TERMINATED

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

Conditions

Ulcerative Colitis mild-to-moderate selective renin inhibitor

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Double-Blind, Placebo-Controlled Trial to Investigate the Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of SPH3127 in Patients With Mild-to-Moderate Ulcerative Colitis

Quick Facts

Study Start:2022-03-21

Study Completion:2022-11-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:TERMINATED

Study ID

NCT05019742

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 70 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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.

Inclusion Criteria

Exclusion 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.

Contacts and Locations

Principal Investigator

Kenneth W. Locke, PhD

STUDY_DIRECTOR

Shanghai Pharma Biotherapeutics USA Inc.

Study Locations (Sites)

Clinical Research Associates, LLC

Huntsville, Alabama, 35801

United States

Southern California Research Institute Medical Group, Inc.

Los Angeles, California, 90045

United States

Facey Medical Group at Facey Medical Foundation

Mission Hills, California, 91345

United States

Precision Research Institute

San Diego, California, 92114

United States

Ventura Clinical Trials

Ventura, California, 93003

United States

Clinical Research of West Florida

Clearwater, Florida, 33765

United States

Velocity Clinical Research

Edgewater, Florida, 32132

United States

Homestead Research Institute, Inc.

Homestead, Florida, 33030

United States

IHS Health

Kissimmee, Florida, 34741

United States

Bayside Clinical Research LLC

Trinity, Florida, 34655

United States

Atlanta Center for Gastroenterology, P.C.

Decatur, Georgia, 30033

United States

Gastroenterology Associates of Western Michigan, PLC

Wyoming, Michigan, 49519

United States

NY Scientific

Brooklyn, New York, 11235

United States

Southern Star Research Institute, LLC

San Antonio, Texas, 78229

United States

Gastro Health & Nutrition - Victoria

Victoria, Texas, 77904

United States

Velocity Clinical Research

Spokane, Washington, 99202

United States

Collaborators and Investigators

Sponsor: Shanghai Pharma Biotherapeutics USA Inc.

Kenneth W. Locke, PhD, STUDY_DIRECTOR, Shanghai Pharma Biotherapeutics USA Inc.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-03-21

Study Completion Date2022-11-01

Study Record Updates

Study Start Date2022-03-21

Study Completion Date2022-11-01

Terms related to this study

Keywords Provided by Researchers

mild-to-moderate
selective renin inhibitor

Additional Relevant MeSH Terms

Ulcerative Colitis