Study to Evaluate Imetelstat (GRN163L) in Participants With International Prognostic Scoring System (IPSS) Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)

This is a Phase 2/3, multicenter study of imetelstat sodium in which 289 participants were enrolled.

* Phase 2 is an open-label, single-arm design to assess the efficacy and safety of imetelstat sodium. A total of 57 participants were enrolled in Phase 2, including the expansion cohort.
* Phase 3 is a double-blind, randomized design to compare the efficacy of imetelstat sodium with placebo. In the Phase 3 study, 178 participants were enrolled and randomized in a 2:1 ratio to receive either imetelstat sodium or placebo, respectively.
* In a separate Ventricular Repolarization (VR) Substudy (QTc Substudy), 54 participants were enrolled and randomized 2:1 to receive either imetelstat sodium or placebo. If after a minimum of 2 treatment cycles in the VR substudy, a participant has no significant change to packed red blood cell (pRBC) transfusion burden or evidence of clinical benefit per Investigator, after discussion with the Sponsor the participant may be unblinded. If the participant was on placebo treatment, he/she may be permitted to start treatment with imetelstat sodium.

The Extension Phase was initiated at the end of the Phase 3 study (24 months after the last participant was randomized in the Phase 3) and will continue until participants who entered Phase 3 study participated in the study for up to 5 years from the first dose of imetelstat sodium (including treatment and follow-up), or 3 years of post-treatment follow-up from the last dose of study treatment, whichever occurs later, or until death, withdrawal of consent, study termination, or until a participant is lost to follow-up. Participants ongoing on imetelstat sodium and considered to be benefiting from treatment per Investigator in the Phase 3 Study or Ventricular Repolarization Substudy, have the option to continue receiving imetelstat sodium in the Extension Phase. Participants in the follow-up phase for the Phase 3 study or Ventricular Repolarization Substudy have the option to continue the follow-up in the Extension Phase.

The Phase 2, Phase 3, and VR Substudy all 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 Extension Phase of the study will consist of an extended treatment phase and an extended follow-up phase which will continue until death, lost to follow-up, withdrawal of consent, or the End of the Study (whichever occurs first).

• Imetelstat Sodium (Drug), also known as GRN163L: Imetelstat sodium IV infusion.
• Placebo (Drug): Imetelstat sodium-matching placebo IV infusion.

Primary outcomes

• Phase 2: Percentage of Participants Without Any Red Blood Cell (RBC) Transfusion During Any Consecutive 8-Weeks Period (All Participants) [Up to 5 years in Phase 2]: Percentage of participants without any RBC transfusion during any consecutive 8 weeks (56 days) starting from Study Day 1 until subsequent anti-cancer therapy if any were reported. Study Day 1 is defined as the day of the first dose for participants enrolled in Phase 2. The 95% confidence interval (CI) was calculated using Clopper-Pearson method. Percentages were rounded off to the nearest single decimal place.
• Phase 2: Percentage of Participants Without Any RBC Transfusion During Any Consecutive 8-Weeks Period in Target Population [Up to 5 years in Phase 2]: Percentage of participants without any RBC transfusion during any consecutive 8 weeks (56 days) starting from Study Day 1 until subsequent anti-cancer therapy if any were reported. Study Day 1 is defined as the day of the first dose for participants enrolled in Phase 2. The 95% confidence interval (CI) was calculated using Clopper-Pearson method. Percentages were rounded off to the nearest single decimal place.
• Phase 3: Percentage of Participants Without Any RBC Transfusion During Any Consecutive 8-Weeks Period [Up to 3.7 years in Phase 3]: Percentage of participants without any RBC transfusion during any consecutive 8 weeks (56 days) starting from Study Day 1 until subsequent anti-cancer therapy if any were reported. Study Day 1 is defined as the day of the first dose for participants enrolled in Phase 2. The 95% CI was calculated using Clopper-Pearson method. Percentages were rounded off to the nearest single decimal place.

Secondary outcomes

• Phase 2 and Phase 3: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Deaths [Adverse events: Up to 5 years in Phase 2 and up to 3.7 years in Phase 3; Deaths: Up to 6.6 years in Phase 2 and up to 4 years in Phase 3]: TEAEs were defined as those events that 1) occurred after the first dose of study drug, through the treatment phase, and for 30 days following the last dose of study drug or until subsequent anti-cancer therapy if earlier; 2) any event that was considered study drug-related regardless of the start date of the event; or 3) any event that was presented at baseline but worsened in severity or was subsequently considered drug-related by the investigator. Serious TEAEs are any TEAEs that result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product, is medically important. Any clinically significant vital sign measurements, clinical laboratory values, and electrocardiogram (ECG) findings were reported as TEAEs. TEAEs included both serious and non-serious TEAEs.
• Phase 2 and Phase 3: Percentage of Participants Without Any RBC Transfusion During Any Consecutive 24-Weeks Period [Up to 5 years in Phase 2 and up to 3.7 years in Phase 3]: Percentage of participants without any RBC transfusion during any consecutive 24 weeks (168 days) starting from Study Day 1 until subsequent anti-cancer therapy if any were reported. Study Day 1 is defined as the day of the first dose for participants enrolled in Phase 2 and the day of randomization for participants enrolled in Phase 3. The 95% CI was calculated using Clopper-Pearson method. Percentages were rounded off to the nearest single decimal place.
• Phase 2 and Phase 3: Time to the 8-Weeks RBC Transfusion Independence (TI) [Up to 5 years in Phase 2 and up to 3.7 years in Phase 3]: Time to 8-week RBC TI was defined as the interval from Study Day 1 to the first day of the first 8-week RBC TI period.
• Phase 2 and Phase 3: Time to the 24-Weeks RBC TI [Up to 5 years in Phase 2 and up to 3.7 years in Phase 3]: Time to 24-week RBC TI was defined as the interval from Study Day 1 to the first day of the first 24-weeks RBC TI period.
• Phase 2 and Phase 3: Duration of RBC TI [Up to 5 years in Phase 2 and up to 3.7 years in Phase 3]: Duration of RBC TI was defined as the first day of the longest RBC TI period to the date of the first RBC transfusion after the TI period started. The 95% CI was based on Kaplan-Meier product limit estimates.
• Phase 2 and Phase 3: Percentage of Participants With Hematologic Improvement Including Erythroid Response (HI-E) as Per International Working Group (IWG) Response Criteria 2006 [Up to 5 years in Phase 2 and up to 3.7 years in Phase 3]: As per IWG Response Criteria 2006: HI-E was defined as a hemoglobin (Hb) increase by greater than or equal to (≥)1.5 grams per deciliter (g/dL) relevant reduction of units of RBC transfusions by an absolute number of at least 4 RBC transfusion units/8 weeks compared with the pretreatment transfusion number in the previous 8 weeks. Only RBC transfusions given for a Hb of less than or equal to (≤)9 g/dL pretreatment were counted in the RBC transfusion response evaluation. The 95% CI was calculated using Clopper-Pearson method. Percentages were rounded off to the nearest single decimal place.
• Phase 2: Percentage of Participants With Complete Remission (CR), Partial Remission (PR), or Marrow Complete Remission (mCR) as Per International Working Group (IWG) Response Criteria 2006 as Assessed by the Investigator [Up to 5 years in Phase 2]: As per the IWG Response Criteria 2006, CR was defined as Bone marrow: ≤5% myeloblasts with normal maturation of all cell lines; Peripheral blood (PB): Hb ≥11 g/dL; platelets ≥100 x 10\^9/dL; neutrophils ≥1.0 x 10\^9/liter; blasts: 0%. PR was defined as Bone marrow: ≤5% myeloblasts and decrease by ≥50% over pretreatment; cellularity and morphology not relevant. mCR was defined as Bone marrow: ≤5% myeloblasts and decreased by ≥50% over pre-treatment PB. Percentages were rounded off to the nearest single decimal place. All participants in Phase 2 were evaluated by the Investigator for CR/PR/mCR regardless of bone marrow blasts at baseline.
• Phase 3: Percentage of Participants With CR, PR, or mCR as Per IWG Response Criteria 2006 as Assessed by the Independent Review Committee (IRC) [Up to 3.7 years in Phase 3]: As per the IWG Response Criteria 2006, CR was defined as Bone marrow: ≤5% myeloblasts with normal maturation of all cell lines; PB: Hb ≥11 g/dL; platelets ≥100 x 10\^9/dL; neutrophils ≥1.0 x 10\^9/liter; blasts: 0%. PR was defined as Bone marrow: ≤5% myeloblasts and decrease by ≥50% over pretreatment; cellularity and morphology not relevant. mCR was defined as Bone marrow: ≤5% myeloblasts and decreased by ≥50% over pre-treatment PB. CR, PR and mCR were assessed by IRC in Phase 3 and participants were required to fit at least one of the following criteria (participants with >5% baseline blasts per central pathology reviewer assessment; participants with CR, PR, mCR, or cytogenetic response as assessed by the investigator) and have at least one post-baseline assessment.
• Phase 2 and Phase 3: Overall Survival (OS) [Up to 6.6 years in Phase 2 and up to 4 years in Phase 3]: OS was defined as the interval from Study Day 1 to death from any cause. Survival time of living participants was censored on the last date a participant is known to be alive or lost to follow-up. The Kaplan-Meier method was used to estimate overall survival.
• Phase 2 and Phase 3: Progression Free Survival (PFS) [Up to 6.6 years in Phase 2 and up to 4 years in Phase 3]: Progression free survival was defined as the time interval from study Day 1 to the first date of disease progression or death from any cause, whichever occurs first. Disease progression as per IWG criteria was defined as: at least one of the following: at least 50 % decrement from maximum response levels in granulocytes or platelets; reduction in hemoglobin by ≥1.5 g/dL; transfusion dependence.
• Phase 2 and Phase 3: Time to Progression to Acute Myeloid Leukemia (AML) [Up to 6.6 years in Phase 2 and up to 4 years in Phase 3]: Time to progression to AML was defined as the interval from Study Day 1 to the date of AML diagnosis. Participants who did not progress to AML and were still alive at the cutoff date for the analysis or who withdrew from the study (withdrawal of consent or lost to follow-up), data was censored at the date of the last disease evaluation.
• Phase 2 and Phase 3: Amount of RBC Transfusions in the Best 8-week Interval [Up to 5 years in Phase 2 and up to 3.7 years in Phase 3]: Amount of RBC transfusions for 8-week interval was defined as the total number of RBC transfusion units in a given 8-week interval during study. The best 8-week interval is a post-baseline 8-week interval where the participant had the fewest post-Study Day 1 RBC transfusion units. A valid 8-week period must start before the date of last dose of study drug + 30 days or end of treatment (EOT) visit whichever occurs first and ends before the first transfusion in post-treatment follow-up or the first day of subsequent anti-cancer therapy whichever occurs first.
• Phase 2 and Phase 3: Percent Change in RBC Transfusions Relative to Prior Transfusion Burden [Up to 5 years in Phase 2 and up to 3.7 years in Phase 3]: Relative percent change in RBC transfusions per 8-week = (amount of RBC transfusions per 8-week - prior RBC transfusion burden) / prior RBC transfusion burden multiplied by 100%. Prior RBC transfusion burden was defined as the maximum number of RBC units transfused over any consecutive 8 weeks prior to study entry.
• Phase 2 and Phase 3: Percentage of Participants Who Received Any Myeloid Growth Factors [Up to 5 years in Phase 2 and up to 3.7 years in Phase 3]: Percentage of participants who received any myeloid growth factors starting from Study Day 1 were reported. Percentages were rounded off to the nearest single decimal place.
• Phase 2 and Phase 3: Duration of Myeloid Growth Factors Administration [Up to 5 years in Phase 2 and up to 3.7 years in Phase 3]: Duration of myeloid growth factor administered starting from Study Day 1 was reported.
• Phase 2 and Phase 3: Maximum Observed Plasma Concentration (Cmax) [Pre-dose on Cycle 1 Day 1 and pre-dose on Day 1 of every 3 cycles from Cycle 4 up to Cycle 66 in Phase 2 and Cycle 34 in Phase 3 (each cycle length= 28 days)]: As pre-specified in the statistical analysis plan (SAP), participants in the imetelstat sodium arm group of Phase 2 and Phase 3 were pooled for pharmacokinetic (PK) data collection and analyses in this outcome measure. PK parameters were determined by population PK model.
• Phase 2 and Phase 3: Area Under the Drug Concentration-Plasma Time Curve From Time Zero to Time 28 Days (AUC0-28d) [Cycle 1 (Days 1 to 28) (Cycle duration= 28 days)]: As pre-specified in the statistical analysis plan (SAP), participants in the imetelstat sodium arm group of Phase 2 and Phase 3 were pooled for PK data collection and analyses in this outcome measure. PK parameters were determined by population PK model.
• Phase 2 and Phase 3: Percentage of Participants With Anti-drug Antibodies (ADA) to Imetelstat Sodium [Pre-dose on Cycle 1 Day 1 and pre-dose on Day 1 of every 3 cycles from Cycle 4 up to Cycle 66 in Phase 2 and Cycle 34 in Phase 3 (each cycle length= 28 days)]: As pre-specified in the SAP, participants in the imetelstat sodium arm group of Phase 2 and Phase 3 were pooled for immunogenicity data collection and analyses in this outcome measure. Percentages were rounded off to the nearest single decimal place.
• Phase 3: Medical Resource Utilization Assessed Based on Percentage of Participants With Outpatient Medical Encounters [Up to 3.7 years in Phase 3]: Outpatient medical encounters included various sites of care: a) emergency room (ER) visits, b) hospital outpatient visits, c) home care visit, d) visit to lab, e) visit to doctor's office, f) other visits. Percentages were rounded off to the nearest single decimal place.
• Phase 3: Medical Resource Utilization Assessed Based on Duration of Hospitalization [Up to 3.7 years in Phase 3]: Hospitalization included any medical encounter defined as hospice, hospital inpatient department, and intensive care unit (ICU). Hospitalizations without end dates were not counted in the calculation of length of stay. If any participant had multiple readmissions, duration was calculated as the sum of all hospital stays.
• QTc Substudy: Change From Baseline in QT Interval by Fridericia's Correction Method (ΔQTcF) [Baseline, Cycle 1, Day 1: 0.5, 1, 2, 4, 6, and 8 hours post-dose (cycle length= 28 days)]: Baseline was defined as the mean of the measured ECG intervals collected at 3 time points (-1 hour, -0.5 hour, and 0 hour) prior to treatment administration on Cycle 1 Day 1 (Cycle length= 28 days)

Other outcomes

• Extension Phase: Number of Participants With AEs [Up to approximately 3 years in the extension phase]: An adverse event (AE) was any untoward medical occurrence in a clinical study participant administered a medicinal product. An AE does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to that medicinal product. AEs included clinically significant vital signs measurements, clinical laboratory values and electrocardiograms (ECGs) changes.
• Extension Phase: Overall Survival [Up to approximately 3 years in the extension phase]
• Extension Phase: Progression Free Survival (PFS) Survival [Up to approximately 3 years in the extension phase]: Progression free survival will be assessed as the time interval from the end of the Phase 3 study until death, withdrawal of consent, study termination, or until a subject is lost to follow-up. As per IWG criteria disease progression is defined as: at least one of the following: at least 50 percent (%) decrement from maximum response levels in granulocytes or platelets; reduction in hemoglobin by greater than or equal to ≥1.5 g/dL; transfusion dependence.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Man or woman greater than or equal to (≥) 18 years of age
* Diagnosis of myelodysplastic syndrome (MDS) according to World Health Organization (WHO) criteria confirmed by bone marrow aspirate and biopsy within 12 weeks prior to Cycle 1 Day 1 (C1D1) (Phase 2) or randomization (Phase 3). In Ventricular Repolarization Substudy, diagnosis of MDS or myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) according to WHO criteria confirmed by bone marrow aspirate and biopsy within 12 weeks prior to C1D1
* International Prognostic Scoring System (IPSS) low Risk or intermediate-1 risk MDS
* Red blood cell (RBC) transfusion dependent, defined as requiring at least 4 RBC units transfused over an 8-week period during the 16 weeks prior to Study Entry; pre-transfusion hemoglobin (Hb) should be less than or equal to (≤) 9.0 gram per deciliter (g/dL) to count towards the 4 units total
* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2

Exclusion Criteria:

* Participant has known allergies, hypersensitivity, or intolerance to imetelstat sodium or its excipients
* Participant has received an investigational drug or used an invasive investigational medical device within 30 days prior to Study Entry or is currently enrolled in an investigational study
* Prior treatment with imetelstat sodium
* Have received corticosteroids greater than (>) 30 milligram per day (mg/day) prednisone or equivalent, or growth factor treatment within 4 weeks prior to study entry
* Has received an erythropoiesis-stimulating agent (ESA) or any chemotherapy, immunomodulatory, or immunosuppressive therapy within 4 weeks prior to study entry (8 weeks for long-acting ESAs)
* Phase 3: a) Prior treatment with a hypomethylating agent (example \[eg\], azacitidine, decitabine); b) Prior treatment with lenalidomide

Additional Exclusion Criteria for the Ventricular Repolarization Substudy:

* Concurrent therapy with medications known to prolong the QT interval and have been associated with Torsade de pointes arrhythmia (TdP)
* Cardiac function abnormalities on screening ECG as follows:

  * Resting heart rate outside of 50 to 100 beats per minute
  * QT interval by Fridericia's correction method (QTcF) >470 millisecond (msec) (or QTcF >490 msec in the presence of a right bundle branch block or ventricular conduction delay \[QRS >119 msec\]), determined by central assessment based on the average value of a triplicate set of ECGs
  * Diagnosed or suspected congenital long QT syndrome
  * Family history of sudden unexpected death from cardiac-related causes if indicative of a pathogenic mutation of cardiac ion channels
  * Family history of congenital long QT syndrome
  * History of Mobitz II second degree or third degree heart block
  * Implantable pacemaker or automatic implantable cardioverter defibrillator
  * Complete left bundle branch block
  * Chronic or persistent atrial arrhythmia including atrial fibrillation and atrial flutter
  * History or presence of clinically relevant heart rhythm disturbances including atrial, junctional, re-entry, and ventricular tachycardia
  * Unusual T-wave morphology (i.e., bifid T-wave) likely to interfere with QT measurements
* History or evidence for any of the following: severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (example, pulmonary embolism, cerebrovascular accident including transient ischemic attacks) within 12 months prior to Cycle 1 Day 1, New York Heart Association (NYHA) Class II to IV heart disease
* Presence of uncontrolled hypertension (persistent systolic blood pressure \[BP\] ≥160 mmHg or diastolic BP ≥100 mmHg). Participants with a history of hypertension are permitted, provided that BP is controlled to within these limits by anti-hypertensive treatment
* Any skin condition likely to interfere with electrocardiographic electrode placement or adhesion
* History of thoracic surgery likely to cause abnormality of the electrical conduction through thoracic tissues

Participant flow

Outcome results

• Phase 2: Percentage of Participants Without Any Red Blood Cell (RBC) Transfusion During Any Consecutive 8-Weeks Period (All Participants) (Primary), Number, percentage of participants: Phase 2: Imetelstat Sodium 36.8 (24.45 to 50.66)
• Phase 2: Percentage of Participants Without Any RBC Transfusion During Any Consecutive 8-Weeks Period in Target Population (Primary), Number, percentage of participants: Phase 2: Imetelstat Sodium 42.1 (26.31 to 59.18)
• Phase 3: Percentage of Participants Without Any RBC Transfusion During Any Consecutive 8-Weeks Period (Primary), Number, percentage of participants: Phase 3: Imetelstat Sodium 39.8 (30.93 to 49.25); Phase 3: Placebo 15.0 (7.10 to 26.57) (p <0.001)
• Phase 2 and Phase 3: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Deaths (Secondary), Count of participants, Participants: Phase 2: Imetelstat Sodium (No Dose Escalation) 50; Phase 2: Imetelstat Sodium (Escalated to 9.4 mg/kg) 6; Phase 3: Imetelstat Sodium 117; Phase 3: Placebo 59
• Phase 2 and Phase 3: Percentage of Participants Without Any RBC Transfusion During Any Consecutive 24-Weeks Period (Secondary), Number, percentage of participants: Phase 2: Imetelstat Sodium 24.6 (14.13 to 37.76); Phase 3: Imetelstat Sodium 28.0 (20.10 to 36.98); Phase 3: Placebo 3.3 (0.41 to 11.53) (p <0.001)
• Phase 2 and Phase 3: Time to the 8-Weeks RBC Transfusion Independence (TI) (Secondary), Median, weeks: Phase 2: Imetelstat Sodium 8.29 (0.1 to 100.6); Phase 3: Imetelstat Sodium 9.29 (0.1 to 64.7); Phase 3: Placebo 8.29 (0.1 to 46.9)
• Phase 2 and Phase 3: Time to the 24-Weeks RBC TI (Secondary), Median, weeks: Phase 2: Imetelstat Sodium 8.79 (3.3 to 100.6); Phase 3: Imetelstat Sodium 8.43 (2.1 to 37.6); Phase 3: Placebo 3.79 (0.3 to 7.3)
• Phase 2 and Phase 3: Duration of RBC TI (Secondary), Median, weeks: Phase 2: Imetelstat Sodium 69.6 (17.00 to 92.43); Phase 3: Imetelstat Sodium 51.6 (26.86 to 80.43); Phase 3: Placebo 13.3 (8.00 to 24.86) (p <0.001)
• Phase 2 and Phase 3: Percentage of Participants With Hematologic Improvement Including Erythroid Response (HI-E) as Per International Working Group (IWG) Response Criteria 2006 (Secondary), Number, percentage of participants: Phase 2: Imetelstat Sodium 61.4 (47.57 to 74.00); Phase 3: Imetelstat Sodium 63.6 (54.20 to 72.22); Phase 3: Placebo 51.7 (38.39 to 64.77) (p 0.112)
• Phase 2: Percentage of Participants With Complete Remission (CR), Partial Remission (PR), or Marrow Complete Remission (mCR) as Per International Working Group (IWG) Response Criteria 2006 as Assessed by the Investigator (Secondary), Number, percentage of participants: Phase 2: Imetelstat Sodium 8.8
• Phase 3: Percentage of Participants With CR, PR, or mCR as Per IWG Response Criteria 2006 as Assessed by the Independent Review Committee (IRC) (Secondary), Number, percentage of participants: Phase 3: Imetelstat Sodium 0; Phase 3: Placebo 0
• Phase 2 and Phase 3: Overall Survival (OS) (Secondary), Median, months: Phase 2: Imetelstat Sodium 55.3 (39.16 to NA); Phase 3: Imetelstat Sodium 40.4 (37.06 to NA); Phase 3: Placebo NA (32.16 to NA) (p 0.949)
• Phase 2 and Phase 3: Progression Free Survival (PFS) (Secondary), Median, months: Phase 2: Imetelstat Sodium 34.2 (25.10 to 39.29); Phase 3: Imetelstat Sodium NA (29.24 to NA); Phase 3: Placebo NA (16.72 to NA)
• Phase 2 and Phase 3: Time to Progression to Acute Myeloid Leukemia (AML) (Secondary), Median, months: Phase 2: Imetelstat Sodium NA (41.36 to NA); Phase 3: Imetelstat Sodium NA (NA to NA); Phase 3: Placebo NA (NA to NA)
• Phase 2 and Phase 3: Amount of RBC Transfusions in the Best 8-week Interval (Secondary), Mean, number of RBC transfusions units: Phase 2: Imetelstat Sodium 3.0 +/- 3.48; Phase 3: Imetelstat Sodium 3.1 +/- 3.62; Phase 3: Placebo 3.4 +/- 2.13
• Phase 2 and Phase 3: Percent Change in RBC Transfusions Relative to Prior Transfusion Burden (Secondary), Mean, percent change: Phase 2: Imetelstat Sodium -62.5 +/- 38.36; Phase 3: Imetelstat Sodium -57.75 +/- 50.220; Phase 3: Placebo -51.01 +/- 31.606
• Phase 2 and Phase 3: Percentage of Participants Who Received Any Myeloid Growth Factors (Secondary), Number, percentage of participants: Phase 2: Imetelstat Sodium 33; Phase 3: Imetelstat Sodium 35.6; Phase 3: Placebo 5.0
• Phase 2 and Phase 3: Duration of Myeloid Growth Factors Administration (Secondary), Median, weeks: Phase 2: Imetelstat Sodium 1.43 (0.1 to 118.0); Phase 3: Imetelstat Sodium 0.71 (0.1 to 12.9); Phase 3: Placebo 3.14 (0.1 to 10.0)
• Phase 2 and Phase 3: Maximum Observed Plasma Concentration (Cmax) (Secondary), Mean, micrograms per milliliter (mcg/mL): Phase 2 and Phase 3: Imetelstat Sodium 89.5 +/- 27.3
• Phase 2 and Phase 3: Area Under the Drug Concentration-Plasma Time Curve From Time Zero to Time 28 Days (AUC0-28d) (Secondary), Mean, hour*micrograms per milliliter(h*mcg/mL): Phase 2 and Phase 3: Imetelstat Sodium 559 +/- 43.2
• 7 more outcome measures not shown.

Adverse events

Time frame: Adverse events: Up to 5 years in Phase 2; up to 3.7 years in Phase 3; up to 1.3 years in QTc substudy; All-cause mortality: Up to 6.6 years in Phase 2; up to 4 years in Phase 3; up to 1.6 years in QTc substudy

Serious adverse events by term

50 more terms not shown.

Other adverse events by term

69 more terms not shown.

26 more sites not listed.

• Results publication: Sekeres MA, Zeidan AM, Santini V, Komrokji RS, Fenaux P, Savona MR, Madanat YF, Valcarcel D, Regnault A, Creel K, Sun L, Wan Y, Navada S, Berry T, Feller F, Platzbecker U, Diez-Campelo M, Oliva EN. Imetelstat improves patient-reported outcomes and quality of life in lower-risk myelodysplastic syndromes: results from the phase III IMerge study. Haematologica. 2026 Jul 1;111(7):2385-2396. doi: 10.3324/haematol.2025.288956. Epub 2026 Jan 22. PMID 41568521
• Results publication: Kim N, Pulte ED, Ehrlich LA, Ionan AC, Haupert S, Vallejo J, Green F, Zheng N, Wang Y, Liu J, Blanco JG, Dorff SE, Booth B, Choe M, Gehrke B, Bhatnagar V, Theoret M, Pazdur R, De Claro RA, Norsworthy KJ. US Food and Drug Administration Approval Summary: Imetelstat for Selected Patients With Low- to Intermediate-1 Risk Myelodysplastic Syndromes With Transfusion-Dependent Anemia. J Clin Oncol. 2025 Dec 10;43(35):3760-3768. doi: 10.1200/JCO-25-01369. Epub 2025 Oct 24. PMID 41135032
• Results publication: Platzbecker U, Santini V, Fenaux P, Sekeres MA, Savona MR, Madanat YF, Diez-Campelo M, Valcarcel D, Illmer T, Jonasova A, Belohlavkova P, Sherman LJ, Berry T, Dougherty S, Shah S, Xia Q, Sun L, Wan Y, Huang F, Ikin A, Navada S, Feller F, Komrokji RS, Zeidan AM. Imetelstat in patients with lower-risk myelodysplastic syndromes who have relapsed or are refractory to erythropoiesis-stimulating agents (IMerge): a multinational, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2024 Jan 20;403(10423):249-260. doi: 10.1016/S0140-6736(23)01724-5. Epub 2023 Dec 1. PMID 38048786
• Results publication: Steensma DP, Fenaux P, Van Eygen K, Raza A, Santini V, Germing U, Font P, Diez-Campelo M, Thepot S, Vellenga E, Patnaik MM, Jang JH, Varsos H, Bussolari J, Rose E, Sherman L, Sun L, Wan Y, Dougherty S, Huang F, Feller F, Rizo A, Platzbecker U. Imetelstat Achieves Meaningful and Durable Transfusion Independence in High Transfusion-Burden Patients With Lower-Risk Myelodysplastic Syndromes in a Phase II Study. J Clin Oncol. 2021 Jan 1;39(1):48-56. doi: 10.1200/JCO.20.01895. Epub 2020 Oct 27. PMID 33108243

• Study Protocol (PDF, 2022-12-13)
• Statistical Analysis Plan (PDF, 2022-09-15)

• Tymara Berry, MD, Study director, Geron Corporation

NIH grants: 2015