A Combined Phase 2/3 Double-Blind, Randomized, Placebo-Controlled, Induction and Maintenance Study Evaluation the Safety and Efficacy of GS-5745 in Subjects with Moderately to Severely Active Ulcerative Colitis.
This study is designed to evaluate the safety and efficacy of GS-5745 in patients with moderate to severely active ulcerative colitis and to determine the optimal dose for Induction and Maintenance therapy. Improvements in patient symptoms and an endoscopy will be measured to determine if the drug is working. In addition, this study will look at the relationship of noninvasive markers of disease activity with the blood levels of GS-5745.
Key eligibility criteria include:
- Between 18-75 years old
- UC diagnosis of at least 6 months
- Willingness to use highly effective birth control method while on study and at least 30 days after last dose of study drug
- Moderate to severely active disease based on symptoms and sigmoidoscopy
- Loss of response or intolerance to one of the following treatments for UC: oral steroids, 6-mercaptopurine (6-MP), azathioprine, TNF-alpha antagonists (infliximab, adalimumab, golimumab, certolizumab, or biosimilars), or vedolizumab
Study Drug is GS-5745.
- GS 5745 is a man-made antibody designed to block the body's own MMP9. MMP9 is one of the proteins that is released by the body during the inflammatory process. MMP9 can cause the breakdown a protective layer in the intestines allowing bacteria, that usually safely lives in the gut, to invade the underlying tissue.
- This movement of bacteria into tissue can lead to more inflammation. This study is designed to see if GS-5745 is safe and effective and if it can block the MMP9 in symptomatic patients in order to interrupt the inflammatory response. The goal of doing this is to see if this drug will reduce symptoms and lead to the restoration of healthy tissue in the intestines.
Description of Treatment or Intervention (Mechanism of Action)
This study will compare two active doses of GS-5745 to a placebo (non-active drug). Patients will be assigned to the treatment randomly, like the flip of a coin, and will be blinded (neither the patient nor the doctor will know if the study drug is active or placebo). Patients who do not respond to study drug in the first 8 weeks will be able to receive open label drug (active and not blinded) through the remainder of the study.
Patient Participation Requirements
Each subject's participation will consist of 4 phases:
- Screening Phase - lasting up to 30 days
- Induction Phase - lasting 8 weeks
- Maintenance Phase - lasting 44 weeks
- Follow-up - 30 days after the last dose of study drug
Patients will need to return to clinic on a regular basis and will have assessments consisting of blood drawing, physical exam, ECG, flexible sigmoidoscopy and health questionnaires. Every patient must use an electronic diary to capture daily symptoms.
Possible Risks & Side Effects
Side effects may include:
- Anemia (low red blood cells)
- Worsening of ulcerative colitis
- Allergic reaction
Patients may experience some discomfort or side effects from study procedures.