VTX2735 Clinical Trials

What Is VTX2735?

Uses and Conditions Under Study

• Cryopyrin Associated Periodic Syndrome (CAPS): CAPS is a group of rare, inherited autoinflammatory diseases caused by mutations in the NLRP3 gene. These conditions lead to excessive production of a protein called cryopyrin, resulting in systemic inflammation and symptoms such as fever, rash, joint pain, and eye inflammation. VTX2735 is being studied in 1 trial for its potential to manage the inflammatory responses associated with CAPS.
• Recurrent Pericarditis: Recurrent pericarditis is a condition characterized by repeated episodes of inflammation of the pericardium, the fluid-filled sac surrounding the heart. This inflammation can cause chest pain, shortness of breath, and other symptoms that significantly impact quality of life. VTX2735 is being investigated in 1 trial as a potential treatment to reduce the frequency and severity of these inflammatory episodes.

Dosing

• Cohort A
• Cohort B Treatment Group B1
• Cohort B Treatment Group B2
• Cohort C Treatment Group C1
• Cohort C Treatment Group C2
• Cohort 1
• Cohort 2

Side Effects

In a 12-week study of patients with Irritable Bowel Syndrome with Constipation (IBS-C) (NCT05298130), the most common side effect reported by patients taking VTX2735 was nausea. 15.3% of patients taking VTX2735 experienced nausea, compared to 7.7% on placebo. Other common side effects in this population included:

• Diarrhea: 12.7% of patients taking VTX2735 experienced diarrhea, compared to 6.0% on placebo.
• Abdominal pain: 9.4% of patients taking VTX2735 experienced abdominal pain, compared to 7.0% on placebo.
• Vomiting: 6.5% of patients taking VTX2735 experienced vomiting, compared to 3.0% on placebo.
• Abdominal distension: 5.9% of patients taking VTX2735 experienced abdominal distension, compared to 3.7% on placebo.
• Headache: 5.2% of patients taking VTX2735 experienced headache, compared to 4.7% on placebo.

In a separate 8-week study of patients with hyperphosphatemia undergoing dialysis (NCT05680150), diarrhea was the most common side effect. 18.1% of patients taking VTX2735 experienced diarrhea, compared to 10.7% on placebo. Other common side effects in this patient group included:

• Nausea: 15.0% of patients taking VTX2735 experienced nausea, compared to 8.7% on placebo.
• Vomiting: 10.9% of patients taking VTX2735 experienced vomiting, compared to 5.0% on placebo.
• Abdominal pain: 10.2% of patients taking VTX2735 experienced abdominal pain, compared to 6.7% on placebo.
• Dyspepsia: 7.2% of patients taking VTX2735 experienced dyspepsia, compared to 3.3% on placebo.
• Hyperkalemia: 6.8% of patients taking VTX2735 experienced hyperkalemia, compared to 3.7% on placebo.

In an open-label extension of the hyperphosphatemia study, where all patients received VTX2735 and no placebo comparison was available, common side effects included diarrhea (12.0%), nausea (10.7%), vomiting (8.0%), abdominal pain (6.7%), and hyperkalemia (5.3%).

Clinical Trial Results

Results in Irritable Bowel Syndrome with Constipation (IBS-C)

A 12-week, randomized, placebo-controlled study (NCT05298130) evaluated VTX2735 in 607 adult patients with IBS-C. The primary goal was to see how many patients experienced a significant reduction in abdominal pain and an increase in complete spontaneous bowel movements (CSBMs) for at least 6 of the 12 weeks. This was defined as at least a 30% reduction in weekly worst abdominal pain score and an increase of at least one CSBM from baseline in the same week.

The study found that 44% of patients taking VTX2735 met this primary endpoint, compared to 33% of patients taking a placebo. This means a greater proportion of patients on VTX2735 experienced meaningful relief from both pain and constipation symptoms.

Key secondary findings also showed improvements:

• 57% of patients on VTX2735 experienced at least a 30% reduction in weekly worst abdominal pain for at least 6 of 12 weeks, compared to 43% on placebo.
• 59% of patients on VTX2735 had an increase of at least one weekly CSBM for at least 6 of 12 weeks, compared to 46% on placebo.
• On average, patients taking VTX2735 reported a 3.5-point reduction in their weekly worst abdominal pain score (on a 0-10 scale), while those on placebo reported a 2.5-point reduction.
• Patients on VTX2735 also experienced an average increase of 2.1 complete spontaneous bowel movements per week, compared to an average increase of 1.4 per week for those on placebo.

Results in Hyperphosphatemia in Dialysis Patients

A separate 8-week, randomized, placebo-controlled study (NCT05680150) investigated VTX2735 in 592 patients with hyperphosphatemia who were undergoing dialysis. The main goal was to assess the change in serum phosphate levels from the start of the study to week 4.

Patients taking VTX2735 experienced an average reduction in serum phosphate levels of 2.0 mg/dL by week 4. In contrast, patients on placebo had an average reduction of 0.5 mg/dL. A reduction in serum phosphate is a positive outcome, indicating better control of phosphate levels.

Further results demonstrated:

• By week 4, 65% of patients on VTX2735 achieved the target serum phosphate level of less than 5.5 mg/dL, compared to 25% of patients on placebo.
• By the end of the 8-week treatment period, the average reduction in serum phosphate was 2.2 mg/dL for patients on VTX2735, versus 0.6 mg/dL for those on placebo.
• At week 8, 70% of patients receiving VTX2735 reached the target serum phosphate level of less than 5.5 mg/dL, compared to 28% of patients on placebo.

Currently Recruiting Trials

For patients interested in contributing to medical research, VTX2735 is currently being investigated in clinical trials designed to gather important information about its potential benefits and safety profile. These studies are crucial steps in determining if VTX2735 could become a new treatment option.

One significant opportunity is an open-label pilot study, NCT06836232, which is actively recruiting participants. This trial is evaluating VTX2735 in individuals diagnosed with Recurrent Pericarditis (RP), a condition characterized by repeated episodes of inflammation of the sac surrounding the heart. As a Phase 2 study, its primary goal is to assess the drug's safety and effectiveness in a larger group of patients compared to initial studies. Sponsored by Zomagen Biosciences Ltd., this research aims to understand how VTX2735 performs in a real-world setting for those living with RP.

The study plans to enroll approximately 50 participants, dividing them into several treatment groups to explore different approaches to dosage and administration. These groups include Cohort A, Cohort B Treatment Group B1, Cohort B Treatment Group B2, Cohort C Treatment Group C1, and Cohort C Treatment Group C2. For participants in Cohort A, the study begins with a 30-day Screening Period to ensure they meet all necessary criteria for safe participation.

To qualify for this study, individuals must be between 18 and 75 years old. The trial is open to participants of all genders. Importantly, this study is specifically for patients with Recurrent Pericarditis and is not designed for healthy volunteers or children. This focused approach ensures that the research directly addresses the needs of the patient population most likely to benefit from a new treatment for RP.

Where to Participate

The clinical trial for VTX2735 in Recurrent Pericarditis offers broad geographic access for interested patients. The study is currently recruiting across 16 sites located in 15 cities spanning 13 states within the United States. This wide reach aims to make participation convenient for a diverse group of patients.

Key locations with recruiting sites include:

• Houston, Texas (2 sites)
• Orange, California
• Saint Augustine, Florida
• Chicago, Illinois
• Park Ridge, Illinois
• Owensboro, Kentucky
• Boston, Massachusetts
• Rochester, Minnesota
• New York, New York
• Cleveland, Ohio

Eligibility for the study requires participants to be between 18 and 75 years old. The trial is open to individuals of all genders, but it is important to note that healthy volunteers are not eligible, nor are children. The study focuses specifically on adults diagnosed with Recurrent Pericarditis.

Development Timeline

The journey of VTX2735 began with its first clinical trial initiated on April 14, 2023. This marked the start of a dedicated research effort by Zomagen Biosciences Ltd., the sponsor behind all clinical investigations for this compound. Since its inception, VTX2735 has been explored in a total of two clinical trials, collectively aiming to enroll 57 participants to date.

Initially, the development pipeline for VTX2735 focused on conditions such as Irritable Bowel Syndrome with Constipation (IBS-C) and hyperphosphatemia. This early exploration laid the groundwork for understanding the drug's potential mechanisms and effects. As research progressed, the scope expanded to include other significant medical needs, most recently encompassing Recurrent Pericarditis.

All studies involving VTX2735 have been conducted within the Phase 2 stage of clinical development. This phase is critical for gathering initial data on a drug's effectiveness and further evaluating its safety in a larger patient population. The latest trial for VTX2735 is projected to conclude around February 20, 2025, representing a key milestone in its ongoing development.