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

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 75

Inclusion Criteria

- Hb SS, Hb SC, sickle ß-thalassemia, sickle ß+ -thalassemia
- Pain consistent with VOC (clinical judgment) and not attributable to other causes.
- Serum sPLA2 level =100 ng/mL (measured on-site)
- Fever defined as oral temperature =38.0°C
- United States (US): age =12 years (through adult)
Europe: age =5 years (through adult)

Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

- New (or suspected new) pulmonary infiltrate diagnosed by chest radiography
- Pregnancy or breastfeeding
- Known hypersensitivity to any of the active constituents of the A-001 or the IV multivitamin preparation (placebo)
- Renal dysfunction: creatinine >1.2 mg/dL for age 18 or less, creatinine >1.5 mg/dL for over age 18
- Hepatic dysfunction (ALT >2 × 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 of entry into the study
- Unwillingness to sign consent form, or if a minor, unwillingness of parent/guardian to sign consent form
- Parenteral or oral corticosteroid therapy (inhaled steroids acceptable) within 7 days of enrollment
- Treatment with any investigational drug or device in the last 30 days
- Any other current or past medical condition that might significantly affect pharmacodynamic responses to the administered drug, or any imminently life-threatening illness

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the safety and tolerability of different doses of A-001 therapy when administered as a 2-day continuous infusion to SCD patients at-risk for ACS.;Secondary Objective: To determine the pharmacokinetic profile of A-001 in SCD patients.<br>To confirm the ability of A-001 infusion to suppress serum sPLA2 activity in SCD patients with elevated serum sPLA2.<br>To determine the efficacy of A-001 infusion in preventing ACS in SCD patients with the combination of VOC, fever, and elevated serum sPLA2.<br>To determine the efficacy of A-001 infusion in reducing pain during VOC.<br>To select the dose(s) to carry forward into pivotal trials.<br>;Primary end point(s): Safety and tolerability of A-001 in SCD patients with VOC

Secondary Outcome Measures

Name	Time	Method

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