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Gene Therapy for Pyruvate Kinase Deficiency (PKD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04105166
Recruitment Status : Recruiting
First Posted : September 26, 2019
Last Update Posted : January 27, 2020
Information provided by (Responsible Party):
Rocket Pharmaceuticals Inc.

Tracking Information
First Submitted Date  ICMJE September 24, 2019
First Posted Date  ICMJE September 26, 2019
Last Update Posted Date January 27, 2020
Estimated Study Start Date  ICMJE January 2020
Estimated Primary Completion Date March 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 25, 2019)
Evaluation of the safety and toxicity of RP-L301: number of participants with treatment-related adverse events [ Time Frame: 2 years ]
The number of participants with treatment-related adverse events as assessed by United States (US) National Cancer Institute (NCI) v.5.0.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 25, 2019)
  • Genetic correction following administration of RP-L301 [ Time Frame: 2 years ]
    Evidence of mult-lineage gene correction in peripheral blood (PB) and bone marrow (BM cells) will be assessed by measuring vector copy number
  • Transfusion independence [ Time Frame: 1 year ]
    Transfusion independence at 12 months defined as need for less than or equal to 1 red blood cell transfusion in the previous 6 months
  • Reduction in transfusion requirements [ Time Frame: 1 year ]
    50% reduction in transfusion requirements at 12 months (assessed in the previous 6 months for the 12-month assessment) relative to the 1-year period prior to enrollment
  • Clinically significant reduction in anemia [ Time Frame: 2 years ]
    Increase in pre-transfusion hemoglobin (Hb) levels of 1.5 g/dL (determined by 2 assessments separated at least three months over the first and second year of follow up) relative to the average of patient's Hb levels before blood transfusions over the year prior to enrollment OR Increase of at least two-fold in the time to pre-transfusion Hb nadir relative to the average transfusion interval over the year prior to enrollment, where pre-transfusion Hb nadir is defined as the average Hb value (during the year prior to enrollment) prior to red blood cell (RBC) transfusions
  • Reduction of hemolysis [ Time Frame: 1 year ]
    Reduction of reticulocytosis, defined as the number of patients with a reduction of 50% from the average of a patient's absolute reticulocyte counts from blood transfusion administrations over the year prior to enrollment at 12 months subsequent to investigational therapy
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Gene Therapy for Pyruvate Kinase Deficiency (PKD)
Official Title  ICMJE Gene Therapy for Pyruvate Kinase Deficiency (PKD): A Phase I Clinical Trial to Evaluate the Safety of the Infusion of Autologous CD34+ Cells Transduced With a Lentiviral Vector Carrying the Codon Optimized Red Cell Pyruvate Kinase (coRPK) Gene in Adult and Pediatric Subjects With PKD
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).
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 PKD gene. The corrected stem cells will be infused intravenously back to the patient with the goal of correcting the hematological manifestations of the disease.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Sequential Assignment
Intervention Model Description:
Initial safety evaluation will occur in an adult cohort (n=2) patients, followed by pediatric patients ages 12-17 (n=2), and pediatric patients ages 8-11 (n=2).
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pyruvate Kinase Deficiency
Intervention  ICMJE Biological: RP-L301
Autologous genetically modified CD34+ hematopoietic stem cells containing the corrected PKD gene
Study Arms  ICMJE Experimental: RP-L301
RP-L301 is a gene therapy product containing autologous genetically modified CD34+ hematopoietic stem cells containing the corrected PKD gene
Intervention: Biological: RP-L301
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 25, 2019)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2023
Estimated Primary Completion Date March 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • PKD diagnosis with a confirmed PKLR mutation.
  • Age ≥18 years old and <45 years for the initial 2 patients enrolled; ≥12-17 years for the next 2 patients; ≥8-11 years for the final 2 patients.
  • History of severe, transfusion-dependent anemia, defined as:

    1. At least 6 red blood cell transfusion episodes over a prior 12-month period, 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
    2. Hb levels <9.5 g/dL in the previous 12 months despite prior splenectomy.
  • Adequate cardiac, pulmonary, renal and hepatic function, as detailed in relevant exclusion criteria.
  • 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.

Exclusion Criteria:

  • 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.
  • Any evidence of severe iron overload that, per Investigator discretion, warrants exclusion.
  • 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
  • Renal dysfunction as defined as serum creatinine > upper limit of normal (ULN). Patients with creatinine above ULN may be eligible pending documentation of a glomerular filtration rate (GFR)≥60 mL/min/1.73m^2 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%.
  • Any medical or other contraindication for both leukapheresis and BM harvest procedure as determined by the treating Investigator.
  • Any medical or psychiatric condition that in the opinion of the Investigator renders the subject unfit for trial participation or at higher than acceptable risk for participation.
  • Poor functional status, evidenced by Karnofsky Index <70 in adults or Lansky <70 in children.
  • Participation in another clinical trial with an investigational drug within 14 days before the informed consent signature. Participation in observational studies is allowed.
  • Pregnant women or women with a positive serum pregnancy test at screening or breast feeding or planning to become pregnant within the next 24 months. Women not willing to use highly effective contraceptive methods during the complete study period.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 8 Years to 44 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Clinical Information 646-901-9276
Listed Location Countries  ICMJE Spain,   United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT04105166
Other Study ID Numbers  ICMJE RP-L301-0119
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Rocket Pharmaceuticals Inc.
Study Sponsor  ICMJE Rocket Pharmaceuticals Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: José Luis López Lorenzo, MD Hospital Universitario Fundación Jiménez Díaz
Principal Investigator: Sandeep Soni, MD Stanford University
PRS Account Rocket Pharmaceuticals Inc.
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP