A Study of Tebapivat (AG-946) in Participants With Anemia Due to Lower-Risk Myelodysplastic Syndromes (LR-MDS)

NCT05490446 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: AG946-C-0022022-500609-42-00
• Study Type: interventional
• Target: 87
• Locations: 12 countries
• Sites: 44

Brief Summary

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 transfusion independence (TI) in participants with LR-MDS in phase 2b.

Conditions

Myelodysplastic Syndromes

Keywords

Anemia; Lower-Risk Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (3)

• Phase 2a: Proportion of Participants With Hemoglobin (Hb) Response

  Hb response is defined as a ≥1.5-grams per deciliter (g/dL) increase from baseline in the average Hb concentration from Week 8 through Week 16.

  Baseline, Week 8 through Week 16

• Phase 2a: Proportion of Participants With Transfusion Independence During the Core Period

  Transfusion Independence is defined as transfusion-free for ≥8 consecutive weeks during the Core Period (participants With Low Transfusion Burden \[LTB\] only).

  Up to 16 weeks

• Phase 2b: Proportion of Participants With Transfusion Independence

  Transfusion independence, defined as transfusion-free for ≥8 consecutive weeks (TI8) during the Core Period.

  Up to 24 weeks

Secondary Outcomes (33)

• Phase 2a: Proportion of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation During the Core Period

  Up to 16 weeks

• Phase 2a: Proportion of Participants With Laboratory Abnormalities During the Core Period

  Up to 16 weeks

• Phase 2a: Proportion of Participants With Hb 1.0+ Response

  Baseline, Week 8 through Week 16

• Phase 2a: Change From Baseline in Hb Concentration During the Core Period

  Baseline up to 16 weeks

• Phase 2a: Proportion of Participants With ≥1.5-g/dL increase From Baseline in the Hb Concentration at ≥2 Consecutive Time Points From Week 8 through Week 16

  Baseline, Week 8 through Week 16

Study Arms (4)

Core Period: Phase 2a - Tebapivat 5 mg

EXPERIMENTAL

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.

Drug: Tebapivat

Core Period: Phase 2b - Tebapivat 10 mg

EXPERIMENTAL

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.

Drug: Tebapivat

Core Period: Phase 2b - Tebapivat 15 mg

EXPERIMENTAL

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.

Drug: Tebapivat

Core Period: Phase 2b - Tebapivat 20 mg

EXPERIMENTAL

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.

Drug: Tebapivat

Interventions

Tebapivat DRUG

Tebapivat Tablet

Also known as: AG-946

Core Period: Phase 2a - Tebapivat 5 mg; Core Period: Phase 2b - Tebapivat 10 mg; Core Period: Phase 2b - Tebapivat 15 mg; Core Period: Phase 2b - Tebapivat 20 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Phase 2a
• At least 18 years of age at the time of providing informed consent;
• Documented diagnosis of myelodysplastic syndromes (MDS) according to World Health Organization (WHO) classification (Arber et al, 2016), that meets Revised International Prognostic Scoring System (IPSS-R) classification of lower-risk disease (risk score: ≤3.5) and \<5% blasts as determined by the participant's bone marrow biopsy/aspirate during the Screening Period;
• Nontransfused or with low transfusion burden (LTB), based on transfusion history from the participant's medical record, according to revised International Working Group (IWG) 2018 criteria:
• Nontransfused (NTD): \<3 red blood cell (RBC) units in the 16-week period before administration of the first dose of study drug and no transfusions in the 8-week period before administration of the first dose of study drug, or
• LTB: 3 to 7 RBC units in the 16-week period before administration of the first dose of study drug and \<4 RBC units in the 8-week period before administration of the first dose of study drug;
• A hemoglobin (Hb) concentration \<11.0 grams per deciliter (g/dL) during the 4-week Screening Period;
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2;
• If taking iron chelation therapy, the iron chelation therapy dose must have been stable and started ≥56 days before administration of the first dose of study drug;
• Women of childbearing potential (WOCBP) must be abstinent of sexual activities that may result in pregnancy as part of their usual lifestyle or agree to use a highly effective method of contraception from the time of providing informed consent, throughout the study, and for 28 days after the last dose of study drug; if the highly effective method of contraception is hormonal contraception, then an acceptable barrier method must also be used. Men with partners who are WOCBP must be abstinent of sexual activities that may result in pregnancy as part of their usual lifestyle or agree to use a condom from the time of providing informed consent throughout the study and for 28 days after the last dose of study drug;
• Written informed consent from the participant before any study-related procedures are conducted and willing to comply with all study procedures for the duration of the study.
• Phase 2b
• At least 18 years of age at the time of providing informed consent;
• Documented diagnosis of MDS according to WHO classification (Arber et al, 2016), that meets IPSS-R classification of lower-risk disease (risk score: ≤3.5) and \<5% blasts as determined by the participant's bone marrow biopsy/aspirate during the Screening Period;
• With LTB, or high transfusion burden (HTB), based on transfusion history from the participant's medical record, according to revised IWG 2018 criteria:

You may not qualify if:

• Phase 2a
• Known history of acute myeloid leukemia (AML);
• Secondary MDS, defined as MDS that is known to have arisen as a result of chemical injury or treatment with chemotherapy and/or radiation for other diseases;
• Prior exposure to a pyruvate kinase activator and/or disease-modifying agents for underlying MDS:
• Immunomodulatory drugs (IMiDs) such as lenalidomide; at the Investigator's discretion and in consultation with the Medical Monitor, participants who received ≤1 week of treatment with IMiDs may not be excluded, provided their last dose was ≥8 weeks before administration of the first dose of study drug
• Hypomethylating agents (HMAs); at the Investigator's discretion and in consultation with the Medical Monitor, participants who received ≤2 doses of HMAs may not be excluded, provided that their last dose was ≥8 weeks before administration of the first dose of study drug
• Isocitrate dehydrogenase (IDH) inhibitors
• Immunosuppressive therapy (IST)
• Allogeneic or autologous stem cell transplant;
• Currently receiving treatment with ESAs±G-CSF and/or luspatercept. Treatment with ESAs±G-CSF must have been stopped for ≥28 days before administration of the first dose of study drug; treatment with luspatercept must have been stopped for ≥65 days before administration of the first dose of study drug;
• History of active and/or uncontrolled cardiac or pulmonary disease within 6 months before providing informed consent, including but not limited to:
• New York Heart Association Class III or IV heart failure or clinically significant dysrhythmia
• Myocardial infarction, unstable angina pectoris, or unstable hypertension; high risk thrombosis; hemorrhagic, embolic, or thrombotic stroke; deep venous thrombosis; or pulmonary or arterial embolism
• Heart rate-corrected QT interval using Fridericia's method of ≥470 milliseconds for female participants and ≥450 milliseconds for male participants, except for right or left bundle branch block
• Severe pulmonary fibrosis as defined by severe hypoxia, evidence of right-sided heart failure, and radiographic pulmonary fibrosis \>50%

Sponsors & Collaborators

• Agios Pharmaceuticals, Inc.: lead

Study Sites (45)

Innovative Clinical Research Institute Whittier

Lakewood, California, 90805, United States

Location

David Geffen School of Medicine at UCLA

Los Angeles, California, 90024, United States

Location

Emad Ibrahim, MD, Inc.

Redlands, California, 92373, United States

Location

Smilow Cancer Hospital at Yale New Haven

New Haven, Connecticut, 06510, United States

Location

Mayo Clinic Jacksonville - PPDS

Jacksonville, Florida, 32224, United States

Location

Edward H. Kaplan MD & Associates

Skokie, Illinois, 60076, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Memorial Sloan Kettering Cancer Center

Long Island City, New York, 11101, United States

Location

Duke Adult Blood and Marrow Clinic

Durham, North Carolina, 27705, United States

Location

Monash Health, Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

Ordensklinikum Linz GmbH Elisabethinen

Linz, Upper Austria, 4020, Austria

Location

Fakultni nemocnice Ostrava

Ostrava, 708 52, Czechia

Location

Hôpital de La Conception

Marseille, Bouches-du-Rhône, 13010, France

Location

CHU Angers

Angers, Maine-et-Loire, 49933, France

Location

CHRU Lille

Lille, 59037, France

Location

Hôpital Saint Louis

Paris, 75475, France

Location

Medizinische Hochschule Hannover

Hanover, Lower Saxony, 30625, Germany

Location

Universitatsklinikum Dusseldorf

Düsseldorf, North Rhine-Westphalia, 40225, Germany

Location

Universitatsklinikum Leipzig

Leipzig, Saxony, 04103, Germany

Location

University Hospital of Alexandroupolis

Alexandroupoli, Greece

Location

Attikon University General Hospital

Athens, Greece

Location

University General Hospital of Patras

Pátrai, Greece

Location

Hippokration Hospital

Thessaloniki, Greece

Location

Shaare Zedek Medical Center

Jerusalem, 9103102, Israel

Location

Tel Aviv Sourasky Medical Center PPDS

Tel Aviv, Israel

Location

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

Milan, Lombardy, Italy

Location

Fondazione IRCCS Policlinico San Matteo di Pavia

Pavia, Lombardy, Italy

Location

Istituto Clinico Humanitas

Rozzano, Lombardy, Italy

Location

Azienda Ospedaliera Ordine Mauriziano di Torino

Turin, Piedmont, Italy

Location

Fondazione PTV Policlinico Tor Vergata

Roma, Italy

Location

MTZ Clinical Research Powered by PRATIA - PPDS

Warsaw, Masovian Voivodeship, Poland

Location

Pratia Onkologia Katowice - PRATIA - PPDS

Katowice, Silesian Voivodeship, Poland

Location

SPZOZ MiSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie

Olsztyn, Warmian-Masurian Voivodeship, Poland

Location

Kyungpook National University Hospital

Daegu, 41944, South Korea

Location

Asan Medical Center - PPDS

Seoul, 05505, South Korea

Location

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, South Korea

Location

C.H. Regional Reina Sofia - PPDS

Córdoba, 14004, Spain

Location

Hospital Universitario La Paz - PPDS

Madrid, 28046, Spain

Location

Hospital Universitario HM Sanchinarro - CIOCC

Madrid, 28050, Spain

Location

Complejo Asistencial Universitario de Salamanca - H. Clinico

Salamanca, 37007, Spain

Location

Hospital Universitario Virgen del Rocio - PPDS

Seville, 41013, Spain

Location

Aberdeen Royal Infirmary - PPDS

Aberdeen, Aberdeen City, AB25 2ZN, United Kingdom

Location

Western General Hospital Edinburgh - PPDS

Edinburgh, EH24 2XU, United Kingdom

Location

Kings College Hospital

London, SE5 9RS, United Kingdom

Location

Churchill Hospital-NHS Oxford

Oxford, OX3 7LE, United Kingdom

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes; Anemia

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Medical Medical Affairs

  Agios Pharmaceuticals, Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2022
• First Posted: August 5, 2022
• Study Start: November 7, 2022
• Primary Completion: March 17, 2026
• Study Completion (Estimated): March 1, 2029
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); CZ (1); ES (5); IL (2); GB (4); DE (3); PL (3); US (9); FR (4); IT (5); GR (4); KR (3)