An Efficacy and Safety Study of Luspatercept (ACE-536) for the Treatment of Anemia Due to IPSS-R Very Low, Low or Intermediate Risk Myelodysplastic Syndromes (MDS) in Japanese Subjects Who Are Not Requiring Red Blood Cell Transfusion

Inclusion Criteria

Subjects must satisfy the following criteria to be enrolled in the study:

• Subject is ≥ 20 years of age the time of signing the informed consent form (ICF)
• Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
• Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
• Subject has a documented diagnosis of MDS according to WHO 2016 classification that meets IPSS-R classification of very low, low, or intermediate risk disease, and:
• < 5% blasts in bone marrow
• Subject has symptomatic anemia with mean Hgb concentration < 10.0 g/dL from 2 measurements (one performed within 1 day prior to W1D1 and the other performed 7 to 35 days prior to W1D1) that does not require RBC transfusion. If more than one measurement exists in the period of 7 to 35 days prior to W1D1, the most recent value will be used.
• Subject must be TI, as documented by the following criteria:
• No RBC transfusion administered within 16 weeks prior to W1D1 (except transfusions due to blood loss or infection that occurred between 16 and 8 weeks prior to W1D1)
• Subject has Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2
• Females of childbearing potential (FCBP), defined as a sexually mature woman who:
• has achieved menarche at some point, 2) not undergone a hysterectomy or bilateral oophorectomy, or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy or amenorrhea due to other medical reasons does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months), must:
• Have two negative pregnancy tests as verified by the investigator prior to starting study therapy (unless the screening pregnancy test was done within 72 hours of W1D1). She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment. This applies even if the subject practices true abstinence1 from heterosexual contact.
• Either commit to true abstinence from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, and be able to comply with, highly effective contraception without interruption, 5 weeks prior to starting investigational product, during the study therapy (including dose interruptions), and for 12 weeks after discontinuation of study therapy.
• If breastfeeding, agree to stop breastfeeding prior to the participation in the study and not to resume breastfeeding after treatment discontinuation.
• Male subjects must:
• Practice true abstinence2 (which must be reviewed prior to each IP administration or on a monthly basis [eg, in the event of dose delays]) or agree to use a condom (latex or non-latex, but not made out of natural [animal] membrane) during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 12 weeks following investigational product discontinuation, even if he has undergone a successful vasectomy.

Exclusion Criteria

The presence of any of the following will exclude a subject from enrollment:

• Subject with the any of the following prior treatments for underlying disease:
• Disease modifying agents (eg, immune-modulatory drug [IMiDs such as lenalidomide])
• Except if the subject received ≤ 1 week of treatment with a disease modifying agent ≥ 8 weeks from W1D1, at the investigator's discretion.
• Hypomethylating agents
• Subjects may be enrolled at the investigator's discretion contingent that the subject received no more than 2 injections of HMA. The last dose must be ≥ 8 weeks from the date of W1D1.
• Luspatercept (ACE-536) or sotatercept (ACE-011)
• Allogeneic and/or autologous hematopoietic cell transplant
• Subject with myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN) according to WHO 2016 cla