CAT-VHL - Exploring the role of Carbonic Anhydrase IX as diagnostic and Theranostic target in Von-Hippel Lindau disease

The primary objective of this study is to explore the role of **Carbonic Anhydrase IX** as a diagnostic and **theranostic target** in **Von-Hippel Lindau disease**. This investigation aims to evaluate the potential utility of Carbonic Anhydrase IX in both identifying disease manifestations and guiding therapeutic interventions in patients with this hereditary cancer syndrome. The clinical relevance lies in potentially improving disease monitoring and treatment strategies through targeted molecular imaging and therapy approaches specific to Von-Hippel Lindau disease pathophysiology.

The sponsor did not provide information regarding the total number of participants enrolled in this clinical trial. The study population includes both **male** and **female** adults aged 18 years and older with **Von-Hippel Lindau (VHL) disease**. The trial comprises two distinct cohorts: a primary cohort consisting of individuals with a diagnosis of VHL disease requiring surveillance following confirmation of a pathogenic variant at genetic testing, and a secondary cohort including patients with clinical or pathological diagnosis of **hemangioblastoma**, **pheochromocytoma**, **pancreatic neuroendocrine tumor**, or **clear cell renal cell carcinoma** requiring surgery. Participants must have a **performance status** of ECOG/WHO score 0-2. Females of reproductive potential are required to have a negative pregnancy test and utilize highly effective contraception for 30 days following investigational medicinal product administration, while males of reproductive potential must also use highly effective contraception during the same period. All participants must provide voluntarily given informed consent prior to enrollment.

This clinical trial investigates the role of **Carbonic Anhydrase IX** as a diagnostic and **theranostic** target in **Von-Hippel Lindau disease**. The study is designed as a **Phase IV** clinical trial evaluating the efficacy and safety of **CAIX-PET** imaging using **zirconium (89Zr) girentuximab** administered as a **solution for injection** via **intravenous injection**. The investigational medicinal product, Zr-DFO-girentuximab, contains the active substance zirconium (89Zr) girentuximab and is administered at a maximum dose of 37 **MBq** (megabecquerels) as a single administration, with a maximum treatment period of one day.

The primary objective is to explore the role of Carbonic Anhydrase IX as a diagnostic and theranostic target in Von-Hippel Lindau disease. The **primary endpoint** focuses on evaluating the efficacy of CAIX-PET for the detection of tumors in patients with VHL disease. **Secondary endpoints** include assessing the diagnostic accuracy of CAIX-PET in VHL-related tumors diagnosed in the sporadic setting, evaluating the overall diagnostic accuracy of CAIX-PET in VHL disease, and assessing the safety profile of CAIX-PET imaging.

The trial enrolls two distinct cohorts. The Primary Cohort includes patients aged 18 years or older with a confirmed diagnosis of Von-Hippel Lindau disease requiring surveillance following confirmation of a **pathogenic variant** at genetic testing. The Secondary Cohort comprises patients with clinical or pathological diagnosis of **hemangioblastoma**, **pheochromocytoma**, **pancreatic neuroendocrine tumor**, or **clear cell renal cell carcinoma** requiring surgery. Principal inclusion criteria encompass voluntarily given informed consent, age 18 years or older, **ECOG/WHO performance status** score of 0-2, and appropriate contraceptive measures for participants of reproductive potential. Females of reproductive potential must have a negative pregnancy test and use highly effective contraception for 30 days following investigational medicinal product administration. Males of reproductive potential must also use highly effective contraception for the same duration.

The estimated recruitment period is scheduled to commence in June 2025, with an anticipated study completion date of September 2026. The overall trial duration spans approximately 16 months from recruitment initiation to study conclusion. Participant involvement includes screening procedures to confirm eligibility, administration of the investigational medicinal product, imaging assessments, and safety monitoring visits. The study visits are designed to evaluate tumor detection efficacy, diagnostic accuracy, and safety parameters following CAIX-PET imaging. Early termination from the study may occur under conditions including withdrawal of consent, adverse events requiring discontinuation, protocol violations, or investigator decision based on participant safety considerations.

The experimental medication utilized in this clinical trial is **Zr-DFO-girentuximab**, also known by its synonym **89Zr-TLX250**. The active substance is **zirconium (89Zr) girentuximab**, which is classified as a protein-based substance. This investigational medicinal product is manufactured by TELIX INTERNATIONAL PTY LTD. The pharmaceutical form is a **solution for injection** administered via **intravenous injection**. The dosage regimen consists of a maximum daily dose of **37 MBq (megabecquerels)**, which also represents the maximum total dose per treatment period. The treatment period is limited to **1 day**. The product serves as the test medication in this clinical trial investigating **Carbonic Anhydrase IX** as a diagnostic and theranostic target in **Von-Hippel Lindau disease**.

Efficacy will be assessed through the evaluation of CAIX-PET for the detection of tumors in patients with Von Hippel-Lindau disease. The diagnostic accuracy of CAIX-PET will be evaluated in VHL-associated tumors diagnosed in the sporadic setting, as well as in Von Hippel-Lindau disease overall. These assessments will serve to determine the effectiveness of Carbonic Anhydrase IX as a diagnostic and theranostic target in this patient population.