Evaluation of SPH3127 in Patients With Mild-to-Moderate Ulcerative Colitis

Eligibility Criteria

• 1. Signed Informed Consent Form (ICF);
• 2. Adult males and females ≥ 18 to \< 70 years of age on the day of signing the ICF.
• 3. A diagnosis of UC (documented or confirmed at screening) will be eligible provided they have mild-to-moderate active UC extending ≥ 15 cm from the anal verge.
• 4. At screening/baseline, a Modified Mayo Clinic Score (MMCS) from 4-9, a rectal bleeding subscore ≥ 1, and a Mayo Clinic Endoscopic Subscale (MCES) score ≥ 2 determined by central reading.
• 5. Patient has a negative urine drug screen (e.g., amphetamines, barbiturates, benzodiazepines, cannabis, cocaine, opiates, methadone) at Screening.
• 6. Patient has a negative alcohol breath test at Screening.
• 7. Female patients who have a negative pregnancy test at Screening and who agree to use adequate birth control methods throughout the entire study (and extension, if applicable) or who is post-menopausal (i.e., amenorrhea ≥ 1 year) or who have been surgically sterilized.
• 8. Male patients with partners of child-bearing potential who agree to use adequate birth control methods throughout the entire study (and extension, if applicable) or who have been surgically sterilized.
• 1. Diagnosis of severe UC, defined as the presence of ≥ 6 bloody stools daily with one or more of the following: (1) oral temperature \> 37.8°C or \> 100.0°F; (2) pulse \> 90 beats/min; (3) hemoglobin concentration \< 10.5 g/dL; or erythrocyte sedimentation ratio (ESR) \> 30.
• 2. Patients treated with oral mesalamine \>2.4 g/d, systemic steroids or rectal steroids within 4 weeks prior to randomization, rectal mesalamine (within 2 weeks), immunomodulators or immunosuppressant drugs, including, but not limited to, IL-6 inhibitors, TNF inhibitors, anti-IL-1 agents and JAK inhibitors within 5 half-lives prior to randomization, antibiotics, anti-diarrheals (within 2 weeks), drugs blocking the renin-angiotensin system (e.g., direct renin inhibitors, angiotensin converting enzyme inhibitors, or angiotensin II receptor blockers) (within 4 weeks) or administration of any investigational drug (within 4 weeks). Because SPH3127 is a direct renin inhibitor with the potential to reduce blood pressure, other classes of antihypertensives (e.g., calcium channel blockers, beta blockers, diuretics, direct vasodilators, alpha blockers, central α2 antagonists) (within 4 weeks) will also be excluded. Drugs, herbal medicines and substances that inhibit or induce CYP3A4 (e.g., ritonavir, itraconazole, grapefruit juice) (within 2 weeks or 5 half-lives, whichever is longer) will be excluded.
• 3. History of colectomy or partial colectomy, colorectal dysplasia, Crohn's disease, toxic megacolon, or bleeding disorders.
• 4. A stool sample positive for enteric pathogens, including Clostridium difficile.
• 5. Patients with an estimated glomerular filtration rate (eGFR) \< 60.
• 6. Patients with hepatic impairment or history of liver cirrhosis.
• 7. Serum creatinine \> 1.5 times the upper limit of normal, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL) or alkaline phosphatase (ALP) \> 2 times the upper limit of normal.
• 8. Serious underlying disease other than UC.
• 9. Previous participation in clinical trials with SPH3127
• 10. Known hypersensitivity to tablet ingredients or history of a significant allergic reaction to any drug as determined by the investigator.
• 11. Known seropositivity or positive test at screening for an active viral/bacterial infection with:
• * Hepatitis B virus (HBV) (except seropositivity due to HBV vaccination)
• * Hepatitis C virus
• * Human immunodeficiency virus
• * COVID-19 (only active infection excluded)
• * Tuberculosis
• 12. Known clinically relevant immunological disorders.
• 13. History of severe allergic or anaphylactic reactions.
• 14. History of malignancy, unless deemed cured by adequate treatment with no evidence of recurrence for a minimum 3 years before screening; completely eradicated non-melanoma skin cancer (such as basal cell carcinoma or squamous cell carcinoma) is not exclusionary.
• 15. Clinically relevant abnormalities detected on ECG regarding either rhythm or conduction (e.g., QTcF \> 450 ms or a known long QT syndrome). A first-degree heart block or sinus arrhythmia will not be considered a significant abnormality.
• 16. Low blood pressure at screening (i.e., SBP \< 90 mmHg or DBP \< 60 mmHg).
• 17. Clinically relevant abnormalities detected on vital signs prior to dosing.
• 18. Significant blood loss (including blood donation \> 500 mL) or transfusion of any blood product within 12 weeks prior to the IP administration or scheduled transfusion within 4 weeks after the end of the trial.
• 19. Treatment with any drug known to have a well-defined potential for toxicity to a major organ in the last 3 months preceding the initial investigational product (IP) administration.
• 20. Concurrent participation, or participation within 30 days prior to the IP administration or 5 half-lives of the investigational drug (whichever is longer), in any drug/device or biologic investigational research trial.
• 21. Women who are breastfeeding.
• 22. Vaccination (including influenza and COVID-19) within the last 4 weeks prior to randomization.
• 23. History of drug or alcohol abuse.
• 24. Is an investigator, sub-investigator, research assistant, pharmacist, trial coordinator, or other staff of a relative who is directly involved in the conduct of the trial.
• 25. Any condition or circumstances that in the opinion of the investigator may make a subject unlikely or unable to complete the trial or comply with trial procedures and requirements.