Mitapivat for Pyruvate Kinase Deficiency

(ACTIVATE-Kids Trial)

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness and safety of mitapivat, a new oral treatment for children with pyruvate kinase deficiency (PKD), a rare blood disorder affecting red blood cell function. The goal is to determine if mitapivat can improve blood counts compared to a placebo. It targets children with PKD who are not receiving regular blood transfusions. This trial may suit children with PKD who have had no more than five blood transfusions in the past year and have low hemoglobin levels, impacting their energy and daily activities. Participants will initially receive either mitapivat or a placebo and may continue on mitapivat for up to five years. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to the development of a promising new treatment.

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.

Is there any evidence suggesting that mitapivat is likely to be safe for humans?

Research has shown that mitapivat is generally safe and well-tolerated in people with pyruvate kinase deficiency (PKD). In earlier studies, serious side effects such as hemolytic anemia (a condition where red blood cells break down too quickly) and pharyngitis (throat inflammation) were rare, affecting only about 4% of patients. About half of the patients experienced some side effects, though these were not always serious. Overall, different studies have consistently demonstrated the safety of mitapivat. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pyruvate kinase deficiency?

Mitapivat is unique because it targets the root cause of pyruvate kinase deficiency by activating the pyruvate kinase enzyme. Most treatments for this condition, like blood transfusions and chelation therapy, only manage symptoms without addressing the underlying enzyme issue. Researchers are excited because mitapivat has the potential to improve red blood cell function and survival, offering a more direct and effective approach to treating this rare blood disorder.

What evidence suggests that mitapivat might be an effective treatment for pyruvate kinase deficiency?

Research has shown that mitapivat can help treat pyruvate kinase deficiency (PKD). In studies, mitapivat significantly raised hemoglobin levels, which is important for reducing anemia, or low red blood cell count, in patients. It also reduced the breakdown of red blood cells. Patients reported feeling less tired and experiencing an overall improvement in well-being. In this trial, participants will receive either mitapivat or a mitapivat-matching placebo during the double-blind period. These findings suggest that mitapivat may help people with PKD manage their symptoms better. ^{2 6 7 8 9}

Who Is on the Research Team?

Medical Affairs

Principal Investigator

Agios Pharmaceuticals, Inc.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2116634

Mitapivat versus Placebo for Pyruvate Kinase Deficiency In patients with pyruvate kinase deficiency, mitapivat significantly increased the hemoglobin level, decreased hemolysis, and improved patient-reported ...

2. investor.agios.com investor.agios.com/static-files/af4512cc-c513-45ac-977a-49bccae1c139

Clinically meaningful improvements in patient‐reported ... Mitapivat, a first-in-class, oral activator of PK approved for adults with PK deficiency4 has demonstrated improvements in anemia and.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31483964/

Safety and Efficacy of Mitapivat in Pyruvate Kinase Deficiency Conclusions: The administration of mitapivat was associated with a rapid increase in the hemoglobin level in 50% of adults with pyruvate kinase ...

4. ashpublications.org ashpublications.org/bloodrci/article/1/2/100014/546279/Long-term-mitapivat-treatment-is-safe-and

Long-term mitapivat treatment is safe and efficacious in ... Median of 2.53-year follow-up of mitapivat showed favorable safety and tolerability in patients with SCD. Sustained improvements in Hb, ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/ajh.27312

Clinically meaningful improvements in patient‐reported ... Treatment with mitapivat showed long-term, durable, and clinically meaningful improvements in signs, symptoms, and functional impacts of PK ...

6. nejm.org nejm.org/doi/full/10.1056/NEJMoa1902678

Safety and Efficacy of Mitapivat in Pyruvate Kinase Deficiency The most common serious adverse events, hemolytic anemia and pharyngitis, each occurred in 2 patients (4%). A total of 26 patients (50%) had an ...

7. investor.agios.com investor.agios.com/news-releases/news-release-details/agios-announces-results-phase-3-activate-kidst-study-mitapivat

Agios Announces Results from Phase 3 ACTIVATE-KidsT ... In the 32-week double-blind treatment period, mitapivat was generally safe and well-tolerated, with safety results consistent with the safety ...

8. ashpublications.org ashpublications.org/blood/article/134/Supplement_1/3512/428360/Long-Term-Safety-and-Efficacy-of-Mitapivat-AG-348

Long-Term Safety and Efficacy of Mitapivat (AG-348), a ... These long-term data support the potential of mitapivat as the first disease-altering therapy for PK deficiency. Two phase 3 trials are underway ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2352302622002149

Mitapivat in adult patients with pyruvate kinase deficiency ... Mitapivat was well tolerated across all doses studied in the ACTIVATE-T trial, and its safety profile was consistent across all previously reported studies.