What side effects are associated with this type of intervention?

Common treatments for Pyruvate Kinase Deficiency (PKD) include blood transfusions, splenectomy, and emerging treatments like pyruvate kinase activators such as Mitapivat. Known side effects of blood transfusions include iron overload and allergic reactions. Splenectomy can increase the risk of infections. For pyruvate kinase activators like Mitapivat, side effects observed in clinical trials may include headache, insomnia, and gastrointestinal issues such as nausea and diarrhea. It is important to discuss these potential side effects with a healthcare provider to manage and mitigate risks effectively.

What prior FDA approvals exist?

As of now, there are limited FDA-approved treatments specifically for Pyruvate Kinase Deficiency (PKD). Mitapivat, a pyruvate kinase activator, is currently being studied for its efficacy and safety in treating PKD, particularly in pediatric patients who are regularly transfused. This represents a novel approach as traditional management of PKD has primarily involved supportive care such as blood transfusions and splenectomy. The development of Mitapivat and similar drugs marks a significant advancement in targeting the underlying metabolic defect in PKD.

What other types of research exist?

Promising novel alternatives to Mitapivat for PKD patients include glycolytic enzyme inhibitors such as Oxamate, which has shown efficacy in inhibiting glycolysis and cancer cell growth. Additionally, combination therapies involving glycolysis inhibitors and other agents, like mTOR inhibitors, may offer synergistic benefits. These approaches warrant further investigation for their potential application in PKD treatment.

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Allosteric Activator

Mitapivat for Pyruvate Kinase Deficiency (ACTIVATE-KidsT Trial)

Q: What is the mechanism of action of this treatment?

The most common treatment for Pyruvate Kinase Deficiency (PKD) involves the activation of the pyruvate kinase enzyme, which is crucial for the glycolytic pathway in red blood cells. Mitapivat, a pyruvate kinase activator, works by increasing the activity of the defective enzyme, thereby improving ATP production and reducing the accumulation of upstream glycolytic intermediates. This is significant for PKD patients as it helps to alleviate hemolytic anemia, decrease the need for regular blood transfusions, and improve overall quality of life by stabilizing red blood cell function and lifespan.

Phase 3

Waitlist Available

Research Sponsored by Agios Pharmaceuticals, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Clinical laboratory confirmation of pyruvate kinase deficiency (PKD), defined as documented presence of at least 2 mutant alleles in the pyruvate kinase L/R (PKLR) gene, of which at least 1 is a missense mutation, as determined per the genotyping performed by the study central genotyping laboratory

Aged 1 to <18 years. Participants between 12 and 24 months of age must weigh a minimum of 7 kilograms (kg)

Must not have

History of active and/or uncontrolled cardiac or pulmonary disease or clinically relevant QT prolongation within 6 months before providing informed consent/assent

Homozygous for the R479H mutation or have 2 nonmissense mutations, without the presence of another missense mutation, in the PKLR gene as determined per the genotyping performed by the study central genotyping laboratory

Timeline

Screening 3 weeks

Treatment Varies

Follow Up week 9 to week 32

Awards & highlights

Pivotal Trial

Summary

This trial is testing mitapivat, a medication that may help children with a blood disorder called pyruvate kinase deficiency. These children often need frequent blood transfusions. Mitapivat aims to improve the function of their red blood cells, potentially reducing the need for these transfusions.

Who is the study for?

This trial is for kids with Pyruvate Kinase Deficiency who need regular blood transfusions. They must be between 1-18 years old, not pregnant or breastfeeding, and without serious heart, liver, or kidney issues. Participants should have a history of receiving multiple transfusions and agree to use contraception if applicable.

What is being tested?

The study tests Mitapivat against a placebo in children with PKD who get regular transfusions. It's randomized (2:1 ratio), considering age and splenectomy status. After an initial period of dose adjustments followed by a fixed-dose period, participants may continue treatment for up to five years.

What are the potential side effects?

Possible side effects of Mitapivat include but are not limited to allergic reactions to the drug's ingredients, potential liver enzyme elevations due to interaction with other medications, and any general risks associated with taking new medication under clinical trial conditions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have a confirmed genetic condition called pyruvate kinase deficiency.

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I am between 1 and 18 years old. If I am 1-2 years old, I weigh at least 7 kg.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I haven't had serious heart or lung problems or abnormal heart rhythms in the last 6 months.

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My genetic test shows I have specific mutations in the PKLR gene.

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I do not have severe liver issues, uncontrolled infections, recent major surgery, or HIV/Hepatitis B/C.

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I have had cancer before.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ week 9 to week 32

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~week 9 to week 32

This trial's timeline: 3 weeks for screening, Varies for treatment, and week 9 to week 32 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Percentage of Participants Achieving Transfusion Reduction Response (TRR)

Secondary study objectives

Change From Baseline in Sexual Maturity Rating with Tanner Stage

Change from Baseline in Pediatric Quality of Life (PedsQL) Multidimensional Fatigue Scale

Change from Baseline in PedsQL Generic Core Scale (GCS)

+4 more

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

3Treatment groups

Experimental Treatment

Placebo Group

Group I: Mitapivat (OLE period)Experimental Treatment2 Interventions

Participants who have completed the double-blind period will be eligible to receive mitapivat for up to 5 years in the OLE period. Participants entering the OLE period will first receive blinded mitapivat and placebo for 8 weeks to maintain the double-blind treatment assignment before being transitioned to only receive active, open-label drug (mitapivat).

Group II: MitapivatExperimental Treatment1 Intervention

Double-Blind Period: Participants will receive mitapivat orally, at doses based on age and weight, for 8 weeks in the dose titration period and for 24 weeks in the fixed-dose period.

Group III: PlaceboPlacebo Group1 Intervention

Double-Blind Period: Participants will receive mitapivat-matching placebo orally for 8 weeks in the dose titration period and for 24 weeks in the fixed-dose period.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Mitapivat

2023

Completed Phase 1

~20

0 / 6Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatment for Pyruvate Kinase Deficiency (PKD) involves the activation of the pyruvate kinase enzyme, which is crucial for the glycolytic pathway in red blood cells. Mitapivat, a pyruvate kinase activator, works by increasing the activity of the defective enzyme, thereby improving ATP production and reducing the accumulation of upstream glycolytic intermediates. This is significant for PKD patients as it helps to alleviate hemolytic anemia, decrease the need for regular blood transfusions, and improve overall quality of life by stabilizing red blood cell function and lifespan.