A Study of IMR-687 in Adult Participants With Sickle Cell Anemia (Homozygous HbSS or Sickle-β0 Thalassemia)

An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An SAE was defined as any AE that resulted in 1 or more of the following outcomes: death, required or prolonged hospitalization, life-threatening, persistent or significant disability/incapacity, congenital anomaly or birth defect, or other medically important event. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

Time frame: Day 1 (after dosing) through up to Week 24

Population: All participants who had received any amount of study drug.

For PK assessments of participants who did not concomitantly receive HU, serial blood samples for IMR-687 plasma concentrations were drawn predose at 0.5, 1, 1.5, 2, 4, 6, and 8 hours after administration of study drug; and at 24 hours after administration of study drug. Day 1 (single-dose) and steady-state (Week 25) assessments are presented.

Time frame: Day 1 and Week 25

Population: PK Analysis population consisted of all participants with sufficient sampling for PK parameter evaluation.

For PK assessments of participants who concomitantly received HU, serial blood samples for HU PK were drawn predose and at 0.5, 1, 1.5, 3, 6, 8, and 10 hours after self-administration of the prescribed dose of HU. HU in the presence (EOT: Week 17) or absence of IMR-687 (Baselines 1 and 2) are presented. HU concentration data were not sorted with respect to HU dose.

Time frame: Baseline (1 and 2) and Week 17

Population: PK Analysis population consisted of all participants with sufficient sampling for PK parameter evaluation.

For PK assessments of participants who concomitantly received HU, serial blood samples for IMR-687 plasma concentrations were drawn predose at 0.5, 1, 1.5, 2, 4, 6, and 8 hours after administration of study drug; and at 24 hours after administration of study drug. Day 1 (single-dose) and steady-state (Week 17) assessments are presented.

Time frame: Day 1 and Week 17

Population: PK Analysis population consisted of all participants with sufficient sampling for PK parameter evaluation.

For PK assessments of participants who concomitantly received HU, serial blood samples for HU PK were drawn predose and at 0.5, 1, 1.5, 3, 6, 8, and 10 hours after self-administration of the prescribed dose of HU. HU in the presence (end of treatment \[EOT\]: Week 17) or absence of IMR-687 (Baselines 1 and 2) are presented. HU concentration data were not sorted with respect to HU dose.

Time frame: Baseline (1 and 2) and Week 17

Population: PK Analysis population consisted of all participants with sufficient sampling for PK parameter evaluation.

For PK assessments of participants who concomitantly received HU, serial blood samples for IMR-687 PK were drawn predose at 0.5, 1, 1.5, 2, 4, 6, and 8 hours after administration of study drug; and at 24 hours after administration of study drug. Day 1 (single-dose) and steady-state (Week 17) assessments are presented.

Time frame: Day 1 and Week 17

Population: PK Analysis population consisted of all participants with sufficient sampling for PK parameter evaluation.

For PK assessments of participants who did not concomitantly receive HU, serial blood samples for IMR-687 plasma concentrations were drawn predose at 0.5, 1, 1.5, 2, 4, 6, and 8 hours after administration of study drug; and at 24 hours after administration of study drug. Day 1 (single-dose) and steady-state (Week 25) assessments are presented.

Time frame: Day 1 and Week 25

Population: PK Analysis population consisted of all participants with sufficient sampling for PK parameter evaluation.

Absolute least squares (LS) mean change from baseline at EOT is presented. Change from baseline in pharmacodynamic (PD) biomarkers was analyzed using mixed models for repeated measures with covariate of treatment, visit, treatment-by-visit interaction, and baseline value.

Time frame: Baseline, EOT (Week 25 for participants without HU and Weeks 17 or 25 for participants with HU)

Population: All participants who had samples for PD analysis sufficient to obtain at least 1 valid PD observation, without protocol deviations or events that would be expected to affect the PD analysis.

VOCs include the events of acute painful crisis and acute chest symptoms (includes fever, cough, sputum production, shortness of breath, tachypnea, hypoxia, and chest pain).

Time frame: Day 1 (after dosing) through up to Week 24

Population: All participants who had received any amount of study drug.

VOCs include the events of acute painful crisis and acute chest symptoms (includes fever, cough, sputum production, shortness of breath, tachypnea, hypoxia, and chest pain). Time to first VOC event was assessed by Kaplan Meier analysis. For this analysis, HU and without HU population groups were pooled for IMR-687 and placebo. In addition, pooled IMR-687 (all doses) are presented.

Time frame: Day 1 (after dosing) through up to Week 24

Population: Pooled data from the IMR-687 dose groups (IMR-687 50mg/100 mg \[Without HU\]+ IMR-687 100mg/200 mg \[Without HU\] + IMR-687 50mg/100 mg \[With HU\]) and pooled data from the placebo arms (With and without HU) were used to provide a larger sample size for the analysis of time to 1st event.