当前位置： SCI文献检索 > Advances in Experimental Medicine and Biology期刊下所有文献 > Clinical Evaluation of MP4CO: A Phase 1b Escalating-Dose, Safety and Tolerability Study in Stable Adult Patients with Sickle Cell Disease.

Clinical Evaluation of MP4CO: A Phase 1b Escalating-Dose, Safety and Tolerability Study in Stable Adult Patients with Sickle Cell Disease.

Abstract：

:MP4CO, developed by Sangart Inc. (San Diego, CA), is a pegylated human hemoglobin-based carbon monoxide (CO) delivery agent and oxygen therapeutic that has shown potential to prevent and reverse red cell sickling. A double blind, comparator controlled, dose-escalation, Phase 1b study was conducted to assess the safety of MP4CO. Adult sickle cell patients with HbSS or S/β(0) Thal genotype who were not experiencing a painful crisis were randomized to receive either MP4CO or normal saline (NS) in a sequential series of six escalating dose cohorts (A-F). In each cohort, three patients received MP4CO (Treatment group) and one patient received NS (Controls). Single IV doses ranged from 15 mg/kg/dose (0.35 mL/kg infusion) to 172 mg/kg/dose (4 mL/kg infusion). Two cohorts received fractionated doses of 172 or 344 mg/kg (4-8 mL/kg, given as two IV infusions, 24 h apart). Overall, 16/24 patients (66.7 %) reported mild to moderate adverse events (AEs); with 13/18 (72 %) in MP4CO group vs. 3/6 (50 %) in NS Controls. No serious adverse events (SAEs) were experienced and no deaths occurred. Most common AEs (reported by >2 patients) included headaches (mild and transient), fatigue and rash at the application site of the Holter electrodes. No treatment-emergent abnormalities in clinical lab values were noted. Vital signs, ECG readings, and pulmonary pressures remained within normal limits. The maximum increase in blood CO-Hb level was ~2 %, which returned to pre-dosing levels within 8 h after dosing. The mean increase in free plasma Hb (an index of MP4CO dose) ranged from 0.20 to 0.35 g/dL in the two highest dose cohorts, with no significant change in total whole blood hemoglobin level. There was no symptomatic or clinical evidence of renal dysfunction in either group based on serum creatinine and urinary albumin results. Two patients had elevated renal biomarkers (β2M and NAG) at Hour 72, which normalized at follow-up visits. Both patients had documented intercurrent illnesses during the study. Further testing of stored urine samples were within normal limits, which suggested the changes were reflective of a generalized inflammatory state rather than direct tubular injury.

journal_name

Adv Exp Med Biol

journal_title

Advances in experimental medicine and biology

authors

Keipert PE,MP4CO-SCD-105 Study Investigators.

doi

10.1007/978-3-319-38810-6_3

subject

Has Abstract

pub_date

2016-01-01 00:00:00

pages

23-29

eissn

0065-2598

issn

2214-8019

journal_volume

923

pub_type

杂志文章,多中心研究,随机对照试验

在线工具

Clinical Evaluation of MP4CO: A Phase 1b Escalating-Dose, Safety and Tolerability Study in Stable Adult Patients with Sickle Cell Disease.