This phase I, first-in-human (FIH) study is open-label, non-randomised and non-placebo-controlled. The study is designed to evaluate the safety, tolerability and pharmacokinetics (PK) of a single intravenous dose of SN132D in approximately 24 patients with breast and pancreatic cancer. Magnetic resonance imaging (MRI) will be performed pre- and post-infusion of SN132D.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
14
Novel manganese-based macromolecular MRI contrast agent
Gothia Forum Clinical Trial Center
Gothenburg, Sweden
CTC Clinical Trial Consultants AB
Uppsala, Sweden
Number of treatment related adverse events (AEs)
Frequency, severity and seriousness of AEs including clinically significant changes in physical examinations, safety laboratory parameters, vital signs, electrocardiograms and injection site reactions will be assessed.
Time frame: Baseline up to 2 weeks
Preliminary efficacy (MRI enhancing effect)
Preliminary efficacy will be evaluated by assessing changes between pre-dose images and post-dose images acquired using T1-weighted imaging sequences, analysing contrast-to-noise in primary tumour vs reference tissue, signal-to-noise in primary tumour, contrast-to-noise in liver and pancreas vs reference tissue and signal-to-noise in liver and pancreas. Additionally, Changes between pre-dose T1 and post-dose T1 in liver and pancreas will be analysed. In pancreatic cancer patients, presence or absence of liver metastases and a number of lesions and diameter of smallest and largest lesion in liver will also be analysed.
Time frame: Day 1
Pharmacokinetics as measured by area under the plasma concentration-time curve from time 0 to the last measurable time point (AUC0-t) for manganese (Mn) (mM x min)
Samples for pharmacokinetic analysis will be collected at predose and at 10 min, 20 min, 60 min, 65 min, 75 min, 90 min, 105 min, 3 h and 9 h post start of dosing.
Time frame: Baseline up to Day 2
Pharmacokinetics as measured by area under the plasma concentration-time curve from time 0 extrapolated to infinite time (AUCinf) for Mn (mM x min)
Samples for pharmacokinetic analysis will be collected at predose and at 10 min, 20 min, 60 min, 65 min, 75 min, 90 min, 105 min, 3 h and 9 h post start of dosing.
Time frame: Baseline up to Day 2
Pharmacokinetics as measured by maximum plasma concentration (Cmax) for Mn (µg Mn/mL)
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Samples for pharmacokinetic analysis will be collected at predose and at 10 min, 20 min, 60 min, 65 min, 75 min, 90 min, 105 min, 3 h and 9 h post start of dosing.
Time frame: Baseline up to Day 2
Pharmacokinetics as measured by time to Cmax (Tmax) for Mn (h)
Samples for pharmacokinetic analysis will be collected at predose and at 10 min, 20 min, 60 min, 65 min, 75 min, 90 min, 105 min, 3 h and 9 h post start of dosing.
Time frame: Baseline up to Day 2
Pharmacokinetics as measured by plasma elimination half-life (T½) for Mn (h)
Samples for pharmacokinetic analysis will be collected at predose and at 10 min, 20 min, 60 min, 65 min, 75 min, 90 min, 105 min, 3 h and 9 h post start of dosing.
Time frame: Baseline up to Day 2
Pharmacokinetics as measured by total body clearance (CL) for Mn (L/h)
Samples for pharmacokinetic analysis will be collected at predose and at 10 min, 20 min, 60 min, 65 min, 75 min, 90 min, 105 min, 3 h and 9 h post start of dosing.
Time frame: Baseline up to Day 2
Pharmacokinetics as measured by apparent volume of distribution at steady state (Vss) for Mn (L) the terminal phase half-life (T½) for manganese (Mn)
Samples for pharmacokinetic analysis will be collected at predose and at 10 min, 20 min, 60 min, 65 min, 75 min, 90 min, 105 min, 3 h and 9 h post start of dosing.
Time frame: Baseline up to Day 2