Ongoing Clinical Trials for Pyruvate Kinase Deficiency Anaemia
There are currently 4 clinical trials investigating new treatments for pyruvate kinase deficiency anaemia. These studies focus on gene therapy approaches and a medication called mitapivat, testing their safety and effectiveness in both children and adults who experience severe anaemia and may require regular blood transfusions.
Clinical trial locations
- Czechia
- Denmark
- France
- Germany
- Italy
- Netherlands
- Spain
- Study on Gene Therapy for Pyruvate Kinase Deficiency Using Autologous CD34+ Cells in Adults and Children
- Study on Long-Term Safety of Gene Therapy for Pyruvate Kinase Deficiency Using Autologous CD34+ Cells in Adults and Children
- Study on the Effectiveness and Safety of Mitapivat for Children with Pyruvate Kinase Deficiency Receiving Regular Blood Transfusions
- Study on the Effectiveness and Safety of Mitapivat in Children with Pyruvate Kinase Deficiency Not Receiving Regular Blood Transfusions
Study on Gene Therapy for Pyruvate Kinase Deficiency Using Autologous CD34+ Cells in Adults and Children
This trial is investigating a novel gene therapy approach for treating pyruvate kinase deficiency. The treatment involves collecting a patient’s own stem cells, modifying them in a laboratory to carry a corrected version of the gene responsible for producing pyruvate kinase, and then infusing these modified cells back into the patient’s bloodstream.
Who can participate: Adults aged 18 to 50 years and children aged 8 to 17 years with confirmed pyruvate kinase deficiency and documented PKLR gene mutations can join this study. Participants must have a history of severe anaemia, which may be shown by requiring at least 6 red blood cell transfusions in the past year with hemoglobin levels below 9.5 g/dL, or having hemoglobin levels below 8.0 g/dL without transfusions. Adequate heart, lung, kidney, and liver function is required, and detailed medical records covering at least the past two years must be available.
Who cannot participate: The trial excludes individuals with other serious health conditions that could interfere with the study, pregnant or breastfeeding women, those with recent participation in another clinical trial within 30 days, individuals with known allergies to study components, those with drug or alcohol abuse history, individuals with certain types of cancer (except treated skin cancers), those with active infections requiring treatment, individuals who received blood transfusions within the last 3 months, and those with certain heart or lung conditions.
What the trial aims to achieve: The primary goal is to assess the safety of this gene therapy approach and monitor for any adverse reactions. The study will also evaluate how well the treatment helps the body produce healthy red blood cells and whether it can reduce the need for blood transfusions. The trial includes monitoring for successful stem cell engraftment within 42 days after the infusion.
Treatment being tested: The investigational treatment consists of autologous CD34+ cells that have been modified using a lentiviral vector to carry the codon-optimized red cell pyruvate kinase gene. Supporting medications include busulfan for bone marrow preparation, filgrastim to stimulate white blood cell production, and plerixafor to help mobilize stem cells for collection.
Study on Long-Term Safety of Gene Therapy for Pyruvate Kinase Deficiency Using Autologous CD34+ Cells in Adults and Children
This is a long-term follow-up study designed to monitor the safety of gene therapy treatment over an extended period. Participants who received gene therapy in the previous study will be observed to track the persistence of the genetic modification and its ongoing effects.
Who can participate: Only patients who participated in the parent study RP-L301-0119 and received an infusion of their own CD34+ cells modified with the lentiviral vector carrying the coRPK gene are eligible. Participants must be willing and able to follow the study visit schedule and meet all protocol requirements, and they must provide written informed consent to continue in this long-term follow-up phase.
Who cannot participate: The study excludes patients with serious medical conditions that might affect participation, those with recent infections, pregnant or breastfeeding women, individuals with a history of cancer (excluding certain skin cancers), those who received other investigational treatments within a specified period, patients with known allergies to study components, individuals with drug or alcohol abuse history, those with mental health conditions affecting study participation, and anyone unable to comply with study requirements.
What the trial aims to achieve: The study focuses on evaluating the long-term safety of the gene therapy, monitoring the persistence of the gene modification in blood cells over time, and assessing whether the treatment continues to reduce anaemia symptoms and transfusion requirements. The trial will track overall health, any adverse events including iron overload complications, and the development of any new health conditions. This follow-up will continue until July 2038.
Treatment being tested: Participants continue to be monitored following their previous infusion of autologous CD34+ cells transduced with a lentiviral vector carrying the codon optimized red cell pyruvate kinase gene. This gene therapy product is also known as Merilen or RP-L301.
Study on the Effectiveness and Safety of Mitapivat for Children with Pyruvate Kinase Deficiency Receiving Regular Blood Transfusions
This trial evaluates mitapivat, an oral medication, in children with pyruvate kinase deficiency who require regular blood transfusions. The study uses a double-blind design where participants are randomly assigned to receive either mitapivat or placebo, followed by an optional five-year extension period where all participants can receive the active treatment.
Who can participate: Children aged 1 to less than 18 years with confirmed pyruvate kinase deficiency (verified by at least two PKLR gene mutations, including at least one missense mutation) can participate. Participants must have received between 6 and 26 blood transfusions in the year before joining and must have complete transfusion records including dates, volumes, and blood test results. Children between 12 and 24 months must weigh at least 7 kilograms. Participants must be taking folic acid supplements for at least 21 days before starting the study medication and continue throughout the trial. Female participants who have started menstruating must use appropriate contraception.
Who cannot participate: No specific exclusion criteria were detailed in the source data for this trial.
What the trial aims to achieve: The primary goal is to determine whether mitapivat can reduce the need for blood transfusions in children with pyruvate kinase deficiency. The study will measure whether there is at least a 33% reduction in transfusion volume from Week 9 through Week 32 compared to the participant’s historical transfusion needs. The five-year extension period allows for assessment of the medication’s long-term safety and effectiveness.
Treatment being tested: Mitapivat (also known as AG-348) is an oral medication that comes in tablet or granule form. It works by activating the pyruvate kinase enzyme, which plays a crucial role in energy production in red blood cells. This Phase 3 trial aims to determine if mitapivat is safe and effective for reducing transfusion requirements in pediatric patients.
Study on the Effectiveness and Safety of Mitapivat in Children with Pyruvate Kinase Deficiency Not Receiving Regular Blood Transfusions
This trial studies mitapivat in children with pyruvate kinase deficiency who do not receive regular transfusions. The study design includes a double-blind period followed by an optional five-year open-label extension where all participants can receive the active medication.
Who can participate: Children aged 1 to less than 18 years with confirmed pyruvate kinase deficiency (at least two PKLR gene mutations with at least one missense mutation) can join. Participants must not have received more than 5 red blood cell transfusions in the year before joining and no transfusions in the 12 weeks before starting the study medication. Hemoglobin levels should be 10 g/dL or lower for those aged 12 to less than 18 years, or 9 g/dL or lower for those aged 1 to less than 12 years, based on at least two tests taken at least 7 days apart. Children between 12 and 24 months must weigh at least 7 kilograms. Participants must be taking folic acid supplements for at least 21 days before starting and continue throughout the study. Female participants who have started menstruating must use appropriate contraception.
Who cannot participate: The trial excludes patients regularly receiving blood transfusions, those with other serious health conditions that might interfere with the study, patients taking medications that could affect study results, those who recently had or are planning surgery, pregnant or breastfeeding women, individuals who participated in another recent clinical trial, those with allergies to the study medication or similar drugs, and patients unable to follow study procedures.
What the trial aims to achieve: The primary objective is to determine whether mitapivat can increase hemoglobin levels in children with pyruvate kinase deficiency. The study will measure changes in hemoglobin levels through regular blood tests at specific intervals, particularly at weeks 12, 16, and 20. The five-year extension period provides an opportunity to monitor long-term safety and continued effectiveness of the treatment.
Treatment being tested: Mitapivat sulfate is administered orally in capsule form. This medication works as a pyruvate kinase activator, helping to improve the energy production process in red blood cells and increase hemoglobin levels. The trial is in Phase 3, representing an advanced stage of clinical research before potential approval for widespread use.
Summary
The four ongoing clinical trials for pyruvate kinase deficiency anaemia represent two distinct therapeutic approaches: gene therapy and enzyme activation. The gene therapy studies, conducted in Spain, focus on adults and children with severe transfusion-dependent disease, offering a potentially curative approach by correcting the genetic defect. These trials include both an initial safety study and a long-term follow-up extending until 2038, demonstrating a commitment to understanding the durability and safety of this innovative treatment.
The mitapivat trials are being conducted across multiple European countries including Denmark, Czechia, Netherlands, Spain, France, Italy, and Germany, reflecting a broader international effort to evaluate this medication. These studies are specifically designed for pediatric patients, with one trial targeting children who require regular transfusions and another for those who do not. Both mitapivat trials include lengthy five-year extension periods, allowing researchers to gather comprehensive data on long-term outcomes.
Spain appears to be the most active location for research into this condition, hosting trials for both gene therapy and mitapivat approaches. The Netherlands and Spain are the only countries participating in multiple mitapivat studies, suggesting these nations have particular expertise or patient populations suitable for this research. The diverse geographic distribution of the mitapivat trials may help ensure the findings are applicable to different populations across Europe.
