, willing and able to comply with all study-related procedures including follow-up visits.
•Negative serum pregnancy test for female subjects of childbearing potential.
•Exclusion Criteria
•Presence of other known causes of hemolysis (in addition to Pyruvate Kinase Deficiency (PKD)). Patients with concurrent G6PD deficiency diagnosed during pre-study evaluation may be considered for eligibility if in the opinion of the Investigator, the hemolytic anemia is the result of PKD and the Glucose-6-phosphate dehydrogenase (G6PD) deficiency is considered an incidental finding.
•A venous thromboembolic event (VTE; i.e., pulmonary embolism or deep vein thrombosis) or arteriothromboembolic event (ATE; including unstable angina, myocardial infarction, stroke or transient ischemic attack) during the prior 12 months.
•Evidence of bridging fibrosis, cirrhosis or active hepatitis on liver biopsy.
•Liver biopsy is required when liver iron concentration (LIC) is ≥15 mg/g on T2\* magnetic resonance imaging (MRI) of liver.
•If a liver biopsy has been performed less than 6 months prior to enrollment, it does not need to be repeated.
•Cardiac T2\* \<10 ms by magnetic resonance imaging (MRI) or left ventricular ejection fraction (LVEF) \<45% by echocardiogram or multiple gated acquisition scan (MUGA).

研究组 & 干预措施

Participant Group/Arm

RP-L301 is a gene therapy product containing autologous genetically modified CD34+ hematopoietic stem cells containing the corrected PKLR (Pyruvate Kinase L/R) gene

干预措施: RP-L301

结局指标

主要结局

Improvement in Anemia

时间窗: 12 months post-infusion

Hemoglobin (Hb) level increase of ≥1.5g/dL at 12 months post-infusion, compared to baseline.

次要结局

Resolution of anemia(12 months post-infusion)
Reduction of transfusion requirements(12 months post-infusion)
Improvements of hemolysis parameters (Lactate Dehydrogenase (LDH))(12 months post-infusion)
Improvement in dyspnea(12 months post-infusion)
Improvement in fatigue(12 months post-infusion)
Improvements of hemolysis parameters (reticulocyte)(12 months post-infusion)
Peripheral blood genetic correction(12 months post-infusion)
Improvement in jaundice(12 months post-infusion)
Durability Improvement anemia sustained(24 months post-infusion)
Improvements of hemolysis parameters (bilirubin)(12 months post-infusion)
Improvements of hemolysis parameters (erythropoietin)(12 months post-infusion)
Safety and tolerability of RP-L301(24 months post-infusion)
Evaluate durable resolution of transfusion requirements (where relevant).(24 months post-infusion)
Evaluate durable resolution of anemia(24 months post-infusion)