A Phase 3b, open-label, single-arm, rollover study to evaluate long-term safety in subjects who have participated in other luspatercept(ACE-536) clinical trials

JRCT ID: jRCT2031220422

Registered date:28/10/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Anemia associated with myelodysplastic syndrom or myelofibrosis
• Date of first enrollment: 25/01/2023
• Target sample size: 18
• Countries of recruitment: Australia,Japan,Belgium,Japan,Bulgaria,Japan,Canada,Japan,France,Japan,Germany,Japan,Greece,Japan,Israel,Japan,Italy,Japan,Lebanon,Japan,Malaysia,Japan,Netherlands,Japan,Spain,Japan,Sweden,Japan,Taiwan,Japan,Thailand,Japan,Tunisia,Japan,Turkey,Japan,United Kingdom,Japan,United States,Japan
• Study type: Interventional
• Intervention(s): Administer luspatercept subcutaneously every 3 weeks (21 days). The starting dose is 1.0 mg/kg and the dose may be increased to 1.75 mg/kg. The dose is adjusted in the range from 0.45 to 1.75 mg/kg depending on a hemoglobin level and the occurrence of adverse events.

Outcome(s)

• Primary Outcome: Type, frequency, severity of AEs, relationship of treatment emergent adverse events to luspatercept, Number and percentage of subjects progressing to high/very high risk MDS or AML, Number and percentage of subjects developing other malignancies/pre-malignancies
• Secondary Outcome: Time from enrollmentuntil death from any cause,Number and percentage of subjects developing treatment emergent EMH masses

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1) Subject is >= 18 years at the time of signing the informed consent form (ICF).
2) Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
3) Subject has been participating in aluspatercepttrial and continues to fulfill all the requirements of the parent protocol and the subjecthas been either:a) Assigned to luspatercepttreatment, continues to receive clinical benefitin the opinion of the investigatorand should continue to receive luspatercepttreatment, ORb) Assigned to placebo arm in the parent protocol (at the time of unblinding or in follow-up)and shouldcross over to luspatercepttreatment,ORc) Assigned to the Follow-up Phase of the parent protocol, previously treated with luspaterceptor placeboin the parent protocol who shall continue into Long -term P ost-treatment Follow-up Phasein the rollover study until the follow- up commitments are met (unless requirements are met as per parent protocol to crossover to luspatercepttreatment).
4) Subject understands and voluntarily signs an informed consent document prior to any study-related assessments or procedures being conducted.
5) Subject demonstrates compliance, as assessed by the investigator, with the parent study protocol requirements.
6)Applies to on treatment subjectsonly- 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 reasonsdoes not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months) and must:a) Have two negative pregnancy tests as verified by the investigator prior to starting study therapy. A medicallysupervisedserumpregnancytest (conducted locally)is to be obtained and verified negative in all female subjects of childbearing potential at e nrollment. She must agree to ongoing pregnancy testing during the course of the study, and after end of study therapy. This applies even if the subject practices true abstinence* from heterosexual contact.b) 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 withhighlyeffective, 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 subjects only- Male subjects must:a) Practice true abstinence* (which must be reviewed on a monthly basis) or agree 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 discontinuationeven if he has undergone a successful vasectomy.

Exclude criteria

1) Applies to on treatment subjects only- Concomitant use of any medications/proceduresthat are prohibited in the parent luspaterceptprotocol.
2) Subjecthas met one or more criteria for study discontinuation as stipulated in the parent luspaterceptprotocol.
3) Applies to on treatment subjects only- More than 26 days between last luspatercept dosein the parent protocol and first dose into ACE-536-LTFU-001 protocol unless dose delay or dose discontinuation criteria met.
4) Applies to on treatment subjects only- Pregnant or breastfeeding females. If breastfeeding, agree to stop breastfeeding prior to the participation in the study and not to resume breastfeeding during treatment with luspatercept and until 3 months after the last dose.
5) Subject has any significant medical condition, laboratory abnormality, psychiatric illness, or is considered vulnerable by local regulations (eg, imprisoned or institutionalized) that would prevent the subject from participating in the study.
6) Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
7) Subject has any condition that confounds the ability to interpret data from the study.

Related Information

• Primary Sponsor: Hayakawa Jin
• Secondary ID(s): NCT04064060