SPH3127 for Ulcerative Colitis

Recruiting at 15 trial locations

Overseen By Dinah Jaunakais, MEd

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Shanghai Pharma Biotherapeutics USA Inc.

Must not be taking: Steroids, Immunosuppressants, Antihypertensives, others

Disqualifiers: Severe UC, Colectomy, Liver impairment, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial tests a new medication called SPH3127 for people with mild-to-moderate ulcerative colitis. The goal is to see if taking this medication by mouth can safely reduce their symptoms.

Will I have to stop taking my current medications?

Yes, you may need to stop taking certain medications before joining the trial. Specifically, you cannot take oral mesalamine over 2.4 g/day, systemic or rectal steroids, certain immunomodulators, antibiotics, anti-diarrheals, and some blood pressure medications within a few weeks before starting the trial. Please consult with the trial team for specific guidance on your medications.

Is SPH3127 safe for humans?

The available research does not provide specific safety data for SPH3127 or its other names. However, a study on a similar treatment, IBD98-M, found it to be safe and well-tolerated in patients with ulcerative colitis, with no new or unexpected safety issues. ^{1 2 3 4 5}

What makes the drug SPH3127 unique for treating ulcerative colitis?

SPH3127 is unique because it is being studied as a potential new treatment for ulcerative colitis, a condition with high placebo response rates in clinical trials, which complicates the evaluation of new therapies. The research highlights the importance of understanding placebo effects in trial design, but specific details about SPH3127's mechanism or administration are not provided in the available studies. ^{1 3 6 7 8}

Research Team

Kenneth W. Locke, PhD

Principal Investigator

Shanghai Pharma Biotherapeutics USA Inc.

Eligibility Criteria

Adults aged 18-70 with mild-to-moderate ulcerative colitis extending at least 15 cm from the anal verge, who are not pregnant or abusing drugs/alcohol, and agree to use birth control. Excluded are those with certain infections, organ dysfunction, recent blood donations/transfusions, other trial participation within 30 days or specific medication use prior to the study.

Inclusion Criteria

I am between 18 and 70 years old.

I am a man and will use birth control with my partner who can have children.

I am not pregnant and agree to use birth control during the study.

Exclusion Criteria

Clinically relevant abnormalities detected on vital signs

I have not taken certain medications recently.

Positive stool sample for enteric pathogens

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily oral administration of SPH3127 or placebo for 8 weeks

8 weeks

Visits on Day 1, 28, and 56

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Active-treatment extension (optional)

Participants may opt into continuation of treatment with SPH3127 for an additional 10 months

10 months

Treatment Details

Interventions

• Placebo (Unknown)
• SPH3127 (Unknown)

Trial Overview The trial is testing SPH3127's safety and effectiveness against a placebo in treating ulcerative colitis. Participants will be randomly assigned to receive either SPH3127 or a placebo without knowing which one they're getting (double-blind).

Participant Groups

Group I: SPH3127 50 mg Experimental Treatment 1 Intervention

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.

Group II: SPH3127 100 mg Experimental Treatment 1 Intervention

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.

Group III: Placebo Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Shanghai Pharma Biotherapeutics USA Inc.

Lead Sponsor

Trials

2

Recruited

40+

Findings from Research

In a study of 287 patients with ulcerative proctitis and proctosigmoiditis, mesalamine enemas (1, 2, and 4 g) significantly improved symptoms and clinical outcomes compared to placebo, with 67% to 75% of patients showing marked improvement.

The safety profile of mesalamine enemas was comparable to that of placebo, indicating that they are a safe and effective treatment option for distal ulcerative colitis without a clear dose-response effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-ranging study of mesalamine (PENTASA) enemas in the treatment of acute ulcerative proctosigmoiditis: results of a multicentered placebo-controlled trial. The U.S. PENTASA Enema Study Group. Hanauer, SB.[2019]

The newer formulations of 5-aminosalicylic acid (5-ASA) were found to be significantly more effective than placebo in inducing remission in active ulcerative colitis, with a pooled odds ratio of 0.51, indicating a lower failure rate in achieving clinical improvement.

While 5-ASA showed a trend towards better outcomes compared to sulfasalazine (SASP), the difference was not statistically significant, and 5-ASA was better tolerated, suggesting it may be a preferable option despite potential cost considerations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral 5-aminosalicylic acid for inducing remission in ulcerative colitis. Sutherland, L., Roth, D., Beck, P., et al.[2018]

In a review of 119 clinical trials for ulcerative colitis, the placebo rates for clinical remission during induction trials were found to be 11%, while maintenance trials showed higher rates of 18%, indicating variability based on trial phase.

Factors such as prior biologic therapy exposure and the number of follow-up visits significantly influenced placebo response rates, which can help in designing more effective clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review and Meta-Analysis: Clinical, Endoscopic, Histological and Safety Placebo Rates in Induction and Maintenance Trials of Ulcerative Colitis. Sedano, R., Hogan, M., Nguyen, TM., et al.[2023]

The newer formulations of 5-aminosalicylic acid (5-ASA) were found to be significantly more effective than placebo in maintaining remission in ulcerative colitis, with a Peto odds ratio of 0.47, indicating a lower risk of relapse or withdrawal due to treatment failure.

However, when compared to sulfasalazine (SASP), 5-ASA showed a statistically significant inferiority in effectiveness, suggesting that while 5-ASA is beneficial, SASP may be a more effective option for some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral 5-aminosalicylic acid for maintaining remission in ulcerative colitis. Sutherland, L., Roth, D., Beck, P., et al.[2020]

In a study of 51 patients with mild to moderate ulcerative colitis, IBD98-M (mesalamine) showed a higher clinical response rate at 31.3% for the 1.2 g/day dose compared to 16.7% for placebo, indicating potential efficacy in treating the condition.

IBD98-M was found to be safe and well tolerated, with no new safety concerns reported, suggesting it could be a viable treatment option for patients with ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 2a, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Trial of IBD98-M Delayed-Release Capsules to Induce Remission in Patients with Active and Mild to Moderate Ulcerative Colitis. Fiorino, G., Sturniolo, GC., Bossa, F., et al.[2021]

5-Aminosalicylic acid (5-ASA) is more effective than placebo for treating active ulcerative colitis, with a significant dose-response effect observed in 16 trials involving various patient populations.

However, 5-ASA does not show superior efficacy compared to sulfasalazine for either treating active disease or maintaining remission, indicating that while it is beneficial, it may not replace sulfasalazine in treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sulfasalazine revisited: a meta-analysis of 5-aminosalicylic acid in the treatment of ulcerative colitis. Sutherland, LR., May, GR., Shaffer, EA.[2019]

In a post hoc analysis of pooled data from multiple clinical trials involving ulcerative colitis, it was found that patients with normal serum C-reactive protein and albumin levels had a significantly higher likelihood of achieving a clinical response to placebo treatment (16.3% vs. 7.4%).

Patients with a higher baseline endoscopic severity (Mayo endoscopic score of 3) were less likely to respond to placebo compared to those with a lower score (18.8% vs. 25.9%), indicating that baseline disease severity influences placebo response rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of Placebo Induction Response and Remission in Ulcerative Colitis. Wong, ECL., Dulai, PS., Marshall, JK., et al.[2023]

A longitudinal placebo response model was developed using data from five clinical trials involving patients with ulcerative colitis, which helps to better understand how the Mayo Clinical Score (MCS) changes over time in response to placebo treatments.

Prior exposure to TNF-α antagonists was found to significantly influence the rectal bleeding and stool frequency subscores, indicating that patients who had previously received these treatments experienced higher symptom scores compared to those who were treatment-naive.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A longitudinal model for the Mayo Clinical Score and its sub-components in patients with ulcerative colitis. Kawakatsu, S., Zhu, R., Zhang, W., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Dose-ranging study of mesalamine (PENTASA) enemas in the treatment of acute ulcerative proctosigmoiditis: results of a multicentered placebo-controlled trial. The U.S. PENTASA Enema Study Group. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Oral 5-aminosalicylic acid for inducing remission in ulcerative colitis. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Systematic Review and Meta-Analysis: Clinical, Endoscopic, Histological and Safety Placebo Rates in Induction and Maintenance Trials of Ulcerative Colitis. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Oral 5-aminosalicylic acid for maintaining remission in ulcerative colitis. [2020]

5. Switzerland pubmed.ncbi.nlm.nih.gov

A Phase 2a, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Trial of IBD98-M Delayed-Release Capsules to Induce Remission in Patients with Active and Mild to Moderate Ulcerative Colitis. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Sulfasalazine revisited: a meta-analysis of 5-aminosalicylic acid in the treatment of ulcerative colitis. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Predictors of Placebo Induction Response and Remission in Ulcerative Colitis. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

A longitudinal model for the Mayo Clinical Score and its sub-components in patients with ulcerative colitis. [2022]