Mitapivat for Pyruvate Kinase Deficiency

(ACTIVATE-KidsT Trial)

Recruiting at 22 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

49 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

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, and any pyruvate kinase activators for a specified period before joining the study. You must also continue taking folic acid supplements during the study.

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

Mitapivat has been shown to improve hemoglobin levels and reduce the need for blood transfusions in adults with pyruvate kinase deficiency. It also enhances quality of life and reduces symptoms of hemolytic anemia, making it a valuable treatment option for this condition. ^{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. It is approved for use in adults with this condition in the USA and Europe, indicating a favorable safety profile. ^{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}

Research Team

Medical Affairs

Principal Investigator

Agios Pharmaceuticals, Inc.

Eligibility Criteria

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.

Inclusion Criteria

Have complete records of transfusion history for the 52 weeks before providing informed consent/assent, defined as having all the following available: (1) all the transfusion dates, (2) the RBC transfusion volume (milliliters and/or number of units) for all the transfusions, and (3) hemoglobin concentrations within 1 week before transfusion for at least 80% of the transfusions

I have been taking folic acid for at least 21 days before starting the study drug and will continue during the study.

I have a confirmed genetic condition called pyruvate kinase deficiency.

Exclusion Criteria

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

Pregnant or breastfeeding

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Titration

Participants undergo an 8-week dose titration period to optimize dosing based on age and weight

8 weeks

Fixed-dose Treatment

Participants receive a fixed dose of mitapivat or placebo for 24 weeks

24 weeks

Open-label Extension

Participants who complete the double-blind period may continue receiving mitapivat in an open-label extension period

Up to 262 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Mitapivat
• Mitapivat-matching placebo

Trial Overview 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.

Participant Groups

Group I: Mitapivat Experimental Treatment 2 Interventions

For participants randomized to receive mitapivat, dosing occurs orally twice daily (BID), and is based on age and weight. Dosing is optimized through 2 potential sequential increases in dose levels (1-5 mg, 4-20 mg and 10-50 mg) at Week 4 and Week 8, and aims to achieve the adult-equivalent exposure at 5, 20, and 50 mg. Following titration, participants remain on their individually optimized dose during the remainder of the Double-blind (DB) Period for 24 weeks. After the DB period, participants will enter an Open-label Extension (OLE) Period. To preserve blinding of treatment allocation, participants will continue mitapivat at their optimized dose and undergo mock titration with placebo for 8 weeks. At the conclusion of 8 weeks, participants may continue receiving mitapivat in the OLE Period for up to 262 weeks (including up to 2 weeks of dose taper).

Group II: Placebo Placebo Group 2 Interventions

For participants randomized to receive matched placebo, dosing is identical to that described above for mitapivat. Following the initial dose titration period, participants remain on their individually optimized dose during the remainder of the DB period for 32 weeks. After the DB period, participants will enter an OLE period. To preserve blinding of treatment allocation, participants will continue placebo at their optimized dose and undergo mitapivat dose optimization through 2 potential sequential increases in dose levels (1-5 mg, 4-20 mg and 10-50 mg) at Week 4 and Week 8 of the OLE Period, and aims to achieve the adult-equivalent exposure at 5, 20, and 50 mg. At the conclusion of 8 weeks, participants may continue receiving mitapivat in the OLE Period for up to 262 weeks (including up to 2 weeks of dose taper).

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]