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

Phase 2

Recruiting

• Conditions: Brain Tumor, Primary; CNS Cancer; Brain Metastases; Brain Neoplasms; Multiple Sclerosis; Acoustic Neuroma; CNS Lesion; CNS Metastases; Central Nervous System (CNS) Lesions; Neurofibroma
• Interventions: Drug: RVP-001

• Registration Number: NCT06322342
• Lead Sponsor: Reveal Pharmaceuticals Inc.

Brief Summary

This Phase 2 clinical trial will study RVP-001, a new manganese-based MRI contrast agent, in people who are known to have gadolinium-enhancing central nervous system (CNS) lesions, for example stable brain tumors or multiple sclerosis.

The goal of this study is to assess safety, efficacy, and pharmacokinetics of RVP-001 at three dose levels. The study will also compare RVP-001 imaging to gadolinium-based contrast agent (GBCA) imaging. A single dose of RVP-001 will be administered to each subject. Subjects will have known gadolinium-enhancing CNS lesions and will be due to have a routine gadolinium-based contrast agent-enhanced MRI of the brain a few days before receiving RVP-001 with imaging.

The ultimate goal of this research program is development of a gadolinium-free alternative to current general purpose MRI contrast agents.

Detailed 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.

Study Timeline

• Study First Submitted: 2024-03-11
• Study Start: 2024-03-15
• Study First Submitted QC: 2024-03-18
• Study First Posted: 2024-03-21
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-04
• Last Update Posted: 2024-10-07
• Primary Completion: 2025-02
• Study Completion: 2025-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

1. Adults of all sexes, aged 18-75 years
2. Patients with known enhancing CNS lesions, including but not limited to gliomas, meningiomas, glioblastomas, schwannomas, brain metastases, multiple sclerosis lesions, that are on an ongoing follow-up MRI schedule
3. Patients who have had a GBCA-enhanced MRI within the past 14 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

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Exclusion Criteria

1. Subjects who received the linear GBCA, gadobenate dimeglumine, 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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
2 mg/Mn/kg	RVP-001	6 subjects each will receive RVP-001 at a dose of 2 mg Mn/kg
7 mg/Mn/kg	RVP-001	6 subjects each will receive RVP-001 at a dose of 7 mg Mn/kg
12 mg/Mn/kg	RVP-001	6 subjects each will receive RVP-001 at a dose of 12 mg Mn/kg

Primary Outcome Measures

Name	Time	Method
Adverse Events	From time of dosing to 7 days post dose	Treatment-emergent adverse events for each dose level will be summarized.
Lesion visualization criteria for RVP-001 enhanced MRI compared to unenhanced MRI	1 day	The lesion visualization criteria is based on 3 criteria: border delineation, lesion contrast, and internal morphology. These criteria will be assessed by independent readers for representative lesions using the images acquired during the MRI performed with RVP-001.
Lesion visualization criteria for RVP-001 compared to gadolinium-based contrast agent (GBCA)	1 day	The lesion visualization criteria is based on 3 criteria: border delineation, lesion contrast, and internal morphology. These criteria will be assessed by independent readers for representative lesions using the images acquired with RVP-001 and those acquired with the GBCA.; For each reader, only matching lesion-pairs present in both MRI image sets (using GBCA and RVP-001) will be considered.

Trial Locations

Locations (4)

Brigham & Women's Hospital; 🇺🇸 Boston, Massachusetts, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Yale New Haven Hospital; 🇺🇸 New Haven, Connecticut, United States