Pyruvate Kinase DeficiencyPhase 1NCT04105166
Gene Therapy for Pyruvate Kinase Deficiency (PKD)
A Phase 1 study testing RP-L301 in people with Pyruvate Kinase Deficiency, run by Rocket Pharmaceuticals Inc. at 3 sites in 2 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 8 to 50 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
- 4 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 6 Jul 2020to 9 Jun 2025
- Phase
- Phase 1
- 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 50 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
- OR
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- 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.
- 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.
Who cannot join
- 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.
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- 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%.
- 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.
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
About this study
Official title: 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
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).
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 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.
- Conditions
- Pyruvate Kinase Deficiency
- Being tested
- RP-L301
- Keywords
- hemolytic anemia, anemia, gene therapy
- Medical subject headings
- Pyruvate Kinase Deficiency of Red Cells, Anemia, Hemolytic, Anemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RP-L301Biological
Autologous genetically modified CD34+ hematopoietic stem cells containing the corrected PKD gene
| Study group | Role | What they receive |
|---|---|---|
| RP-L301 | Experimental | RP-L301 is a gene therapy product containing autologous genetically modified CD34+ hematopoietic stem cells containing the corrected PKD gene Receives: Biological: RP-L301 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 years
Secondary outcomes (5)
Genetic correction following administration of RP-L301
Evidence of multi-lineage gene correction in peripheral blood (PB) and bone marrow (BM cells) will be assessed by measuring vector copy number
Measured: 2 years
Transfusion independence
Transfusion independence (when relevant) at 12 months defined as need for less than or equal to 1 red blood cell transfusion in the previous 6 months
Measured: 1 year
Reduction in transfusion requirements
50% reduction in transfusion requirements (when relevant) at 12 months (assessed in the previous 6 months for the 12-month assessment) relative to the 1-year period prior to enrollment
Measured: 1 year
Clinically significant reduction in anemia
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
Measured: 2 years
Reduction of hemolysis
Reduction of reticulocytosis, defined as the number of patients with a reduction of 50% from the average of a patient's absolute reticulocyte counts (obtained prior to therapeutic blood transfusions) over the year prior to enrollment at 12 months subsequent to investigational therapy
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2019
- Study start6 Jul 2020
- Primary completion9 Jun 2025
- Study completion9 Jun 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pyruvate Kinase DeficiencyStudies of the same condition, open and under way.
- More trials run by Rocket Pharmaceuticals Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- Initial safety evaluation will occur in an adult cohort (n=2) patients, followed by pediatric patients ages 8-17 (n=2-3).
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rocket Pharmaceuticals Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- José Luis López Lorenzo, MD, Principal investigator, Hospital Universitario Fundación Jiménez DíazAmi Shah, MD, Principal investigator, Stanford UniversityJulián Sevilla Navarro, MD, PhD, Principal investigator, Hospital Universitario Fundación Jiménez Díaz
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04105166
- Sponsor's protocol ID
- RP-L301-0119
- Status last verified
- Aug 2025
- First submitted
- 24 Sep 2019
- Last updated
- 5 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04105166
- Acronym / sponsor ID
- RP-L301-0119
- Conditions
- Pyruvate Kinase Deficiency
- Keywords
- hemolytic anemia, anemia, gene therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Rocket Pharmaceuticals Inc.Industry (pharma, biotech, devices)
- Study start
- 6 Jul 2020 (actual)
- Primary completion
- 9 Jun 2025 (actual)
- Study completion
- 9 Jun 2025 (actual)
- First posted
- 26 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Initial safety evaluation will occur in an adult cohort (n=2) patients, followed by pediatric patients ages 8-17 (n=2-3).
| Arm | Type | Receives |
|---|---|---|
| RP-L301 | Experimental | Biological: RP-L301RP-L301 is a gene therapy product containing autologous genetically modified CD34+ hematopoietic stem cells containing the corrected PKD gene |
Who may qualify
- Ages
- 8 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (11 listed)
- 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:
- OR
- Adequate cardiac, pulmonary, renal and hepatic function, as detailed in relevant exclusion criteria.
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RP-L301Autologous genetically modified CD34+ hematopoietic stem cells containing the corrected PKD gene | Biological | RP-L301 |
Primary outcome
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.
5 secondary outcomes
Genetic correction following administration of RP-L301
Time frame: 2 years
Transfusion independence
Time frame: 1 year
Reduction in transfusion requirements
Time frame: 1 year
Clinically significant reduction in anemia
Time frame: 2 years
Reduction of hemolysis
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2025.
- Individual participant dataSharing planned: Undecided
Related trials for Pyruvate Kinase Deficiency
Active, not recruitingPhase 3
A Study to Evaluate the Efficacy and Safety of Mitapivat in Pediatric Participants With Pyruvate Kinase Deficiency (PKD) Who Are Regularly Transfused, Followed by a 5-Year Extension Period
Pediatric Pyruvate Kinase Deficiency, Pediatric Hemolytic Anemia
Active, not recruitingObservational study
Pyruvate Kinase Deficiency Global Longitudinal Registry
Pyruvate Kinase Deficiency
Active, not recruitingPhase 3
A Study to Evaluate the Efficacy and Safety of Mitapivat in Pediatric Participants With Pyruvate Kinase Deficiency (PKD) Who Are Not Regularly Transfused, Followed by a 5-Year Extension Period
Pediatric Pyruvate Kinase Deficiency, Pediatric Hemolytic Anemia
Enrolling by invitationPhase 4
A Study to Provide Access to Mitapivat for Participants Who Previously Participated in an Agios-Sponsored Mitapivat Study
Pyruvate Kinase Deficiency, Anemia, Hemolytic
Not yet recruitingPhase 1
High-Dose Vitamin C in G6PDA and Pyruvate Kinase Deficiency: A Safety Study
Pyruvate Kinase Deficiency, Glucose 6 Phosphate Dehydrogenase Deficiency
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
José Luis López Lorenzo, MD principal investigator
Hospital Universitario Fundación Jiménez Díaz
Ami Shah, MD principal investigator
Stanford University
Julián Sevilla Navarro, MD, PhD principal investigator
Hospital Universitario Fundación Jiménez Díaz
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 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 11 inclusion and 18 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: finished, as of the sponsor's last update on 5 Sep 2025. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Evaluation of the safety and toxicity of RP-L301: number of participants with treatment-related adverse events (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Sep 2025.