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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase II, Multicenter, Twelve-Week, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Dose-Range-Finding Study of the Efficacy and Safety of ICA-17043 With or Without Hydroxyurea Therapy in Patients With Sickle Cell Anemia

Conditions
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Sickle Cell Disease, Sickle Cell Anemia

Intervention / Treatment
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* Drug: Low Dose ICA-17043
* Drug: High dose ICA-17043
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ICA-17043 Low Dose 6 mg/day<br>Active study medication: 100 mg loading dose; 6 mg maintenance dose per day | Drug: Low Dose ICA-17043<br>* Low dose arm<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo Loading dose capsules and maintenance dose tablets matched 10 mg active treatment group<br>|
| Experimental: ICA-17043 High Dose 10 mg/day<br>Active study medication: 150 mg loading dose; 10 mg maintenance dose per day | Drug: High dose ICA-17043<br>* 150 mg Loading Dose; 10 mg daily dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary efficacy endpoint was the change from Baseline in hemoglobin (Hb) |  | 12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sickle cell anemia, sickle cell disease, anemia, ICA-17043, senicapoc