A Study of the Efficacy and Safety of ICA-17043 (With or Without Hydroxyurea) in Patients With Sickle Cell Anemia.

Phase 2

Completed

Interventions: Drug: Low Dose ICA-17043
Drug: Placebo
Drug: High dose ICA-17043

Brief Summary: ICA-17043 is being developed for the chronic treatment of patients with sickle cell disease (SCD) in both adults and children. ICA-17043 is a potent and specific inhibitor of a channel in human red blood cells (RBCs) that blocks RBC dehydration. ICA-17043 is expected to inhibit RBC dehydration and thus should prevent or delay the sickling process. By reducing sickled cells, an improvement in anemia, a reduction in painful crises, and ultimately, less end-organ disease is anticipated.

Recruitment & Eligibility

Inclusion Criteria

Homozygous (HbSS) Sickle Cell Anemia
Otherwise healthy (based on medical history, physical examination, 12-lead ECG, and clinical laboratory tests)
Patients may be receiving hydroxyurea, but must have been dose stabilized for at least 3 months
Patient has a history of at least one acute vaso-occlusive event requiring hospitalization

Exclusion Criteria

Patient participating in a chronic transfusion program
Patient having a total hemoglobin of < 4.0 g/dL or > 10.0 g/dL
Patient having a HbA > 10%
Patient considering undergoing an elective surgery
Patient taking prohibited medications such as Epoetin, Warfarin, etc.
Patient who has had previous gastrointestinal surgery, except cholecystectomy or appendectomy
Patient with significant active cardiovascular, neurologic, endocrine, hepatic, or renal disorders unrelated to sickle cell anemia

Arm && Interventions

Group	Intervention	Description
ICA-17043 Low Dose 6 mg/day	Low Dose ICA-17043	Active study medication: 100 mg loading dose; 6 mg maintenance dose per day
Placebo	Placebo	-
ICA-17043 High Dose 10 mg/day	High dose ICA-17043	Active study medication: 150 mg loading dose; 10 mg maintenance dose per day

Primary Outcome Measures

Name	Time	Method
The primary efficacy endpoint was the change from Baseline in hemoglobin (Hb)	12 Weeks

Secondary Outcome Measures

Name	Time	Method
Changes in other hematologic measurements	12 weeks
Changes in RBC indices, including: mean corpuscular volume (MCV), mean corpuscular Hb concentration (MCHC), and mean corpuscular Hb (MCH	12 weeks
Other laboratory measures associated with sickle cell crises activity including: direct and indirect bilirubin and lactic dehydrogenase (LDH)	12 weeks
Rate of painful crises	12 weeks
Time to first painful crisis	12 weeks
Morbidity of painful crises (maximum morbidity index, derived variable)	12 weeks
Pain intensity scores	12 weeks
Quality of Life (SF 36)	12 Weeks
Health economic data	12 weeks
Average plasma concentration	12 weeks
Correlation between the average plasma concentration and the change in Hb from Baseline to study endpoint	12 weeks