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