Mitapivat for Thalassemia

(ENERGIZE Trial)

Not currently recruiting at 121 trial locations

Overseen By Medical Affairs

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Agios Pharmaceuticals, Inc.

Must not be taking: Luspatercept, Hematopoietic stimulants, others

Disqualifiers: Pregnancy, Sickle cell, Malignancy, 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 of mitapivat, a new potential drug, for individuals with anemia linked to thalassemia, a blood disorder. The study compares mitapivat to a placebo (a pill with no active medicine) to determine if it reduces the breakdown of red blood cells. It is suitable for those diagnosed with thalassemia who are not regularly receiving blood transfusions and have not had any recent transfusions. Participants will initially receive either mitapivat or a placebo for about six months, after which all participants will switch to mitapivat for up to five years. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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. If you are on strong CYP3A4/5 inhibitors or inducers, or anabolic steroids, you must stop them for a certain period before starting the trial.

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

Research has shown that mitapivat is generally safe for people. Studies have found that long-term use of mitapivat maintains a good safety record. For example, one study found that only a few patients experienced serious side effects, none of which were caused by the treatment. This suggests that mitapivat is safe at the doses being tested. In other research, patients taking mitapivat did not experience any severe side effects from the medication, which is promising for those considering joining a trial. Overall, mitapivat appears to be a safe choice based on the available evidence. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Mitapivat is unique because it targets a different mechanism than most current treatments for thalassemia, which often rely on blood transfusions and iron chelation therapy. Mitapivat works by activating the pyruvate kinase enzyme, which is crucial for red blood cell energy production and survival. This could potentially improve hemoglobin levels and reduce the need for transfusions. Researchers are excited because this approach could offer a more sustainable and less invasive option for managing thalassemia, addressing the root of the problem rather than just the symptoms.

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

Studies have shown that mitapivat can greatly help people with non-transfusion-dependent thalassemia (NTDT). Research indicates that patients taking mitapivat experienced lasting improvements in their hemoglobin levels, crucial for oxygen transport in the blood. In this trial, participants in the mitapivat arm will receive mitapivat, which significantly reduced the need for blood transfusions compared to a placebo. Mitapivat works by activating an enzyme called pyruvate kinase, improving the health and function of red blood cells. These findings suggest that mitapivat could effectively manage NTDT. ^{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 individuals with alpha- or beta-non-transfusion dependent thalassemia (NTDT) who have stable hemoglobin levels ≤10.0 g/dL and haven't had more than 5 blood transfusions in the past 24 weeks. Participants must not be pregnant, breastfeeding, or have certain other health conditions like uncontrolled heart disease, severe kidney issues, or active infections.

Inclusion Criteria

I have not needed more than 5 blood transfusions in the last 6 months and none in the last 2 months.

I have been diagnosed with thalassemia based on specific blood tests or DNA analysis.

My hydroxyurea dose has been the same for at least 16 weeks.

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)

Current enrollment or past participation (≤12 weeks before administration of the first dose of study drug or a timeframe equivalent to 5 half-lives of the investigational study drug, whichever is longer) in any other clinical study involving an investigational treatment or device

I do not have any health conditions that my doctor thinks would make this study unsafe for me.

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 24 weeks

24 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 study is testing Mitapivat against a placebo to see if it helps improve anemia in people with NTDT. Patients will either receive the actual drug or a placebo that has no therapeutic effect to compare outcomes between the two groups.

How Is the Trial Designed?

Group I: Mitapivat Experimental Treatment 1 Intervention

Mitapivat 100 milligrams (mg), orally, twice daily (BID) for 24 weeks in double blind (DB) period and for up to 5 years in open label extension (OLE) period.

Group II: Placebo Placebo Group 2 Interventions

Placebo matching mitapivat, orally, BID for 24 weeks in double blind period followed by Mitapivat 100 mg, orally, BID for up to 5 years in open label extension period.

Who Is Running the Clinical Trial?

Agios Pharmaceuticals, Inc.

Lead Sponsor

Trials

55

Recruited

4,200+

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 ...