Phase 2 Ascending Dose Safety and Efficacy Study of RVP-001, a Manganese-based MRI Contrast Agent

Overview

This Phase 2 trial will assess the safety, tolerability, efficacy, imaging pharmacodynamics, and pharmacokinetics of RVP-001, a novel manganese-based MRI contrast agent, at three escalating dose levels. RVP-001 will be administered as a single IV bolus to subjects with known gadolinium-enhancing central nervous system (CNS) lesions (for example stable brain tumor or multiple sclerosis) who have recently had a gadolinium-based contrast agent (GBCA)-enhanced MRI of the brain.

Description

Subjects will be pre-screened by study site personnel based on their upcoming appointment date for standard of care GBCA-enhanced MR imaging. Subjects may include individuals who have a stable primary brain tumor, metastatic brain tumors, multiple sclerosis, or other gadolinium-enhancing CNS lesions. Screening to select subjects for study participation will occur at or around the time of the subject's scheduled appointment. The appointment for standard of care imaging should take place at the designated study site.

Following GBCA-enhanced MRI scan to confirm presence of target lesion(s), a baseline unenhanced MRI scan will be performed prior to RVP-001 injection. Dynamic imaging will be performed in conjunction with RVP-001 injection. Steady state imaging will follow at multiple time points during the first hour following dose administration to characterize the pharmacodynamics of RVP-001 and to assess its ability to enhance visualization of areas with disrupted blood brain barrier and/or abnormal vascularity of the central nervous system.

Three dose cohorts are planned.

An unenhanced MRI scan follow-up study will be performed between one week and six weeks following the administration of RVP-001.

Safety will be evaluated throughout the study by assessing the following parameters: adverse events (AEs), physical examinations, injection site monitoring, electrocardiograms (ECGs), vital signs, clinical laboratory evaluations, medical history, and prior and concomitant medications.

Eligibility

Inclusion Criteria:

1. Adults of both sexes, aged 18-65 years
2. Patients with known enhancing CNS lesions, that are: (a) on an ongoing follow-up MRI at up to six week intervals, or (ii) are on imaging surveillance at longer intervals, but who are willing to return for unenhanced MRI at up to six weeks post-administration of RVP-001
3. Patients who have had a GBCA-enhanced MRI within the past 2 to 7 days which demonstrated focal areas of disrupted Blood Brain Barrier (BBB) (e.g., primary and secondary tumors, focal inflammatory disorders) including at least one enhancing lesion of minimum 5 mm (long axis)
4. Acceptable renal function

Exclusion Criteria:

1. Subjects who received either the linear GBCA, gadobenate dimeglumine, or high-relaxivity GBCA, gadopiclenol, for standard-of-care GBCA
2. Serious non-malignant disease that could compromise protocol objectives in the opinion of the investigator and/or the Sponsor
3. Patients with clinically significant cardiac disease
4. MRI incompatibility