Clinical Trials Logo

Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT05490446
Other study ID # AG946-C-002
Secondary ID 2022-500609-42-0
Status Active, not recruiting
Phase Phase 2
First received
Last updated
Start date November 7, 2022
Est. completion date November 2028

Study information

Verified date May 2024
Source Agios Pharmaceuticals, Inc.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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 placebo and to detect a dose response for erythroid response in participants with LR-MDS in Phase 2b.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 116
Est. completion date November 2028
Est. primary completion date November 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: 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; - An 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; - Nontransfused, with LTB, or with high transfusion burden (HTB), based on transfusion history from the participant's medical record, according to revised IWG 2018 criteria: - NTD: <3 RBC units in the 16-week period before randomization and no transfusions in the 8-week period before randomization, or - LTB: 3 to 7 RBC units in the 16-week period before randomization and <4 RBC units in the 8-week period before randomization, or - HTB: =8 RBC units in the 16-week period before randomization and =4 RBC units in the 8-week period before randomization; - An Hb concentration <11.0 g/dL during the 4-week Screening Period; - Up to 2 prior therapies including erythropoiesis-stimulating agents (ESAs) (eg, erythropoietin [EPO], EPO + granulocyte colony-stimulating factor [G-CSF]) and/or luspatercept; - 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 randomization; - 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; - 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 - 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% - Severe pulmonary hypertension as defined by severe symptoms associated with hypoxia, right-sided heart failure, and oxygen indicated; - 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; - Renal dysfunction, as defined by an estimated glomerular filtration rate (eGFR) <45 milliliters per minute (mL/min)/1.73 m^2; - 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; - 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; - 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; - Positive test for hepatitis C virus (HCV) antibody (Ab) with evidence of active HCV infection, or positive test for hepatitis B surface antigen (HBsAg); - Positive test for HIV-1 Ab or HIV-2 Ab; - Absolute neutrophil count (ANC) <500/microliter (µL) (0.5 × 109/L); - Platelet count =75,000/µL during Screening (75 × 109/L) platelet transfusions within 28 days before Screening or during Screening; - Nonfasting triglyceride concentration >500 mg/dL; - 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; - 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; - Known allergy to AG-946 or its excipients; - Pregnant or breastfeeding; - 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 - Known history of 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, including exposure to AG-946 in the Phase 2a part of this study, and/or disease-modifying agents for underlying MDS: - 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 randomization - 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 randomization - IDH inhibitors - 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 randomization; treatment with luspatercept must have been stopped for =65 days before randomization; - 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; - 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; - Renal dysfunction, as defined by an eGFR <45 mL/min/1.73 m^2; - 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 randomization; - Major surgery within 12 weeks before randomization. Participants must have completely recovered from any previous surgery before randomization; - 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.; - Positive test for HCV Ab with evidence of active HCV infection, or positive test for HBsAg; - Positive test for HIV-1 Ab or HIV-2 Ab; - ANC <500/µL (0.5 × 109/L); - Platelet count <50,000/µL (50 × 109/L) during Screening; platelet transfusions within 28 days before Screening or during Screening; - Nonfasting triglyceride concentration >500 mg/dL; - 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) before randomization; - Current enrollment or past participation (within 4 weeks or a time frame equivalent to 5 half-lives of the investigational study drug before randomization or, whichever is longer) in any other clinical study involving an investigational treatment or device; - Known allergy to AG-946 or its excipients, including placebo; - Pregnant or breastfeeding; - 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).

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
AG-946
AG-946 Tablet
Placebo
Matching-placebo Tablet

Locations

Country Name City State
Australia Monash Health, Monash Medical Centre Clayton Victoria
Austria Ordensklinikum Linz GmbH Elisabethinen Linz Oberösterreich
Czechia Fakultni nemocnice Ostrava Ostrava
France CHU Angers Angers Maine-et-Loire
France CHRU Lille Lille
France Hôpital de La Conception Marseille Bouches-du-Rhône
France Hôpital Saint Louis Paris
Germany Universitatsklinikum Dusseldorf Düsseldorf Nordrhein-Westfalen
Germany Medizinische Hochschule Hannover Hannover Niedersachsen
Germany Universitatsklinikum Leipzig Leipzig Sachsen
Greece University Hospital of Alexandroupolis Alexandroupolis
Greece Attikon University General Hospital Athens
Greece University General Hospital of Patras Patras
Greece Hippokration Hospital Thessaloniki
Israel Shaare Zedek Medical Center Jerusalem
Israel Tel Aviv Sourasky Medical Center PPDS Tel Aviv
Italy Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Milano Lombardia
Italy Fondazione IRCCS Policlinico San Matteo di Pavia Pavia Lombardia
Italy Fondazione PTV Policlinico Tor Vergata Roma
Italy Istituto Clinico Humanitas Rozzano Lombardia
Italy Azienda Ospedaliera Ordine Mauriziano di Torino Torino Piemonte
Korea, Republic of Kyungpook National University Hospital Daegu
Korea, Republic of Asan Medical Center - PPDS Seoul
Korea, Republic of The Catholic University of Korea, Seoul St. Mary's Hospital Seoul
Poland Pratia Onkologia Katowice - PRATIA - PPDS Katowice Slaskie
Poland SPZOZ MiSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie Olsztyn Warminsko-mazurskie
Poland MTZ Clinical Research Powered by PRATIA - PPDS Warszawa Mazowieckie
Spain C.H. Regional Reina Sofia - PPDS Cordoba
Spain Hospital Universitario HM Sanchinarro - CIOCC Madrid
Spain Hospital Universitario La Paz - PPDS Madrid
Spain Complejo Asistencial Universitario de Salamanca - H. Clinico Salamanca
Spain Hospital Universitario Virgen del Rocio - PPDS Sevilla
United Kingdom Aberdeen Royal Infirmary - PPDS Aberdeen Aberdeen City
United Kingdom Western General Hospital Edinburgh - PPDS Edinburgh
United Kingdom Kings College Hospital London
United Kingdom Churchill Hospital-NHS Oxford Oxford
United States Duke Adult Blood and Marrow Clinic Durham North Carolina
United States Mayo Clinic Jacksonville - PPDS Jacksonville Florida
United States Innovative Clinical Research Institute Whittier Lakewood California
United States Memorial Sloan Kettering Cancer Center Long Island City New York
United States David Geffen School of Medicine at UCLA Los Angeles California
United States Emad Ibrahim, MD, Inc. Redlands California
United States Washington University School of Medicine Saint Louis Missouri
United States Edward H. Kaplan MD & Associates Skokie Illinois

Sponsors (1)

Lead Sponsor Collaborator
Agios Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Czechia,  France,  Germany,  Greece,  Israel,  Italy,  Korea, Republic of,  Poland,  Spain,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Phase 2a: Number 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
Primary Phase 2a: Number 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
Primary Phase 2b: Number of Participants With Modified Hematologic Improvement-erythroid (mHI-E) Response mHI-E Response is defined as:
=1.5-g/dL increase from baseline in Hb concentration for =8 consecutive weeks during the Double-blind Period (participants who are nontransfused [NTD])
Transfusion independence, defined as transfusion-free for =8 consecutive weeks during the Double-blind Period (participants with LTB only)
=50% reduction in total transfused RBC units for =8 consecutive weeks during the Double-blind Period compared with baseline (participants with high transfusion burden [HTB] only)
Up to 24 weeks
Secondary Phase 2a: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation During the Core Period An AE is any untoward medical occurrence in a patient 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
Secondary Phase 2a: Number of Participants With Laboratory Abnormalities During the Core Period Up to 16 weeks
Secondary Phase 2a: Number of Participants With Hb 1.0+ Response 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
Secondary Phase 2a: Change From Baseline in Hb Concentration During the Core Period Baseline up to 16 weeks
Secondary Phase 2a: Number 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
Secondary Phase 2a: Change from Baseline in Total Transfused Red Blood Cell (RBC) Units During the Core Period Baseline up to 16 weeks
Secondary Phase 2a: Number of Participants With =50% Reduction in Total Transfused RBC Units for =8 Consecutive Weeks During the Core Period Compared With Baseline Baseline up to 16 weeks
Secondary Phase 2a: Plasma Concentration of AG-946 During the Core Period Day 1 and Week 8 (=60 minutes predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and at Weeks 2, 4, 12, and 16 (=60 minutes predose)
Secondary Phase 2a: Maximum (Peak) Concentration (Cmax) of AG-946 During the Core Period Day 1 and Week 8 (=60 minutes predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and at Weeks 2, 4, 12, and 16 (=60 minutes predose)
Secondary Phase 2a: Time to Cmax (tmax) of AG-946 During the Core Period Day 1 and Week 8 (=60 minutes predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and at Weeks 2, 4, 12, and 16 (=60 minutes predose)
Secondary Phase 2a: Area Under the Concentration-time Curve From 0 to t Hours (AUC0-t) of AG-946 During the Core Period Day 1 and Week 8 (=60 minutes predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and at Weeks 2, 4, 12, and 16 (=60 minutes predose)
Secondary Phase 2a: Area Under the Concentration-time Curve From 0 to the End of the Dosing Interval (AUC0-t) of AG-946 During the Core Period Day 1 and Week 8 (=60 minutes predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and at Weeks 2, 4, 12, and 16 (=60 minutes predose)
Secondary Phase 2a: Apparent Terminal Elimination Half-life (t½) of AG-946 During the Core Period Day 1 and Week 8 (=60 minutes predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and at Weeks 2, 4, 12, and 16 (=60 minutes predose)
Secondary Phase 2a: Whole Blood Concentrations of 2,3-diphosphoglycerate (2,3-DPG) During the Core Period Day 1 and Week 8 (=60 minutes predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and at Weeks 2, 4, 12, and 16 (=60 minutes predose)
Secondary Phase 2a: Whole Blood Concentrations of Adenosine Triphosphate (ATP) During the Core Period Day 1 and Week 8 (=60 minutes predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and at Weeks 2, 4, 12, and 16 (=60 minutes predose)
Secondary Phase 2b: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation During the Double-blind Period An AE is any untoward medical occurrence in a patient 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
Secondary Phase 2b: Change From Baseline in Hb Concentration During the Double-Blind Period Baseline up to 24 weeks
Secondary Phase 2b: Change From Baseline in Total Transfused RBC Units From Week 8 Through Week 24 Baseline, Week 8 through Week 24
Secondary Phase 2b: Number of Participants With Transfusion Independence during the Double-blind Period Transfusion independence is defined as transfusion-free for =8 consecutive weeks during the Double-blind Period. Baseline up to 24 weeks
Secondary Phase 2b: Time to First mHI-E Response During the Double-blind Period mHI-E Response is defined as:
=1.5-g/dL increase from baseline in Hb concentration for =8 consecutive weeks during the Double-blind Period (participants who are NTD)
Transfusion independence, defined as transfusion-free for =8 consecutive weeks during the Double-blind Period (participants with LTB only)
=50% reduction in total transfused RBC units for =8 consecutive weeks during the Double-blind Period compared with baseline (participants with HTB only)
Baseline up to 24 weeks
Secondary Phase 2b: Maximum Duration of mHI-E Response for Participants Who Achieved an mHI-E Response During the Double-blind Period mHI-E Response is defined as:
=1.5-g/dL increase from baseline in Hb concentration for =8 consecutive weeks during the Double-blind Period (participants who are NTD)
Transfusion independence, defined as transfusion-free for =8 consecutive weeks during the Double-blind Period (participants with LTB only)
=50% reduction in total transfused RBC units for =8 consecutive weeks during the Double-blind Period compared with baseline (participants with HTB only)
Baseline up to 24 weeks
Secondary Phase 2b: Plasma Concentration of AG-946 During the Double-blind Period Day 1 and Week 8 (=60 minutes predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and at Weeks 2, 4, 12, and 16 (=60 minutes predose)
Secondary Phase 2b: Maximum (Peak) Concentration (Cmax) of AG-946 During the Double-blind Period Day 1 and Week 8 (=60 minutes predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and at Weeks 2, 4, 12, and 16 (=60 minutes predose)
Secondary Phase 2b: Time to Cmax (tmax) of AG-946 During the Double-blind Period Day 1 and Week 8 (=60 minutes predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and at Weeks 2, 4, 12, and 16 (=60 minutes predose)
Secondary Phase 2b: Area Under the Concentration-time Curve From 0 to t Hours (AUC0-t) of AG-946 During the Double-blind Period Day 1 and Week 8 (=60 minutes predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and at Weeks 2, 4, 12, and 16 (=60 minutes predose)
Secondary Phase 2b: Area Under the Concentration-time Curve From 0 to the End of the Dosing Interval (AUC0-t) of AG-946 During the Double-blind Period Day 1 and Week 8 (=60 minutes predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and at Weeks 2, 4, 12, and 16 (=60 minutes predose)
Secondary Phase 2b: Apparent Terminal Elimination Half-life (t½) of AG-946 During the Double-blind Period Day 1 and Week 8 (=60 minutes predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and at Weeks 2, 4, 12, and 16 (=60 minutes predose)
Secondary Phase 2b: Whole Blood Concentrations of 2,3-diphosphoglycerate (2,3-DPG) During the Double-blind Period Day 1 and Week 8 (=60 minutes predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and at Weeks 2, 4, 12, and 16 (=60 minutes predose)
Secondary Phase 2b: Whole Blood Concentrations of Adenosine Triphosphate (ATP) During the Double-blind Period Day 1 and Week 8 (=60 minutes predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and at Weeks 2, 4, 12, and 16 (=60 minutes predose)
Secondary Phase 2b: Correlation Between AG-946 Plasma Concentration/exposure and Percentage of Participants With mHI-E Response During the Double-blind Period, as Assessed by Regression Analysis mHI-E Response is defined as:
=1.5-g/dL increase from baseline in Hb concentration for =8 consecutive weeks during the Double-blind Period (participants who are NTD)
Transfusion independence, defined as transfusion-free for =8 consecutive weeks during the Double-blind Period (participants with LTB only)
=50% reduction in total transfused RBC units for =8 consecutive weeks during the Double-blind Period compared with baseline (participants with HTB only)
Baseline up to 24 weeks
Secondary Phase 2b: Correlation Between AG-946 Plasma Concentration/exposure and Change From Baseline in Hb Concentration During the Double-blind Period, as Assessed by Regression Analysis Baseline up to 24 weeks
Secondary Phase 2b: Correlation Between AG-946 Plasma Concentration/exposure and Percentage of Participants Having AEs of Clinical Interest During the Double-blind Period, as Assessed by Regression Analysis AEs of special interest will be determined during the study. Baseline up to 24 weeks
See also
  Status Clinical Trial Phase
Recruiting NCT05400122 - Natural Killer (NK) Cells in Combination With Interleukin-2 (IL-2) and Transforming Growth Factor Beta (TGFbeta) Receptor I Inhibitor Vactosertib in Cancer Phase 1
Terminated NCT04313881 - Magrolimab + Azacitidine Versus Azacitidine + Placebo in Untreated Participants With Myelodysplastic Syndrome (MDS) Phase 3
Recruiting NCT05088356 - Reduced Intensity Allogeneic HCT in Advanced Hematologic Malignancies w/T-Cell Depleted Graft Phase 1
Recruiting NCT04003220 - Idiopathic Chronic Thrombocytopenia of Undetermined Significance : Pathogenesis and Biomarker
Completed NCT02916979 - Myeloid-Derived Suppressor Cells and Checkpoint Immune Regulators' Expression in Allogeneic SCT Using FluBuATG Phase 1
Active, not recruiting NCT03755414 - Study of Itacitinib for the Prophylaxis of Graft-Versus-Host Disease and Cytokine Release Syndrome After T-cell Replete Haploidentical Peripheral Blood Hematopoietic Cell Transplantation Phase 1
Completed NCT00003270 - Chemotherapy, Radiation Therapy, and Umbilical Cord Blood Transplantation in Treating Patients With Hematologic Cancer Phase 2
Recruiting NCT04904588 - HLA-Mismatched Unrelated Donor Hematopoietic Cell Transplantation With Post-Transplantation Cyclophosphamide Phase 2
Terminated NCT04866056 - Jaktinib and Azacitidine In Treating Patients With MDS With MF or MDS/MPN With MF. Phase 1/Phase 2
Recruiting NCT04701229 - Haploinsufficiency of the RBM22 and SLU7 Genes in Del(5q) Myelodysplastic Syndromes
Suspended NCT04485065 - Safety and Efficacy of IBI188 With Azacitidine in Subjects With Newly Diagnosed Higher Risk MDS Phase 1
Recruiting NCT04174547 - An European Platform for Translational Research in Myelodysplastic Syndromes
Enrolling by invitation NCT04093570 - A Study for Participants Who Participated in Prior Clinical Studies of ASTX727 (Standard Dose), With a Food Effect Substudy at Select Study Centers Phase 2
Completed NCT02508870 - A Study of Atezolizumab Administered Alone or in Combination With Azacitidine in Participants With Myelodysplastic Syndromes Phase 1
Completed NCT04543305 - A Study of PRT1419 in Patients With Relapsed/Refractory Hematologic Malignancies Phase 1
Recruiting NCT05384691 - Efficacy of Luspatercept in ESA-naive LR-MDS Patients With or Without Ring Sideroblasts Who do Not Require Transfusions Phase 2
Recruiting NCT05365035 - A Phase II Study of Cladribine and Low Dose Cytarabine in Combination With Venetoclax, Alternating With Azacitidine and Venetoclax, in Patients With Higher-risk Myeloproliferative Chronic Myelomonocytic Leukemia or Higher-risk Myelodysplastic Syndromes With Excess Blasts Phase 2
Recruiting NCT06008405 - Clinical Trial Evaluating the Safety of the TQB2928 Injection Combination Therapy Phase 1
Not yet recruiting NCT05969821 - Clonal Hematopoiesis of Immunological Significance
Withdrawn NCT05170828 - Cryopreserved MMUD BM With PTCy for Hematologic Malignancies Phase 1