Gene Therapy for Pyruvate Kinase Deficiency

Not yet recruiting at 2 trial locations

Overseen By Rocket Clinical Trials

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Rocket Pharmaceuticals Inc.

Disqualifiers: HIV, Hepatitis, Hypertension, Malignancy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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 causing severe anemia and fatigue. The goal is to determine if this treatment can effectively improve symptoms by correcting the genetic mutation responsible for PKD. Suitable candidates have a confirmed PKD diagnosis, experience significant anemia, and have undergone spleen removal. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are taking mitapivat, you must stop it at least 90 days before starting the trial.

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

Research has shown that RP-L301, the gene therapy being tested for Pyruvate Kinase Deficiency (PKD), was safe in earlier studies. Importantly, these studies did not link RP-L301 to any serious side effects. This indicates that patients generally tolerated the treatment well. In simpler terms, recipients of this gene therapy did not experience major problems caused by the treatment itself. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Pyruvate Kinase Deficiency?

RP-L301 is unique because it uses gene therapy to address pyruvate kinase deficiency by directly correcting the underlying genetic issue. Unlike current treatments that mainly focus on managing symptoms through blood transfusions or splenectomy, RP-L301 introduces autologous genetically modified CD34+ hematopoietic stem cells with a corrected PKLR gene. This approach potentially offers a long-term solution by targeting the root cause of the disease rather than just alleviating its symptoms, which is why researchers are excited about its potential to change the treatment landscape.

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

Research has shown that RP-L301, a type of gene therapy, holds promise for treating Pyruvate Kinase Deficiency (PKD). In earlier studies, both adults and children with PKD experienced improved hemoglobin levels, crucial for oxygen transport in the blood, and reduced red blood cell breakdown. Remarkably, all patients treated with RP-L301 no longer required regular blood transfusions to manage their condition. These findings suggest that RP-L301 could be an effective treatment option for people with PKD. ^{1 2 3 5 6}

Who Is on the Research Team?

Elieen Nicoletti, MD

Principal Investigator

Rocket Pharmaceuticals Inc.

Ami Shah, MD

Principal Investigator

Stanford University

Julian Sevilla Navarro, MD, PhD

Principal Investigator

Hospital Infantil Universitario Niño Jesús

José Luis López Lorenzo, MD

Principal Investigator

Hospital Universitario Fundación Jiménez Díaz

Are You a Good Fit for This Trial?

This trial is for individuals with Pyruvate Kinase Deficiency, a condition that can lead to congenital hemolytic anemia. Participants should have a confirmed diagnosis and may be experiencing symptoms affecting their quality of life.

Inclusion Criteria

My heart, lungs, kidneys, and liver are functioning well.

I have detailed medical records and blood test results for the last 2 years.

I have had my spleen removed.

Exclusion Criteria

My doctor has not found any reasons I can't undergo leukapheresis.

I have no active cancer except for non-melanoma skin cancer or carcinoma in situ, or any cancer I had has been inactive for 3 years.

I do not have HIV, active hepatitis, uncontrolled high blood pressure, serious heart issues, or recent severe blood clots.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Gene Therapy Infusion

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 and effectiveness after treatment

24 months

Regular visits as per protocol

Long-term Follow-up

Participants are monitored for long-term safety and durability of gene therapy effects

Additional 12 months

What Are the Treatments Tested in This Trial?

Interventions

• RP-L301

Trial Overview The trial is testing RP-L301, a gene therapy aimed at correcting the genetic defect in hematopoietic (blood-forming) cells responsible for PKD. It's an open-label study, meaning everyone knows they're getting the therapy.

How Is the Trial Designed?

Group I: Participant Group/Arm Experimental Treatment 1 Intervention

RP-L301 is a gene therapy product containing autologous genetically modified CD34+ hematopoietic stem cells containing the corrected PKLR (Pyruvate Kinase L/R) 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. 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).

3. ashpublications.org ashpublications.org/blood/article/140/Supplement%201/4902/490593/Lentiviral-mediated-Gene-Therapy-for-Adults-and

Lentiviral-mediated Gene Therapy for Adults and Children ... Results: As of April 2022, 2 adult patients (age 31 and 47 years at enrollment) with severe anemia have received RP-L301. Patient 1 (age 31 ...

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

Gene Therapy for Adult and Pediatric Patients with Severe ... Pyruvate Kinase Deficiency: Results from a Global Study of RP-L301 ... Trial Outcome Index (TOI) Score (Score range: 0–136). Total Score ...

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

Pyruvate kinase activators for treatment of ... Additional long-term benefits include rapid and ongoing reduction in iron overload and potential stabilization of bone health. Clinical trials ...

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

Lentiviral Mediated Gene Therapy for Pyruvate Kinase ... No serious adverse events have been attributed to RP-L301. Updated safety and efficacy data will be presented. Conclusions: Hematopoietic stem ...