Clinical trial NCT06322342: Phase 2 Ascending Dose Safety and Efficacy Study of RVP-001, a Manganese-based MRI Contrast Agent
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Central Nervous System (CNS) Lesions
Brain Metastases
Brain Neoplasms
Brain Neoplasms, Benign
Brain Tumor, Primary
Brain Tumor, Recurrent
Brain Tumors
Brain Cancer
Brain Tumor
Brain Neoplasm, Primary
Multiple Sclerosis
Multiple Sclerosis Brain Lesion
Neurofibroma
Acoustic Neuroma
CNS Tumor
CNS Lesion
CNS Metastases
CNS Cancer
CNS Lymphoma
Lead sponsor: Reveal Pharmaceuticals Inc.
Sponsor class: INDUSTRY
Collaborators: name: National Cancer Institute (NCI)
First posted: 2024-03-21
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: DIAGNOSTIC

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 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 have a gadolinium-based contrast agent-enhanced MRI of the brain 2-14 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 may include individuals who have a stable primary brain tumor, metastatic brain tumors, multiple sclerosis, or other gadolinium-enhancing CNS lesions. Following the screening 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 criteria: 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

Exclusion Criteria:

1. Serious non-malignant disease that could compromise protocol objectives in the opinion of the investigator and/or the Sponsor
2. Body mass index (BMI) greater than 35
3. Patients with clinically significant cardiac disease
4. MRI incompatibility

Primary outcomes:
measure: Adverse Events
timeFrame: From time of dosing to 7 days post dose
measure: Lesion visualization criteria for RVP-001 enhanced MRI compared to unenhanced MRI
timeFrame: 1 day
measure: Lesion visualization criteria for RVP-001 compared to gadolinium-based contrast agent (GBCA)
timeFrame: 1 day
Secondary outcomes:
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
References: