SAR443122 for Ulcerative Colitis

(RESOLUTE Trial)

Recruiting at 148 trial locations

Overseen By Trial Transparency email recommended (Toll free number for US & Canada)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Sanofi

Must be taking: Corticosteroids, Methotrexate

Must not be taking: Antidiarrheals, Cyclosporine

Disqualifiers: Crohn's disease, Active malignancies, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing SAR443122, a new drug, to see if it can help people with moderate to severe ulcerative colitis by reducing gut inflammation and controlling symptoms. The study will last over a year and includes different phases to assess the drug's effectiveness and safety.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you must stop all current medications. However, you must be on stable doses of certain medications like corticosteroids, methotrexate, azathioprine, or 6-mercaptopurine before and during screening. Some medications, like cyclosporine and antidiarrheals, must be stopped at least 4 weeks before screening. Check with the trial team for specific guidance on your medications.

What data supports the idea that SAR443122 for Ulcerative Colitis is an effective treatment?

The available research does not provide any specific data on the effectiveness of SAR443122 for Ulcerative Colitis. Instead, it focuses on other treatments like tofacitinib, vedolizumab, and 5-aminosalicylic acid, which are used for this condition. Without direct evidence or studies on SAR443122, we cannot conclude its effectiveness for Ulcerative Colitis based on the provided information. ^{1 2 3 4 5}

What safety data exists for SAR443122 in treating ulcerative colitis?

The provided research does not contain specific safety data for SAR443122, Eclitasertib, DNL-758, or any of its other names. The studies focus on the safety and effectiveness of tofacitinib and upadacitinib for ulcerative colitis, not SAR443122. ^{1 6 7 8 9}

Is the drug SAR443122 a promising treatment for Ulcerative Colitis?

SAR443122, also known as Eclitasertib, is being studied as a potential treatment for Ulcerative Colitis. While the specific articles provided do not mention SAR443122 directly, they highlight the importance of targeting pathways like IL-23 in treating Ulcerative Colitis. This suggests that SAR443122, if it targets similar pathways, could be promising in managing the disease. ^{1 9 10 11 12}

Eligibility Criteria

Adults with active Ulcerative Colitis for at least 3 months, who haven't responded well to certain treatments like corticosteroids or biologics. They must not have Crohn's Disease, a history of significant infections including COVID-19 recently, or be on conflicting medications. Stable doses of some meds are required and women shouldn't be pregnant or breastfeeding.

Inclusion Criteria

My disease extends at least 15 cm from the anal verge.

Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Women participants should not be pregnant or breastfeeding

I have not responded well or am intolerant to certain ulcerative colitis or Crohn's disease treatments.

Exclusion Criteria

I haven't had corticosteroids or cytapheresis therapy in the last 2 weeks.

Participants with a known history of Human Immunodeficiency Virus (HIV) infection or positive HIV serology at screening

I am currently on dialysis.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

up to 4 weeks

Induction Treatment

Participants receive SAR443122 or placebo for 12 weeks to assess initial efficacy and safety

12 weeks

Regular visits as per study protocol

Maintenance Treatment

Participants in clinical response or remission continue blinded treatment for up to 40 weeks; others may switch to open-label SAR443122

40 weeks

Regular visits as per study protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Treatment Details

Interventions

• Placebo (Other)
• SAR443122 (Other)

Trial Overview The trial is testing SAR443122 against a placebo in people with moderate to severe Ulcerative Colitis over 52 weeks. It includes an initial treatment phase followed by maintenance or switch to the highest dose if no improvement is seen. The goal is to find the right dose based on safety and effectiveness.

Participant Groups

Group I: SAR443122 level 3 Experimental Treatment 1 Intervention

Dose level 3

Group II: SAR443122 level 2 Experimental Treatment 1 Intervention

Dose level 2

Group III: SAR443122 level 1 Experimental Treatment 1 Intervention

Dose level 1

Group IV: Placebo Placebo Group 1 Intervention

Matching Placebo

Who Is Running the Clinical Trial?

Sanofi

Lead Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Findings from Research

Tofacitinib demonstrated effectiveness in treating ulcerative colitis, with a 60% response rate and 31% remission rate at Week 8 among 113 patients treated for a median of 44 weeks.

Despite its efficacy, 40% of patients discontinued tofacitinib, primarily due to inadequate response, highlighting the need for careful monitoring and potential dose adjustments in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib in Ulcerative Colitis: Real-world Evidence From the ENEIDA Registry. Chaparro, M., Garre, A., Mesonero, F., et al.[2021]

In a study of 304 patients with ulcerative colitis who had previously failed anti-TNF therapy, tofacitinib achieved higher rates of endoscopic improvement and histological healing compared to vedolizumab at week 16.

Tofacitinib was particularly more effective in patients with severe disease and those who had experienced primary failure to biologic treatments, suggesting it may be a better option for these individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world comparison of effectiveness between tofacitinib and vedolizumab in patients with ulcerative colitis exposed to at least one anti-TNF agent. Buisson, A., Nachury, M., Guilmoteau, T., et al.[2023]

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]

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 334 ulcerative colitis patients treated with tofacitinib, approximately 35% achieved clinical remission at 12, 24, and 52 weeks, indicating its effectiveness in real-world settings.

While tofacitinib had a low incidence of serious adverse events, nearly 45% of patients lost their response after reducing the dose, highlighting the need for careful management and monitoring, especially for those with higher risk factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

REMIT-UC: Real-World Effectiveness and Safety of Tofacitinib for Moderate-to-Severely Active Ulcerative Colitis: A Canadian IBD Research Consortium Multicenter National Cohort Study. Ma, C., Panaccione, R., Xiao, Y., et al.[2023]

Tofacitinib is effective for treating moderate to severely active ulcerative colitis (UC), achieving clinical remission in 34.7% of patients by week 8 and 47% by weeks 12 to 16, based on a meta-analysis of 17 studies involving 1162 patients.

The safety profile of tofacitinib is acceptable, with serious adverse events occurring at a rate of 8.9 per 100 patient-years, which aligns with findings from clinical trials, supporting its use in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Effectiveness and Safety of Tofacitinib in Patients With Ulcerative Colitis: Systematic Review With Meta-Analysis. Taxonera, C., Olivares, D., Alba, C.[2022]

In a phase 2b trial involving 250 adults with moderately to severely active ulcerative colitis, upadacitinib showed significant efficacy in inducing clinical remission compared to placebo, with remission rates increasing with higher doses (up to 19.6% at 45 mg).

While upadacitinib was effective, there were safety concerns, including reported cases of herpes zoster and thromboembolic events, as well as increases in serum lipid levels and creatine phosphokinase, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Upadacitinib in a Randomized Trial of Patients With Active Ulcerative Colitis. Sandborn, WJ., Ghosh, S., Panes, J., et al.[2021]

Tofacitinib is a new oral medication that works by inhibiting Janus kinases, which are important in the inflammation process of ulcerative colitis (UC), and has been approved by the FDA and EMA for treating moderate-to-severe UC.

Clinical trials (Phase II and III) have shown that tofacitinib is effective in inducing and maintaining remission in UC, especially for patients who do not respond to traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profile of Tofacitinib in the Treatment of Ulcerative Colitis: An Evidence-Based Review of Recent Data. Varyani, F., Argyriou, K., Phillips, F., et al.[2023]

In a study of 11 patients with acute severe colitis (ASUC) who were resistant to steroid and infliximab treatments, high-dose tofacitinib (10 mg three times daily) resulted in a clinical and biochemical response in 10 out of 11 patients during their hospital stay.

At the 6 and 12-month follow-ups, 9 of the initial responders maintained low disease activity (median Mayo score of 1) and remained free from colectomy, with no major complications observed, suggesting that tofacitinib may be a safe and effective treatment option for ASUC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes out to 12 months after sequential use of high-dose tofacitinib following infliximab in acute severe ulcerative colitis. Eqbal, A., Hilley, P., Choy, M., et al.[2023]

References

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

Tofacitinib in Ulcerative Colitis: Real-world Evidence From the ENEIDA Registry. [2021]

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

Real-world comparison of effectiveness between tofacitinib and vedolizumab in patients with ulcerative colitis exposed to at least one anti-TNF agent. [2023]

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

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

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

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

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

In active UC, upadacitinib induced and maintained remission. [2022]

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

REMIT-UC: Real-World Effectiveness and Safety of Tofacitinib for Moderate-to-Severely Active Ulcerative Colitis: A Canadian IBD Research Consortium Multicenter National Cohort Study. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Real-World Effectiveness and Safety of Tofacitinib in Patients With Ulcerative Colitis: Systematic Review With Meta-Analysis. [2022]

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

Efficacy of Upadacitinib in a Randomized Trial of Patients With Active Ulcerative Colitis. [2021]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Profile of Tofacitinib in the Treatment of Ulcerative Colitis: An Evidence-Based Review of Recent Data. [2023]

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

Vedolizumab as induction and maintenance therapy for ulcerative colitis. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Anti-interleukin-23 agents for the treatment of ulcerative colitis. [2020]

12. Australia pubmed.ncbi.nlm.nih.gov

Outcomes out to 12 months after sequential use of high-dose tofacitinib following infliximab in acute severe ulcerative colitis. [2023]