Evaluation of Safety, Tolerability, Efficacy, and Pharmacokinetics of Intra-articular AMB-05X in Patients with Tenosynovial Giant Cell Tumor

The primary objective of this study is to evaluate the **safety**, **efficacy**, **pharmacokinetics** (PK), and **pharmacodynamics** of intra-articular AMB-05X in the treatment of **tenosynovial giant cell tumor** (TGCT). This evaluation will occur after an initial 24 weeks of treatment (Part 1) and will continue through extended treatment and/or observation (Part 2). The clinical relevance of this study lies in its potential to provide a new therapeutic option for patients with TGCT, a condition characterized by joint pain and swelling, which can significantly impact quality of life. The study aims to determine the optimal dosing regimen and assess the long-term effects of AMB-05X, thereby contributing to the understanding of its therapeutic profile in managing TGCT.

The clinical trial involves a total of **27 participants** diagnosed with **Tenosynovial Giant Cell Tumor** (TGCT). The study population includes both male and female subjects aged 18 years and older. Participants were selected based on their diagnosis of symptomatic TGCT with measurable disease of at least 1 cm, as assessed by MRI scans. The trial population is characterized by adequate hematologic, hepatic, and renal function at screening, and individuals must adhere to contraception guidelines. Participants are required to have a stable prescription analgesic regimen if applicable. The study includes individuals with TGCT involving only one joint, with eligibility extending to those with TGCT of the knee, and potentially the hip and shoulder joints, depending on prior cohort results. The trial does not exclude vulnerable populations, ensuring a comprehensive evaluation of the treatment's safety and efficacy.

The clinical trial is designed as a **Phase II, open-label, adaptive, dose-ranging study** with a long-term extension to evaluate the safety, tolerability, efficacy, and pharmacokinetics of intra-articular AMB-05X injections in subjects with **tenosynovial giant cell tumor** (TGCT). The trial is structured into two parts: Part 1 involves an initial 24 weeks of treatment, while Part 2 includes extended treatment and/or observation. The study aims to assess the primary endpoint of the proportion of subjects achieving an objective response by central radiology review at Week 24, alongside the frequency and severity of treatment-emergent adverse events. Secondary endpoints include various measures of response and changes in patient-reported outcomes.

Participants will undergo a sequence of study visits, beginning with a screening visit to confirm eligibility based on criteria such as measurable disease, adequate organ function, and symptomatic TGCT. Following the screening, eligible participants will enter the treatment phase, with regular follow-up visits to monitor safety, efficacy, and pharmacokinetics. The end-of-study visit will conclude the participant's involvement, assessing the overall response and any long-term effects of the treatment. The expected duration of participant involvement is up to 112 days, with conditions for early termination including withdrawal of consent, adverse events, or non-compliance with study protocols.

The trial is expected to conclude by July 2025, with recruitment having commenced in December 2022. Participants are required to adhere to contraception guidelines and maintain stable prescription analgesic regimens if applicable. The study excludes individuals who have previously received AMB-05X in another study. The investigational product, AMB-05X, is administered as a solution for injection/infusion, with a maximum daily dose of 3 mg and a total dose limit of 350 mg over the treatment period. The study is not classified as a low-intervention trial and does not involve a pediatric formulation.

The clinical trial involves the administration of **AMB-05X**, an experimental medication developed by AMMAX BIO, INC. **AMB-05X** is formulated as a **solution for injection/infusion** and is classified as an antibody with a protein origin. The medication is administered intra-articularly, specifically targeting the treatment of tenosynovial giant cell tumor (TGCT). The dosing regimen for **AMB-05X** includes a maximum daily dose of 3 mg, with a total maximum dose of 350 mg over the course of the treatment. The maximum treatment period is set at 112 days. The administration of the drug is conducted through an injectable solution, ensuring precise delivery to the affected area.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus remains solely on evaluating the safety, tolerability, efficacy, and pharmacokinetics of **AMB-05X**. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol and to accurately assess the outcomes of the treatment. The trial is designed to provide comprehensive data on the effects of **AMB-05X** in subjects with TGCT, both during the initial 24-week treatment phase and any subsequent extended treatment or observation periods.

The efficacy of the investigational product AMB-05X in the treatment of **Tenosynovial Giant Cell Tumor (TGCT)** will be assessed through a series of primary and secondary endpoints. The primary efficacy endpoint is the proportion of subjects achieving an objective response (OR), defined as either a complete response (CR) or partial response (PR), as evaluated by central radiology review using the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) at Week 24 for Part 1 of the study. Additionally, the frequency and severity of treatment-emergent adverse events (TEAEs) will be monitored.

Secondary efficacy endpoints include the proportion of subjects achieving an OR by central radiology review per RECIST v1.1 for Part 2, and the proportion of subjects re-treated with AMB-05X who achieve an OR. Other secondary measures involve the proportion of subjects achieving an OR per modified RECIST and tumor volume score (TVS), median duration of response, time to response, and changes from baseline in various patient-reported outcomes. These include joint range of motion (ROM) score, PROMIS Physical Function score, Worst Stiffness Numeric Rating Scale (NRS) score, Brief Pain Inventory (BPI) score, PROMIS Pain Interference score, and Patient Global Impression of Change (PGIC) scores. Additional assessments will measure serum and synovial levels of AMB-05X, antidrug antibodies (ADA), and CSF1 levels.