Revista Brasileira de Hematologia e Hemoterapia Revista Brasileira de Hematologia e Hemoterapia
Rev Bras Hematol Hemoter 2017;39:20-7 DOI: 10.1016/j.bjhh.2016.08.004
Original article
A Phase Ib open label, randomized, safety study of SANGUINATE™ in patients with sickle cell anemia
Hemant Misraa,, , James Bainbridgea, John Berrymana, Abraham Abuchowskia, Kenneth Mauricio Galvezb, Luis Fernando Uribec, Angel Luis Hernandezd, Nestor Rodolfo Sosae
a Prolong Pharmaceuticals, South Plainfield, United States
b Hospital Pablo Tobon Uribe, Medellin, Colombia
c Fundación Reina Isabel, Cali, Colombia
d Fundación BIOS, Barranquilla, Colombia
e Pan American Medical Research Institute, Pamri, Panama
Recebido 22 Fevereiro 2016, Aceitaram 22 Agosto 2016
Abstract
Background

Treatment of sickle cell anemia is a challenging task and despite the well understood genetic and biochemical pathway of sickle hemoglobin, current therapy continues to be limited to the symptomatic treatment of pain, supplemental oxygen, antibiotics, red blood cell transfusions and hydroxyurea. SANGUINATE is a carbon monoxide releasing molecule and oxygen transfer agent under clinical development for the treatment of sickle cell anemia and comorbidities.

Methods

An open-label randomized Phase Ib study was performed in adult sickle cell anemia patients. Two dose levels of SANGUINATE were compared to hydroxyurea in 24 homozygotes for Hb SS. Twelve subjects received either a low dose (160mg/kg) of SANGUINATE or 15mg/kg hydroxyurea. Another 12 subjects received either a high dose (320mg/kg) of SANGUINATE or 15mg/kg hydroxyurea. The primary endpoint was the safety of SANGUINATE versus hydroxyurea in sickle cell anemia patients. Secondary endpoints included determination of the plasma pharmacokinetics and assessment of hematologic measurements.

Results

Musculoskeletal related adverse events were the most common. Transient troponin I levels increased in three patients, one of whom had an increase in tricuspid regurgitant velocity; however, no clinical signs were noted. Following an assessment of vital signs, tricuspid regurgitant velocity, electrocardiogram, serum biochemistry, hematology, urinalysis, and analysis of reported adverse events, SANGUINATE was found to be safe in stable sickle cell anemia patients.

Conclusions

The clinical trial met its primary objective of demonstrating an acceptable safety profile for SANGUINATE in patients with sickle cell anemia. This trial established the safety of SANGUINATE at both dose levels and permitted its advance to Phase II trials.

Keywords
Sickle cell disease, SANGUINATE, Safety, Clinical trial
Rev Bras Hematol Hemoter 2017;39:20-7 DOI: 10.1016/j.bjhh.2016.08.004