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

Sickle Cell Disease Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00434473
• Other study ID #: AN-SCD1121
• Status: Completed
• Phase: Phase 2
• First received: February 9, 2007
• Last updated: January 30, 2014
• Start date: December 2006
• Est. completion date: December 2009

Study information

• Verified date: January 2014
• Source: Anthera Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: December 2009
• Est. primary completion date: August 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 5 Years and older

Eligibility

Patients are eligible for inclusion if they meet the following criteria:

• Sickle cell variant (Hb SS, Hb SC, sickle ß°—thalassemia, sickle ß+—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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Acute Chest Syndrome
• Anemia, Sickle Cell
• Sickle Cell Disease
• Syndrome
• Vaso-occlusive Crisis

Intervention

Drug:
• A-001
A-001

Other:
• Placebo
Placebo

Locations

Country	Name	City	State
United States	Children's Healthcare of Atlanta	Atlanta	Georgia
United States	SUNY Downstate Medical Center	Brooklyn	New York
United States	Children's Memorial Hospital	Chicago	Illinois
United States	Duke University Comprehensive Sickle Cell Center	Durham	North Carolina
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Howard University Hospital	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Anthera Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	To determine the pharmacokinetic profile of A-001 in SCD patients		Study end	No
Secondary	To confirm the ability of A-001 infusion to suppress serum sPLA2 activity in SCD patients with elevated serum sPLA2		Study end	No
Secondary	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	No