Phase I, SAD study of IV doses
Research type
Research Study
Full title
First-In-Man, Phase I, Single-Blind , Placebo-Controlled, Ascending Single Dose Study Of Intravenous YQ23 In Healthy Male And Female Subjects To Assess Safety, Tolerability And Pharmacokinetics
IRAS ID
181763
Contact name
Jim Bush
Contact email
Sponsor organisation
New B Innovation Limited
Eudract number
2015-001488-38
Duration of Study in the UK
0 years, 3 months, 2 days
Research summary
Research Summary
The study drug (YQ23) is an investigational drug which is being developed by the sponsor with an aim to help people with severe haemorrhage (blood loss) in the future.
The study drug is a bovine derived (from cattle such as domestic cow) oxygen carrier. The study drug has the potential to fulfil an unmet medical need for patients by increasing delivery of oxygen to tissues/ organs when high levels of blood loss are experienced e.g. following severe trauma or during surgery. The study drug aims to prevent a process in the body called ischemia reperfusion which is where blood supply returns to the tissue(s) after a period of restriction but can overwhelm the body and lead to inflammation and further damage. This carries a mortality (death) rate of approximately 30 – 40 % and is the main cause of death for patients admitted to intensive care units.
This study is the first time that the study drug is being given to humans. It has been tested extensively in animals at doses of up to 2000 mg/kg/day, more than 16 times higher than the highest dose planned for this study, with no serious adverse effects.Thirty two subjects will be studied in four groups (Groups A to D), each consisting of eight subjects. Each subject will participate in one treatment period only, residing at the Clinical Research Unit (CRU) from Day –1 (the day before dosing) to Day 3 (48 hours post-dose). Within each group, six subjects will receive YQ23 and two placebo. All doses will be administered in the morning of Day 1 as an intravenous (IV) infusion.
Subject participation is expected to last approximately 2 months from the time of screening to the post study visit.Summary of Results
Safety results:
In this first-in-human study, YQ23 was administered to 30 subjects (n = 6/dose). Five dose levels (15, 30, 60, 90, and 120 mg/kg YQ23) or placebo (n = 2/dose) were administered via IV infusion over a 15-minute period. YQ23 was considered to be safe and well tolerated. There were no serious AEs or AEs leading to treatment or subject discontinuation. The only AEs considered possibly related to study drug were a skin rash in 1 subject in the 90 mg/kg YQ23 group and elevated C-reactive protein (CRP) in 2 subjects in the 120 mg/kg YQ23 group. The elevated CRP results were initially identified as clinically significant by the Investigator because they met the dose escalation stopping criteria. The Sponsor and Investigator subsequently agreed that the elevations in CRP, in the absence of any other associated symptoms, were not clinically significant.
There were no clinically significant effects at any dose for cardiovascular safety, vital signs, local tolerability, or physical examinations.
Thirty-nine of 40 total subjects in the study were negative for YQ23 specific immunoglobulin G at predose and Day 28 postdose. One subject (female, 28 years of age, administered placebo) tested positive at both predose and Day 28 postdose, with a titre of 1:320 at both assessments. The subject declined to return to the CRU for the optional visit 3 to 6 months postdose for further immunogenicity testing.
Pharmacokinetic results:
The HemoCue® Plasma/Low Haemoglobin Photometer method is semi-quantitative and cannot distinguish endogenous haemoglobin from YQ23. After correction of the YQ23 concentration data for suspected haemolysis, the resultant PK exposure data showed generally low between-subject variability. Systemic exposure to YQ23 increased in an approximately dose-proportional manner for AUC0-t and AUC0-∞, and in a less than dose-proportional manner for Cmax. The Vss appeared slightly low compared to plasma volume in human, which may indicate that the YQ23 systemic exposure estimates in this study were still confounded with haemolysis.Conclusions:
• In healthy male and female subjects, single doses of YQ23 administered intravenously over a 15-minute interval up to 120 mg/kg were generally safe and well tolerated.
• One possibly drug-related treatment-emergent adverse event (TEAE) of rash generalised (skin rash) was reported by 1 (2.5%) of 40 subjects. This TEAE was not associated with any relevant symptoms or other clinically significant laboratory results.
• There was no evidence of potential myocardial damage in any treatment group.
• No obvious treatment- or dose-related trends were observed in clinical laboratory evaluations (including erythrocyte sedimentation rate, platelet counts, serum creatinine, or serum Troponin I), vital signs, 12-lead safety ECGs, or physical examinations following single doses of YQ23 administered intravenously over a 15-minute interval up to 120 mg/kg.
• The PK of ascending single IV doses of YQ23 in healthy male and female subjects was characterised by approximate linear increases in systemic exposure (AUC0-t and AUC0-∞) across dose and a mean t1/2 of 8 to 9 hours.
• Between-subject variability of systemic exposure to YQ23 was generally low (< 25%).REC name
North West - Greater Manchester Central Research Ethics Committee
REC reference
15/NW/0574
Date of REC Opinion
9 Sep 2015
REC opinion
Further Information Favourable Opinion