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

Trial ID: 2024-519745-30-01
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. The secondary objectives include:

Investigation of potential doses for subsequent dose-finding studies.
Characterization of the pharmacokinetic profile of budoprutug.
Evaluation of the pharmacodynamic response through assessment of B-cell depletion.
Assessment of clinical effectiveness by measuring the effect on platelet counts.

Participants

This clinical trial involves 11 participants diagnosed with immune thrombocytopenia. The study population includes both males and females within the age ranges categorized as 3 and 4. Eligible subjects must be at least 18 years of age and have a confirmed platelet count of less than 30,000/μL following at least one prior therapeutic attempt. Inclusion requires primary immune thrombocytopenia and adequate hematologic, hepatic, and renal function. Laboratory parameters must show a partial thromboplastin time, prothrombin time, total bilirubin, or international normalized ratio of less than 1.5 times the upper limit of normal. Additionally, participants receiving corticosteroids or thrombopoietin agonists must maintain a stable dosage.

Plans and Procedures

This Phase 1b/2a, open-label, sequential-cohort, dose escalation and expansion study is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical effectiveness of budoprutug in subjects with immune thrombocytopenia. The research methodology involves administering budoprutug via intravenous infusion to assess treatment-emergent adverse events and dose-limiting toxicities. The study protocol includes a screening visit to confirm diagnosis and ensure adequate hematologic, hepatic, and renal function, followed by treatment and subsequent monitoring to evaluate changes in platelet count, CD20+ B-cell count, and serum immunoglobulin levels. The trial design incorporates assessments of antibody development and the ability to discontinue corticosteroids. The total duration of the clinical trial is estimated to conclude by August 2028.

Treatment

The experimental treatment consists of budoprutug, which is supplied as a solution for infusion. This substance is administered via intravenous infusion to subjects diagnosed with immune thrombocytopenia.

Efficacy

The preliminary clinical effectiveness of budoprutug in subjects with immune thrombocytopenia will be assessed through several secondary endpoints. Efficacy evaluation includes the measurement of the change from baseline in absolute peripheral CD20+ B-cell count and the longitudinal change in platelet count. Additionally, changes in serum IgG, IgM, and IgA levels from baseline will be monitored over time. The percentage of subjects capable of discontinuing steroid treatment is also an evaluative parameter.

Response rates will be determined at Week 12 based on specific platelet count thresholds. A stable, partial, or complete response is defined as a platelet count of ≥ 30,000/μL, ≥ 50,000/μL, or ≥ 100,000/μL, respectively, occurring on at least two occasions with a minimum of 7 days separation within a 30-day window. The incidence of anti-drug antibodies following administration will be monitored throughout the study.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Aged > 18 years at the time of informed consent.
Mean platelet count of <30,000/μL (and individually ≤35,000/μL), despite at least one adequate therapeutic attempt, on at least 2 measurements at least 5 days apart, but no more than 14 days apart. Local laboratory values may be used for one of the values to determine eligibility if collected within 14 days prior to signing of Informed Consent Form (ICF) or if collected during screening.
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 ((e.g., rituximab, or if the subject has received or is receiving other immunosuppressive or immunomodulatory agent with the potential to reduce circulating B-cell levels).
Diagnosis of paroxysmal nocturnal hemoglobinuria, Evan’s Syndrome, or any other bleeding disorder that could confound results and impact subject 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, chronic, or latent /occult infection at the time of informed consent or study drug initiation.
Hospitalization within 14 days prior to Screening. Certain subjects may be included after consultation with 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).