Gene Therapy for Pyruvate Kinase Deficiency

Recruiting in Palo Alto (>99 mi)

+2 other 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

10 Participants Needed

Trial Summary

What is the purpose of this trial?

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).

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.

What data supports the effectiveness of the treatment RP-L301 for pyruvate kinase deficiency?

Gene therapy, like RP-L301, has shown promise in correcting pyruvate kinase deficiency by introducing healthy genes into cells, as seen in studies where similar approaches led to stable expression of the needed enzyme in cells. This suggests that RP-L301 could potentially help manage the condition by restoring normal enzyme function. ^{1 2 3 4 5}

Is gene therapy for pyruvate kinase deficiency safe for humans?

Preclinical studies show that gene therapy using lentiviral vectors for pyruvate kinase deficiency appears safe, as genetically corrected cells did not cause additional side effects in animal models, and there was no evidence of harmful genetic changes in transplanted cells. ^{1 2 3 6 7}

How is the treatment RP-L301 for pyruvate kinase deficiency different from other treatments?

RP-L301 is a gene therapy that uses lentiviral vectors to introduce a normal pyruvate kinase gene into a patient's stem cells, potentially curing the disorder by correcting the genetic defect. This approach is unique because it targets the root cause of the disease, unlike other treatments that may only manage symptoms. ^{1 2 3 6 8}

Research Team

Julian Sevilla Navarro, MD, PhD

Principal Investigator

Hospital Infantil Universitario Niño Jesús

Elieen Nicoletti, MD

Principal Investigator

Rocket Pharmaceuticals Inc.

Ami Shah, MD

Principal Investigator

Stanford University

José Luis López Lorenzo, MD

Principal Investigator

Hospital Universitario Fundación Jiménez Díaz

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

References

1. China pubmed.ncbi.nlm.nih.gov

[Analysis and prenatal diagnosis of PKLR gene mutations in a family with pyruvate kinase deficiency]. [2016]

2. United States pubmed.ncbi.nlm.nih.gov

AG-348 enhances pyruvate kinase activity in red blood cells from patients with pyruvate kinase deficiency. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

In vitro and in vivo expression of human erythrocyte pyruvate kinase in erythroid cells: a gene therapy approach. [2014]

4. Italy pubmed.ncbi.nlm.nih.gov

AG-348 (Mitapivat), an allosteric activator of red blood cell pyruvate kinase, increases enzymatic activity, protein stability, and ATP levels over a broad range of PKLR genotypes. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Pyruvate kinase activators for treatment of pyruvate kinase deficiency. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Preclinical studies of efficacy thresholds and tolerability of a clinically ready lentiviral vector for pyruvate kinase deficiency treatment. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Safe and Efficient Gene Therapy for Pyruvate Kinase Deficiency. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Retrovirus-mediated gene transfer of human pyruvate kinase (PK) cDNA into murine hematopoietic cells: implications for gene therapy of human PK deficiency. [2021]