SAR443122 for Ulcerative Colitis

(RESOLUTE Trial)

Recruiting at 188 trial locations

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

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sanofi

Must be taking: Corticosteroids, Methotrexate

Must not be taking: Antidiarrheals, Cyclosporine

Disqualifiers: Crohn's disease, Active malignancies, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

182 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called SAR443122 (also known as Eclitasertib or DNL-758) for individuals with moderate to severe ulcerative colitis, a condition that inflames the colon and can cause symptoms like frequent diarrhea and abdominal pain. The study aims to evaluate the effectiveness and safety of different doses of SAR443122 compared to a placebo (a treatment with no active drug) over a year. Participants who respond well to the treatment after 12 weeks continue with it; those who do not may try a higher dose. This trial may suit those who have had ulcerative colitis for at least three months and have not responded well to treatments like corticosteroids or immunosuppressants. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important advancements in ulcerative colitis treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that eclitasertib, also known as SAR443122, was well tolerated in previous studies. For example, patients with severe COVID-19 consistently improved without major safety issues when treated with eclitasertib. Although this medication is still being tested for ulcerative colitis, these results suggest it may be safe for people. However, this study is in the second phase, meaning researchers are still examining both safety and effectiveness. More information is needed to confirm these early findings. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for ulcerative colitis?

Researchers are excited about SAR443122 for ulcerative colitis because it offers a novel approach to treatment. Unlike traditional therapies that often focus on suppressing the immune system broadly, SAR443122 targets specific inflammatory pathways, potentially reducing inflammation with fewer side effects. Additionally, the trial includes different dosage levels, which allows researchers to fine-tune the treatment's effectiveness and safety. This could lead to a more personalized and effective management strategy for patients with ulcerative colitis.

What evidence suggests that this trial's treatments could be effective for ulcerative colitis?

Research has shown that SAR443122, also known as eclitasertib, may help treat inflammatory conditions. Early results suggest this medication can reduce inflammation, a major issue in ulcerative colitis. Previous studies found that SAR443122 was safe and generally well tolerated, showing signs of improvement in conditions like severe COVID-19. This suggests that SAR443122 might also help manage inflammation in ulcerative colitis. While more research is needed, these early findings offer hope for its effectiveness in treating this condition. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• SAR443122

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

Anti-IL-23 agents, such as mirikizumab and ustekinumab, have shown significant efficacy in treating ulcerative colitis (UC) in clinical trials, achieving both clinical and endoscopic improvements with a favorable safety profile.

Ongoing trials are exploring the effectiveness of various anti-IL-23 agents compared to existing treatments and investigating the potential for combination therapies, which could enhance treatment strategies for UC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-interleukin-23 agents for the treatment of ulcerative colitis. Hanžel, J., D'Haens, GR.[2020]

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]

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 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]

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 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]

In two randomized trials involving 895 patients, vedolizumab significantly improved response rates in patients with active ulcerative colitis, with 47.1% of those treated showing a response at week 6 compared to only 25.5% in the placebo group.

Vedolizumab also demonstrated sustained efficacy in maintenance therapy, with 41.8% and 44.8% of patients remaining in clinical remission at week 52 when treated every 8 or 4 weeks, respectively, compared to just 15.9% in the placebo group, while showing a similar safety profile between treatment and placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vedolizumab as induction and maintenance therapy for ulcerative colitis. Feagan, BG., Rutgeerts, P., Sands, BE., et al.[2022]

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]

Upadacitinib has been shown to be effective as both an induction and maintenance therapy for patients with moderately to severely active ulcerative colitis, based on results from three phase 3 clinical trials.

The trials demonstrated significant improvements in clinical remission rates and symptom control, highlighting upadacitinib's potential as a valuable treatment option for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05588843

NCT05588843 | Dose-finding Study of SAR443122 in Adult ... A randomized, double-blind, placebo controlled, dose-finding study to assess the efficacy and safety of SAR443122 in adult patients with moderate to severe ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12313750/

A Randomized Phase I Trial Evaluating Safety and ... The results of this first-in-human study demonstrate that single and repeated doses of eclitasertib were safe and well tolerated in healthy ...

3. crohnscolitisfoundation.org crohnscolitisfoundation.org/a-randomized-double-blind-placebo-controlled-dose-finding-study-to-assess-the-efficacy-and-safety

A randomized, double-blind, placebo controlled, dose ... A randomized, double-blind, placebo controlled, dose finding study to assess the efficacy and safety of SAR443122 in adult patients with moderate to severe ...

4. delta.larvol.com delta.larvol.com/Products/?ProductId=1c656147-1f57-483b-bd9b-c3bfd3da6f8e

eclitasertib (SAR443122) / Denali Therap, Sanofi, Harvard ... Eclitasertib was well tolerated with consistent trends toward more rapid resolution of inflammatory biomarkers and clinical improvement in severe COVID-19 ...

5. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-effects-of-eclitasertib-in-adults-with-moderate-to-severe-ulcerative-colitis/

Study on the Effects of Eclitasertib in Adults with Moderate ... This clinical trial investigates the efficacy and safety of SAR443122, an oral medication, in treating adults with moderate to severe ulcerative colitis.

6. clinicaltrials.eu clinicaltrials.eu/inn/eclitasertib/

Eclitasertib – Application in Therapy and Current Clinical ... Eclitasertib, also known as SAR443122, is an investigational drug currently being studied in clinical trials for the treatment of moderate to severe ulcerative ...