A phase 1 study of ACE-536, a regulator of erythroid differentiation, in healthy volunteers

American Journal of Hematology

Volumn 89, Issue 7, 2014, Pages 766-770

  Attie, Kenneth M ^a   Allison, Mark J ^b   Mcclure, Ty ^a   Boyd, Ingrid E ^a   Wilson, Dawn M ^a   Pearsall, Amelia E ^a   Sherman, Matthew L ^a  

^a Acceleron Pharma Inc   (United States)

^b CELERION   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HEMOGLOBIN; LUSPATERCEPT; PLACEBO;

ADULT; AREA UNDER THE CURVE; ARTICLE; CELL DIFFERENTIATION; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG ABSORPTION; DRUG CLEARANCE; DRUG SAFETY; DRUG TOLERABILITY; DRY SKIN; ELEVATED BLOOD PRESSURE; ERYTHROID PRECURSOR CELL; FEMALE; HEADACHE; HEMOGLOBIN BLOOD LEVEL; HEMOGLOBIN DETERMINATION; HUMAN; HUMAN EXPERIMENT; HYPERESTHESIA; INJECTION SITE BLEEDING; INJECTION SITE PAIN; MAXIMUM PLASMA CONCENTRATION; MIDDLE AGED; MUSCLE SPASM; MYALGIA; NORMAL HUMAN; PAPULAR RASH; PHASE 1 CLINICAL TRIAL; POSTMENOPAUSE; PRIORITY JOURNAL; PRURITUS; RANDOMIZED CONTROLLED TRIAL; TREATMENT OUTCOME; VITAL SIGN;

ACTIVIN RECEPTORS, TYPE II; AGED; CELL DIFFERENTIATION; COHORT STUDIES; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; ERYTHROID PRECURSOR CELLS; ERYTHROPOIESIS; FEMALE; HUMANS; INJECTIONS, SUBCUTANEOUS; MIDDLE AGED; POSTMENOPAUSE;

EID: 84902829071     PISSN: 03618609     EISSN: 10968652     Source Type: Journal    
DOI: 10.1002/ajh.23732     Document Type: Article

References (15)

1. Doshi S, Krzyzanski W, Yue S, et al. Clinical pharmacokinetics and pharmacodynamics of erythropoiesis-stimulating agents. Clin Pharmacokinet 2013;52:1063-1083.
2. Söderberg SS, Karlsson G, Karlsson S. Complex and context dependent regulation of hematopoiesis by TGF-β superfamily signaling. Ann NY Acad Sci 2009;1176:55-69.
3. Iancu-Rubin C, Mosoyan G, Wang J, et al. Stromal cell-mediated inhibition of erythropoiesis can be attenuated by sotatercept (ACE-011), an activin receptor type II ligand trap. Exp Hematol 2013;41:155-166.
4. Ginzburg Y, Rivella S. β-thalassemia: A model for elucidating the dynamic regulation of ineffective erythropoiesis and iron metabolism. Blood 2011;118:4321-4330.
5. Gardenghi S, Marongiu MF, Ramos P, et al. Ineffective erythropoiesis in β-thalassemia is characterized by increased iron absorption mediated by down-regulation of hepcidin and up-regulation of ferroportin. Blood 2007;109:5027-5035.
6. Santini V, Girelli D, Sanna A, et al. Hepcidin levels and their determinants in different types of myelodysplastic syndromes. PLoS One 2011;6:e23109.
7. Zhou L, Nguyen AN, Sohal D, et al. Inhibition of the TGF-beta receptor I kinase promotes hematopoiesis in MDS. Blood 2008;112:3434-3443.
8. Oh SP, Yeo CY, Lee Y, et al. Activin type IIA and IIB receptors mediate GDF11 signaling in axial vertebral patterning. Gene Dev 2002;16:2749-2754.
9. McPherron AC, Lawler AM, Lee SJ. Regulation of anterior/posterior patterning of the axial skeleton by growth/differentiation factor 11. Nat Genet 1999;22:260.
10. Suragani RN, Cadena SM, Cawley SM, et al. Transforming growth factor-β superfamily ligand trap ACE-536 corrects anemia by promoting late-stage erythropoiesis. Nat Med 2014;20:408-414.
11. Ruckle J, Jacobs M, Kramer W, et al. Single-dose, randomized, double-blind, placebo-controlled study of ACE-011 (ActRIIA-IgG1) in postmenopausal women. J Bone Miner Res 2009;24:744-752.
12. Sherman ML, Borgstein NG, Mook L, et al. Multiple-dose, safety, pharmacokinetic, and pharmacodynamic study of sotatercept (ActRIIA-IgG1), a novel erythropoietic agent, in healthy postmenopausal women. J Clin Pharmacol 2013;53:1121-1130.
13. Dussiot M, Taciel TT, Fricot A, et al. An activin receptor IIA ligand trap corrects ineffective erythropoiesis in β-thalassemia. Nat Med 2014;20:398-407.
14. Sako D, Grinberg AV, Liu J, et al. Characterization of the ligand binding functionality of the extracellular domain of activin receptor type IIb. J Biol Chem 2010;285:21037-21048.
15. Suragani RN, Li R, Cawley S, et al. ACE-536 improves ineffective erythropoiesis, anemia and co-morbidities in β-thalassemia. Blood 2012;120:248.