Mitapivat for Thalassemia

(ENERGIZE-T Trial)

Not currently recruiting at 123 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a new drug, mitapivat, can reduce the need for blood transfusions in people with thalassemia, a blood disorder that causes anemia and fatigue. Participants will receive either mitapivat or a placebo (a non-active pill) to compare effects. Those who regularly receive blood transfusions to manage their thalassemia may be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that mitapivat is generally safe for patients. In one study, only five out of 29 patients experienced serious side effects, and none were directly caused by the treatment. Another study found that using mitapivat over a long period was not only safe but also improved patients' red blood cells.

For patients with sickle cell disease, taking mitapivat at doses up to 100 mg twice a day proved safe, as most people did not experience severe side effects. Overall, these studies suggest that mitapivat is safe for people, with most side effects being mild or unrelated to the treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for thalassemia?

Mitapivat is unique because it targets thalassemia by activating pyruvate kinase, an enzyme crucial for red blood cell energy production and survival. Most traditional treatments for thalassemia, like blood transfusions and iron chelation therapy, focus on managing symptoms rather than addressing the root cause. Mitapivat offers a novel approach by potentially improving red blood cell function and lifespan, which could reduce the need for frequent transfusions. This new mechanism of action is what has researchers excited about its potential to change the standard of care for thalassemia patients.

What evidence suggests that mitapivat might be an effective treatment for thalassemia?

Research has shown that mitapivat, one of the treatments studied in this trial, can help people with thalassemia. One study found that mitapivat significantly reduced the need for blood transfusions compared to a placebo, meaning patients required fewer transfusions to manage their condition. Other studies have found that mitapivat improved hemoglobin levels, which are crucial for carrying oxygen in the blood. Mitapivat activates an enzyme called pyruvate kinase, enhancing the function of red blood cells. Overall, evidence suggests mitapivat could improve symptoms for people with thalassemia. Participants in this trial will be randomized to receive either mitapivat or a placebo. ^{1 3 5 6 7}

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 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 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 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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Mitapivat Experimental Treatment 1 Intervention

Participants randomized to receive mitapivat 100 milligrams (mg), orally, twice daily (BID) for 48 weeks in the double-blind (DB) period and for up to 5 years in the open label extension (OLE) period.

Group II: Placebo Placebo Group 2 Interventions

Participants randomized to receive placebo matching mitapivat, orally, BID for 48 weeks in the DB period followed by mitapivat 100 mg, orally, BID for up to 5 years in the OLE period.

Who Is Running the Clinical Trial?

Agios Pharmaceuticals, Inc.

Lead Sponsor

Trials

55

Recruited

4,200+

Published Research Related to This Trial

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40394935/

Long-term efficacy and safety of mitapivat in non- ... Patients receiving mitapivat demonstrated sustained improvements in haemoglobin concentrations and markers of erythropoietic activity, haemolysis and iron ...

2. investor.agios.com investor.agios.com/news-releases/news-release-details/agios-presents-positive-results-phase-3-energize-t-study

Agios Presents Positive Results from Phase 3 ENERGIZE ... In the ENERGIZE-T trial, mitapivat demonstrated a statistically significant reduction in transfusion burden compared to placebo in patients with ...

3. hematologyadvisor.com hematologyadvisor.com/news/thalassemia-mitapivat-phase-2-study-long-term-efficacy-treatment-risk/

Phase 2 Study Shows Long-Term Efficacy of Mitapivat in ... Treatment with mitapivat was associated with sustained improvements in hemoglobin concentration in patients with non–transfusion-dependent thalassemia (NTDT)

4. ashpublications.org ashpublications.org/ashclinicalnews/news/8687/Mitapivat-Shown-to-Boost-Hemoglobin-Response-in

Mitapivat Shown to Boost Hemoglobin Response in ... Mitapivat Shown to Boost Hemoglobin Response in Thalassemia Available ... Mitapivat is a first-in-class allosteric activator of pyruvate kinase.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S014067362500635X

Mitapivat in adults with non-transfusion-dependent α ... 17, 18 Preclinical studies in thalassaemia models have shown that mitapivat might ameliorate oxidative stress, enhance erythropoiesis, diminish ...

6. investor.agios.com investor.agios.com/news-releases/news-release-details/agios-presents-mitapivat-data-highlighting-long-term-safety

Agios Presents Mitapivat Data Highlighting Long-term ... “The data presented today continue to demonstrate that chronic treatment with mitapivat is well tolerated and has the potential to meaningfully ...

7. ashpublications.org ashpublications.org/bloodadvances/article/7/24/7539/498652/One-year-safety-and-efficacy-of-mitapivat-in

One-year safety and efficacy of mitapivat in sickle cell disease Treatment with mitapivat demonstrated durable beneficial mechanistic effects and a favorable safety profile at doses up to 100 mg twice daily ...