AG-348 for Pyruvate Kinase Deficiency

No longer recruiting at 13 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Agios Pharmaceuticals, Inc.

Must be taking: Folic acid

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Blood disorders, Heart failure, Diabetes, 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

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a drug called AG-348 (mitapivat) for individuals with pyruvate kinase (PK) deficiency, a rare blood disorder affecting red blood cells. Participants will receive either a low or high dose of AG-348 to evaluate its efficacy and potential side effects. Individuals with a known history of PK deficiency who have not required frequent blood transfusions in the past year might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking certain medications that affect liver enzymes or are known to interact with the study drug within a specific time before starting the trial. Specifically, you must avoid medications that strongly affect cytochrome P450 (CYP) 3A4 or P-glycoprotein within 5 to 28 days 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 with pyruvate kinase (PK) deficiency. In earlier studies, serious side effects such as hemolytic anemia (where red blood cells break down too quickly) and pharyngitis (throat inflammation) occurred in about 4% of patients. Overall, about half of the patients experienced some side effects, though these were not always serious.

Long-term research indicates that mitapivat is well-tolerated, meaning most people can take it without major problems. In a 32-week study with children, mitapivat was safe, with side effects similar to those seen in earlier studies. This ongoing research supports mitapivat as a promising treatment for PK deficiency, but individual experiences with the drug can vary. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about AG-348 for treating pyruvate kinase deficiency because it offers a novel approach by directly activating the pyruvate kinase enzyme, which is deficient in patients with this condition. Unlike current treatments that primarily focus on managing symptoms or require blood transfusions, AG-348 directly targets the root cause of the disease. This unique mechanism of action could lead to a more effective and sustainable management of the condition, potentially reducing the need for frequent blood transfusions and improving patients' quality of life.

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

Research has shown that mitapivat, also known as AG-348, may help treat pyruvate kinase (PK) deficiency. In earlier studies, mitapivat significantly increased hemoglobin levels in about half of the adults with this condition. Hemoglobin is crucial for carrying oxygen in the blood. Patients also experienced less breakdown of red blood cells, a common issue in PK deficiency. Additionally, mitapivat improved symptoms of anemia, making it the first potential treatment to directly target this disease. These findings suggest that mitapivat could be an effective treatment option for people with PK deficiency. Participants in this trial will receive either 50 mg or 300 mg of AG-348 twice daily to further evaluate its effectiveness. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

Adults with Pyruvate Kinase (PK) Deficiency who are not pregnant or breastfeeding, have a hemoglobin level below set thresholds, and haven't had recent blood transfusions can join. They must be in stable health, not on certain medications, and agree to use contraception. Those with psychiatric disorders or other conditions that could affect study participation are excluded.

Inclusion Criteria

You have been diagnosed with pyruvate kinase deficiency through a specific test.

My hemoglobin level is low, below 12 g/dL if I'm male, or below 11 g/dL if I'm female.

I had my spleen removed over 6 months ago and my vaccinations are current.

Exclusion Criteria

Any other medical or psychological condition deemed by the Investigator to be likely to interfere with a patient's ability to participate in the study

You have a mental health condition that might make it hard for you to take part in the study.

Your blood has high levels of bilirubin for reasons other than a specific type of genetic condition or breakdown of red blood cells.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive multiple doses of AG-348 for up to 24 weeks

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Eligible participants may enter an Extension Period to receive AG-348 for up to 8 additional years

Up to 8 years

What Are the Treatments Tested in This Trial?

Interventions

• AG-348

Trial Overview The trial is testing the safety and effectiveness of AG-348 (mitapivat) at various doses for treating PK deficiency. It's a multicenter study where participants receive different amounts of this medication to see how well it works and what side effects occur.

How Is the Trial Designed?

Group I: AG-348 50 mg BID Experimental Treatment 1 Intervention

Participants with PK deficiency received AG-348, 50 milligrams (mg), as initial dose, twice daily (BID) for the Core Period (Week 24).

Group II: AG-348 300 mg BID Experimental Treatment 1 Intervention

Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for the Core Period (Week 24).

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. 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 ...

3. 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.

4. 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 ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02476916

NCT02476916 | A Study of AG-348 in Adult Participants ... A multicenter study designed to evaluate the safety and efficacy of different dose levels of AG-348 (mitapivat) in participants with PK deficiency.

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. clinicaltrials.gov clinicaltrials.gov/study/NCT03548220

A Study to Evaluate Efficacy and Safety of AG-348 in Not ... Study AG348-C-006 evaluated the efficacy and safety of orally administered AG-348 as compared with placebo in participants with pyruvate kinase (PK) deficiency.

8. 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 ...