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En studie av AG-946 hos deltakere med anemi på grunn av myelodysplastiske syndromer med lavere risiko (LR-MDS)

25. september 2026 oppdatert av: Agios Pharmaceuticals, Inc.

En fase 2a/2b, åpen etikett, bevis på konsept (fase 2a) og dobbeltblind, randomisert, placebokontrollert (fase 2b), multisenter-, effektivitets- og sikkerhetsstudie av AG-946 hos deltakere med anemi på grunn av lavere -Risiko myelodysplastiske syndromer

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.

Studieoversikt

Status

Aktiv, ikke rekrutterende

Forhold

Intervensjon / Behandling

Studietype

Intervensjonell

Registrering (Faktiske)

87

Fase

  • Fase 2

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • Australia
    • Victoria
      • Clayton, Victoria, Australia, 3168
        • Monash Health, Monash Medical Centre
  • Forente stater
    • California
      • Lakewood, California, Forente stater, 90805
        • Innovative Clinical Research Institute Whittier
      • Los Angeles, California, Forente stater, 90024
        • David Geffen School of Medicine at UCLA
      • Redlands, California, Forente stater, 92373
        • Emad Ibrahim, MD, Inc.
    • Connecticut
      • New Haven, Connecticut, Forente stater, 06510
        • Smilow Cancer Hospital at Yale New Haven
    • Florida
      • Jacksonville, Florida, Forente stater, 32224
        • Mayo Clinic Jacksonville - PPDS
    • Illinois
      • Skokie, Illinois, Forente stater, 60076
        • Edward H. Kaplan MD & Associates
    • Missouri
      • St Louis, Missouri, Forente stater, 63110
        • Washington University School of Medicine
    • New York
      • Long Island City, New York, Forente stater, 11101
        • Memorial Sloan Kettering Cancer Center
    • North Carolina
      • Durham, North Carolina, Forente stater, 27705
        • Duke Adult Blood and Marrow Clinic
  • Frankrike
      • Lille, Frankrike, 59037
        • CHRU Lille
      • Paris, Frankrike, 75475
        • Hôpital Saint Louis
    • Bouches-du-Rhône
      • Marseille, Bouches-du-Rhône, Frankrike, 13010
        • Hôpital de La Conception
    • Maine-et-Loire
      • Angers, Maine-et-Loire, Frankrike, 49933
        • CHU Angers
  • Hellas
      • Alexandroupoli, Hellas
        • University Hospital of Alexandroupolis
      • Athens, Hellas
        • Attikon University General Hospital
      • Pátrai, Hellas
        • University General Hospital of Patras
      • Thessaloniki, Hellas
        • Hippokration Hospital
  • Israel
      • Jerusalem, Israel, 9103102
        • Shaare Zedek Medical Center
      • Tel Aviv, Israel
        • Tel Aviv Sourasky Medical Center PPDS
  • Italia
      • Roma, Italia
        • Fondazione PTV Policlinico Tor Vergata
    • Lombardy
      • Milan, Lombardy, Italia
        • Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
      • Pavia, Lombardy, Italia
        • Fondazione IRCCS Policlinico San Matteo di Pavia
      • Rozzano, Lombardy, Italia
        • Istituto Clinico Humanitas
    • Piedmont
      • Turin, Piedmont, Italia
        • Azienda Ospedaliera Ordine Mauriziano di Torino
  • Polen
    • Masovian Voivodeship
      • Warsaw, Masovian Voivodeship, Polen
        • MTZ Clinical Research Powered by PRATIA - PPDS
    • Silesian Voivodeship
      • Katowice, Silesian Voivodeship, Polen
        • Pratia Onkologia Katowice - PRATIA - PPDS
    • Warmian-Masurian Voivodeship
      • Olsztyn, Warmian-Masurian Voivodeship, Polen
        • SPZOZ MiSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie
  • Spania
      • Córdoba, Spania, 14004
        • C.H. Regional Reina Sofia - PPDS
      • Madrid, Spania, 28046
        • Hospital Universitario La Paz - PPDS
      • Madrid, Spania, 28050
        • Hospital Universitario HM Sanchinarro - CIOCC
      • Salamanca, Spania, 37007
        • Complejo Asistencial Universitario de Salamanca - H. Clinico
      • Seville, Spania, 41013
        • Hospital Universitario Virgen del Rocio - PPDS
  • Storbritannia
      • Edinburgh, Storbritannia, EH24 2XU
        • Western General Hospital Edinburgh - PPDS
      • London, Storbritannia, SE5 9RS
        • Kings College Hospital
      • Oxford, Storbritannia, OX3 7LE
        • Churchill Hospital-NHS Oxford
    • Aberdeen City
      • Aberdeen, Aberdeen City, Storbritannia, AB25 2ZN
        • Aberdeen Royal Infirmary - PPDS
  • Sør -Korea
      • Daegu, Sør -Korea, 41944
        • Kyungpook National University Hospital
      • Seoul, Sør -Korea, 05505
        • Asan Medical Center - PPDS
      • Seoul, Sør -Korea
        • The Catholic University of Korea, Seoul St. Mary's Hospital
  • Tsjekkia
      • Ostrava, Tsjekkia, 708 52
        • Fakultni nemocnice Ostrava
  • Tyskland
    • Lower Saxony
      • Hanover, Lower Saxony, Tyskland, 30625
        • Medizinische Hochschule Hannover
    • North Rhine-Westphalia
      • Düsseldorf, North Rhine-Westphalia, Tyskland, 40225
        • Universitatsklinikum Dusseldorf
    • Saxony
      • Leipzig, Saxony, Tyskland, 04103
        • Universitatsklinikum Leipzig
  • Østerrike
    • Upper Austria
      • Linz, Upper Austria, Østerrike, 4020
        • Ordensklinikum Linz GmbH Elisabethinen

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

Inclusion Criteria:

Phase 2a

  1. At least 18 years of age at the time of providing informed consent;

  2. 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;

  3. 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;

  4. A hemoglobin (Hb) concentration <11.0 grams per deciliter (g/dL) during the 4-week Screening Period;

  5. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2;

  6. 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;

  7. 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;

  8. 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

  1. At least 18 years of age at the time of providing informed consent;

  2. 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;

  3. With LTB, or high transfusion burden (HTB), based on transfusion history from the participant's medical record, according to revised IWG 2018 criteria:

    1. LTB: 3 to 7 RBC units from at least 2 transfusion episodes 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, or
    2. HTB: ≥8 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

    If a participant's transfusion burden does not fall into either the LTB or HTB category, as defined per IWG 2018 criteria, then the transfusion burden will be categorized based on their transfusion history in the 16-week period before administration of the first dose of study drug.

  4. Pretransfusion Hb concentration available for a minimum of 2 and at least half (50%) of the transfusions received in the 16-week period before administration of the first dose of study drug

  5. A Hb concentration <10.0 g/dL during the 4-week Screening Period;

  6. Up to 2 prior therapies including erythropoiesis-stimulating agents (ESAs) (eg, erythropoietin [EPO], EPO + granulocyte colony-stimulating factor [G-CSF]) and/or luspatercept;

  7. ECOG Performance Status score of 0, 1, or 2;

  8. 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;

  9. 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, 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 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;

  10. 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.

Exclusion Criteria:

Phase 2a

  1. Known history of acute myeloid leukemia (AML);

  2. 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;

  3. 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;

  4. 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;

  5. 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%
    • Severe pulmonary hypertension as defined by severe symptoms associated with hypoxia, right-sided heart failure, and oxygen indicated;

  6. History of hepatobiliary disorders, as defined by:

    • Serum aspartate aminotransferase (AST) >2.5 × upper limit of normal (ULN) (unless due to hemolysis and/or hepatic iron deposition) and alanine aminotransferase (ALT) >2.5 × ULN (unless due to hepatic iron deposition)
    • Serum bilirubin >ULN, if the elevation is associated with clinically symptomatic choledocholithiasis, cholecystitis, biliary obstruction, or hepatocellular disease;

  7. Renal dysfunction, as defined by an estimated glomerular filtration rate (eGFR) <45 milliliters per minute (mL/min)/1.73 m^2;

  8. Active infection requiring systemic antimicrobial therapy at the time of providing informed consent. If antimicrobial therapy is required during the Screening Period, screening procedures should not be performed while antimicrobial therapy is being administered, and the last dose of antimicrobial therapy must be administered ≥7 days before administration of the first dose of study drug;

  9. Major surgery within 12 weeks before administration of the first dose of study drug. Participants must have completely recovered from any previous surgery before administration of the first dose of study drug;

  10. For any malignancy except MDS: History of malignancy (active or treated) ≤5 years before providing informed consent for nonmelanomatous skin cancer in situ, cervical carcinoma in situ, or breast carcinoma in situ;

  11. Positive test for hepatitis C virus (HCV) antibody (Ab) with evidence of active HCV infection, or positive test for hepatitis B surface antigen (HBsAg);

  12. Positive test for HIV-1 Ab or HIV-2 Ab;

  13. Absolute neutrophil count (ANC) <500/microliter (μL) (0.5 × 10^9/L);

  14. Platelet count ≤75,000/μL during Screening (75 × 10^9/L) platelet transfusions within 28 days before Screening or during Screening;

  15. Nonfasting triglyceride concentration >500 mg/dL;

  16. Receiving inhibitors of P-glycoprotein (P-gp) that have not been stopped for ≥5 days or a time frame equivalent to 5 half-lives (whichever is longer) before administration of the first dose of study drug;

  17. Current enrollment or past participation (within 4 weeks or a time frame equivalent to 5 half-lives of the investigational study drug before administration of the first dose of study drug or, whichever is longer) in any other clinical study involving an investigational treatment or device;

  18. Known allergy to tebapivat or its excipients;

  19. Pregnant or breastfeeding;

  20. Any medical, hematologic, psychological, or behavioral condition(s) or prior or current therapy that, in the opinion of the Investigator, may confer an unacceptable risk to participating in the study and/or could confound the interpretation of the study data. Also excluded are:

    • Participants who are institutionalized by regulatory or court order;
    • Participants with any condition(s) that could create undue influence (including but not limited to incarceration, involuntary psychiatric confinement, and financial or familial affiliation with the Investigator or Sponsor).

Phase 2b

  1. Known history of AML;

  2. 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;

  3. Prior exposure to a pyruvate kinase activator, including exposure to tebapivat in the Phase 2a part of this study, and/or disease-modifying agents for underlying MDS:

    • Imetelstat; at the Investigator's discretion and in consultation with the Medical Monitor, participants who received ≤2 doses of imetelstat may not be excluded, provided that their last dose was ≥8 weeks before administration of the first dose of study drug
    • 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
    • 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
    • IDH inhibitors
    • IST
    • Allogeneic or autologous stem cell transplant;

  4. 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;

  5. 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%
    • Severe pulmonary hypertension as defined by severe symptoms associated with hypoxia, right-sided heart failure, and oxygen indicated

  6. History of hepatobiliary disorders, as defined by:

    • Serum AST >2.5 × ULN (unless due to hemolysis and/or hepatic iron deposition) and ALT >2.5 × ULN (unless due to hepatic iron deposition)
    • Serum bilirubin >ULN, if the elevation is associated with clinically symptomatic choledocholithiasis, cholecystitis, biliary obstruction, or hepatocellular disease

  7. Renal dysfunction, as defined by an eGFR <45 mL/min/1.73 m^2;

  8. Active infection requiring systemic antimicrobial therapy at the time of providing informed consent. If antimicrobial therapy is required during the Screening Period, screening procedures should not be performed while antimicrobial therapy is being administered, and the last dose of antimicrobial therapy must be administered ≥7 days before administration of the first dose of study drug;

  9. Major surgery within 12 weeks before administration of the first dose of study drug. Participants must have completely recovered from any previous surgery before administration of the first dose of study drug;

  10. For any malignancy except MDS: History of malignancy (active or treated) ≤5 years before providing informed consent, except for nonmelanomatous skin cancer in situ, cervical carcinoma in situ, or breast carcinoma in situ.;

  11. Positive test for HCV Ab with evidence of active HCV infection, or positive test for HBsAg;

  12. Positive test for HIV-1 Ab or HIV-2 Ab;

  13. ANC <500/μL (0.5 × 10^9/L);

  14. Platelet count < 75,000/μL (75 × 10^9 /L) during Screening; platelet transfusions within 28 days before Screening or during Screening;

  15. Nonfasting triglyceride concentration >500 mg/dL;

  16. Receiving inhibitors of P-gp that have not been stopped for ≥5 days or a time frame equivalent to 5 half-lives (whichever is longer) beforeadministration of the first dose of study drug;

  17. Current enrollment or past participation (within 4 weeks or a time frame equivalent to 5 half-lives of the investigational study drug before administration of the first dose of study drug or, whichever is longer) in any other clinical study involving an investigational treatment or device;

  18. Known allergy to tebapivat or its excipients;

  19. Pregnant or breastfeeding;

  20. Any medical, hematologic, psychological, or behavioral condition(s) or prior or current therapy that, in the opinion of the Investigator, may confer an unacceptable risk to participating in the study and/or could confound the interpretation of the study data. Also excluded are:

    • Participants who are institutionalized by regulatory or court order
    • Participants with any condition(s) that could create undue influence (including but not limited to incarceration, involuntary psychiatric confinement, and financial or familial affiliation with the Investigator or Sponsor).

  21. Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, autoimmune or hereditary hemolytic anemia, hypothyroidism, or any type of known clinically significant bleeding.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Ikke-randomisert
  • Intervensjonsmodell: Sekvensiell tildeling
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Core Period: Phase 2a - Tebapivat 5 mg

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.
Legemiddel: Tebapivat

Tebapivat Tablet

Andre navn:
  • AG-946
Eksperimentell: Core Period: Phase 2b - Tebapivat 10 mg

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.
Legemiddel: Tebapivat

Tebapivat Tablet

Andre navn:
  • AG-946
Eksperimentell: Core Period: Phase 2b - Tebapivat 15 mg

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.
Legemiddel: Tebapivat

Tebapivat Tablet

Andre navn:
  • AG-946
Eksperimentell: Core Period: Phase 2b - Tebapivat 20 mg

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.
Legemiddel: Tebapivat

Tebapivat Tablet

Andre navn:
  • AG-946

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Phase 2a: Proportion of Participants With Hemoglobin (Hb) Response
Tidsramme: Baseline, Week 8 through Week 16

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
Tidsramme: Up to 16 weeks

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
Tidsramme: Up to 24 weeks

Transfusion independence, defined as transfusion-free for ≥8 consecutive weeks (TI8) during the Core Period.
Up to 24 weeks

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Fase 2a: Endring fra baseline i Hb-konsentrasjon i løpet av kjerneperioden
Tidsramme: Baseline opptil 16 uker
Baseline opptil 16 uker
Fase 2a: Endring fra baseline i totalt transfuserte røde blodlegemer (RBC) enheter i løpet av kjerneperioden
Tidsramme: Baseline opptil 16 uker
Baseline opptil 16 uker
Fase 2a: Fullblodskonsentrasjoner av 2,3-difosfoglyserat (2,3-DPG) i løpet av kjerneperioden
Tidsramme: Dag 1 og uke 8 (≤60 minutter før dose og 0,5, 1, 2, 3, 4, 6 og 8 timer etter dose) og ved uke 2, 4, 12 og 16 (≤60 minutter før dose)
Dag 1 og uke 8 (≤60 minutter før dose og 0,5, 1, 2, 3, 4, 6 og 8 timer etter dose) og ved uke 2, 4, 12 og 16 (≤60 minutter før dose)
Fase 2a: Fullblodskonsentrasjoner av adenosintrifosfat (ATP) i løpet av kjerneperioden
Tidsramme: Dag 1 og uke 8 (≤60 minutter før dose og 0,5, 1, 2, 3, 4, 6 og 8 timer etter dose) og ved uke 2, 4, 12 og 16 (≤60 minutter før dose)
Dag 1 og uke 8 (≤60 minutter før dose og 0,5, 1, 2, 3, 4, 6 og 8 timer etter dose) og ved uke 2, 4, 12 og 16 (≤60 minutter før dose)
Fase 2b: Endring fra baseline i totalt transfunderte RBC-enheter fra uke 8 til uke 24
Tidsramme: Baseline, uke 8 til og med uke 24
Baseline, uke 8 til og med uke 24
Fase 2a: Andel deltakere med laboratorieavvik i kjerneperioden
Tidsramme: Inntil 16 uker
Inntil 16 uker
Fase 2a: Andel deltakere med ≥1,5-g/dL økning fra baseline i Hb-konsentrasjonen ved ≥2 påfølgende tidspunkter fra uke 8 til uke 16
Tidsramme: Baseline, uke 8 til og med uke 16
Baseline, uke 8 til og med uke 16
Fase 2a: Andel deltakere med ≥50 % reduksjon i totale transfunderte RBC-enheter i ≥8 påfølgende uker i løpet av kjerneperioden sammenlignet med baseline
Tidsramme: Baseline opptil 16 uker
Baseline opptil 16 uker
Fase 2a: Plasmakonsentrasjon av Tebapivat i løpet av kjerneperioden
Tidsramme: Dag 1 og uke 8 (≤60 minutter før dose og 0,5, 1, 2, 3, 4, 6 og 8 timer etter dose) og ved uke 2, 4, 12 og 16 (≤60 minutter før dose)
Dag 1 og uke 8 (≤60 minutter før dose og 0,5, 1, 2, 3, 4, 6 og 8 timer etter dose) og ved uke 2, 4, 12 og 16 (≤60 minutter før dose)
Fase 2a: Maksimal (topp) konsentrasjon (Cmax) av Tebapivat i løpet av kjerneperioden
Tidsramme: Dag 1 og uke 8 (≤60 minutter før dose og 0,5, 1, 2, 3, 4, 6 og 8 timer etter dose) og ved uke 2, 4, 12 og 16 (≤60 minutter før dose)
Dag 1 og uke 8 (≤60 minutter før dose og 0,5, 1, 2, 3, 4, 6 og 8 timer etter dose) og ved uke 2, 4, 12 og 16 (≤60 minutter før dose)
Fase 2a: Tid til Cmax (tmax) av Tebapivat under kjerneperioden
Tidsramme: Dag 1 og uke 8 (≤60 minutter før dose og 0,5, 1, 2, 3, 4, 6 og 8 timer etter dose) og ved uke 2, 4, 12 og 16 (≤60 minutter før dose)
Dag 1 og uke 8 (≤60 minutter før dose og 0,5, 1, 2, 3, 4, 6 og 8 timer etter dose) og ved uke 2, 4, 12 og 16 (≤60 minutter før dose)
Fase 2a: Areal under konsentrasjon-tidskurven fra 0 til t timer (AUC0-t) av Tebapivat i løpet av kjerneperioden
Tidsramme: Dag 1 og uke 8 (≤60 minutter før dose og 0,5, 1, 2, 3, 4, 6 og 8 timer etter dose) og ved uke 2, 4, 12 og 16 (≤60 minutter før dose)
Dag 1 og uke 8 (≤60 minutter før dose og 0,5, 1, 2, 3, 4, 6 og 8 timer etter dose) og ved uke 2, 4, 12 og 16 (≤60 minutter før dose)
Fase 2a: Areal under konsentrasjon-tidskurven fra 0 til slutten av doseringsintervallet (AUC0-τ) for Tebapivat i løpet av kjerneperioden
Tidsramme: Dag 1 og uke 8 (≤60 minutter før dose og 0,5, 1, 2, 3, 4, 6 og 8 timer etter dose) og ved uke 2, 4, 12 og 16 (≤60 minutter før dose)
Dag 1 og uke 8 (≤60 minutter før dose og 0,5, 1, 2, 3, 4, 6 og 8 timer etter dose) og ved uke 2, 4, 12 og 16 (≤60 minutter før dose)
Fase 2a: Tilsynelatende terminal eliminering Halveringstid (t½) av Tebapivat i løpet av kjerneperioden
Tidsramme: Dag 1 og uke 8 (≤60 minutter før dose og 0,5, 1, 2, 3, 4, 6 og 8 timer etter dose) og ved uke 2, 4, 12 og 16 (≤60 minutter før dose)
Dag 1 og uke 8 (≤60 minutter før dose og 0,5, 1, 2, 3, 4, 6 og 8 timer etter dose) og ved uke 2, 4, 12 og 16 (≤60 minutter før dose)
Fase 2b: Andel deltakere med laboratorieavvik i kjerneperioden
Tidsramme: Inntil 24 uker
Inntil 24 uker
Fase 2b: Endring fra baseline i Hb-konsentrasjon i løpet av kjerneperioden
Tidsramme: Baseline opptil 24 uker
Baseline opptil 24 uker
Fase 2b: Andel deltakere med ≥50 % reduksjon i totale transfunderte RBC-enheter i ≥8 påfølgende uker i løpet av kjerneperioden sammenlignet med baseline
Tidsramme: Baseline opptil 24 uker
Baseline opptil 24 uker
Fase 2b: Tid til første TI8 i løpet av kjerneperioden
Tidsramme: Baseline opptil 24 uker
Baseline opptil 24 uker
Fase 2b: Andel av deltakere som blir transfusjonsfrie i ≥12 sammenhengende uker (TI12) i løpet av kjerneperioden
Tidsramme: Inntil 24 uker
Inntil 24 uker
Fase 2b: Andel deltakere med ≥50 % reduksjon i totalt transfunderte RBC-enheter i ≥12 påfølgende uker i løpet av kjerneperioden sammenlignet med baseline
Tidsramme: Baseline opptil 24 uker
Baseline opptil 24 uker
Fase 2b: Tid til første TI12 i kjerneperioden
Tidsramme: Baseline opptil 24 uker
Baseline opptil 24 uker
Fase 2b: Plasmakonsentrasjon av Tebapivat i løpet av kjerneperioden
Tidsramme: Forhåndsdosering og flere tidspunkter etter dose fra dag 1 til uke 20
Forhåndsdosering og flere tidspunkter etter dose fra dag 1 til uke 20
Fase 2b: Maksimal (topp) konsentrasjon (Cmax) av Tebapivat i løpet av kjerneperioden
Tidsramme: Forhåndsdosering og flere tidspunkter etter dose fra dag 1 til uke 20
Forhåndsdosering og flere tidspunkter etter dose fra dag 1 til uke 20
Fase 2b: Tid til Cmax (tmax) av Tebapivat under kjerneperioden
Tidsramme: Forhåndsdosering og flere tidspunkter etter dose fra dag 1 til uke 20
Forhåndsdosering og flere tidspunkter etter dose fra dag 1 til uke 20
Fase 2b: Areal under konsentrasjon-tidskurven fra 0 til t timer (AUC0-t) av Tebapivat i løpet av kjerneperioden
Tidsramme: Forhåndsdosering og flere tidspunkter etter dose fra dag 1 til uke 20
Forhåndsdosering og flere tidspunkter etter dose fra dag 1 til uke 20
Fase 2b: Areal under konsentrasjon-tidskurven fra 0 til slutten av doseringsintervallet (AUC0-τ) av Tebapivat i løpet av kjerneperioden
Tidsramme: Forhåndsdosering og flere tidspunkter etter dose fra dag 1 til uke 20
Forhåndsdosering og flere tidspunkter etter dose fra dag 1 til uke 20
Fase 2b: Tilsynelatende terminal eliminering Halveringstid (t½) av Tebapivat i løpet av kjerneperioden
Tidsramme: Forhåndsdosering og flere tidspunkter etter dose fra dag 1 til uke 20
Forhåndsdosering og flere tidspunkter etter dose fra dag 1 til uke 20
Fase 2b: Fullblodskonsentrasjoner av 2,3-difosfoglyserat (2,3-DPG) i løpet av kjerneperioden
Tidsramme: Forhåndsdosering og flere tidspunkter etter dose fra dag 1 til uke 20
Forhåndsdosering og flere tidspunkter etter dose fra dag 1 til uke 20
Fase 2b: Fullblodskonsentrasjoner av adenosintrifosfat (ATP) i løpet av kjerneperioden
Tidsramme: Forhåndsdosering og flere tidspunkter etter dose fra dag 1 til uke 20
Forhåndsdosering og flere tidspunkter etter dose fra dag 1 til uke 20
Phase 2a: Proportion of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation During the Core Period
Tidsramme: Up to 16 weeks

An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. An SAE is any AE or suspected adverse reaction that results in death, is immediately life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, results in congenital anomaly/birth defect, or is considered an important medical event.
Up to 16 weeks
Phase 2a: Proportion of Participants With Hb 1.0+ Response
Tidsramme: Baseline, Week 8 through Week 16

Hb 1.0+ response is defined as a ≥1.0-g/dL increase from baseline in the average Hb concentration from Week 8 through Week 16
Baseline, Week 8 through Week 16
Phase 2b: Proportion of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation During the Core Period
Tidsramme: Up to 24 weeks

An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. An SAE is any AE or suspected adverse reaction that results in death, is immediately life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, results in congenital anomaly/birth defect, or is considered an important medical event.
Up to 24 weeks
Phase 2b: Duration of Transfusion Independence (TI)
Tidsramme: Baseline up to 24 weeks

The duration of TI will be calculated as the number of days in the longest transfusion-free period starting on or after the start of study treatment through the end of the Core Period.
Baseline up to 24 weeks

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Agios Pharmaceuticals, Inc.

Etterforskere

  • Studiestol: Medical Medical Affairs, Agios Pharmaceuticals, Inc.

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

7. november 2022

Primær fullføring (Faktiske)

17. mars 2026

Studiet fullført (Antatt)

1. mars 2029

Datoer for studieregistrering

Først innsendt

26. juli 2022

Først innsendt som oppfylte QC-kriteriene

4. august 2022

Først lagt ut (Faktiske)

5. august 2022

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

28. september 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

25. september 2026

Sist bekreftet

1. september 2026

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • AG946-C-002
  • 2022-500609-42-00 (Annen identifikator: EU-CTR)

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

NEI

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Ja

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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