Mitapivat for Thalassemia

(ENERGIZE-T Trial)

Recruiting at 112 trial locations

Overseen By Medical Affairs

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Agios Pharmaceuticals, Inc.

Must be taking: Hydroxyurea

Must not be taking: Luspatercept, Hematopoietic stimulants, others

Disqualifiers: Sickle cell, 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

258 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary purpose of this study is to compare the effect of mitapivat versus placebo on transfusion burden in participants with transfusion-dependent alpha- or beta-thalassemia (TDT).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but if you are taking hydroxyurea, your dose must be stable for at least 16 weeks before joining. Some medications, like strong CYP3A4/5 inhibitors or inducers, must be stopped for a certain period before joining.

What data supports the effectiveness of the drug Mitapivat for Thalassemia?

Research shows that Mitapivat, a drug that activates pyruvate kinase (an enzyme important for energy production in red blood cells), has been effective in increasing hemoglobin levels in adults with non-transfusion-dependent α-thalassemia or β-thalassemia, suggesting it could help manage these conditions. ^{1 2 3 4 5}

Is mitapivat safe for humans?

Mitapivat has been studied in adults with thalassemia and other conditions, showing a tolerable safety profile with good tolerability and no major safety concerns reported in the studies. ^{1 2 3 4 6}

Research Team

Medical Affairs

Principal Investigator

Agios Pharmaceuticals, Inc.

Eligibility Criteria

This trial is for people with transfusion-dependent alpha- or beta-thalassemia who need regular blood transfusions. They must have a confirmed diagnosis, stable treatment if using hydroxyurea, and agree to use effective contraception if applicable. Excluded are those with certain medical conditions, recent treatments that could interfere, or risks that might affect study results.

Inclusion Criteria

I have needed 6 to 20 blood transfusions in the last 6 months without going more than 6 weeks without one.

Women of childbearing potential (WOCBP) must be abstinent of sexual activities that may induce pregnancy as part of their usual lifestyle or agree to use two forms of contraception, one of which must be considered highly effective, from the time of providing informed consent, throughout the study, and for 28 days after the last dose of study drug. The second form of contraception can be an acceptable barrier method

I have been diagnosed with thalassemia based on DNA analysis.

Exclusion Criteria

Participants with any condition(s) that could create undue influence (including but not limited to incarceration, involuntary psychiatric confinement, and financial or familial affiliation with the Investigator or Sponsor).

Pregnant, breastfeeding, or parturient

My kidney function is reduced, with an eGFR less than 45 mL/min/1.73m^2.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-Blind Treatment

Participants receive either mitapivat or placebo orally, twice daily for 48 weeks

48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label Extension

Participants may opt into continuation of mitapivat treatment for up to 5 years

Up to 5 years

Treatment Details

Interventions

• Mitapivat
• Placebo Matching Mitapivat

Trial Overview The trial is testing the effectiveness of Mitapivat versus a placebo in reducing the need for blood transfusions in patients with thalassemia. Participants will be randomly assigned to receive either Mitapivat or a placebo to compare outcomes between the two groups.

Participant Groups

Group I: Mitapivat Experimental Treatment 1 Intervention

Double-Blind Period: Participants will receive mitapivat 100 milligrams (mg) orally, twice daily (BID) for 48 weeks. Open-label Extension Period: Participants who do not discontinue study drug may choose to continue to receive mitapivat for up to an additional 5 years after the Double-blind Period.

Group II: Placebo Placebo Group 2 Interventions

Double-Blind Period: Participants will receive placebo matching mitapivat orally, BID for 48 weeks. Open-label Extension Period: Participants who do not discontinue study drug may choose to receive mitapivat for up to an additional 5 years after the Double-blind Period.

Who Is Running the Clinical Trial?

Agios Pharmaceuticals, Inc.

Lead Sponsor

Trials

55

Recruited

4,200+

Findings from Research

In a review of 15 randomized controlled trials involving 1003 β-Thalassemia major patients, deferiprone (DFP) was found to be more effective than deferoxamine (DFO) in improving cardiac ejection fraction and reducing endocrine dysfunction.

Combination therapy of DFP and DFO showed even greater efficacy in improving cardiac ejection fraction compared to either drug alone, but overall evidence quality was low, indicating a need for larger studies to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review and meta-analysis of deferiprone monotherapy and in combination with deferoxamine for reduction of iron overload in chronically transfused patients with β-thalassemia. Kuo, KH., Mrkobrada, M.[2018]

References

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

Safety and efficacy of mitapivat, an oral pyruvate kinase activator, in adults with non-transfusion dependent α-thalassaemia or β-thalassaemia: an open-label, multicentre, phase 2 study. [2022]

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

Efficacy and Safety of Luspatercept in the Treatment of β-Thalassemia: A Systematic Review. [2023]

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

Right in time: Mitapivat for the treatment of anemia in α- and β-thalassemia. [2022]

4. England pubmed.ncbi.nlm.nih.gov

A systematic review and meta-analysis of deferiprone monotherapy and in combination with deferoxamine for reduction of iron overload in chronically transfused patients with β-thalassemia. [2018]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Novel Therapeutic Advances in β-Thalassemia. [2021]

6. Spain pubmed.ncbi.nlm.nih.gov

Mitapivat for sickle cell disease and thalassemia. [2023]