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

NCT06422351 | Suspended Phase 2 DMC FDA Drug

• 1 other identifier: RP-L301-0124
• Study Type: interventional
• Target: 10
• Locations: 2 countries
• Sites: 3

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).

Conditions

Pyruvate Kinase Deficiency

Outcome Measures

Primary Outcomes (1)

• Improvement in Anemia

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

  12 months post-infusion

Secondary Outcomes (14)

• Durability Improvement anemia sustained

  24 months post-infusion

• Resolution of anemia

  12 months post-infusion

• Reduction of transfusion requirements

  12 months post-infusion

• Improvements of hemolysis parameters (bilirubin)

  12 months post-infusion

• Improvements of hemolysis parameters (Lactate Dehydrogenase (LDH))

  12 months post-infusion

Study Arms (1)

Participant Group/Arm

EXPERIMENTAL

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

Biological: RP-L301

Interventions

RP-L301 BIOLOGICAL

Autologous genetically modified CD34+ hematopoietic stem cells containing the corrected PKLR (Pyruvate Kinase L/R) gene

Also known as: Intervention/Treatment

Participant Group/Arm

Eligibility Criteria

• Age: 8 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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;
• Subject age: age ≥8 years and ≤55 years
• Prior splenectomy

You may not qualify if:

• 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.
• 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).
• Significant medical conditions including documented HIV (human immunodeficiency virus) infection, active viral hepatitis, poorly controlled hypertension, pulmonary hypertension, cardiac arrhythmia or congestive heart failure; or arteriothromboembolic events (ATEs) (including stroke or myocardial infarction) within the 12 prior months.
• Active hematologic or solid organ malignancy, not including non-melanoma skin cancer or another carcinoma in situ. Patients with previously resected solid organ malignancies or definitively treated hematologic malignancies may be eligible if there has been no evidence of active malignancy during the prior 3 years.
• Uncontrolled seizure disorder.
• Hepatic dysfunction as defined by Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2.5× the upper limit normal (ULN).
• Renal dysfunction defined as serum creatinine \>upper limit normal (ULN). Patients with creatinine above ULN may be eligible pending documentation of a glomerular filtration rate ≥60 mL/min/1.73m2 as calculated by Modification of Diet in Renal Disease equation (Stevens 2006), or 24-hour urine collection.
• Pulmonary dysfunction as defined by either:

Sponsors & Collaborators

• Rocket Pharmaceuticals Inc.: lead

Study Sites (3)

Stanford University

Palo Alto, California, 94305, United States

Location

Hospital Infantil Universitario Niño Jesús

Madrid, 28009, Spain

Location

Hospital Universitario Fundación Jiménez Díaz

Madrid, Spain

Location

MeSH Terms

Conditions

Pyruvate Kinase Deficiency of Red Cells

Interventions

Methods; Therapeutics

Intervention Hierarchy (Ancestors)

Investigative Techniques

Study Officials

• Ami Shah, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

• Julian Sevilla Navarro, MD, PhD

  Hospital Infantil Universitario Niño Jesús

  PRINCIPAL INVESTIGATOR

• José Luis López Lorenzo, MD

  Hospital Universitario Fundación Jiménez Díaz

  PRINCIPAL INVESTIGATOR

• Maria Chitty-Lopez, MD

  Rocket Pharmaceuticals Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2024
• First Posted: May 21, 2024
• Study Start: April 1, 2026
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2029
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (2); US (1)