Gene Therapy for Pyruvate Kinase Deficiency (PKD)

NCT04105166 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: RP-L301-0119
• Study Type: interventional
• Target: 4
• Locations: 2 countries
• Sites: 3

Brief Summary

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

Conditions

Pyruvate Kinase Deficiency

Keywords

hemolytic anemia; anemia; gene therapy

Outcome Measures

Primary Outcomes (1)

• Evaluation of the safety and toxicity of RP-L301: number of participants with treatment-related adverse events

  The number of participants with treatment-related adverse events as assessed by United States (US) National Cancer Institute (NCI) v.5.0.

  2 years

Secondary Outcomes (5)

• Genetic correction following administration of RP-L301

  2 years

• Transfusion independence

  1 year

• Reduction in transfusion requirements

  1 year

• Clinically significant reduction in anemia

  2 years

• Reduction of hemolysis

  1 year

Study Arms (1)

RP-L301

EXPERIMENTAL

RP-L301 is a gene therapy product containing autologous genetically modified CD34+ hematopoietic stem cells containing the corrected PKD gene

Biological: RP-L301

Interventions

RP-L301 BIOLOGICAL

Autologous genetically modified CD34+ hematopoietic stem cells containing the corrected PKD gene

RP-L301

Eligibility Criteria

• Age: 8 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• PKD diagnosis with a confirmed PKLR mutation.
• Adult Cohort ≥18 years old and \<50 years for the initial 2 patients enrolled; Pediatric Cohort ≥8-17 years for the next 2-3 patients.
• History of severe, transfusion-dependent anemia, defined as:
• At least 6 red blood cell transfusion episodes over a prior 12-month period and Hb levels \<9.5 g/dL in the previous 12 months despite splenectomy OR
• At least 3 red blood cell transfusion episodes per year over 2 prior years (in the absence of precipitating events such as infection or surgery) and Hb levels \<9.5 g/dL in the previous 12 months despite prior splenectomy.
• Hb levels \<8.0 g/dL despite prior splenectomy in the absence of transfusions (documented during 2 or more assessments during the prior 1-2 years) regardless of transfusion requirements.

You may not qualify if:

• Availability of detailed medical records, including transfusion requirements, for at least 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.
• Negative serum pregnancy test for female patients of childbearing potential.
• Presence of other known causes of hemolysis (in addition to 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 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.
• Significant medical conditions including documented HIV infection, active viral hepatitis, poorly-controlled hypertension, pulmonary hypertension cardiac arrhythmia or congestive heart failure; pulmonary hypertension or ATEs (including stroke or myocardial infarction) within the 6 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.
• Cardiac T2\*\<10 ms by magnetic resonance imaging (MRI) or left ventricular ejection fraction (LVEF) \<45% by echocardiogram or multiple gated acquisition (MUGA) scanning.
• Hepatic dysfunction as defined by: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2.5× the upper limit of normal.(ULN).
• Renal dysfunction as defined as serum creatinine \> ULN. Patients with creatinine above ULN may be eligible pending documentation of a GFR ≥60 mL/min/1.73m2 as calculated by the Modification of Diet in Renal Disease equation (Stevens 2006), the revised Schwartz formula (for patients under 18 years old) (Schwartz 2009), or 24-hour urine collection.
• Pulmonary dysfunction as defined by either:
• Need for supplemental oxygen during the prior 2 weeks (in absence of acute infection) or
• Oxygen saturation (by pulse oximetry) \<90%.

Sponsors & Collaborators

• Rocket Pharmaceuticals Inc.: lead

Study Sites (3)

Stanford University

Stanford, California, 94304, 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; Anemia, Hemolytic; Anemia

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• José Luis López Lorenzo, MD

  Hospital Universitario Fundación Jiménez Díaz

  PRINCIPAL INVESTIGATOR

• Ami Shah, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

• Julián Sevilla Navarro, MD, PhD

  Hospital Universitario Fundación Jiménez Díaz

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Initial safety evaluation will occur in an adult cohort (n=2) patients, followed by pediatric patients ages 8-17 (n=2-3).

Study Record Dates

• First Submitted: September 24, 2019
• First Posted: September 26, 2019
• Study Start: July 6, 2020
• Primary Completion: June 9, 2025
• Study Completion: June 9, 2025
• Last Updated: September 5, 2025

Record last verified: 2025-08

Locations

ES (2); US (1)