Gene Therapy for Pyruvate Kinase Deficiency

No longer recruiting at 2 trial locations

Overseen By PKD Clinical Trial

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Rocket Pharmaceuticals Inc.

Disqualifiers: HIV, Hepatitis, Hypertension, Seizure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new gene therapy called RP-L301 for individuals with pyruvate kinase deficiency (PKD), a condition that can cause severe anemia and often necessitates frequent blood transfusions. The trial's primary goal is to determine the safety of this gene therapy for patients. It seeks participants with PKD who have a specific genetic mutation and have experienced severe anemia requiring multiple blood transfusions, even after spleen removal. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Previous studies have shown that RP-L301 has been well-tolerated by patients with Pyruvate Kinase Deficiency (PKD). Research shows no serious side effects linked to this gene therapy. This treatment uses a patient's own modified cells to correct the PKD gene. Safety data indicates that patients did not experience major side effects. This suggests RP-L301 might be safe for humans, but further testing is needed to confirm this. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for pyruvate kinase deficiency, which often involve blood transfusions or splenectomy, RP-L301 offers a novel approach by using gene therapy. This treatment involves genetically modifying a patient's own stem cells to correct the faulty PKD gene, potentially addressing the root cause of the disorder rather than just managing symptoms. Researchers are excited because RP-L301 could provide a long-lasting solution, significantly improving the quality of life for patients by reducing or eliminating the need for regular transfusions.

What evidence suggests that this gene therapy might be an effective treatment for Pyruvate Kinase Deficiency?

Research has shown that RP-L301, the investigational gene therapy studied in this trial for Pyruvate Kinase Deficiency (PKD), yields promising results. Studies have found that it improves hemoglobin levels and reduces the breakdown of red blood cells in both adults and children with PKD. Importantly, patients treated with RP-L301 no longer require blood transfusions. This therapy repairs the faulty PKD gene in a patient's stem cells, enabling the body to produce healthy red blood cells. Early findings also suggest that this treatment enhances patients' quality of life. ^{1 2 3 4 6}

Who Is on the Research Team?

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

Are You a Good Fit for This Trial?

This trial is for people with Pyruvate Kinase Deficiency (PKD) who are between 8-50 years old, depending on enrollment phase. They must have a history of multiple blood transfusions and low hemoglobin levels despite treatment like splenectomy. Participants need to be in good health regarding heart, lung, kidney, and liver function.

Inclusion Criteria

I have been diagnosed with PKD and have a confirmed PKLR mutation.

Willing and able to read and understand the patient information sheet and provide consent (or informed assent for minors)

Negative serum pregnancy test for female patients of childbearing potential

Exclusion Criteria

I have had a recent blood clot in my veins or arteries.

I have a high level of iron in my body.

My lung function is not normal.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Gene Therapy Treatment

Autologous hematopoietic stem cells are transduced with a lentiviral vector and infused back into the patient

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety, toxicity, and genetic correction over a period of time

2 years

Regular visits (frequency not specified)

What Are the Treatments Tested in This Trial?

Interventions

• RP-L301

Trial Overview The trial is testing RP-L301, a gene therapy aimed at treating PKD. It's an early-phase study focusing on the safety of this new treatment where all participants receive the intervention without any comparison group.

How Is the Trial Designed?

Group I: RP-L301 Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Rocket Pharmaceuticals Inc.

Lead Sponsor

Trials

17

Recruited

430+

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/3583.1/529064/RP-L301-a-Lentiviral-Mediated-Gene-Therapy-for

RP-L301, a Lentiviral-Mediated Gene Therapy for Pyruvate ... Hb improvement and hemolysis reduction were observed in both adult and pediatric patients with PKD; all patients remain transfusion independent ...

2. rocketpharma.com rocketpharma.com/wp-content/uploads/JulianSevilla_0800_May-8_Ballroom1_GenetherapyPKD.pdf

Gene Therapy for Adult and Pediatric Patients with Severe ... Gene Therapy for Adult and Pediatric Patients with Severe. Pyruvate Kinase Deficiency: Results from a Global Study of RP-L301. 27th Annual ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04105166

Gene Therapy for Pyruvate Kinase Deficiency (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).

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10985542/

Pyruvate kinase activators for treatment of ... PK activation and gene therapy have the potential to change the natural history of PK deficiency by improving clinical manifestations and ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0006497121025556

Lentiviral Mediated Gene Therapy for Pyruvate Kinase ... Both report improved quality of life. PB mononuclear cell VCNs for both patients were >2.0 at last evaluated timepoint (6- and 3-months post- ...

6. rocketpharma.com rocketpharma.com/clinical-trials/pyruvate-kinase-deficiency/

Pyruvate Kinase Deficiency (PKD) Rocket is the first company demonstrating safety and efficacy data in clinical studies for gene therapy targeting the heart. ... RP-L301 is an investigational ...