Evaluation of Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Budoprutug (TNT119) in Patients with Immune Thrombocytopenia

Trial ID: 2024-519745-30-00
Protocol: TNT119-ITP-201
Sponsor: Climb Bio Inc.

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Diseases & Conditions

Immune thrombocytopenia

Objectives

The primary objective of this study is to evaluate the **safety** and **tolerability** of ascending doses of budoprutug in subjects with **Immune Thrombocytopenia (ITP)**. This is clinically relevant as it aims to establish a safe dosage range for budoprutug, which is crucial for ensuring patient safety and optimizing therapeutic outcomes in the management of ITP.

Secondary objectives include:

Investigating potential doses for subsequent dose-finding studies in subjects with ITP.
Characterizing the pharmacokinetic (PK) profile of budoprutug in subjects with ITP.
Evaluating the effects of budoprutug on B-cell depletion, assessing the pharmacodynamic (PD) response.
Evaluating the effects of budoprutug on platelet counts, determining the ITP clinical response.

These objectives are essential for understanding the drug's pharmacological profile and its potential therapeutic impact on ITP, thereby guiding future clinical applications and dose optimization strategies.

Participants

The clinical trial involves a total of **11 participants** diagnosed with **Immune Thrombocytopenia (ITP)**. The study population includes both male and female subjects, aged over 18 years, who have been confirmed to have a platelet count of less than 30,000/μL despite previous therapeutic attempts. Participants were selected based on specific inclusion criteria, ensuring they have adequate hematologic, hepatic, and renal function, and are on a stable dose of corticosteroids or thrombopoietin agonists if applicable. The trial does not include a vulnerable population, and no specific lifestyle considerations such as diet or physical activity were highlighted. The selection process focused on individuals with primary ITP, ensuring a targeted and relevant study group for evaluating the safety and tolerability of ascending doses of budoprutug.

Plans and Procedures

The clinical trial is designed to evaluate the **safety** and tolerability of ascending doses of **budoprutug** in subjects with **immune thrombocytopenia** (ITP). This is a Phase 1b/2a, open-label, sequential-cohort, dose escalation and expansion study. The trial will assess the pharmacokinetics, pharmacodynamics, and preliminary clinical effectiveness of the investigational product. The study is expected to commence recruitment on August 1, 2025, and conclude by August 31, 2028. Participants will be administered **budoprutug** via intravenous infusion, and the trial will not involve a pediatric formulation.

Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on criteria such as age, platelet count, and adequate organ function. The inclusion criteria specify that participants must be over 18 years old, have a platelet count of less than 30,000/μL despite previous treatment attempts, and meet specific laboratory parameters. The study will exclude individuals who do not meet these criteria. Following the screening, participants will receive the investigational product and attend regular follow-up visits to monitor safety and efficacy outcomes. The primary endpoint will focus on the incidence, relatedness, severity, and duration of treatment-emergent adverse events and dose-limiting toxicities. Secondary endpoints will include pharmacokinetic parameters, changes in platelet count, and the percentage of subjects achieving a stable response.

The expected duration of participant involvement will vary depending on the cohort and response to treatment, with the possibility of early termination if adverse events occur or if the participant does not adhere to the study protocol. The study will also monitor the development of anti-drug antibodies and changes in immunoglobulin levels over time. Participants on corticosteroids at baseline will be evaluated for their ability to discontinue steroid treatment. The trial is categorized as a Phase I and Phase II integrated clinical trial, aligning with the Revised Transparency Rules. The investigational product, **budoprutug**, is a humanized IgG1 kappa monoclonal antibody against CD19, and the study aims to provide valuable insights into its potential as a treatment for ITP.

Treatment

The clinical trial involves the administration of **Budoprutug**, an investigational medication developed by CLIMB BIO INC. Budoprutug is a **solution for infusion** and is administered via **intravenous (IV) infusion**. The active substance in Budoprutug is a humanised IgG1 kappa monoclonal antibody targeting CD19, also known by the synonym VB119. This protein-based therapeutic agent is designed to evaluate its safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical effectiveness in subjects with **immune thrombocytopenia (ITP)**. The study follows a dose escalation and expansion protocol, with the primary objective of assessing the safety and tolerability of ascending doses of Budoprutug.

In this trial, Budoprutug is the sole investigational product, and no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The dosing schedule and participant compliance monitoring details are not explicitly provided in the available data. The trial is not focused on a pediatric population, as the formulation is not pediatric-specific. The study is conducted under the authorization status of the product, with the sponsor product code being Budoprutug, and it is not classified as an orphan drug.

Efficacy

The clinical trial aims to assess the efficacy of **Budoprutug** in subjects with Immune Thrombocytopenia (ITP) through a series of primary and secondary endpoints. The primary endpoint focuses on the incidence, relatedness, severity, and duration of treatment-emergent adverse events (TEAEs) and dose-limiting toxicities (DLTs). Secondary endpoints include pharmacokinetic (PK) parameters such as the area under the concentration-time curve, time to maximum observed concentration, terminal half-life, apparent clearance, and volume of distribution. Additionally, the trial will evaluate the change from baseline in absolute peripheral cluster of differentiation (CD)20+ B-cell count and the change in platelet count over time in subjects with ITP.

Further secondary endpoints involve assessing the percentage of subjects achieving a stable, partial, and complete response by Week 12, defined by specific platelet count thresholds. The trial will also measure changes in serum IgG, IgM, and IgA from baseline over time, the incidence of subjects developing anti-drug antibodies (ADAs) post-administration, and the percentage of subjects on steroids at baseline who can discontinue steroid treatment. These efficacy parameters will be collected and analyzed at specified timepoints to determine the preliminary clinical effectiveness of Budoprutug in the target population.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Aged > 18 years at the time of informed consent.
Platelet count < 30,000/μL despite an adequate trial of at least one prior therapeutic attempt. Platelet counts of < 30,000/μL must be confirmed on 2 occasions at least 5 days apart, but no more than 14 days apart.
Partial thromboplastin time < 1.5 × upper limit of normal (ULN), prothrombin time < 1.5 × ULN, total bilirubin < 1.5 × ULN unless due to Gilbert’s syndrome, or an international normalized ratio < 1.5 at screening.
Adequate hematologic, hepatic, and renal function
If being treated with corticosteroids or thrombopoietin (TPO) agonists, subjects must be on a stable dose (< 20% change in dose over the 14 days prior to the first dose of study drug). Corticosteroid treatment should not be > 1 mg/kg methylprednisolone (or equivalent) for 2 weeks prior to the first dose of study drug.
Diagnosed with primary ITP

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Exclusion Criteria

CD19+ B-cell count < 80 cells/μL at Screening or < 40 cells/μL if B-cell depleting treatment was received within 24 weeks to 2 years prior to Screening.
Diagnosis of paroxysmal nocturnal hemoglobinuria, Evan’s Syndrome, or any other bleeding disorder that could confound results and impact patient safety.
Prior treatment with rituximab or other B-cell depleting agents within 24 weeks prior to the first dose of study drug or plan to receive B-cell depleting agents during the study.
Current or planned treatment with any chronic anticoagulants or platelet aggregation-inhibiting drugs such as aspirin, nonsteroidal anti-inflammatory drugs, or thienopyridines within 14 days of planned dosing through the end of follow-up. Symptom-based intermittent dosing of nonsteroidal anti-inflammatory drugs is permitted.
Prior treatment with immunosuppressants (other than corticosteroids) within 30 days or 5 times the elimination half-life (whichever is longer) of the Screening Visit (e.g., calcineurin inhibitors, mycophenolate mofetil, azathioprine), or alkylating agents within 180 days of the Screening Visit.
Active or uncontrolled infection at the time of informed consent or study drug initiation.
Recent hospitalization for any reason within 14 days prior to Screening, unless approved by the Medical Monitor.
Receipt of a live vaccine within 28 days prior to the first dose of study drug or during the study. All other vaccines must be completed within 21 days prior to the first dose of study drug.
Secondary cause of ITP (e.g., malignancy, hepatitis B or C, HIV, or other autoimmune diseases [e.g., thyroiditis], or drug-induced ITP).