TRR is defined as ≥50 percent (%) reduction in transfused red blood cells (RBC) volume (normalized by weight) in any consecutive 12-week period through Week 48 compared with historical RBC transfusion volume (normalized by weight) and standardized to 12 weeks.

Hb response is defined as a ≥1.0 grams per deciliter (g/dL) increase in average Hb concentration from Week 12 through Week 24 compared with baseline.

TRR is defined as ≥33% reduction in total red blood cell (RBC) transfusion volume from Week 9 through Week 32 of the double-blind period, normalized by weight and actual study drug duration compared with the historical transfusion volume, standardized by weight, and to 24 weeks.

Hb response is defined as a ≥1.5 grams per deciliter (g/dL) (0.93 millimoles per liter \[mmol/L\]) increase in Hb concentration from baseline that is sustained at 2 or more scheduled assessments at Weeks 12, 16, and 20 during the double-blind period. The individual participant's baseline Hb concentration is defined as the average of all available Hb concentrations collected for that participant during the screening period up to the first dose of study drug.

Hb response is defined as ≥10 grams/ liter (g/L) (1.0 gram per deciliter) (g/dL) increase in average Hb concentration from Week 12 through Week 24 compared with baseline. Hb response was tested using the Mantel-Haenszel stratum weighted method adjusting for randomization stratification factors. Baseline is defined as the average of all assessments within 42 days before randomization for subjects randomized and not dosed or within 42 days before the start of study treatment for subjects randomized and dosed.

TRR is defined as ≥50% reduction in transfused red blood cells (RBC) units with a reduction of ≥2 units of transfused RBCs in any consecutive 12-week period through Week 48 compared with baseline transfusion burden standardized to 12 weeks. Baseline transfusion burden standardized to 12 weeks= (12/24) × total number of RBC units transfused during 24-week period before the randomization date for participants randomized and not dosed or the start of study treatment for participants randomized and dosed. Participants withdrawn from the study before Week 12 (Day 85) were considered nonresponders.

A clinical adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the study drug. TEAEs are AEs with an initial onset date during the on-treatment period or worsening from baseline and include both serious and non-serious TEAEs. Severity of AEs was evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE; Version 4.03): grade 1: mild; grade 2: moderate; grade 3: severe or medically significant but not immediately life-threatening; grade 4: life threatening or disabling; grade 5: death related to AE.

A clinical AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the study drug. TEAEs are AEs with an initial onset date during the on-treatment period or worsening from baseline and include both serious and non-serious TEAEs. Number of participants with TEAEs leading to dose reduction, treatment interruption and treatment discontinuation are reported.

Clinical laboratory assessments including hematology, clinical chemistry, triglycerides, urate, coagulation, urinalysis, and liver function tests were performed in the study. Clinically significant treatment-emergent laboratory abnormalities were graded according to the NCI CTCAE; Version 4.03: grade 1: mild; grade 2: moderate; grade 3: severe or medically significant but not immediately life-threatening; grade 4: life threatening or disabling; grade 5: death related to AE. Clinical significance was determined based on the judgment of the Investigator.

Vital signs and physical examinations including height, weight, body mass index (BMI), systolic blood pressure, diastolic blood pressure, pulse rate, temperature were assessed. Number of participants who experienced clinically significant abnormalities in vital signs and physical examinations as TEAEs were reported. Clinical significance was determined based on the judgment of the Investigator.

BMD was measured by dual-energy X-ray absorptiometry (DXA) scans during the study. Number of participants with clinically significant abnormalities were reported. Clinical significance was determined based on the judgment of the Investigator.

T-score of adjusted spine were assessed by DXA scans. The T-score is the number of standard deviations that bone density is above or below the average. A score of ≥ -1 indicates normal bone density; score between \< -1 and \> -2.5 indicates a sign of osteopenia (bone density below normal), and score of ≤ -2.5 indicates a sign of osteoporosis.

The Z-score is a statistical measure to describe whether a value was above or below the standard. A Z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard.

T-score of femoral total were assessed by DXA scans. The T-score is the number of standard deviations that bone density is above or below the average. A score of ≥ -1 indicates normal bone density; score between \< -1 and \> -2.5 indicates a sign of osteopenia (bone density below normal), and score of ≤ -2.5 indicates a sign of osteoporosis.

The Z-score is a statistical measure to describe whether a value was above or below the standard. A Z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard.

The following ECG parameters including RR, PR, heart rate-corrected QT interval using the Fridericia's formula (QRS), QT, and QTc were assessed during the study. Number of Participants with clinically significant abnormalities in ECG parameters as TEAEs were reported. Clinical significance was determined based on the judgment of the Investigator.