What side effects are associated with this type of intervention?

Mitapivat, an oral pyruvate kinase activator, has been studied for its efficacy and safety in treating PKD. Common side effects reported include initial insomnia, dizziness, and headache. In a study involving adults with thalassemia, treatment-emergent adverse events were frequent, though most were mild to moderate in severity. Serious adverse events were rare but included grade 3 renal impairment. Other treatments for PKD, such as hydroxyurea, can cause cytopenias, mucocutaneous ulcers, diarrhea, peripheral neuropathy, and potential teratogenicity. Overall, while mitapivat shows promise, monitoring for these side effects is essential.

What prior FDA approvals exist?

As of now, there are limited FDA-approved treatments specifically for Pyruvate Kinase Deficiency (PKD). Mitapivat, an oral drug that activates pyruvate kinase to improve red blood cell metabolism, is currently being studied for its efficacy and safety in pediatric patients with PKD. This trial represents a significant step forward, as traditional management of PKD has primarily involved supportive care measures such as blood transfusions and splenectomy rather than targeted pharmacological treatments.

What other types of research exist?

The provided context does not mention specific novel alternatives to Mitapivat for treating Pyruvate Kinase Deficiency. Patients should consult with their healthcare provider to explore the latest research and treatment options available in 2024.

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Activator

Mitapivat for Pyruvate Kinase Deficiency (ACTIVATE-Kids Trial)

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

The most common treatments for Pyruvate Kinase Deficiency (PKD) focus on improving red blood cell metabolism. Mitapivat, an oral medication, activates pyruvate kinase, an enzyme essential for glycolysis in red blood cells. By increasing pyruvate kinase activity, mitapivat enhances ATP production, which is crucial for red blood cell function and survival. This is particularly important for PKD patients, who suffer from hemolytic anemia due to ATP deficiency in their red blood cells. Other treatments, such as blood transfusions and splenectomy, provide supportive care but do not address the underlying metabolic defect.

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

Hemoglobin concentration ≤10 grams per deciliter (g/dL) for participants 12 to <18 years of age or ≤9 g/dL for participants 1 to <12 years of age during the screening period. Hb concentration must be based on an average of at least 2 Hb concentration measurements (separated by ≥7 days) collected during the screening period

Must not have

History of malignancy

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

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline up to week 286

Awards & highlights

Pivotal Trial

Summary

This trial is testing an oral medication called mitapivat in children with a genetic condition affecting their red blood cells. The goal is to see if mitapivat can help their red blood cells work better and improve their health without needing frequent blood transfusions.

Who is the study for?

This trial is for children and teenagers aged 1 to less than 18 with Pyruvate Kinase Deficiency (PKD) who aren't getting regular blood transfusions. They must have a certain level of hemoglobin, not had many blood transfusions recently, be on folic acid supplements, and agree to use contraception if applicable. Those with severe liver or heart issues, recent major surgery like splenectomy, or specific genetic mutations are excluded.

What is being tested?

The study tests the oral drug Mitapivat against a placebo in young patients with PKD. Participants will randomly receive either the drug or placebo in a ratio of 2:1 and will be grouped by age for dosing. The trial includes an initial dose adjustment phase followed by a fixed-dose period before moving into a long-term extension phase lasting up to five years.

What are the potential side effects?

While specific side effects for Mitapivat in this pediatric population are not detailed here, common side effects may include digestive discomforts such as nausea or diarrhea, headaches, tiredness, potential liver enzyme changes which would be monitored closely during the trial.

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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My average hemoglobin level is low according to my age group's requirement.

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I have had 5 or fewer blood transfusions in the last year and none in the past 3 months.

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

Exclusion Criteria

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

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I have had cancer before.

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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.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline up to week 286

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline up to week 286

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline up to week 286 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 a Hemoglobin (Hb) Response

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)

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 12 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 12 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 / 7Eligibility 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 treatments for Pyruvate Kinase Deficiency (PKD) focus on improving red blood cell metabolism. Mitapivat, an oral medication, activates pyruvate kinase, an enzyme essential for glycolysis in red blood cells. By increasing pyruvate kinase activity, mitapivat enhances ATP production, which is crucial for red blood cell function and survival. This is particularly important for PKD patients, who suffer from hemolytic anemia due to ATP deficiency in their red blood cells. Other treatments, such as blood transfusions and splenectomy, provide supportive care but do not address the underlying metabolic defect.

Differential effect of glucose deprivation on MAPK activation in drug sensitive human breast carcinoma MCF-7 and multidrug resistant MCF-7/ADR cells.