Schéma : STUDY DESIGN:
This is a Phase 2/3, multicenter study of imetelstat that consists of 2 parts.
- Part 1 is an open-label, single-arm design to assess the efficacy and safety of imetelstat. Approximately 55 participants will be enrolled in Part 1, including the expansion cohort, and be followed-up for safety, hematologic improvement and reduction in transfusion requirement.
- Part 2 of the study will be initiated if data from Part 1 are supportive of a satisfactory benefit/risk profile. Part 2 is a double-blind, randomized design to compare the efficacy of imetelstat with placebo. Approximately 170 eligible participants will be randomized in a 2:1 ratio to receive either imetelstat or placebo, respectively.
Each part of the study will consist of 3 phases: a Screening phase (up to 28 days); a treatment phase; and a post-treatment follow-up phase which will continue until death, lost to follow-up, withdrawal of consent, or the End of the Study (whichever occurs first). The End of the Study is defined as 2 years after the study entry of the last participant or anytime the sponsor terminates the study, whichever comes first.

STUDY ARMS:
- Experimental: Part 1: Imetelstat
Imetelstat will be administered at a starting dose of 7.5 milligram per kilogram (mg/kg) given intravenously every 4 weeks, until disease progression, unacceptable toxicity, or withdrawal of consent, or lack of response.
- Experimental: Part 2: Imetelstat
Imetelstat will be administered at a starting dose of 7.5 milligram per kilogram (mg/kg) given intravenously every 4 weeks, until disease progression, unacceptable toxicity, or withdrawal of consent, or lack of response.
- Placebo Comparator: Part 2: Placebo
Matching Placebo to Imetelstat will be administered.

MAIN OBJECTIVE:
- Part 1: To evaluate the efficacy and safety of imetelstat in transfusion dependent subjects with low or intermediate-1 risk MDS that is relapsed/refractory to ESA treatment.
- Part 2: To compare the efficacy, in terms of RBC TI, of imetelstat to placebo in transfusion dependent subjects with low or intermediate-1 risk MDS that is relapsed/refractory to ESA treatment.

SECONDARY OBJECTIVES:
- To assess the safety of imetelstat in subjects with MDS
- To assess the time to RBC TI and duration of RBC TI
- To assess the rate of hematologic improvement
- To assess the rates of CR or PR
- To assess OS
- To assess time to progression to AML
- To assess the rate and amount of supportive care, including transfusions and myeloid growth factors
- To evaluate the pharmacokinetics and immunogenicity of imetelstat in subjects with MDS
- To assess the effect of imetelstat treatment on patient reported outcomes (PROs)
- To assess the effect of treatment on medical resource utilization