AG-946 for Myelodysplastic Syndrome

Recruiting at35 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Agios Pharmaceuticals, Inc.

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

Disqualifiers: AML, Secondary MDS, Cardiac disease, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called AG-946 to see if it can help people with a blood disorder called Low-Risk Myelodysplastic Syndromes (LR-MDS). The goal is to find out if the drug can improve the production of healthy red blood cells.

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.

What makes the drug AG-946 unique for treating myelodysplastic syndrome?

AG-946, also known as Tebapivat, is a novel treatment for myelodysplastic syndrome, which is a condition with limited effective treatment options. Unlike traditional therapies, AG-946 may offer a new mechanism of action or administration route, but specific details about its uniqueness compared to existing treatments are not provided in the available research. ^{1 2 3 4 5}

Research Team

Medical Medical Affairs

Principal Investigator

Agios Pharmaceuticals, Inc.

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• AG-946 (Other)
• Placebo (Other)

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.

Participant Groups

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+

Findings from Research

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Pharmacodynamics with Extended Dosing of CC-486 in Patients with Hematologic Malignancies. [2018]

2. Switzerland pubmed.ncbi.nlm.nih.gov

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

3. Italy pubmed.ncbi.nlm.nih.gov

Oral idarubicin as treatment for advanced myelodysplastic syndrome. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Novel agents for myelodysplastic syndromes. [2022]

5. Cyprus pubmed.ncbi.nlm.nih.gov

New options in the treatment of myelodysplastic syndrome. [2007]