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

Multiple Sclerosis Clinical Trial

Official title:

A Multi-Center, Phase 2, Open Label, Ascending Dose Study to Evaluate the Safety and Efficacy of RVP-001 and to Identify an Appropriate Dose to Detect CNS Lesions in Adult Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06322342
• Other study ID #: RVL-102-23
• Secondary ID: 9R44CA261240-04A
• Status: Recruiting
• Phase: Phase 2
• Start date: March 15, 2024
• Est. completion date: March 2025

Study information

• Verified date: June 2024
• Source: Reveal Pharmaceuticals Inc.
• Contact: Srini Mukundan, M.D./PhD.
• Phone: 617-306-3242
• Email: clinicaltrials[@]revealpharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: March 2025
• Est. primary completion date: February 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

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

Related Conditions & MeSH terms

• Acoustic Neuroma
• Brain Cancer
• Brain Metastases
• Brain Neoplasm, Primary
• Brain Neoplasms
• Brain Neoplasms, Benign
• Brain Tumor
• Brain Tumor, Primary
• Brain Tumor, Recurrent
• Brain Tumors
• CNS Cancer
• CNS Lesion
• CNS Lymphoma
• CNS Metastases
• CNS Tumor
• Multiple Sclerosis
• Neoplasm Metastasis
• Neoplasms
• Neurofibroma
• Neuroma
• Neuroma, Acoustic
• Sclerosis

Intervention

Drug:
• RVP-001
MRI contrast agent

Locations

Country	Name	City	State
United States	Brigham & Women's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Duke University Medical Center	Durham	North Carolina
United States	Yale New Haven Hospital	New Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Reveal Pharmaceuticals Inc.	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse Events	Treatment-emergent adverse events for each dose level will be summarized.	From time of dosing to 7 days post dose
Primary	Lesion visualization criteria for RVP-001 enhanced MRI compared to unenhanced MRI	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.	1 day
Primary	Lesion visualization criteria for RVP-001 compared to gadolinium-based contrast agent (GBCA)	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.	1 day