A Study of Varespladib Infusion in Subjects With Sickle Cell Disease.

Study Overview
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Brief Summary
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The purpose of this study is to determine the effectiveness of A 001 infusion in preventing acute chest syndrome in sickle cell disease (SCD) subjects with vaso-occlusive crisis, fever, and elevated serum C-reactive protein (CRP).

Official Title
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A Randomized, Double-blind, Placebo-Controlled Study With Varespladib Infusion (A-001) in Subjects With Sickle Cell Disease and Vaso-Occlusive Crisis for the Prevention of Acute Chest Syndrome At-Risk Subjects.

Conditions
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Sickle Cell Disease, Vaso-occlusive Crisis

Intervention / Treatment
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* Drug: Varespladib
* Other: Placebo (Normal Saline)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Genotypes Hb SS, Hb SC, sickle β°-thalassemia, sickle β+ -thalassemia Pain consistent with vaso-occlusive crisis (clinical judgment) and not attributable to other causes Serum CRP ≥5.0 mg/L at time of screening Fever defined as oral temperature ≥38.0°C at time of screening Age ≥5 years Exclusion Criteria: New or suspected new pulmonary infiltrate diagnosed by chest radiography Females who are nursing, pregnant or intend to become pregnant Renal dysfunction defined as a creatinine level >1.2 mg/dL for subjects aged 18 or less or a creatinine level >1.5 mg/dL for subjects over the age of 18 Hepatic dysfunction (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] >3 × upper limit of normal) Acute neurologic dysfunction Any medical condition for which transfusion may be needed imminently, and/or hemoglobin <5 g/dL Red blood cell transfusion within 30 days prior to screening Parenteral or oral corticosteroid therapy (inhaled steroids acceptable) within 7 days prior to screening

Ages Eligible for Study
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Minimum Age: 5 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Varespladib<br>48 hour continuous infusion delivered intravenously (IV) | Drug: Varespladib<br>* 48 hour continuous infusion delivered intravenously (IV)at a rate of 110µg/kg/hr.<br>|
| Placebo Comparator: Placebo<br>48 hour continuous infusion delivered intravenously (IV) | Other: Placebo (Normal Saline)<br>* 48 hour continuous infusion delivered intravenously (IV)at a rate of 110µg/kg/hr.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of A 001 infusion in preventing acute chest syndrome in sickle cell disease (SCD) subjects with the combination of vaso-occlusive crisis, fever, and elevated serum C-reactive protein (CRP). |  | Various time points up to Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of A 001 therapy when administered as a 48-hour continuous infusion to SCD subjects at-risk for acute chest syndrome. |  | Various time points up to Day 30 | 
| Impact of A-001 treatment on sPLA2 levels and CRP. |  | Various time points up to Day 30 | 
| Impact of A-001 treatment on the signs and symptoms of vaso-occlusive crisis. |  | Various time points up to Day 30 | 
| Impact of A-001 treatment on opioid use for pain in the treatment of vaso-occlusive crisis. |  | Various time points up to Day 30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SCD