Mitapivat for Pyruvate Kinase Deficiency

(ACTIVATE-Kids Trial)

Recruiting at 21 trial locations

Overseen By Agios Medical Affairs

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Agios Pharmaceuticals, Inc.

Must be taking: Folic acid

Must not be taking: Hematopoietic stimulants, CYP3A4 inhibitors

Disqualifiers: Pregnancy, Malignancy, Cardiac disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before participating. Specifically, you must stop taking strong inhibitors or inducers of CYP3A4, anabolic steroids, hematopoietic stimulating agents, and any pyruvate kinase activators for specified periods before joining the trial.

What data supports the effectiveness of the drug Mitapivat for pyruvate kinase deficiency?

Mitapivat has been shown to improve hemoglobin levels and reduce the need for blood transfusions in adults with pyruvate kinase deficiency, a condition that causes anemia. It also improves quality of life and has a generally mild to moderate side effect profile. ^{1 2 3 4 5}

Is Mitapivat safe for humans?

Mitapivat has been generally well tolerated in clinical trials for pyruvate kinase deficiency, with most side effects being mild to moderate. ^{1 2 3 4 6}

What makes the drug Mitapivat unique for treating pyruvate kinase deficiency?

Mitapivat is unique because it is the first approved drug that directly targets the underlying cause of pyruvate kinase deficiency by activating the pyruvate kinase enzyme in red blood cells, improving hemoglobin levels and reducing the need for blood transfusions. ^{1 2 3 4 6}

What is the purpose of this trial?

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.

Research Team

Medical Affairs

Principal Investigator

Agios Pharmaceuticals, Inc.

Eligibility Criteria

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.

Inclusion Criteria

I have a confirmed genetic condition called pyruvate kinase deficiency.

Written informed consent from the participant, or the participant's legally authorized representative, parent(s), or legal guardian, and the participant's assent, where applicable (informed consent/assent) must be obtained before any study-related procedures are conducted, and participants must be willing to comply with all study procedures for the duration of the study

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

Exclusion Criteria

I have had cancer before.

Pregnant or breastfeeding

Criterion: You have liver or kidney problems, high triglycerides, active infections, or a history of certain diseases. You also can't be in the study if you've had certain surgeries, are participating in other studies, or have specific medical conditions.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-blind Treatment

Participants receive either mitapivat or placebo during an 8-week dose titration period followed by a 12-week fixed-dose period

20 weeks

Open-label Extension

Participants who complete the double-blind period receive mitapivat for up to 5 years

5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

Treatment Details

Interventions

• Mitapivat
• Mitapivat-matching placebo

Trial Overview 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.

Participant Groups

Group I: Mitapivat (OLE period) Experimental Treatment 2 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: Mitapivat Experimental Treatment 1 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: Placebo Placebo Group 1 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.

Who Is Running the Clinical Trial?

Agios Pharmaceuticals, Inc.

Lead Sponsor

Trials

55

Recruited

4,200+

References

1. England pubmed.ncbi.nlm.nih.gov

Mitapivat in adult patients with pyruvate kinase deficiency receiving regular transfusions (ACTIVATE-T): a multicentre, open-label, single-arm, phase 3 trial. [2022]

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

Safety and Efficacy of Mitapivat in Pyruvate Kinase Deficiency. [2019]

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

Mitapivat versus Placebo for Pyruvate Kinase Deficiency. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Mitapivat: A Review in Pyruvate Kinase Deficiency in Adults. [2023]

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

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

6. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Mitapivat: A Novel Treatment of Hemolytic Anemia in Adults with Pyruvate Kinase Deficiency. [2023]