AG-946 for Myelodysplastic Syndrome

Recruiting at 43 trial locations

Overseen By Agios Medical Affairs

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Agios Pharmaceuticals, Inc.

Must not be taking: ESAs, Luspatercept, IMiDs, HMAs

Disqualifiers: AML, Secondary MDS, Cardiac disease, 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

82 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called AG-946 (also known as Tebapivat) for individuals with myelodysplastic syndromes (MDS), a condition where blood cells in the bone marrow don't develop properly. Researchers aim to determine if AG-946 can reduce patients' dependence on blood transfusions. The trial includes different groups receiving various doses to identify the most effective one. It seeks participants diagnosed with lower-risk MDS who regularly require blood transfusions. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that certain medications be stopped before starting the study drug. If you are currently receiving treatment with erythropoiesis-stimulating agents (ESAs) or luspatercept, these must be stopped for at least 28 days and 65 days, respectively, before the first dose of the study drug. Additionally, if you are taking inhibitors of P-glycoprotein, they must be stopped for at least 5 days before starting the study drug.

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

Research has shown that tebapivat (AG-946) has undergone safety testing for treating anemia. In earlier studies, its safety profile was similar to that observed in healthy individuals, indicating it is generally well-tolerated. No unexpected side effects emerged, which is encouraging for potential trial participants.

The current clinical trial is in Phase 2, meaning earlier stages have already checked the treatment for basic safety. This phase aims to further assess the treatment's safety and effectiveness for patients with specific conditions, such as Myelodysplastic Syndrome (MDS). While side effects can occur with any medication, data so far suggests that tebapivat is generally safe. ^{1 2 3 4 5}

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

Researchers are excited about AG-946 because it targets myelodysplastic syndrome (MDS) differently than most current treatments. While standard therapies often involve supportive care like blood transfusions or medications that promote blood cell production, AG-946 uses a novel approach with its active ingredient, tebapivat. Tebapivat works by enhancing the function of red blood cells, potentially improving their lifespan and efficiency. This unique mechanism could offer a more direct way to address anemia symptoms in MDS patients, providing hope for improved quality of life.

What evidence suggests that this trial's treatments could be effective for Myelodysplastic Syndrome?

Research shows that tebapivat (AG-946) may help treat anemia in people with lower-risk myelodysplastic syndromes (LR-MDS). Early studies have found that this drug can increase hemoglobin levels, which are crucial for oxygen transport in the blood. Some patients required fewer blood transfusions, a significant advantage. These early findings suggest that tebapivat could be a valuable new option for managing anemia in LR-MDS. Participants in this trial will receive different dosages of tebapivat to evaluate its effectiveness and safety. ^{1 2 3 6 7}

Who Is on the Research Team?

Medical Medical Affairs

Principal Investigator

Agios Pharmaceuticals, Inc.

Are You a Good Fit for This Trial?

Adults with low-risk myelodysplastic syndromes (LR-MDS) and anemia can join this trial. They should have hemoglobin levels below 11.0 g/dL, a good performance status, and less than 5% bone marrow blasts. Participants must not be heavily dependent on blood transfusions and agree to use effective contraception if applicable.

Inclusion Criteria

I have been on a stable dose of iron chelation therapy for at least 56 days.

I am using two forms of birth control, one highly effective, during and after the study.

I have been on a stable dose of iron chelation therapy for at least 56 days.

Exclusion Criteria

My platelet count is below 50,000 without recent transfusions.

Positive test for HIV-1 Ab or HIV-2 Ab

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

Treatment Phase 2a

Participants receive 5 mg tebapivat orally, once daily for up to 16 weeks

16 weeks

Treatment Phase 2b

Participants receive 10 mg, 15 mg, or 20 mg tebapivat orally, once daily for up to 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 treatment long-term for up to 156 weeks

156 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AG-946
• Placebo

Trial Overview The study is testing AG-946 against a placebo in two phases to see if it helps improve anemia in LR-MDS patients. Phase 2a establishes the concept while Phase 2b compares AG-946's effectiveness at different doses versus placebo.

How Is the Trial Designed?

Group I: Core Period: Phase 2b - Tebapivat 20 mg Experimental Treatment 1 Intervention

Participants will receive 20 mg tebapivat, orally, once daily for up to 24 weeks. At the discretion of the investigator, participants who complete the Core Period will be eligible to receive the same dose in Extension Period for up to 156 weeks.

Group II: Core Period: Phase 2b - Tebapivat 15 mg Experimental Treatment 1 Intervention

Participants will receive 15 mg tebapivat, orally, once daily for up to 24 weeks. At the discretion of the investigator, participants who complete the Core Period will be eligible to receive the same dose in Extension Period for up to 156 weeks.

Group III: Core Period: Phase 2b - Tebapivat 10 mg Experimental Treatment 1 Intervention

Participants will receive 10 mg tebapivat, orally, once daily for up to 24 weeks. At the discretion of the investigator, participants who complete the Core Period will be eligible to receive the same dose in Extension Period for up to 156 weeks.

Group IV: Core Period: Phase 2a - Tebapivat 5 mg Experimental Treatment 1 Intervention

Participants will receive 5 milligrams (mg) tebapivat orally, once daily for up to 16 weeks. At the discretion of the investigator, participants who complete the Core Period will be eligible to receive the same dose in Extension Period for up to 156 weeks.

Who Is Running the Clinical Trial?

Agios Pharmaceuticals, Inc.

Lead Sponsor

Trials

55

Recruited

4,200+

Published Research Related to This Trial

Extended dosing of CC-486 (oral azacitidine) in patients with myelodysplastic syndromes and acute myeloid leukemia showed significant reductions in global DNA methylation, indicating sustained epigenetic activity throughout the treatment cycle.

The study involved 59 patients and demonstrated that both 300mg once-daily and 200mg twice-daily dosing schedules effectively maintained hypomethylation, with greater reductions in methylation correlating with hematologic responses, suggesting a potential link between epigenetic changes and treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Pharmacodynamics with Extended Dosing of CC-486 in Patients with Hematologic Malignancies. Laille, E., Shi, T., Garcia-Manero, G., et al.[2018]

Myelodysplastic syndromes (MDS) are characterized by ineffective blood cell production and can lead to acute myeloid leukemia, making the search for new treatments crucial, especially for elderly patients with other health issues.

Despite over 12 years without new FDA-approved drugs for MDS, only five treatments exist, highlighting the urgent need for less toxic and more effective therapeutic options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myelodysplastic syndrome from theoretical review to clinical application view. Mohammad, AA.[2023]

In a phase I-II study involving 14 elderly patients with advanced myelodysplastic syndromes (MDS), oral idarubicin (IDA) showed an overall response rate of 14%, with one complete remission and one partial response.

While IDA demonstrated some efficacy, it also caused significant side effects, including severe infections and two deaths due to cytopenias, indicating that while it may be a potential treatment, careful monitoring for toxicity is essential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral idarubicin as treatment for advanced myelodysplastic syndrome. Lowenthal, RM., Lambertenghi-Deliliers, G.[2019]

Luspatercept-aamt, approved by the FDA in April 2020, effectively promotes erythroid maturation and demonstrated significant efficacy in the MEDALIST trial, achieving transfusion independence in patients with refractory myelodysplastic syndromes.

Decitabine/cedazuridine, approved in July 2020, acts as a nucleoside metabolic inhibitor and showed comparable safety and efficacy to IV decitabine in the ASCERTAIN study, making it a viable treatment option for patients with intermediate or high-risk myelodysplastic syndromes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel agents for myelodysplastic syndromes. Xu, K., Hansen, E.[2022]

Myelodysplastic syndrome (MDS) is a complex blood disorder with a significant risk of progressing to acute myeloid leukemia (AML) and currently lacks a proven curative treatment.

Emerging biological therapies that target both the cancerous blood cells and their surrounding environment show promise in overcoming resistance to existing treatments and may improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New options in the treatment of myelodysplastic syndrome. Grudeva-Popova, J.[2007]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05490446

A Study of Tebapivat (AG-946) in Participants With Anemia ... This purpose of this study is to establish proof of concept of tebapivat in participants with LR-MDS in Phase 2a and to evaluate the effect of tebapivat on ...

2. agios.com agios.com/wp-content/uploads/2022/12/1773.pdf

A phase 2a/2b multicenter study of AG-946 in patients with ... METHODS. Study design. • Phase 2a/2b multicenter study evaluating proof of concept and the efficacy and safety of. AG-946 in adult (≥18 ...

3. yalemedicine.org yalemedicine.org/clinical-trials/a-study-of-ag-946-in-participants-with-anemia-due-to-lower-risk-myelodysplastic-syndromes-lr-mds

A Phase 2a/2b, Open-label, Proof of Concept ... This purpose of this study is to establish proof of concept of tebapivat in participants with LR-MDS in Phase 2a and to evaluate the effect ...

4. mdsf.sparkcures.com mdsf.sparkcures.com/trial/1361/NCT05490446

AG-946 - Myelodysplastic Syndrome Clinical Trials This purpose of this study is to establish proof of concept of AG-946 in participants with LR-MDS in Phase 2a and to compare the effect of AG-946 versus ...

5. investor.agios.com investor.agios.com/news-releases/news-release-details/agios-announces-clinical-proof-concept-phase-2a-trial-ag-946

Agios Announces Clinical Proof-of-Concept in Phase 2a ... Agios announces clinical proof-of-concept in Phase 2a trial of AG-946 for the treatment of anemia in lower-risk myelodysplastic syndromes.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10429337/

P717: AG946, A PYRUVATE KINASE (PK) ACTIVATOR ... We show that ex vivo treatment with AG946 increases PK activity, ATP levels and stabilizes PK. Moreover, ex vivo treatment with AG946 improves RBC hydration.

7. investor.agios.com investor.agios.com/news-releases/news-release-details/agios-announces-fda-orphan-drug-designation-granted-tebapivat-ag

Agios Announces FDA Orphan Drug Designation Granted ... Press Release Details · Agios Announces FDA Orphan Drug Designation Granted to Tebapivat (AG-946) for Treatment of Myelodysplastic Syndromes (MDS).