A Study to Evaluate Long-term Safety in Participants Who Have Participated in Other Luspatercept (ACE-536) Clinical Trials

Inclusion Criteria

• •Participants must meet all the following criteria to be enrolled in this study:
• •1. Participant is ≥ 18 years at the time of signing the informed consent form (ICF).
• •2. Participant is willing and able to adhere to the study visit schedule and other protocol requirements.
• •3. Participant has been participating in a luspatercept trial and continues to fulfill all the requirements of the parent protocol and the participant has been either:
• •1. Assigned to luspatercept treatment, continues to receive clinical benefit in the opinion of the investigator and should continue to receive luspatercept treatment, OR
• •2. Assigned to placebo arm in the parent protocol (at the time of unblinding or in follow-up) and should cross over to luspatercept treatment, OR
• •3. Assigned to the Follow-up Phase of the parent protocol, previously treated with luspatercept or placebo in the parent protocol who shall continue into LTPTFU phase in the rollover study until the follow-up commitments are met (unless requirements are met as per parent protocol to crossover to luspatercept treatment).
• •4. Participant understands and voluntarily signs an informed consent document prior to any study-related assessments or procedures being conducted.
• •5. Participant demonstrates compliance, as assessed by the investigator, with the parent study protocol requirements.
• •6. Applies to on treatment Participants only- females of childbearing potential (FCBP) defined as a sexually mature woman who:
• •1\) has achieved menarche at some point, 2) has 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:
• •1. Have two negative pregnancy tests as verified by the investigator prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study therapy. This applies even if the participant practices true abstinence from heterosexual contact.
• •2. Agrees to use, and be able to comply with highly effective, contraception without interruption, 35 days prior to starting investigational product (IP), during the study therapy (including dose interruptions), and for 84 days after discontinuation of study therapy.
• •7\. Applies to on treatment participants only- Male participants must:
• •a. Agrees to use a condom 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 84 days following investigational product discontinuation even if he has undergone a successful vasectomy.