#1 Clinical Trials Search in Europe

BUDOPRUTUG

BUDOPRUTUG (also known as TNT119) is a promising new humanized immunoglobulin G1 monoclonal antibody being investigated in clinical trials. This innovative medication works by selectively binding to CD19, a protein found on B cells, and is designed to deplete these targeted cells through antibody-dependent cellular cytotoxicity (ADCC). Current clinical trials are evaluating BUDOPRUTUG’s safety, effectiveness, and dosing across several autoimmune conditions, including primary membranous nephropathy (PMN), systemic lupus erythematosus (SLE), and immune thrombocytopenia (ITP). These trials represent an important step in developing new treatment options for patients with challenging autoimmune disorders that often have limited effective therapies.

Table of Contents

What is Budoprutug?

Budoprutug (also known as TNT119) is a humanized, immunoglobulin G1 monoclonal antibody that selectively binds to a protein called CD19 found on the surface of certain immune cells. This medication is currently being investigated in clinical trials for several autoimmune conditions[1][2].

A monoclonal antibody is a laboratory-made protein that mimics the immune system’s ability to fight off harmful pathogens. In the case of Budoprutug, it is designed to target specific cells in the immune system that may be contributing to autoimmune diseases.

How Budoprutug Works

Budoprutug works by selectively binding to CD19, a protein found on B cells. B cells are a type of white blood cell that plays a crucial role in the immune system, particularly in producing antibodies to fight infections. However, in autoimmune conditions, these B cells can sometimes malfunction and produce antibodies that attack the body’s own tissues[3].

When Budoprutug binds to CD19 on B cells, it is designed to deplete these cells through a process called antibody-dependent cellular cytotoxicity (ADCC). This is a mechanism in which antibodies flag cells for destruction by the immune system. By reducing the number of B cells, Budoprutug aims to decrease the production of harmful antibodies that cause autoimmune conditions[1].

Medical Conditions Treated with Budoprutug

Based on current clinical trials, Budoprutug is being investigated for several autoimmune conditions:

Primary Membranous Nephropathy (PMN)

Primary Membranous Nephropathy is a kidney disease characterized by thickening of the glomerular basement membrane (a part of the kidney’s filtering system) and the presence of immune deposits. This condition often leads to significant protein loss in the urine (proteinuria) and can progress to kidney failure if not treated[1].

In PMN, many patients have antibodies against a protein called PLA2R (phospholipase A2 receptor) that is found in the kidneys. Budoprutug aims to reduce these antibodies by targeting the B cells that produce them[1].

Systemic Lupus Erythematosus (SLE)

Systemic Lupus Erythematosus, commonly known as lupus, is a chronic autoimmune disease that can affect multiple organs and systems in the body. In SLE, the immune system produces antibodies that attack healthy tissues, leading to inflammation and damage. Common symptoms include joint pain, skin rashes, fatigue, and kidney problems[2][4].

Budoprutug is being studied in patients with active SLE who have not responded adequately to standard therapy. The goal is to reduce disease activity by decreasing harmful antibody production[2].

Immune Thrombocytopenia (ITP)

Immune Thrombocytopenia is a blood disorder characterized by a low platelet count. Platelets are blood cells that help with clotting, and when their numbers are reduced, patients can experience easy bruising, bleeding gums, and potentially dangerous internal bleeding. In ITP, the immune system produces antibodies that destroy platelets[3].

Budoprutug is being investigated in patients with ITP who have not responded to at least one previous treatment and have a platelet count below 30,000/μL (normal range is typically 150,000-450,000/μL)[3].

How Budoprutug is Administered

Budoprutug is administered in two main ways, depending on the clinical trial and condition being treated:

Intravenous (IV) Administration

Most current trials use intravenous administration, where the medication is delivered directly into the bloodstream through a vein. The dosing schedule varies by condition:

  • For Primary Membranous Nephropathy: Patients receive a single IV dose on Day 1, Day 15, Day 169, and Day 183[1].
  • For Systemic Lupus Erythematosus: In one trial, patients receive a single IV dose on Day 1[2].
  • For Immune Thrombocytopenia: Patients receive a single IV dose on Day 1 and on Day 15[3].

Subcutaneous (SC) Administration

Budoprutug is also being tested in a subcutaneous form, where the medication is injected under the skin. This method is being evaluated in healthy volunteers to compare its effectiveness with IV administration[5].

Current Clinical Trials

Budoprutug is currently being evaluated in several clinical trials:

Phase 2 Trial in Primary Membranous Nephropathy

This open-label study is evaluating the safety, pharmacodynamics, and preliminary efficacy of three intravenous dose regimens of Budoprutug in adults with PMN who are anti-PLA2R antibody positive and have persistent proteinuria despite optimized treatment with renin-angiotensin-aldosterone system (RAAS) inhibitors. Approximately 45 subjects will be enrolled across three dose cohorts[1].

Phase 1b/2a Trials in Systemic Lupus Erythematosus

Multiple studies are evaluating Budoprutug in patients with SLE, including a Phase 1b open-label, single ascending dose study and a Phase 1b/2a open-label dose escalating study. These trials aim to assess safety, tolerability, pharmacokinetics, and pharmacodynamics in adults with active SLE who have had an inadequate response to standard therapy[2][4].

Phase 1b/2a Study in Immune Thrombocytopenia

This open-label, sequential-cohort, dose escalation and expansion study is evaluating the safety, tolerability, and preliminary clinical effectiveness of Budoprutug in subjects with ITP. The study involves three dose-ascending cohorts followed by an expansion cohort at the selected dose level(s)[3].

Phase 1 Study in Healthy Volunteers

A randomized, double-blind, placebo-controlled, single-ascending-dose study is evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of subcutaneous and intravenous injections of Budoprutug in normal healthy volunteers[5].

Safety Information

As Budoprutug is still in clinical trials, comprehensive safety information is not yet available. However, all current trials are monitoring for Treatment-Emergent Adverse Events (TEAEs), which are unwanted medical occurrences that emerge during treatment[1][2][3].

Some specific safety aspects being monitored include:

  • Infusion-related reactions: Reactions that can occur during or shortly after receiving an IV infusion[5].
  • Injection site reactions: Local reactions at the site where subcutaneous injections are given[5].
  • Anti-drug antibodies (ADAs): Antibodies that the body might develop against Budoprutug, which could potentially reduce its effectiveness[2][3].
  • Changes in vital signs, laboratory values, and heart rhythm parameters[2].

Since Budoprutug depletes B cells, patients may be at increased risk for infections. Long-term follow-up is planned in the trials to monitor for B-cell recovery[1].

Effectiveness of Budoprutug

As Budoprutug is still in clinical trials, definitive information about its effectiveness is not yet available. The current trials are designed to evaluate various effectiveness measures specific to each condition:

For Primary Membranous Nephropathy:

  • Change in anti-PLA2R antibody levels over time[1]
  • Complete or partial remission rates at Week 48[1]
  • Change in proteinuria over time, measured via urine protein-creatinine ratio (UPCR)[1]
  • Change in kidney function, measured by estimated glomerular filtration rate (eGFR)[1]

For Systemic Lupus Erythematosus:

  • Change in disease activity scores (BILAG-2004, SLEDAI-2K)[2]
  • Proportion of participants achieving SRI-4 response (a standard measure of improvement in lupus)[2]
  • Change in urine protein creatinine ratio for patients with kidney involvement[2][4]
  • Change in fatigue scores[2][4]

For Immune Thrombocytopenia:

  • Change in platelet count over time[3]
  • Proportion of participants with stable, partial, or complete platelet response[3]
  • Rate of steroid discontinuation among baseline steroid users[3]

In all studies, researchers are also monitoring changes in B-cell counts to confirm that Budoprutug is working as expected to reduce these cells[1][2][3].

Condition Trial Phase Dosing Regimen Key Measurements Number of Participants
Primary Membranous Nephropathy (PMN) Phase 2 Four IV doses: Days 1, 15, 169, and 183 B cell counts, Anti-PLA2R antibodies, Proteinuria (UPCR), Complete/partial remission Approximately 45 subjects
Systemic Lupus Erythematosus (SLE) Phase 1b Single IV dose in ascending dose cohorts B cell counts, SLEDAI-2K scores, BILAG-2004 scores, Physician’s Global Assessment Four single-dose ascending cohorts
Systemic Lupus Erythematosus (SLE) Phase 1b/2a Three sequential escalating dose cohorts B cell subsets, SLEDAI, FACIT, Global disease assessments, Urine protein Three dose cohorts + expansion cohort (16-20 participants)
Immune Thrombocytopenia (ITP) Phase 1b/2a Two IV doses: Days 1 and 15 CD20+ B-cell counts, Platelet counts, Steroid discontinuation rates Three dose escalation cohorts + expansion cohort
Healthy Volunteers Phase 1 Single dose (SC or IV) Safety, Pharmacokinetics, Injection/infusion reactions Approximately 38 participants

FAQ

  • What is BUDOPRUTUG and how does it work? BUDOPRUTUG (also known as TNT119) is a humanized immunoglobulin G1 monoclonal antibody that selectively binds to a protein called CD19, which is found on B cells. It works by depleting these targeted B cells through a process called antibody-dependent cellular cytotoxicity (ADCC). Since B cells play a significant role in many autoimmune diseases by producing harmful antibodies, reducing their numbers may help control disease activity.
  • What conditions is BUDOPRUTUG being tested for? Current clinical trials are investigating BUDOPRUTUG for several autoimmune conditions, including primary membranous nephropathy (PMN), systemic lupus erythematosus (SLE), and immune thrombocytopenia (ITP). These are all conditions where B cells and the antibodies they produce play an important role in causing disease.
  • How is BUDOPRUTUG administered to patients? BUDOPRUTUG is being tested in both intravenous (IV) and subcutaneous (under the skin) formulations. In most of the current trials, it's administered as an IV infusion. For example, in the PMN trial, patients receive doses on Days 1, 15, 169, and 183. In the ITP trial, patients receive two IV infusions 14 days apart. Some trials are also exploring subcutaneous injections as an alternative administration method.
  • What are the main outcomes being measured in these trials? The trials primarily assess safety and tolerability by monitoring adverse events, laboratory abnormalities, and vital signs. They also measure how the drug moves through the body (pharmacokinetics) and its effects on B cell counts (pharmacodynamics). For effectiveness, researchers are tracking disease-specific measures like changes in proteinuria for kidney conditions, platelet counts for ITP, and disease activity scores for lupus. The studies also monitor for the development of anti-drug antibodies.
  • What phase are the BUDOPRUTUG clinical trials currently in? BUDOPRUTUG is being evaluated in early to mid-stage clinical trials. There are Phase 1, Phase 1b, and Phase 2 studies underway. Phase 1 trials focus primarily on safety in healthy volunteers or small groups of patients. Phase 1b trials continue to study safety but in patients with the target disease. Phase 2 trials begin to assess both safety and effectiveness in larger groups of patients. These early phases help determine the right dose and identify potential side effects before larger, more definitive studies are conducted.

Ongoing Clinical Trials on BUDOPRUTUG

  • A Study to Test How Safe Budoprutug Is and How Well It Works in Patients with Immune Thrombocytopenia

    Recruiting

    1 1
    Investigated drugs:
    Bulgaria Greece Spain

  • Study on the Safety and Effectiveness of Budoprutug in Patients with Immune Thrombocytopenia

    Not yet recruiting

    1 1
    Investigated drugs:
    Bulgaria Greece Spain

Glossary

  • Monoclonal Antibody: A laboratory-created protein that targets a specific antigen (like a protein) in the body. Monoclonal antibodies are designed to bind to those specific proteins to help the immune system identify and destroy particular cells.
  • CD19: A protein found on the surface of B cells. It serves as a target for BUDOPRUTUG, allowing the drug to identify and attach to B cells specifically.
  • Antibody-Dependent Cellular Cytotoxicity (ADCC): A mechanism where antibodies bind to target cells (like B cells), flagging them for destruction by certain immune cells. This is how BUDOPRUTUG is thought to reduce B cell numbers.
  • Primary Membranous Nephropathy (PMN): A kidney disease where the body's immune system attacks the filtering membranes in the kidney, causing protein to leak into the urine. It can lead to kidney damage over time.
  • Systemic Lupus Erythematosus (SLE): A chronic autoimmune disease that can affect multiple body systems, including joints, skin, kidneys, brain, heart, and lungs. It occurs when the immune system attacks healthy tissues.
  • Immune Thrombocytopenia (ITP): A blood disorder characterized by abnormally low platelet counts caused by the immune system destroying platelets. This can lead to easy bruising and bleeding.
  • B Cells: A type of white blood cell that makes antibodies to fight infections and plays a key role in many autoimmune diseases by producing antibodies that attack the body's own tissues.
  • Proteinuria: The presence of excess protein in the urine, often a sign of kidney damage or disease. This is measured in PMN trials as a way to track disease activity.
  • UPCR (Urine Protein-Creatinine Ratio): A measurement that compares the amount of protein to creatinine in a urine sample, providing a standardized way to assess protein excretion. Used to monitor kidney function in trials.
  • Pharmacokinetics (PK): The study of how drugs move through the body, including absorption, distribution, metabolism, and excretion. PK measures include maximum concentration (Cmax), time to maximum concentration (Tmax), and half-life.
  • Pharmacodynamics (PD): The study of how drugs affect the body and how the body responds to drugs. For BUDOPRUTUG, this includes measuring changes in B cell counts after administration.
  • Anti-PLA2R Antibodies: Autoantibodies that target the phospholipase A2 receptor in the kidney. These are important markers in primary membranous nephropathy and their levels are being tracked in BUDOPRUTUG trials.
  • Complete Remission: The absence or significant reduction of disease signs and symptoms, often defined differently for each condition. In kidney diseases, this typically means normalization of protein levels in urine.
  • Partial Remission: A significant improvement in disease signs and symptoms that doesn't meet the criteria for complete remission. Often represents a meaningful clinical benefit for patients.
  • SLEDAI (Systemic Lupus Erythematosus Disease Activity Index): A scoring system used to measure lupus disease activity. Higher scores indicate more active disease.
  • Anti-Drug Antibodies (ADAs): Antibodies that the body develops against a therapeutic drug. These can potentially reduce the effectiveness of the treatment and are being monitored in BUDOPRUTUG trials.
  • Open-Label Study: A type of clinical trial where both researchers and participants know which treatment is being administered (as opposed to a blinded study).
  • RAAS Inhibition: Treatment that blocks the renin-angiotensin-aldosterone system, commonly used to manage blood pressure and reduce proteinuria in kidney diseases.

References

  1. https://clinicaltrials.gov/study/NCT07096843
  2. https://clinicaltrials.gov/study/NCT07011043
  3. https://clinicaltrials.gov/study/NCT07043946
  4. https://clinicaltrials.gov/study/NCT06570434
  5. https://clinicaltrials.gov/study/NCT07090655