Introduction: Lower-risk MDS is characterized by anemia and ineffective erythropoiesis leading to RBC transfusion dependence. Effective treatment for anemia remains an unmet medical need. Patients with MDS may also experience additional cytopenias that may complicate treatment and contribute to infections and bleeding events. Here, we report hematologic improvement (HI) outcomes for patients in the MEDALIST trial (ClinicalTrials.gov identifier: NCT02631070), a phase 3, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of luspatercept, a first-in-class erythroid maturation agent that binds select TGF-β superfamily ligands to reduce aberrant Smad2/3 signaling and enhance late-stage erythropoiesis. Methods: Eligible patients in the MEDALIST trial were adults with anemia due to Very low-, Low-, or Intermediate-risk MDS with RS according to the Revised International Prognostic Scoring System; were refractory, intolerant, or ineligible to receive erythropoiesis-stimulating agents (ESAs); and required RBC transfusions. Patients received luspatercept (starting dose of 1.0 mg/kg and titration up to 1.75 mg/kg, if needed) or placebo subcutaneously every 3 weeks for ≥ 24 weeks. Platelet and neutrophil counts were assessed by the central laboratory. Secondary endpoints included HI-neutrophil (HI-N) and -platelet (HI-P) responses, using International Working Group 2006 criteria, over any consecutive 56-day period. Mean changes from baseline in platelets and neutrophils were also evaluated. Results*: A total of 94.8% patients in the luspatercept arm and 97.4% in the placebo arm had refractory cytopenia with multilineage dysplasia and RS at baseline. Mean neutrophil and platelet counts at baseline for patients in the luspatercept arm were 2.8 x 109/L and 259 x 109/L, respectively, and in the placebo arm were 2.7 x 109/L and 252 x 109/L, respectively. Neutropenia (< 1 x 109/L) was confirmed at baseline in 15 (9.8%) and 10 (13.2%) patients in the luspatercept and placebo arms, respectively. Fifty-one (33.3%) patients in the luspatercept arm and 22 (28.9%) in the placebo arm received granulocyte colony-stimulating factor in combination with ESAs prior to randomization. A total of 8 (5.2%) and 6 (7.9%) patients receiving luspatercept and placebo, respectively, had baseline thrombocytopenia (< 100 x 109/L); no patients received prior platelet transfusions. Fifteen (9.8%) and 10 (13.2%) patients in the luspatercept and placebo arms, respectively, were evaluable for HI-N (i.e. baseline neutrophils < 1 x 109/L); 3/15 (20%) of those receiving luspatercept and 1/10 (10%) of those receiving placebo achieved HI-N in Weeks 1-48. Among patients who were evaluable for HI-P (i.e. baseline platelets < 100 x 109/L), 5/8 (62.5%) of those receiving luspatercept and 2/6 (33%) of those receiving placebo achieved HI-P in Weeks 1-48 (Table). None of the luspatercept HI-P responders received platelet transfusions. Mean changes from baseline in neutrophils of 0.94 x 109/L with luspatercept and 0.04 x 109/L with placebo were observed at Week 15, with early increases reported for luspatercept by Day 8 (0.86 vs 0.08 x 109/L for placebo). Mean increases in neutrophils at Day 8 occurred in both luspatercept responders (by MEDALIST primary endpoint; 1.0 x 109/L) and non-responders (0.8 x 109/L). Mean changes from baseline in platelets of 29 x 109/L were observed with luspatercept and 0.9 x 109/L with placebo by Week 12, but early increases were observed with luspatercept by Day 8 (18 vs 3 x 109/L for placebo) and mean increases in platelets at Day 8 occurred in both luspatercept responders (21.4 x 109/L) and non-responders (16.5 x 109/L). No patients in either arm experienced grade 3 or 4 treatment-emergent thrombocytopenia. Treatment-related grade 3 or 4 neutropenia was reported in 1 (0.7%) patient receiving luspatercept and 1 (1.3%) patient receiving placebo. Conclusions: Although only a minority of patients were evaluable for HI-P/HI-N response based on entry criteria for the study, luspatercept treatment resulted in a mean increase from baseline in platelet and neutrophil counts in most patients overall vs placebo, regardless of response status. These improvements were observed early following treatment initiation and then stabilized. Luspatercept did not contribute to the worsening of cytopenias vs placebo. *Data cutoff: May 8, 2018. [Formula presented] Disclosures: Garcia-Manero: Amphivena: Consultancy, Research Funding; Helsinn: Research Funding; Novartis: Research Funding; AbbVie: Research Funding; Celgene: Consultancy, Research Funding; Astex: Consultancy, Research Funding; Onconova: Research Funding; H3 Biomedicine: Research Funding; Merck: Research Funding. Mufti: Celgene Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Cellectis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Fenaux: Celgene Corporation: Honoraria, Research Funding; Astex: Honoraria, Research Funding; Jazz: Honoraria, Research Funding; Aprea: Research Funding. Buckstein: Takeda: Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Santini: Acceleron: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Menarini: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Honoraria. Díez-Campelo: Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Finelli: Celgene Corporation: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau. Sekeres: Syros: Membership on an entity's Board of Directors or advisory committees; Millenium: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. List: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Laadem: Celgene Corporation: Employment, Equity Ownership. Ito: Celgene Corporation: Employment, Equity Ownership. Zhang: Celgene Corporation: Employment, Equity Ownership. Rampersad: Celgene Corp: Employment, Equity Ownership. Sinsimer: Celgene Corporation: Employment, Equity Ownership. Linde: Fibrogen, Inc.: Equity Ownership; Abbott Laboratories, Inc.: Equity Ownership; Acceleron Pharma: Employment, Equity Ownership. Platzbecker: Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria. Komrokji: Alexion: Speakers Bureau; Incyte: Consultancy; Janssen: Consultancy; Agios: Consultancy; Celgene: Consultancy; Pfizer: Consultancy; Jazz: Speakers Bureau;

DSI:

Consultancy; Novartis: Speakers Bureau. OffLabel Disclosure: Luspatercept is an investigational therapy that is not approved for any use in any country. Luspatercept is currently being evaluated for potential use in patients with anemia due to myelodysplastic syndromes, beta-thalassemia, or myelofibrosis.

Background: Current therapies for ITP and wAIHA are mostly symptomatic and rarely lead to durable responses after discontinuation; thus, chronic treatment is often needed, which may be associated with toxicity and substantial quality‐of‐life burden for patients. There is an unmet need for disease‐modifying therapies that can induce and maintain durable responses beyond treatment completion in ITP and wAIHA. BAFF is an important regulator of B‐cell differentiation, proliferation and survival through interactions with BAFF‐R. Autoreactive B cells play a key role in the pathophysiology of ITP and wAIHA and are fueled by increased BAFF pathway activity; therefore, there is a strong rationale for investigating BAFF‐R as a target in both diseases. Ianalumab is a fully human mAb that targets BAFF‐R. It has a novel dual mechanism of action: blockade of BAFF‐R‐mediated signaling and potent depletion of B cells mediated by antibody‐dependent cellular cytotoxicity. Ianalumab has shown favorable safety and encouraging efficacy in other indications, including SjS, SLE and CLL, and is a promising potential treatment for ITP and wAIHA. As ianalumab is being investigated in ongoing, blinded Phase III trials in ITP and wAIHA, we present the safety profile of ianalumab from completed Phase I/II studies in SjS, SLE or CLL. Methods: Data for patients with SjS were from a randomized Phase IIb trial (NCT02962895); patients (N=190) received subcutaneous (SC) placebo or ianalumab 5, 50 or 300 mg every 4 weeks (wks) for 24 wks. Patients then entered a second treatment period; patients in the ianalumab 5 or 50 mg arm continued the same dose, patients in the ianalumab 300 mg arm were randomized to continue the same dose or receive placebo, and patients in the placebo arm switched to ianalumab 150 mg. Safety data in patients with SLE were collected from a randomized Phase II trial (NCT03656562). Patients (N=67) received SC ianalumab 300 mg or placebo every 4 wks for 28 wks; patients in the placebo group could switch to ianalumab in a 20‐wk open‐label extension. Data for patients with CLL were from a Phase Ib trial (NCT03400176); patients (N=32) received intravenous (IV) ianalumab 0.3, 1, 3 or 9 mg/kg every 2 wks plus ibrutinib 420 mg once daily for up to 8 28‐day cycles. Safety assessments included adverse events (AEs), serious AEs (SAEs) and AEs of special interest. Results: Ianalumab was safe and well tolerated in patients with SjS. Most AEs were mild or moderate in severity; severe AEs were reported in 5 patients receiving ianalumab. Three ianalumab‐treated patients had SAEs; 2 SAEs in 1 patient (appendicitis and tubo‐ovarian abscess) were considered related to ianalumab treatment. Frequency of infections/infestations was similar between patients treated with ianalumab and placebo. Discontinuation rates were low, with only 4 patients discontinuing ianalumab for non‐serious AEs (infection [n=2], lymphopenia, local injection‐site reaction [n=1 each]); no SAEs led to treatment discontinuation. Ianalumab continued to be well tolerated in the second treatment period. There were no dose‐dependent differences in the rate of AEs except for injection‐site reactions (mostly local and not severe). In ianalumab‐treated patients with SLE, there were no serious infections during the blinded period; only 1 SAE (renal impairment) was reported. In the open‐label extension, 4 SAEs were reported. No SAEs in the blinded period or open‐label extension were considered treatment related. Most AEs in patients with CLL were Grade 1 or 2 and not correlated with dose. Twelve patients experienced Grade ≥3 AEs; decreased neutrophil count (n=5) was most common. No dose‐limiting toxicities were reported. Discussion: Data from patients with SjS, SLE or CLL receiving ianalumab for up to 52 wks show it has a favorable safety profile. There was a low risk of infections irrespective of dosing regimen. No cases of hypogammaglobulinemia were clinically significant in any trial. New treatments are needed for ITP and wAIHA that have disease‐modifying potential and allow patients to achieve and maintain high response rates after a short therapeutic course. Ianalumab has the potential to address this unmet need and is currently being assessed as an IV dose every 4 wks in Phase III trials as both a first‐ (VAYHIT1 [NCT05653349]) and second‐line (VAYHIT2 [NCT05653219]) treatment for ITP and as a second‐line treatment for wAIHA (VAYHIA [NCT05648968]).

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Este artículo no tiene resumen

INTERVENTION:

Trade Name: EXJADE Product Name: EXJADE Product Code: ICL670 Pharmaceutical Form: Dispersible tablet INN or Proposed

INN:

deferasirox CAS Number: 201530‐41‐8 Current Sponsor code: ICL670 Other descriptive name: EXJADE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 125‐ Trade Name: EXJADE Product Name: EXJADE Product Code: ICL670 Pharmaceutical Form: Dispersible tablet INN or Proposed

INN:

deferasirox CAS Number: 201530‐41‐8 Current Sponsor code: ICL670 Other descriptive name: EXJADE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 250‐ Trade Name: EXJADE Product Name: EXJADE Product Code: ICL670 Pharmaceutical Form: Dispersible tablet INN or Proposed

INN:

deferasirox CAS Number: 201530‐41‐8 Current Sponsor code: ICL670 Other descriptive name: EXJADE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 500‐

CONDITION:

Pacientes con diagnóstico de sobrecarga de hierro crónica con anemia dependiente de transfusiones distintas a ß‐talasemia y drepanocitosis

PRIMARY OUTCOME:

Main Objective: ?Evaluar la eficacia del tratamiento con deferasirox según el cambio de la CHH, con dosis iniciales de deferasirox según la tasa de transfusión y el objetivo terapéutico, en pacientes con anemias crónicas y hemosiderosis transfusional distintas a la ?‐talassemia2 y la drepanocitosis Primary end point(s): ? Como principales parámetros de la eficacia se emplearán las variaciones en la CHH en la población global después de un año de tratamiento Secondary Objective: ? ? Evaluar la eficacia del tratamiento con deferasirox según el cambio en los niveles de ferritina; ? Evaluar la seguridad y la tolerabilidad de deferasirox durante un año; ? Evaluar la eficacia y la seguridad en pacientes japoneses; ? Analizar el balance del hierro después de un año de tratamiento; ? Confirmar el valor de la ferritina como marcador para la monitorización precisa del tratamiento quelante; ? Realizar exploraciones oftalmológicas en pacientes tratados con deferasirox. Se monitorizarán al menos 60 pacientes durante 2 años.

INCLUSION CRITERIA:

? ? Pacientes con anemia cr?nica que requieren transfusi?nes de sangre distinta a la ?‐talasemia y a la drepanocitosis. ? Varones o mujeres ? 2 años de edad con sobrecarga de hierro transfusional debido a: Riesgo de SMD bajo o intermedio (INT‐1) determinado mediante los criterios del IPSS. Otras anemias congénitas o adquiridas, excluyendo la ? ‐talasemia y la drepanocitosis ? Antecedentes de haber recibido ? 20 unidades (aproximadamente 100 ml/kg) de concentrado de eritrocitos a lo largo de toda la vida del paciente o signos de sobrecarga de hierro (ferritina en suero > 1000 µg/l) . ? Capaz de proporcionar el consentimiento informado escrito ? Esperanza de vida ? 12 meses ? Si el paciente ya había sido tratado con deferiprona se debe realizar un periodo de lavado de un mes antes de administrar la primera dosis de deferasirox. Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18‐64 years)

Este artículo no tiene resumen

INTERVENTION:

Product Name: CERA® Product Code: RO0503821 Pharmaceutical Form: Solution for injection INN or Proposed

INN:

methoxy polyethylene glycol‐epoetin beta CAS Number: 67734‐53‐7 Current Sponsor code: RO0503821 Concentration unit: µg/ml microgram(s)/millilitre Concentration type: equal Concentration number: 30‐ Product Name: CERA® Product Code: RO0503821 Pharmaceutical Form: Solution for injection INN or Proposed

INN:

methoxy polyethylene glycol‐epoetin beta CAS Number: 67734‐53‐7 Current Sponsor code: RO0503821 Concentration unit: µg/ml microgram(s)/millilitre Concentration type: equal Concentration number: 40‐ Product Name: CERA® Product Code: RO0503821 Pharmaceutical Form: Solution for injection INN or Proposed

INN:

methoxy polyethylene glycol‐epoetin beta CAS Number: 67734‐53‐7 Current Sponsor code: RO0503821 Concentration unit: µg/ml microgram(s)/millilitre Concentration type: equal Concentration number: 50‐ Product Name: CERA® Product Code: RO0503821 Pharmaceutical Form: Solution for injection INN or Proposed

INN:

methoxy polyethylene glycol‐epoetin beta CAS Number: 67734‐53‐7 Current Sponsor code: RO0503821 Concentration unit: µg/ml microgram(s)/millilitre Concentration type: equal Concentration number: 60‐ Product Name: CERA® Product Code: RO0503821 Pharmaceutical Form: Solution for injection INN or Proposed

INN:

methoxy polyethylene glycol‐epoetin beta CAS Number: 67734‐53‐7 Current Sponsor code: RO0503821 Concentration unit: µg/ml microgram(s)/millilitre Concentration type: equal Concentration number: 75‐ Product Name: CERA® Product Code: RO0503821 Pharmaceutical Form: Solution for injection INN or Proposed

INN:

methoxy polyethylene glycol‐epoetin beta CAS Number: 67734‐53‐7 Current Sponsor code: RO0503821 Concentration unit: µg/ml microgram(s)/millilitre Concentration type: equal Concentration number: 100‐ Product Name: CERA® Product Code: RO0503821 Pharmaceutical Form: Solution for injection INN or Proposed

INN:

methoxy polyethylene glycol‐epoetin beta

CONDITION:

Nefropatía crónica ; MedDRA version: 8.1 Level: LLT Classification code 10058124 Term: Nephrogenic anemia

PRIMARY OUTCOME:

Main Objective: Comparar el mantenimiento a largo plazo de las concentraciones de hemoglobina con la administración intravenosa una vez al mes de C.E.R.A. frente a epoetina alfa intravenosa en pacientes con anemia renal crónica sometidos a hemodiálisis Primary end point(s): Las variables principales se evaluarán durante las 8 semanas siguientes al período de corrección de dosis de 16 semanas, es decir, durante el período de evaluación de la eficacia (PEE).; La concentración de hemoglobina de referencia se define como la media de las cuatro determinaciones registradas durante el PVE (semanas ‐4,‐3,‐2,‐1); A los efectos de la evaluación de la eficacia, el rango diana de la concentración de hemoglobina se definirá como ± 1 g/dl de la concentración de hemoglobina de referencia Y un valor que esté dentro del rango de 10,5 – 12,5 g/dl. ; Variable de eficacia principal ; • Proporción de pacientes en los que se mantiene la concentración media de hemoglobina dentro del rango diana durante el período PEE; Variables de eficacia secundarias ; • Variación en la concentración de hemoglobina entre el valor de referencia (PVE) y el PEE; • Proporción de pacientes en los que se mantiene la concentración de hemoglobina dentro del rango de 10,5‐12,5 g/dl durante todo el PEE ; • Tiempo medio durante el que se mantiene la concentración de hemoglobina en el rango de 10,5‐12,5 g/dl ; ; Durante los períodos de corrección de dosis y de evaluación de la eficacia ; • Proporción de pacientes que precisan cualquier ajuste de dosis; • Incidencia de transfusiones de hematíes ; Variables de valoración adicionales; • Concentraciones séricas de NT‐proBNP y posibles asociaciones clinicas; Secondary Objective: Comparar la seguridad y tolerancia de la administración intravenosa una vez al mes de C.E.R.A. frente a epoetina alfa para el tratamiento de la anemia en pacientes con enfermedad renal crónica. ; ; Objetivos exploratorios:; •determinar los puntos de corte de las concentraciones de NT‐proBNP para la estratificación del riesgo de acontecimientos cardiovasculares en pacientes tratados con AEE que reciben hemodiálisis.; •evaluar el valor predictivo del riesgo de NT‐proBNP para el control del tratamiento con AEE en pacientes sometidos a hemodiálisis, comparando el grupo de riesgo bajo con el grupo de riesgo alto.; •Investigar los costes potenciales (en cuanto a tiempo dedicado y materiales empleados) relacionados con la administración de AEE;

INCLUSION CRITERIA:

1Consentimiento informado por escrito 2Pacientes = 18 años con anemia renal crónica 3Concentración de hemoglobina basal entre 10,5 g/dl y 12,5 g/dl (media de los valores de hemoglobina semanales determinados en las semanas ‐4 a ‐1) 3Estado de hierro adecuado, que se define como una concentración de ferritina sérica >100 ng/ml O TSAT>20% (O porcentaje de hematíes hipocrómicos <10%) 4Tratamiento de mantenimiento continuado con epoetina alfa intravenosa con la misma frecuencia de administración durante los 2 meses previos a la evaluación de selección y durante el período de verificación de la estabilidad 5Tratamiento prolongado con hemodiálisis de forma regular durante al menos los 3 meses previos al período de verificación de la estabilidad y durante el período de verificación de la estabilidad/basal 6Kt/V = 1,0 en la evaluación de selección (o URR =55%) Are the trial subjects under 18? no Number of subjects for this age range: F.1

Background: CC-486 is an oral formulation of the epigenetic modifier azacitidine. In an expanded phase 1 trial, CC-486 demonstrated clinical and biological activity in patients with International Prognostic Scoring System (IPSS) lower-risk (low- and intermediate-1–risk) myelodysplastic syndromes (MDS) with poor prognostic features including anemia and/or thrombocytopenia who may have required red blood cell or platelet transfusions. The overall response rate was 40 %, including hematologic improvement in 28 % of patients and RBC transfusion independence sustained for 56 days in 47 % of patients with baseline transfusion dependence. Based on the results of this study, the randomized, placebo-controlled phase 3 QUAZAR Lower-Risk MDS trial (AZA-MDS-003) was initiated. The design and rationale for this trial comparing CC-486 with placebo for the treatment of patients with IPSS lower-risk MDS with poor prognostic features are described. Methods: Patients must have IPSS lower-risk MDS with red blood cell (RBC) transfusion–dependent anemia and thrombocytopenia. Eligible patients are randomized 1:1 to receive 300 mg of CC-486 or placebo once daily for the first 21 days of 28-day treatment cycles. Disease status assessments occur at the end of cycle 6 and patients may continue to receive treatment unless there is evidence of progressive disease, lack of efficacy, or unacceptable toxicity. The primary endpoint is RBC transfusion independence for ≥ 84 days, assessed according to International Working Group 2006 criteria. Secondary endpoints include overall survival, hematologic response including platelet response and erythroid response, RBC transfusion independence for ≥ 56 days, duration of RBC transfusion independence, time to RBC transfusion independence, rate of acute myeloid leukemia (AML) progression, time to AML progression, clinically significant bleeding events, safety, health-related quality of life, and healthcare resource utilization. Conclusions: This study will provide data on the efficacy and safety of CC-486 in the treatment of IPSS lower-risk MDS with poor prognosis due to the presence of both RBC transfusion–dependent anemia and thrombocytopenia. Positive results of the AZA-MDS-003 study may expand treatment options for patients with IPSS lower-risk MDS.

INTERVENTION:

Product Code: GSK1278863 Pharmaceutical Form: Film‐coated tablet INN or Proposed

INN:

None CAS Number: None Other descriptive name: GSK1278863 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 1.0‐ Pharmaceutical form of the placebo: Film‐coated tablet Route of administration of the placebo: Oral use Product Code: GSK1278863 Pharmaceutical Form: Film‐coated tablet INN or Proposed

INN:

None CAS Number: None Other descriptive name: GSK1278863 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 2‐ Pharmaceutical form of the placebo: Film‐coated tablet Route of administration of the placebo: Oral use Product Code: GSK1278863 Pharmaceutical Form: Film‐coated tablet INN or Proposed

INN:

None CAS Number: None Other descriptive name: GSK1278863 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 5‐ Pharmaceutical form of the placebo: Film‐coated tablet Route of administration of the placebo: Oral use Product Code: GSK1278863 Pharmaceutical Form: Film‐coated tablet INN or Proposed

INN:

None CAS Number: None Other descriptive name: GSK1278863 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 25‐ Pharmaceutical form of the placebo: Film‐coated tablet Route of administration of the placebo: Oral use

CONDITION:

Anemia associated with chronic kidney disease ; MedDRA version: 16.1 Level: LLT Classification code 10064848 Term: Chronic kidney disease System Organ Class: 100000004857 Therapeutic area: Diseases [C] ‐ Blood and lymphatic diseases [C15]

PRIMARY OUTCOME:

Main Objective: Characterize the dose‐response relationship; between GSK1278863 and Hgb at Week 4. Primary end point(s): Hemoglobin change from baseline at Week 4 Secondary Objective: ‐Characterize the ability of GSK1278863 to; achieve Hgb within the target range (10.0 to; 11.5 g/dL).; ‐Characterize the effect of GSK1278863 on; measures of iron metabolism and utilization, on indices of hematopoiesis, EPO and on Vascular Endothelial Growth Factor (VEGF); ‐Characterize the steady‐state population; pharmacokinetic (PK) of GSK1278863 and; metabolites.; ‐Assess the safety and tolerability of GSK1278863 following once daily (QD) administration for 24 weeks. ; ; Timepoint(s) of evaluation of this end point: Week 4

SECONDARY OUTCOME:

Secondary end point(s): •Hgb concentration at Week 24 ; •Percentage of time within, below, and above target range between Week 20 and 24 ; •Number (%) of subjects with Hgb in the target range at Week 24 ; •Number (%) of subjects reaching pre‐defined Hgb ; stopping criteria ; •Change from baseline in hepcidin, ferritin, transferrin, transferrin saturation, total iron, total iron binding capacity (TIBC), reticulocyte Hgb (CHr), %hypochromic red blood cells (RBCs) at Week 24 ; •Change from baseline in hematocrit, RBC, reticulocyte number at Week 24 ; •Maximum observed change from baseline in EPO ; •Maximum observed change from baseline in VEGF ; •Population plasma PK parameters of GSK1278863 and metabolites ; •Incidence and severity of adverse events (AE)s and serious AEs (SAEs) ; •Reasons for discontinuation of study drug ; •Discontinuation for safety‐related reasons, e.g. pre‐specified stopping criteria or AE ; •Preliminary assessment of major adverse cardiovascular events (MACE) and other cardiovascular (CV) events ; Timepoint(s) of evaluation of this end point: week 24

INCLUSION CRITERIA:

Subjects are eligible if they meet all of the inclusion criteria below. Generalcriteria (Week ‐4 verification only) 1.Age: >18 years of age. 2.Gender: Female and male subjects. ; •Absolute values and changes from baseline in laboratory parameters, systolic pulmonary artery pressure (sPAP) left ventricular ejection fraction (LVEF), ophthalmology assessments, and vital signs • Females: If of childbearing potential, must agree to use one of the approved contraception methods as outlined in Section 11.5 from Screening until completion of the Follow‐up Visit OR Of non‐childbearing potential defined as pre‐menopausal females with a documented tubal ligation, hysterectomy , or oophorectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) 23.0‐116.3 IU/L and estradiol <or= 10 pmol/L is confirmatory]. Females on hormone replacement therapy (HRT) whose menopausal status is in doubt will be required to use one of the approved contraception methods if they wish to continue their HRT during the stud Otherwise they must discontinue HRT to allow confir

This is a prospective multicenter randomized controlled trial with a total duration of 36 months aiming to evaluate the effectiveness and the safety of low protein diet on top of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and renin-angiotensin-aldosterone inhibitors (RAASi) in reducing the progression of chronic kidney disease in patients with type 2 Diabetes Mellitus