PMID- 27526120 OWN - NLM STAT- MEDLINE DCOM- 20171103 LR - 20181202 IS - 0065-2598 (Print) IS - 0065-2598 (Linking) VI - 923 DP - 2016 TI - Clinical Evaluation of MP4CO: A Phase 1b Escalating-Dose, Safety and Tolerability Study in Stable Adult Patients with Sickle Cell Disease. PG - 23-29 LID - 10.1007/978-3-319-38810-6_3 [doi] AB - 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/beta(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 (beta2M 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. FAU - Keipert, Peter E AU - Keipert PE AD - KEIPERT Corp. Life Sciences Consulting, San Diego, CA, 92130, USA. peterkeipert@gmail.com. CN - MP4CO-SCD-105 Study Investigators LA - eng PT - Clinical Trial, Phase I PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PL - United States TA - Adv Exp Med Biol JT - Advances in experimental medicine and biology JID - 0121103 RN - 0 (Antisickling Agents) RN - 0 (Biomarkers) RN - 0 (Hemoglobin, Sickle) RN - 0 (Hemoglobins) RN - 0 (MP4CO hemoglobin) RN - 0 (carboxyhemoglobin, sickle) RN - 3WJQ0SDW1A (Polyethylene Glycols) SB - IM MH - Adolescent MH - Adult MH - Anemia, Sickle Cell/blood/diagnosis/*drug therapy MH - Antisickling Agents/*administration & dosage/adverse effects MH - Biomarkers/blood MH - Double-Blind Method MH - Drug Administration Schedule MH - Female MH - Hemoglobin, Sickle/metabolism MH - Hemoglobins/*administration & dosage/adverse effects MH - Humans MH - Infusions, Intravenous MH - Male MH - Middle Aged MH - Polyethylene Glycols/*administration & dosage/adverse effects MH - Time Factors MH - Treatment Outcome MH - Young Adult OTO - NOTNLM OT - HBOC OT - MP4CO OT - Oxygen therapeutic OT - Pegylated hemoglobin OT - Sickle cell disease EDAT- 2016/08/16 06:00 MHDA- 2017/11/04 06:00 CRDT- 2016/08/16 06:00 PHST- 2016/08/16 06:00 [entrez] PHST- 2016/08/16 06:00 [pubmed] PHST- 2017/11/04 06:00 [medline] AID - 10.1007/978-3-319-38810-6_3 [doi] PST - ppublish SO - Adv Exp Med Biol. 2016;923:23-29. doi: 10.1007/978-3-319-38810-6_3.