Clinical Trial to Evaluate the Efficacy of Gene Therapy for Pyruvate Kinase Deficiency

Phase 2

Not yet recruiting

• Conditions: Pyruvate Kinase Deficiency
• Interventions: Biological: RP-L301

• Registration Number: NCT06422351
• Lead Sponsor: Rocket Pharmaceuticals Inc.

Brief Summary

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).

Detailed Description

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.

Study Timeline

• Status Verified: 2024-05
• Study First Submitted: 2024-05-15
• Study First Submitted QC: 2024-05-15
• Last Update Submitted: 2024-05-20
• Study First Posted: 2024-05-21
• Last Update Posted: 2024-05-22
• Study Start: 2024-08
• Primary Completion: 2026-11
• Study Completion: 2029-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Improvement in Anemia	12 months post-infusion	Hemoglobin (Hb) level increase of ≥1.5g/dL at 12 months post-infusion, compared to baseline.

Secondary Outcome Measures

Name	Time	Method
Resolution of anemia	12 months post-infusion	Hemoglobin level within normal range (≥ lower limit of normal) at 12 months post-infusion.
Reduction of transfusion requirements	12 months post-infusion	* a: ≥50% reduction in Pyruvate Kinase Deficiency (PKD)-related Red Blood Cells (RBC) transfusion requirements in the 12 months post-infusion, relative to the annualized event rate for 24 months prior to enrollment; or,; * b: Absence of PKD-related RBC transfusion requirements in the 12 months post-infusion.
Improvements of hemolysis parameters (Lactate Dehydrogenase (LDH))	12 months post-infusion	Improvements in Lactate Dehydrogenase (LDH), each evaluated at 12 months post-infusion, compared to baseline.
Improvements of hemolysis parameters (reticulocyte)	12 months post-infusion	Improvements in reticulocyte, each evaluated at 12 months post-infusion, compared to baseline.
Improvement in fatigue	12 months post-infusion	Improvement in fatigue as compared with baseline, as assessed by: * Age ≥18: FACIT Fatigue; or,; * Age \<18: PROMIS Fatigue Short Form 10a
Improvement in dyspnea	12 months post-infusion	Improvement in Pyruvate Kinase Deficiency symptoms, compared with baseline, as assessed by: * PROMIS Dyspnea Severity SF10; or,; * Dyspnea severity
Peripheral blood genetic correction	12 months post-infusion	Genetic correction demonstrated by vector copy number (VCN) of 0.1 in Peripheral Blood mononuclear cells, evaluated at 12 months post-infusion.
Improvement in jaundice	12 months post-infusion	Improvement in Pyruvate Kinase Deficiency symptoms, compared with baseline, as assessed by: * jaundice severity evaluated at 12 months post-infusion; or,; * and jaundice severity
Durability Improvement anemia sustained	24 months post-infusion	Time to Hemoglobin level increase of ≥1.5g/dL post-infusion, compared to baseline.
Improvements of hemolysis parameters (bilirubin)	12 months post-infusion	Improvements in bilirubin, each evaluated at 12 months post-infusion, compared to baseline.
Improvements of hemolysis parameters (erythropoietin)	12 months post-infusion	Improvements in erythropoietin, each evaluated at 12 months post-infusion, compared to baseline.
Safety and tolerability of RP-L301	24 months post-infusion	Incidence, type, severity, frequency, time to onset, and duration of treatment emergent adverse events (TEAEs), serious adverse events (SAEs), clinical laboratory abnormalities, and adverse events of special interest (AESIs).
Evaluate durable resolution of transfusion requirements (where relevant).	24 months post-infusion	1. ≥50% reduction in Pyruvate Kinase Deficiency (PKD)-related Red Blood Cell (RBC) transfusion requirements in the 24 months post-infusion, relative to the annualized event rate for 24 months prior to enrollment; or,; 2. Absence of PKD-related RBC transfusion requirements in the 24 months post-infusion.
Evaluate durable resolution of anemia	24 months post-infusion	Hemoglobin (Hb) level within normal range (≥ lower limit of normal).

Trial Locations

Locations (3)

Stanford University; 🇺🇸 Palo Alto, California, United States

Hospital Infantil Universitario Niño Jesús; 🇪🇸 Madrid, Spain

Hospital Universitario Fundación Jiménez Díaz; 🇪🇸 Madrid, Spain