An Adaptive Dose Escalation and Expansion Trial to Evaluate the Safety and Clinical Activity of TGD001 in Patients with Immune-Mediated Thrombotic Thrombocytopenic Purpura and Other Thrombotic Microangiopathies

The primary objective of this study is to evaluate the safety and tolerability of TGD001 in patients with a suspected or clinical diagnosis of an acute episode of immune-mediated thrombotic thrombocytopenic purpura. 4, 5.

Secondary objectives include the assessment of the following outcomes:

• Time to clinical response
• Changes in platelet count
• Changes in organ damage markers
• Changes in clinical symptoms and organ function until Day 90
• Duration of ICU admission and hospitalization
• All-cause mortality and disease-specific mortality until Day 90
• Pharmacokinetic characteristics of TGD001
• Immunogenicity of TGD001

This clinical trial involves 30 participants diagnosed with or suspected of having an acute episode of immune-mediated thrombotic thrombocytopenic purpura. The study population consists of adults, including both male and female individuals. Eligible participants must present with a symptomatic episode of thrombotic microangiopathy. Inclusion requires the ability to provide informed consent and the necessity for individuals of childbearing potential to utilize highly effective contraception during the study and for a period of 90 days following the final administration of the investigational product. The study focuses on evaluating the safety and tolerability of TGD001 in this specific patient group.

This integrated Phase I/II adaptive dose escalation and expansion basket trial is designed to evaluate the safety, pharmacology, and clinical activity of TGD001 in patients with immune-mediated thrombotic thrombocytopenic purpura and other forms of thrombotic microangiopathy. The primary objective is to assess the safety and tolerability of the investigational product, an intravenous solution containing urokinase catalytic domain fused with a single-chain antibody against von Willebrand factor. The research methodology involves monitoring treatment-emergent adverse events as the primary endpoint, alongside secondary measures including platelet count changes, lactate dehydrogenase recovery, pharmacokinetics, and mortality rates. Study procedures include a screening visit to confirm diagnosis and eligibility, followed by administration of the study drug and subsequent follow-up visits to monitor clinical response and organ damage markers. The trial is expected to conclude by December 31, 2028.

The experimental therapeutic, designated as TGD001, consists of urokinase catalytic domain fused with a single-chain antibody against von Willebrand factor. This substance is administered as a solution for injection via the intravenous route.

The assessment of efficacy in this clinical trial involves several secondary endpoints. The time to clinical response and the change in platelet count from baseline will be evaluated. Additionally, the time to recovery of platelets to ≥150×10⁹/L and the change of organ damage markers from baseline are monitored. The time to recovery of LDH to ≤2 × ULN is also an established parameter. The improvement of disease-related signs and symptoms, defined as an improvement of ≥1 grade on the CTCAE v5.0 scale within 90 days post intervention, will be quantified by the number of unique participants and total number of adverse events. Further metrics include the number of days in the intensive care unit, the number of days hospitalized, and all-cause and disease-specific mortality within 90 days post-intervention.

Pharmacological assessments include the measurement of plasma concentrations of TGD001 and pharmacokinetic parameters, specifically Cmax, Tmax, AUC, and t1/2. The development of ADA will also be monitored to evaluate the immunological response.