AdventHealth Participating in Phase I Clinical Trial of Potential New Oral Immunotherapy Treatment for Mild to Moderate Ulcerative Colitis

Under the leadership of principal investigator Jennifer Seminerio, MD, AdventHealth Research Institute is the first site in Central Florida to participate in the expansion phase of the RISE-3750-01 clinical trial, a multi-site, open-label, Phase I study to characterize the safety and tolerability of R-3750 orally delivered to patients with mild to moderate ulcerative colitis. The study aims to identify the maximum tolerated dose of a single dose and repeat doses of R-3750 either alone or in combination with aminosalicylates as standard of care. Additionally, it will assess R-3750 intestinal availability, disease biomarkers, and potential mitigation of colitis.

Ulcerative Colitis – A Challenging, Chronic Condition
With a reported incidence of 1.2 – 20.3 cases per 100,000 persons each year, ulcerative colitis is a chronic inflammatory bowel disorder (IBD) of the colon that typically has a relapsing and remitting course. The most common symptoms include diarrhea, fatigue, abdominal pain, and intestinal blood loss. Because there is no cure, current treatments focus on improving patients’ quality of life, achieving steroid-free remission, and minimizing the risk of cancer. Up to 15% of patients may require colectomy to control the disease.

“Ulcerative colitis can be debilitating and dangerous,” shares Dr. Seminerio, who specializes in the care of patients with ulcerative colitis and serves as medical director of AdventHealth’s dedicated, multidisciplinary Orlando IBD Clinic (Add link to new Clinician’s View). “The therapies we currently have available come with some serious side effects, and patients’ symptoms can flare even with treatment. That is why we continue to look for new, better approaches that are both safe and effective. In recent research, gut microbiota has emerged as a risk factor for ulcerative colitis, so we are especially interested in exploring the potential of specialized probiotics to help restore the natural interaction between the immune system and gut microbiome.”

About R-3750
A novel oral immunotherapy, R-3750 consists of the probiotic Lactococcus (L.) lactis engineered to express surface layer protein A (SlpA), which is expressed by certain gut flora bacteria such as Lactobacilli. In animal models, SlpA has been shown to promote a stronger intestinal epithelial barrier function and reduce inflammatory processes that contribute to ulcerative colitis. R-3750 was designed with three main mechanisms of action:

• Enhancement of the gut barrier
• Reduction of inflammation that contributes to gut inflammation
• Correction of dysbiosis, an imbalance in the microbiota

R-3750 is formulated in enteric coated capsules for oral delivery and is meant to remain localized in the GI tract without systemic exposure.

Study Design for the RISE 3750-01 Clinical Trial
This trial has both a dose escalation stage and expansion stage. The dose escalation portion of the study will examine the safety of three different dose levels of R-3750. The expansion stage dosing will be based upon the highest tolerated multiple dose cohort.

Safety will be determined by the self-reporting of adverse events, including any that are severe, as well as by findings on physical exams and vital signs, including complete blood count (CBC), serum chemistry determinations, and kidney and liver function. Potential systemic levels of R-3750 will be measured through a qPCR assay that is specific for R-3750. In addition, measurements of immune function will be followed by evaluating T cells and cytokines.

Key inclusion criteria include the following:

1. 18–72 years of age
2. Confirmed diagnosed of mild to moderate ulcerative colitis as defined by modified Mayo Score (mMS) with a score of 4-9, an endoscopy sub-score of at least 2, and a rectal bleeding sub-score of at least 1
3. On a stable dose of aminosalicylate (i.e. no change in medication within 4 weeks of study enrollment) and not planning to initiate new medication other than the study drug

Those who enroll in the study should expect to participate for 19 months.

To learn more about this clinical trial, including the full inclusion and exclusion criteria, visit our AdventHealth Research Institute website.