Trusted Resources: Evidence & Education
Scientific literature and patient education texts
Pegylated carboxyhemoglobin bovine (sanguinate) restores RBCs roundness and reduces pain during a sickle cell vaso-occlusive crisis
source: American Society of Hematology
year: 2017
authors: Peter Buontempo, Ronald G. Jubin, Cathy Buontempo, Rosa Real, Friedericke Kazo, Siobhan O'Brien, Faiza Adeel, Abraham Abuchowski
summary/abstract:Background: Pain during Vaso-Occlusive Crisis (VOC) is a hallmark of sickle cell disease (SCD) as deoxygenated (sickled) red blood cells (RBC) aggregate in the microvasculature due to Hemoglobin S (HbS) polymerization. PEGylated carboxyhemoglobin bovine (PEG-COHb; SANGUINATE®) was designed as a gas transfer agent to depolymerize HbS resulting from hypoxia. Prior in vitro studies have shown PEG-COHb capability to transfer carbon monoxide (CO) and oxygen (O2) to SCD hypoxic RBCs, reversing sickling. A prospective, randomized, single-dose Phase II clinical study is in progress (NCT02411708) evaluating the safety and efficacy of PEG-COHb in the treatment of severe VOC including pain reduction in the ambulatory setting. This study is also evaluating the levels of RBC sickling following treatment and association with pain scoring.
Methods: Participants were randomized to a PEG-COHb (320 mg/kg) or saline (placebo) arm, in addition to standard treatment and IV opioid per institutional practice. Pain was assessed using a 10-point pain scale at screening, pre-infusion, hourly until discharge, 24-hours, 72-hours, and Day 7 post-infusion. Blood was collected at pre-infusion, time for readiness to discharge and 72 hours post-infusion to assess RBC shape morphology changes using image-based flow cytometry.
Results: Interim results showed PEG-COHb treated subjects experienced significant reduction at discharge in pain score of 4.3 (±0.3) compared to 2.4 (±0.6) reduction in the placebo arm (p<0.01) (Fig 1). All PEG-COHb participants exhibited RBC morphology changes consistent with unsickling shortly after administration (Fig 2). There were no drug-related severe adverse events. Conclusions: PEG-COHb appeared to be safe, well tolerated, and associated with significantly reduced pain scores. The flow cytometry analysis of blood samples revealed PEG-COHb treatment reverted RBC to a more normal round morphology when compared to the placebo group. Individual patient data showed a trend between RBC unsickling (roundness) and pain score reductions. These results are consistent with depolymerization of HbS resulting from transfer of CO and/or O2 to sickled RBCs and O2 delivery to hypoxic tissue. This study supports advanced clinical trials of PEG-COHb as a potential therapy to reduce the pain associated with VOC.
organization: Prolong Pharmaceuticals, South Plainfield, NJread more
Related Content
-
Gene Therapy & Clinical Trials Webinarhttps://www.youtube.com/watch?v=yYexIUgH...
-
Unanticipated consequences identified after implementation of a pediatric emergency department (PED)-based intranasa...Background: The 2014 National Heart Lun...
-
Sickle cell disease usual careSickle cells are in crescent shape and t...
-
SCDAA News Advisory: SCDAA Statement on Exa-cel Gene TherapyOn October 31, 2023, the Food and Drug A...
-
Webinar Series: Sickle Cell Science: Path to Progress – Genetic Therapies in Sickle Cell DiseaseTo commemorate Sickle Cell Awareness Mon...
-
Annual Sickle Cell Disease and Thalassaemia Conference (ASCAT) 2022The Annual Scientific Conference on Sick...
-
New Guidelines for Managing Sickle Cell Disease Presented at ACP Internal Medicine MeetingNew guidelines for therapeutic strategie...
To improve your experience on this site, we use cookies. This includes cookies essential for the basic functioning of our website, cookies for analytics purposes, and cookies enabling us to personalize site content. By clicking on 'Accept' or any content on this site, you agree that cookies can be placed. You may adjust your browser's cookie settings to suit your preferences. More Information
The cookie settings on this website are set to "allow cookies" to give you the best browsing experience possible. If you continue to use this website without changing your cookie settings or you click "Accept" below then you are consenting to this.