Evaluation of 89Zr-Df-crefmirlimab PET/CT Imaging in Newly Diagnosed Giant Cell Arteritis and Active Rheumatoid Arthritis Patients

The primary objective of this study is to evaluate the uptake of **89Zr-Df-crefmirlimab** in arterial and synovial tissues using positron emission tomography/computed tomography (PET/CT) in patients with newly diagnosed **giant cell arteritis** (GCA) or active **rheumatoid arthritis** (RA). This evaluation is clinically relevant as it aims to enhance the understanding of inflammatory processes in these conditions, potentially leading to improved diagnostic and therapeutic strategies. No secondary objectives are specified for this study.

The clinical trial involves participants diagnosed with **rheumatoid arthritis** or **giant cell arteritis**. The study population includes both male and female subjects, with an age range starting from 30 years for those with rheumatoid arthritis and over 50 years for those with giant cell arteritis. Participants are required to have clinically active disease and must be capable of adhering to study appointments and protocol requirements. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Selection criteria include the ability to provide informed consent and stable treatment regimens for those on disease-modifying anti-rheumatic drugs or non-steroidal anti-inflammatory drugs. Lifestyle factors such as diet and physical activity are not specified as part of the trial's considerations.

The clinical trial is designed to evaluate the uptake of **89Zr-Df-crefmirlimab** on PET/CT scans in patients with newly diagnosed **giant cell arteritis** (GCA) or active **rheumatoid arthritis** (RA). This is a phase II, randomized, double-blind, controlled study. The trial will commence on July 16, 2024, and is expected to conclude by December 1, 2026. Participants will receive an intravenous bolus of the investigational product, **Zr89**, which is an aqueous solution for intravenous administration. The maximum daily and total dose is 22.2 MBq, with a treatment period limited to one day.

The study involves several key visits. Initially, a screening visit will be conducted to confirm eligibility based on specific inclusion criteria, such as age and clinical symptoms for GCA, or diagnosis according to the 2010 ACR/EULAR criteria for RA. Participants must be able to adhere to study appointments and provide informed consent. Following the screening, eligible participants will undergo baseline assessments, including PET/CT imaging to measure tracer uptake in arteries or joints, expressed as Standardized Uptake Values (SUVs). Follow-up visits will be scheduled to monitor safety and efficacy, with the primary endpoint being the tracer uptake in different regions of interest.

The expected duration of participant involvement is approximately one day for the administration of the investigational product, with additional time allocated for follow-up assessments. Conditions that may lead to early termination from the study include the inability to adhere to protocol requirements or withdrawal of consent. The study aims to provide valuable insights into the imaging of inflamed tissues in GCA and RA, contributing to the understanding of these conditions and the potential role of PET/CT imaging in their management.

The clinical trial involves the use of an experimental medication known as **Zirconium (89Zr) crefmirlimab berdoxam**, also referred to as Zr89. This investigational product is formulated as an **aqueous solution for intravenous (IV) administration**. The administration route is specified as an **intravenous bolus use**. The maximum daily and total dose is set at 22.2 MBq (megabecquerel), with a treatment period limited to a single day. The active substance, zirconium (89Zr) crefmirlimab berdoxam, is a protein-based compound, specifically a minibody against CD8 conjugated to desferrioxamine and labeled with zirconium Zr 89. The product is developed by IMAGINAB, INC. and is not designated as a pediatric formulation or an orphan drug.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The primary objective of the trial is to evaluate the uptake of 89Zr-Df-crefmirlimab in arterial and synovial tissues using positron emission tomography (PET/CT) in patients with newly diagnosed giant cell arteritis (GCA) or active rheumatoid arthritis (RA). Participant compliance with the dosing schedule will be monitored to ensure adherence to the protocol. The trial does not include any additional medicinal products or devices.

Efficacy in this clinical trial will be assessed through the primary endpoint of **89Zr-Df-crefmirlimab** PET/CT measurements. The focus will be on evaluating the tracer uptake in different arteries or joints, with radioactivity concentration in Regions-of-Interest (ROIs) expressed as Standardized Uptake Values (SUVs). This method allows for the quantification of tracer distribution and uptake, providing insights into the presence and activity of CD8 T cells in patients with newly-diagnosed giant cell arteritis (GCA) or active rheumatoid arthritis (RA). The primary objective is to evaluate arterial and synovial uptake of **89Zr-Df-crefmirlimab** on PET/CT scans. The trial will involve patients with specific inclusion criteria, such as age and clinical symptoms for GCA, or a diagnosis according to the 2010 ACR/EULAR Rheumatoid Arthritis classification criteria for RA. The study will ensure that patients are capable of adhering to study appointments and protocol requirements, and informed consent will be obtained prior to any study-related procedures. The trial is categorized as a phase II clinical trial, with an estimated recruitment start date of July 16, 2024, and an estimated end date of December 1, 2026.