Tulisokibart Clinical Trials

What Is Tulisokibart?

Tulisokibart is an investigational drug currently being studied in clinical trials for various inflammatory and autoimmune conditions. It is a humanized monoclonal antibody, which is a type of protein designed to target specific substances in the body. Tulisokibart works by binding to human tumor necrosis factor-like cytokine 1A (TL1A). TL1A is a protein believed to play a significant role in inflammation and immune responses. By blocking TL1A, tulisokibart aims to reduce inflammation and manage conditions where the immune system is overactive.

This drug is being developed by Merck Sharp & Dohme LLC and Prometheus Biosciences, Inc., a subsidiary of Merck & Co., Inc. As of the latest data, 13 clinical trials involving tulisokibart have been conducted or are ongoing, with a total enrollment of 5,209 participants. The first trial began in 2021, and the latest is expected to conclude in 2026. Tulisokibart is primarily administered subcutaneously, meaning it is injected under the skin, and is being investigated for conditions such as ulcerative colitis, Crohn disease, and rheumatoid arthritis.

Uses and Conditions Under Study

Tulisokibart is being investigated for its potential to treat several inflammatory and autoimmune conditions. The majority of studies focus on inflammatory bowel diseases (IBD) and other systemic inflammatory disorders.

• Inflammatory Bowel Diseases (IBD): This group includes Ulcerative Colitis and Crohn Disease. Ulcerative colitis affects the large intestine, while Crohn disease can affect any part of the digestive tract. Both are chronic conditions characterized by inflammation, leading to symptoms like abdominal pain, diarrhea, and weight loss. Tulisokibart, by targeting TL1A, may help reduce the inflammation that drives these conditions. A total of seven trials are studying tulisokibart for Ulcerative Colitis, Colitis, Ulcerative, Crohn Disease, and Crohn's Disease.
• Other Inflammatory and Autoimmune Conditions: Tulisokibart is also being investigated for a range of other conditions where inflammation plays a key role. These include Diffuse Cutaneous Systemic Sclerosis, Rheumatoid Arthritis, Hidradenitis Suppurativa, Interstitial Lung Disease, and Psoriatic Arthritis. In each of these conditions, targeting TL1A could potentially modulate the immune response and reduce disease activity. Each of these conditions is being studied in one trial.
• Healthy Participants: Two trials are being conducted in healthy participants. These studies typically focus on understanding how the drug is absorbed, distributed, metabolized, and excreted (pharmacokinetics), as well as evaluating its safety and tolerability in individuals without the target disease.

Dosing

Tulisokibart has been studied in various dosage forms and regimens during its clinical development. It is primarily administered as a solution for injection.

The main routes of administration being investigated are:

• Subcutaneous (SC) Injection: This involves injecting the solution under the skin, often using an autoinjector. Many trials specify subcutaneous administration, sometimes referred to as "SC administration."
• Intravenous (IV) Infusion: Some studies also explore intravenous administration, where the drug is delivered directly into a vein.

Different dosing strategies have been explored, including:

• Dose Levels: Trials have investigated various dose levels, such as a "High-Dose Regimen," "Medium-Dose Regimen," and "Low-Dose Regimen." These are sometimes referred to as "Tulisokibart Dose 1," "Tulisokibart Dose 2," and "Tulisokibart Dose 3."
• Treatment Forms: The drug has been studied in different formulations, noted as "Tulisokibart Form 1" and "Tulisokibart Form 2."
• Treatment Phases: Dosing can vary depending on the phase of treatment. This includes "Induction Tulisokibart" (initial treatment to achieve a response), "Maintenance" (ongoing treatment to sustain the response), and "Extension" phases (long-term follow-up). Specific maintenance doses like "OLE Tulisokibart 100 mg" and "OLE Tulisokibart 250 mg" have also been studied.
• Blinded vs. Unblinded: Some trials also include groups with "Low Dose Unblinded," "High Dose Unblinded," "High Dose Blinded," and "Low Dose Blinded" regimens to assess the drug's effects while controlling for participant and researcher awareness of the treatment assignment.

Side Effects

In a Phase 2 study (NCT04996797) evaluating Tulisokibart for moderately to severely active ulcerative colitis, the overall rate of adverse events (side effects) was similar between treatment and placebo groups. 45.6% of participants taking Tulisokibart experienced at least one adverse event, compared to 43.2% of participants on placebo.

Serious adverse events were less common in the Tulisokibart group. Only 1.1% of participants receiving Tulisokibart experienced one or more serious adverse events, compared to 8.0% of participants on placebo. Discontinuations due to adverse events were also lower with Tulisokibart, with 1.1% of participants stopping treatment compared to 3.4% on placebo.

In an open-label Phase 2a study (NCT05013905) of Tulisokibart for moderately to severely active Crohn's disease, where no placebo comparison was used, 43 participants experienced adverse events. Among these participants, 8 experienced serious adverse events, and 2 discontinued the study due to an adverse event.

Clinical Trial Results

Ulcerative Colitis

In a Phase 2 study (NCT04996797) of Tulisokibart for moderately to severely active ulcerative colitis, participants treated with Tulisokibart showed significant improvements in various measures compared to those on placebo. Key findings from Cohort 1 include:

• Clinical remission was achieved by 26.5% of participants taking Tulisokibart, compared to 1.5% on placebo.
• Clinical response was observed in 66.2% of participants receiving Tulisokibart, versus 22.4% on placebo.
• Endoscopic improvement, indicating healing of the colon lining, occurred in 36.8% of the Tulisokibart group, compared to 6.0% on placebo.
• Patient-reported quality of life, as measured by an Inflammatory Bowel Disease Questionnaire (IBDQ) response, improved for 82.4% of Tulisokibart-treated participants, versus 49.3% on placebo.
• Histologic-endoscopic mucosal healing, a measure of deep tissue healing, was achieved by 30.8% of participants on Tulisokibart, compared to 3.5% on placebo.

For participants who were CDx+ (a biomarker-positive subgroup across Cohorts 1 and 2), Tulisokibart also demonstrated benefits:

• Clinical remission was achieved by 31.6% of CDx+ participants on Tulisokibart, compared to 10.8% on placebo.
• Clinical response was seen in 55.3% of CDx+ participants on Tulisokibart, versus 32.4% on placebo.
• Histologic-endoscopic mucosal healing occurred in 38.9% of CDx+ participants receiving Tulisokibart, compared to 16.7% on placebo.

Crohn's Disease

An open-label Phase 2a study (NCT05013905) investigated Tulisokibart in 43 participants with moderately to severely active Crohn's disease. Since this was an open-label study, there was no placebo group for comparison. Results showed:

• 62.8% (27 out of 43) of participants achieved clinical remission.
• 86.0% (37 out of 43) of participants achieved clinical response.
• Endoscopic improvement was observed in 30.2% (13 out of 43) of participants.
• A composite response, combining multiple measures of improvement, was achieved by 39.5% (17 out of 43) of participants.
• The average Simple Endoscopy Score for Crohn's Disease (SES-CD) improved by 2.6 points from baseline, indicating a reduction in disease activity.

Currently Recruiting Trials

Where to Participate

• Orlando, Florida (4 sites)
• New York, New York (4 sites)
• Lubbock, Texas (4 sites)
• Houston, Texas (4 sites)
• Kansas City, Missouri (3 sites)
• Chicago, Illinois (3 sites)
• Duncansville, Pennsylvania (3 sites)
• Tucson, Arizona (3 sites)
• Seattle, Washington (2 sites)
• Dallas, Texas (2 sites)

Development Timeline