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Pyruvate Kinase DeficiencyPhase 2NCT06422351

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

A Phase 2 study testing RP-L301 in people with Pyruvate Kinase Deficiency, run by Rocket Pharmaceuticals Inc. at 3 sites in 2 countries.

Suspended

Paused. Enrolment is on hold for now and may resume.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 8 to 55 years
Conditions the study is for
Pyruvate Kinase Deficiency
What is being tested?
RP-L301
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
3 sitesin 2 countries
Study dates
Apr 2026to Jan 2029
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 8 to 55 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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
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  • 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
  • Adequate cardiac, pulmonary, renal and hepatic function, as detailed in relevant exclusion criteria
  • 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.

Who cannot join

  • 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).
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  • Any evidence of severe iron overload beyond parameters stipulated in exclusion criteria 3 and 4 that, per Investigator discretion, warrants exclusion.
  • 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:
  • Need for supplemental oxygen during the prior 2 weeks (in absence of acute infection) OR
  • Clinically significant pulmonary disease that may impair ability to tolerate study procedures and treatments.
  • Any medical or other contraindication for leukapheresis as determined by the treating Investigator.
  • Any medical or psychiatric condition that in the opinion of the Investigator renders the patient unfit for trial participation or at higher than acceptable risk for participation.
  • Poor functional status evidenced by Karnofsky Index <70 in subjects ≥16 years old and Lansky Play-Performance Scale <70 in subjects <16 years old.
  • Participation in another clinical trial with an investigational drug within 14 days before the informed consent signature. Participation in observational studies is allowed. Patients who are receiving mitapivat in non-investigational settings are eligible provided they discontinue mitapivat at least 90 days prior to the start of mobilization.
  • 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. Female participants or female partners of male participants not willing to use highly effective contraceptive methods during the complete study period.
  • Previous allogeneic or other hematopoietic stem cell transplant.

Trial locations and contacts

3 sites in 2 countries.

3 sites in 2 countries

Spain2 sites

  • Hospital Infantil Universitario Niño Jesús

    Madrid, 28009

  • Hospital Universitario Fundación Jiménez Díaz

    Madrid

Other trials in Spain

United States1 site

  • Stanford University

    Palo Alto, California, 94305

Other trials in United States

About this study

Official title: 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

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).

Read the 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.

Being tested
RP-L301
Medical subject headings
Pyruvate Kinase Deficiency of Red Cells

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RP-L301Biological

    Also called Intervention/Treatment

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

Study groups in NCT06422351
Study groupRoleWhat they receive
Participant Group/ArmExperimentalRP-L301 is a gene therapy product containing autologous genetically modified CD34+ hematopoietic stem cells containing the corrected PKLR (Pyruvate Kinase L/R) gene
Receives: Biological: RP-L301

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Improvement in Anemia

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

    Measured: 12 months post-infusion

Secondary outcomes (14)

  1. Durability Improvement anemia sustained

    Time to Hemoglobin level increase of ≥1.5g/dL post-infusion, compared to baseline.

    Measured: 24 months post-infusion

  2. Resolution of anemia

    Hemoglobin level within normal range (≥ lower limit of normal) at 12 months post-infusion.

    Measured: 12 months post-infusion

  3. Reduction of transfusion requirements

    • 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.

    Measured: 12 months post-infusion

  4. Improvements of hemolysis parameters (bilirubin)

    Improvements in bilirubin, each evaluated at 12 months post-infusion, compared to baseline.

    Measured: 12 months post-infusion

  5. Improvements of hemolysis parameters (Lactate Dehydrogenase (LDH))

    Improvements in Lactate Dehydrogenase (LDH), each evaluated at 12 months post-infusion, compared to baseline.

    Measured: 12 months post-infusion

  6. Improvements of hemolysis parameters (erythropoietin)

    Improvements in erythropoietin, each evaluated at 12 months post-infusion, compared to baseline.

    Measured: 12 months post-infusion

  7. Improvements of hemolysis parameters (reticulocyte)

    Improvements in reticulocyte, each evaluated at 12 months post-infusion, compared to baseline.

    Measured: 12 months post-infusion

  8. Peripheral blood genetic correction

    Genetic correction demonstrated by vector copy number (VCN) of 0.1 in Peripheral Blood mononuclear cells, evaluated at 12 months post-infusion.

    Measured: 12 months post-infusion

  9. Improvement in fatigue

    Improvement in fatigue as compared with baseline, as assessed by:

    • Age ≥18: FACIT Fatigue; or,
    • Age <18: PROMIS Fatigue Short Form 10a

    Measured: 12 months post-infusion

  10. Improvement in dyspnea

    Improvement in Pyruvate Kinase Deficiency symptoms, compared with baseline, as assessed by:

    • PROMIS Dyspnea Severity SF10; or,
    • Dyspnea severity

    Measured: 12 months post-infusion

  11. Improvement in jaundice

    Improvement in Pyruvate Kinase Deficiency symptoms, compared with baseline, as assessed by:

    • jaundice severity evaluated at 12 months post-infusion; or,
    • and jaundice severity

    Measured: 12 months post-infusion

  12. Safety and tolerability of RP-L301

    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).

    Measured: 24 months post-infusion

  13. Evaluate durable resolution of anemia

    Hemoglobin (Hb) level within normal range (≥ lower limit of normal).

    Measured: 24 months post-infusion

  14. Evaluate durable resolution of transfusion requirements (where relevant).

    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.

    Measured: 24 months post-infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 May 2024
  2. Study startApr 2026 (estimated)
  3. Primary completionJan 2029 (estimated)
  4. Study completionJan 2029 (estimated)

Why it stopped: Initiation of study has been paused, but may re-start in the future.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
10 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06422351
Sponsor's protocol ID
RP-L301-0124
Status last verified
Apr 2026
First submitted
15 May 2024
Last updated
16 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing RP-L301 in people with Pyruvate Kinase Deficiency, run by Rocket Pharmaceuticals Inc. at 3 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: paused, as of the sponsor's last update on 16 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Spain, United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Improvement in Anemia (time frame: 12 months post-infusion). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06422351.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Apr 2026.

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