A Double-Blind, Placebo-Controlled Trial to Investigate the Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of SPH3127 in Patients With Mild-to-Moderate Ulcerative Colitis
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 15
- 主要终点
- Number of Patients With Clinical Remission
研究概览
简要总结
SPH3127-US-01 is a multi-center, randomized, double-blind, placebo-controlled study to evaluate the safety, pharmacokinetics, and preliminary efficacy of SPH3127 for the treatment of mild-to-moderate ulcerative colitis.
详细描述
SPH3127-US-01 is a proof-of-concept multi-center, randomized, double-blind, placebo-controlled study to evaluate the safety, pharmacokinetics, and preliminary efficacy of of daily oral administration of SPH3127 or placebo for 8 weeks in patients with mild-to-moderate ulcerative colitis. After meeting all inclusion and exclusion criteria, eligible patients will be randomized to receive SPH3127 (50 mg daily, 50 mg twice daily) or placebo tablets; all patients will take 2 tablets (SPH3127 or placebo) twice a day for 8 weeks. All randomized subjects will have the opportunity to enter an active-treatment extension (50 mg SPH3127 once or twice daily) for an additional 10 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed Informed Consent Form (ICF);
- •Adult males and females ≥ 18 to < 70 years of age on the day of signing the ICF.
- •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.
- •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.
- •Patient has a negative urine drug screen (e.g., amphetamines, barbiturates, benzodiazepines, cannabis, cocaine, opiates, methadone) at Screening.
- •Patient has a negative alcohol breath test at Screening.
- •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.
- •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.
排除标准
- •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) >
- •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.
- •History of colectomy or partial colectomy, colorectal dysplasia, Crohn's disease, toxic megacolon, or bleeding disorders.
- •A stool sample positive for enteric pathogens, including Clostridium difficile.
- •Patients with an estimated glomerular filtration rate (eGFR) <
- •Patients with hepatic impairment or history of liver cirrhosis.
- •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.
- •Serious underlying disease other than UC.
- •Previous participation in clinical trials with SPH3127
- •Known hypersensitivity to tablet ingredients or history of a significant allergic reaction to any drug as determined by the investigator.
- •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
- •Known clinically relevant immunological disorders.
- •History of severe allergic or anaphylactic reactions.
- •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.
- •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.
- •Low blood pressure at screening (i.e., SBP < 90 mmHg or DBP < 60 mmHg).
- •Clinically relevant abnormalities detected on vital signs prior to dosing.
- •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.
- •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.
- •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.
- •Women who are breastfeeding.
- •Vaccination (including influenza and COVID-19) within the last 4 weeks prior to randomization.
- •History of drug or alcohol abuse.
- •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.
- •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.
研究组 & 干预措施
Placebo
2 placebo tablets, 1 in the morning and 1 in the evening, daily for 8 weeks. After 8 weeks, optional randomization to 1 of 2 SPH3127 daily treatment arms for an additional 10 months
干预措施: Placebo (Drug)
SPH3127 50 mg
1 50 mg SPH3127 tablet in the morning and 1 placebo tablet in the evening daily for 8 weeks.
After 8 weeks, optional continuation of daily treatment for an additional 10 months.
干预措施: SPH3127 (Drug)
SPH3127 100 mg
1 50 mg SPH3127 tablet in the morning and 1 50 mg SPH3127 tablet in the evening daily for 8 weeks.
After 8 weeks, optional continuation of daily treatment for an additional 10 months.
干预措施: SPH3127 (Drug)
结局指标
主要结局
Number of Patients With Clinical Remission
时间窗: Screening (baseline) to Day 56
Number of patients with Clinical remission from baseline to Day 56
Number of Patients With Endoscopic Remission
时间窗: Screening (baseline) to Day 56
Number of patients with Endoscopic remission from baseline to Day 56
次要结局
- Number of Patients Reporting Adverse Events(Baseline to Day 56 or date of study termination for the 3 patients (i.e., < 80 days per patient))