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

Sponsor

Icagen (Industry)

Overall Status

Completed

CT.gov ID

NCT00040677

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

4.7

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Sickle Cell Disease Sickle Cell Anemia	Drug: Low Dose ICA-17043 Drug: High dose ICA-17043 Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

90 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Feb 1, 2002

Actual Primary Completion Date :

Nov 1, 2003

Actual Study Completion Date :

Jan 1, 2004

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: ICA-17043 Low Dose 6 mg/day

Active study medication: 100 mg loading dose; 6 mg maintenance dose per day

Drug: Low Dose ICA-17043

Low dose arm

Placebo Comparator: Placebo

Drug: Placebo

Placebo Loading dose capsules and maintenance dose tablets matched 10 mg active treatment group

Experimental: ICA-17043 High Dose 10 mg/day

Active study medication: 150 mg loading dose; 10 mg maintenance dose per day

Drug: High dose ICA-17043

150 mg Loading Dose; 10 mg daily dose

Outcome Measures

Primary Outcome Measures

The primary efficacy endpoint was the change from Baseline in hemoglobin (Hb) [12 Weeks]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country
1	Study Site	Birmingham	Alabama	United States
2	Study Site	Oakland	California	United States
3	Study Site	San Francisco	California	United States
4	Study Site	Washington	District of Columbia	United States
5	Study Site	Augusta	Georgia	United States
6	Study Site	Chicago	Illinois	United States
7	Study Site	Baltimore	Maryland	United States
8	Study Site	Boston	Massachusetts	United States
9	Study Site	Detroit	Michigan	United States
10	Study Site	Jackson	Mississippi	United States
11	Study Site	Brooklyn	New York	United States
12	Study Site	New York	New York	United States
13	Study Site	Chapel Hill	North Carolina	United States
14	Study Site	Durham	North Carolina	United States
15	Study Site	Philadelphia	Pennsylvania	United States
16	Study Site	Pittsburgh	Pennsylvania	United States
17	Study Site	Nashville	Tennessee	United States
18	Study Site	Houston	Texas	United States
19	Study Site	Richmond	Virginia	United States