IMPACTS Trial: Investigation of the Modulation of Phospholipase in Acute Chest Syndrome

Study Overview
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Brief Summary
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The study will be conducted at 15-20 US centers in a randomized, placebo-controlled, double-blind fashion. Enrollees will be hospitalized sickle cell disease (SCD) patients at-risk for acute chest syndrome (ACS) based on the presence of vaso-occlusive crisis (VOC), fever (T ≥38.0°C) and serum sPLA2 concentration ≥50 ng/mL.

Detailed Description
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This is a double-blind randomized, parallel group, placebo-controlled dose escalation study (2 cohorts) in patients with sickle cell disease (SCD) and vaso-occlusive crisis (VOC) who are at-risk for development of acute chest syndrome (ACS) based on the combination of VOC, fever (T ≥38.0ºC), and a serum sPLA2 concentration ≥50 ng/mL. The first group of patients will be randomized 2:1 to receive low dose A-001 or placebo as a 48-hour continuous infusion. Pharmacokinetic and clinical data from this group will undergo review by the Independent Data Monitoring Committee (IDMC). If there is no significant toxicity associated with A-001, then an additional group of patients will be enrolled and randomized 2:1 to high dose A-001 versus placebo as a 48-hour continuous infusion.

Official Title
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IMPACTS Trial: Investigation of the Modulation of Phospholipase in Acute Chest Syndrome (Dose Escalation Study: Varespladib Infusion [A-001] for the Prevention of Acute Chest Syndrome in At-Risk Patients With Sickle Cell Disease and Vaso-occlusive Crisis)

Conditions
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Sickle Cell Disease, Vaso-occlusive Crisis, Acute Chest Syndrome

Intervention / Treatment
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* Drug: A-001
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Patients are eligible for inclusion if they meet the following criteria: Sickle cell variant (Hb SS, Hb SC, sickle β°-thalassemia, sickle β+-thalassemia) Pain consistent with vaso-occlusive crisis Elevated serum sPLA2 level (measured on-site) Fever Age ≥5 years (through adult) Patients must NOT meet any of the following exclusion criteria: New lung infiltrate by chest radiography Pregnancy or breastfeeding Significant renal dysfunction Significant hepatic dysfunction 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 of entry into the study

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Placebo<br>|
| Experimental: A-001<br> | Drug: A-001<br>* A-001<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the safety and tolerability of different doses of A 001 therapy when administered as a 2-day continuous infusion to sickle cell disease (SCD) patients at-risk for the acute chest syndrome (ACS). |  | Study end | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the pharmacokinetic profile of A-001 in SCD patients |  | Study end | 
| To confirm the ability of A-001 infusion to suppress serum sPLA2 activity in SCD patients with elevated serum sPLA2 |  | Study end | 
| To determine the efficacy of A-001 infusion in preventing ACS in SCD patients with the combination of vaso-occlusive crisis (VOC), fever, and elevated serum sPLA2 |  | Study end |