A Study to Evaluate Long-term Safety in Subjects Who Have Participated in Other Luspatercept (ACE-536) Clinical Trials
Beta-thalassemia / Posted 1 year ago
A Phase 3b, open-label, single-arm, rollover study to evaluate the long-term safety of luspatercept, to the following subjects:
- Subjects receiving luspatercept on a parent protocol at the time of their transition to the rollover study, who tolerate the protocol-prescribed regimen in the parent trial and, in the opinion of the investigator, may derive clinical benefit in the opinion of the investigator from continuing treatment with luspatercept.
- Placebo arm subjects from parent protocol (at the time of unblinding or in follow-up) crossing over to luspatercept treatment (provided subjects have met all requirements for entering the rollover study as per the parent protocol).
- Subjects in the follow-up phase previously treated with luspatercept or placebo in the parent protocol will continue into long-term post-treatment follow-up in the rollover study until the follow-up commitments are met (unless they meet requirements as per parent protocol to cross-over to luspatercept treatment).
The study design is divided into the Transition Phase, Treatment Phase and Follow-up Phase. Subjects will enter transition phase and depending on their background will enter either the treatment phase or the Long-term Post-treatment Follow-up (LTPTFU) phase.
- Transition Phase (Screening): up to 21 days prior to enrollment
- Treatment Phase: For subjects in luspatercept treatment the dose and schedule of luspatercept in this study will be the same as the last dose and schedule in the parent luspatercept study. For placebo arm subjects from parent protocol (at the time of unblinding or in follow-up) crossing over to luspatercept treatment (provided subjects have met all requirements for entering the rollover study as per the parent protocol) will start at a luspatercept dose of 1.0 mg/kg every 3 weeks (Q3W). This does not apply to subjects that are in long-term follow-up from the parent protocol.
- Follow-up Phase:
- 42 Day Safety Follow-up Phase: subjects will be followed for 42 days after the last dose of luspatercept, for the assessment of safety-related parameters and adverse event (AE) reporting.
- Long-term Post-treatment Follow-up (LTPTFU) Phase:
All subjects who are continuing in the LTPTFU Phase, will continue to be followed for 5 years from Dose 1 of the parent protocol, or 3 years of post-treatment from last dose of the parent protocol, whichever occurs later. Subjects will be followed every 6 months until death, withdrawal of consent, study termination, or until a subject is lost to follow-up. Subjects will also be monitored for progression to AML or any malignancies/pre- malignancies. New anticancer or disease related therapies should be collected at the same time schedule.
Subjects transitioning from a parent luspatercept study in post-treatment follow-up (safety or LTPTFU) will continue from the same equivalent point in this rollover study.
The rollover study will be terminated, and relevant subjects will discontinue from the study when all subjects fulfill 5 years from Dose 1 of the parent protocol, or 3 years of post-treatment from last dose of the parent protocol, whichever occurs later. The shift to commercial drug is an alternative way to stop the study.
Inclusion Criteria :
- Subject is at least 18 years at the time of signing the informed consent form (ICF).
- Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
- Subject has been participating in a luspatercept trial and continues to fulfill all the requirements of the parent protocol and the subject has been either:
- Assigned to luspatercept treatment, continues to receive clinical benefit in the opinion of the investigator and should continue to receive luspatercept treatment
- OR 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 assigned to the Follow-up Phase of the parent protocol, previously treated with luspatercept or placebo in the parent protocol who shall continue into long-term Post-treatment Follow-up 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).
- Subject understands and voluntarily signs an informed consent document prior to any study-related assessments or procedures being conducted.
- Subject demonstrates compliance, as assessed by the investigator, with the parent study protocol requirements.
- Applies to on treatment subjects 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
- 3) has not been naturally postmenopausal (amenorrhea following cancer therapy 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) and must:
- 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 subject practices true abstinence* 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, 35 days prior to starting investigational product (IP), during the study therapy (including dose interruptions), and for 84 days after discontinuation of study therapy.
- 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 discontinuation even if he has undergone a successful vasectomy.
Exclusion Criteria :
- Applies to on treatment subjects only- Concomitant use of any medications/procedures that are prohibited in the parent luspatercept protocol.
- Subject has met one or more criteria for study discontinuation as stipulated in the parent luspatercept protocol.
- First luspatercept transition visit into rollover study &gt; 21 days after end of study (EOS) visit (last dose/visit in case of no EOS visit) of the parent luspatercept study with the exception of those subjects already in the Post-treatment Follow up Phase from the parent study. Note-Subject with current dose delays from the parent protocol during the Transition Phase, will continue in the rollover protocol regardless of the delay.
- Applies to on treatment subjects only- Pregnant or breastfeeding females.
- 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.
- 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.
- Subject has any condition that confounds the ability to interpret data from the study.
- Study start date : August 12, 2019
- Study end date : March 25, 2030
- Wales-Based Study Contact : Please speak to your clinician
- Principal Investigator : Rodrigo Ito, M.D. Celgene Corporation