AG-348 for Thalassemia

Not currently recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Agios Pharmaceuticals, Inc.

Must not be taking: CYP3A4 inhibitors, P-gp inhibitors

Disqualifiers: Hb S or C thalassemia, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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 tests a new drug, AG-348, to evaluate its effectiveness and safety for individuals with non-transfusion-dependent thalassemia (NTDT). The study examines whether AG-348 alleviates symptoms and improves long-term health for those who do not regularly require blood transfusions. It suits individuals with a known history of thalassemia who haven't needed frequent transfusions. Participants will take the medication for at least six months, with the possibility of continuing for several years. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to significant findings.

Will I have to stop taking my current medications?

You may need to stop taking certain medications before joining the trial. Specifically, if you are on medications that strongly affect certain liver enzymes (CYP3A4) or P-glycoprotein, or if you are taking digoxin, you must stop them at least 5 days before starting the study drug. Also, if you are on chronic anticoagulant therapy, anabolic steroids, or hematopoietic stimulating agents, you need to be on a stable dose for a specific period before starting the trial.

Is there any evidence suggesting that AG-348 is likely to be safe for humans?

Research has shown that AG-348, also known as mitapivat, is generally safe for people. Studies have found it to be a safe treatment for various blood disorders. In earlier research, participants taking AG-348 mostly experienced mild side effects like headaches and nausea, which are common with many medications. Serious side effects were rare.

AG-348 works by activating an enzyme called pyruvate kinase, which improves the function of red blood cells. This is important for people with thalassemia, a condition where the body doesn't make enough healthy red blood cells. Since AG-348 is already being tested for other blood conditions, this increases confidence in its safety for humans.

For those considering joining a trial with AG-348, existing research supports its safety. However, discussing any concerns with a doctor before joining a trial is essential. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for thalassemia, which often involve regular blood transfusions and iron chelation therapy to manage symptoms, AG-348 introduces a novel approach by targeting the pyruvate kinase enzyme pathway. This innovative mechanism helps to increase hemoglobin levels by enhancing the energy production in red blood cells, potentially reducing the need for transfusions. Researchers are excited about AG-348 because it offers the possibility of a more convenient oral treatment that could significantly improve the quality of life for patients with thalassemia by addressing the root cause rather than just alleviating symptoms.

What evidence suggests that AG-348 might be an effective treatment for thalassemia?

Research has shown that AG-348, also known as Mitapivat, may help treat non-transfusion-dependent thalassemia (NTDT). Studies have found that Mitapivat can raise hemoglobin levels, which is crucial for people with thalassemia who often have low hemoglobin. In earlier studies, patients experienced improved red blood cell function with this treatment. Mitapivat activates an enzyme called pyruvate kinase, which aids red blood cells in producing energy. This process enhances the health and lifespan of these cells. Overall, early findings suggest that AG-348 could be an effective pill for managing NTDT. Participants in this trial will receive AG-348 to further evaluate its effectiveness and safety. ^{1 2 3 4 6}

Who Is on the Research Team?

Medical Affairs

Principal Investigator

Agios Pharmaceuticals, Inc.

Are You a Good Fit for This Trial?

Adults with non-transfusion-dependent thalassemia (NTDT) who haven't had more than 5 blood transfusions in the last 24 weeks and none in the past 8 weeks. Participants must have a documented history of thalassemia, adequate organ function, and agree to use two forms of contraception if applicable. Exclusions include prior treatments like gene therapy or certain drugs, recent major surgery, or serious allergies.

Inclusion Criteria

Informed consent

My average hemoglobin level is 10 g/dL or less, based on two tests.

I haven't needed more than 5 blood transfusions in the last 6 months and none in the last 2 months.

Exclusion Criteria

Currently pregnant or breastfeeding

Exposure to any investigational drug, device, or procedure within 3 months prior to the first day of study drug

Currently enrolled in another therapeutic clinical trial involving ongoing therapy with any investigational or marketed product or placebo

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Up to 4 weeks

Core Treatment

Participants receive AG-348 50 mg BID, with a potential increase to 100 mg BID based on safety and hemoglobin levels

24 weeks

Weekly visits for dose adjustment and monitoring

Extension

Eligible participants continue to receive AG-348 for long-term evaluation

Up to 10 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AG-348

Trial Overview The trial is testing AG-348's effectiveness for NTDT over up to 10 years. Starting with a dose of 50 mg twice daily, which may increase to 100 mg based on safety and hemoglobin levels after six weeks. The study aims to understand how well AG-348 works and its effects on the body.

How Is the Trial Designed?

Group I: AG-348 Experimental Treatment 1 Intervention

Participants with alpha or beta thalassemia received AG-348 50 mg twice daily (BID), orally up to Week 6. Following Week 6, depending on the participants' safety and hemoglobin (Hb) concentrations, they could undergo one potential dose-level increase from 50 to 100 mg BID. After completion of the Core Period of 24 weeks, participants were eligible to continue to receive AG-348 in the Extension Period which is up to 10 years.

Who Is Running the Clinical Trial?

Agios Pharmaceuticals, Inc.

Lead Sponsor

Trials

55

Recruited

4,200+

Published Research Related to This Trial

In a study of 220 transfusion-dependent beta-thalassemia patients, those treated with the oral iron chelator deferasirox (Exjade®) showed significantly higher compliance and convenience compared to those receiving the standard treatment, deferoxamine (DFO).

While both treatments had comparable efficacy, nearly 45% of patients on DFO reported irritation and pain at the injection site, highlighting Exjade® as a potentially preferable option for iron chelation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Compliance and satisfaction with deferasirox (Exjade®) compared with deferoxamine in patients with transfusion-dependent beta-thalassemia. Haghpanah, S., Zarei, T., Zahedi, Z., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03692052

NCT03692052 | A Study to Determine the Efficacy, Safety ... A Study to Determine the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of AG-348 in Adult Participants With Non-transfusion-dependent Thalassemia.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8721383/

Mitapivat, a novel pyruvate kinase activator, for the ... Mitapivat is a promising, first-in-class allosteric activator of pyruvate kinase with documented safety and efficacy across a wide spectrum of hereditary ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04770779

NCT04770779 | A Study Evaluating the Efficacy and Safety ... A Study Evaluating the Efficacy and Safety of Mitapivat in Participants With Transfusion-Dependent Alpha- or Beta-Thalassemia (α- or β-TDT) (ENERGIZE-T).

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

Mitapivat in adults with non-transfusion-dependent α ... Mitapivat could be a new oral treatment for adults with NTD α-thalassaemia or NTD β-thalassaemia by increasing haemoglobin concentration and ...

5. investor.agios.com investor.agios.com/static-files/85923ced-930a-446e-bbdb-dc530b8bcf04

Long-term safety and efficacy of mitapivat (AG-348), a ... Thalassemia is a red blood cell (RBC) disorder in which ineffective erythropoiesis and hemolysis occur due to imbalanced globin.

6. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(22)01337-X/abstract

Safety and efficacy of mitapivat, an oral pyruvate kinase ... We aimed to investigate the safety and efficacy of mitapivat (Agios Pharmaceuticals, Cambridge, MA, USA), a pyruvate kinase activator, in adults with non- ...