Optimal Treatment Strategies for Ulcerative Colitis

(VERDICT Trial)

Recruiting at 69 trial locations

Overseen By Luiza Nita

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Alimentiv Inc.

Must not be taking: Vedolizumab, Etrolizumab, Natalizumab

Disqualifiers: Hepatitis, TB, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

Duration: 32 weeks

672 Participants Needed

Trial Summary

What is the purpose of this trial?

Disease activity and response to therapy in ulcerative colitis (UC) can be assessed by a range of endpoints including symptoms, endoscopic mucosal activity, histological disease activity, and biomarkers. This study aims to determine the optimal treatment target, which is a research priority for the management of UC both to inform clinical practice and to help inform regulatory endpoints and targets for drug development. Participants with active UC will be randomized in a 5:4:1 (initially 2:3:5) ratio to 1 of 3 groups, each with a different treatment target. Treatment targets will be defined as: * Group 1: corticosteroid-free symptomatic remission * Group 2: corticosteroid-free endoscopic + symptomatic remission * Group 3: corticosteroid-free histological + endoscopic + symptomatic remission An interim analysis was performed to assess the proportion of subjects that reached their assigned treatment target after 50 subjects in each group had reached the first 32-week assessment. The interim analysis and projections made based on target achievement rates for all subjects included in the interim analysis resulted in a recommendation to adjust the randomization ratio from 2:3:5 to 5:4:1 for Groups 1, 2 and 3 respectively as of May 5th, 2023. This change was necessary in order to complete the study with approximately 100 subjects achieving treatment target within each group.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use topical therapies like corticosteroids or 5-aminosalicylates within 2 weeks before the screening endoscopy. Also, you cannot change your oral corticosteroid dose within 2 weeks before randomization or take more than 30 mg of prednisone or equivalent at randomization.

What data supports the effectiveness of the drug Treatment Algorithm A for ulcerative colitis?

Anti-tumor necrosis factor (TNF) agents, which are part of some treatment algorithms, have been added to the management of ulcerative colitis and are considered effective. New therapies like adalimumab and infliximab have provided additional options for treating this condition. ^{1 2 3 4 5}

What safety data exists for treatments evaluated under different names for ulcerative colitis?

Adalimumab has been shown to be safe for people with moderately to severely active ulcerative colitis in clinical trials. Non-biological treatments like aminosalicylates are generally safe, but corticosteroids and immunosuppressive drugs can have serious side effects, so patients need to be monitored closely. ^{6 7 8 9 10}

What makes the treatment strategies for ulcerative colitis in this trial unique?

The treatment strategies in this trial are unique because they use adaptive treatment strategies (ATS) that adjust based on the patient's response, optimizing the treatment plan over time. This approach is more personalized compared to standard treatments, which often follow a fixed regimen. ^{11 12 13 14 15}

Research Team

Vipul Jairath

Principal Investigator

Alimentiv Inc.

Eligibility Criteria

Adults with active Ulcerative Colitis (UC) confirmed by clinical, endoscopic, and histological evidence can join this trial. They must be experiencing moderate to severe symptoms and not responding to current treatments. Participants should agree not to join other investigational trials during this study, be up-to-date on colorectal cancer screenings, and willing to undergo TB and hepatitis tests. Contraception is required for sexually active participants.

Inclusion Criteria

Negative standard of care tuberculosis (TB) test and hepatitis B and C test prior to randomization unless negative results available from within 12 months prior

Written informed consent must be obtained and documented

My ulcerative colitis is active, with bleeding and inflammation seen in a colonoscopy.

Exclusion Criteria

I have short gut syndrome.

I have been treated with vedolizumab, etrolizumab, or natalizumab.

Hypersensitivity to any excipient of vedolizumab

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized into one of three groups with different treatment targets, including corticosteroid-free symptomatic remission, endoscopic remission, and histological remission.

32 weeks

Interim Analysis

An interim analysis is conducted to assess the proportion of subjects reaching their treatment targets.

Ongoing until 50 subjects per group reach the 32-week assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments including Mayo Clinic Score, Geboes scores, and other histological indices.

Up to 96 weeks

Treatment Details

Interventions

• Treatment Algorithm A
• Treatment Algorithm B
• Treatment Algorithm C

Trial Overview The trial aims to find the best treatment target for UC by comparing three groups: one targeting symptom remission without steroids; another adding endoscopic remission; the third includes histological remission as well. Patients are randomly assigned in a 2:3:5 ratio respectively.

Participant Groups

Group I: Symptomatic, endoscopic and histological remission Experimental Treatment 3 Interventions

Treatment target defined as achievement of corticosteroid-free symptomatic remission plus endoscopic remission plus histological remission.

Group II: Symptomatic remission Experimental Treatment 3 Interventions

Treatment target defined as achievement of corticosteroid-free symptomatic remission.

Group III: Symptomatic and endoscopic remission Experimental Treatment 3 Interventions

Treatment target defined as achievement of corticosteroid-free symptomatic remission plus endoscopic remission.

Who Is Running the Clinical Trial?

Alimentiv Inc.

Lead Sponsor

Trials

15

Recruited

3,300+

Takeda Development Center Americas, Inc.

Industry Sponsor

Trials

58

Recruited

10,800+

Findings from Research

A systematic review of 83 randomized controlled trials involving 17,737 patients with ulcerative colitis revealed significant variability in the definitions of clinical response and remission, with over 50 different definitions used.

Despite advancements in trial design, there is a need for a standardized core outcome set to improve the consistency of efficacy and safety reporting in clinical trials for ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heterogeneity in Definitions of Endpoints for Clinical Trials of Ulcerative Colitis: A Systematic Review for Development of a Core Outcome Set. Ma, C., Panaccione, R., Fedorak, RN., et al.[2019]

References

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

Review article: the role of anti-TNF in the management of ulcerative colitis -- past, present and future. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Treatment algorithm for moderate to severe ulcerative colitis. [2018]

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

The outcome of infliximab dose doubling in 157 patients with ulcerative colitis after loss of response to infliximab. [2018]

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

Positioning Therapy for Ulcerative Colitis. [2018]

5. Australia pubmed.ncbi.nlm.nih.gov

Clinical outcomes and factors for response prediction after the first course of corticosteroid therapy in patients with active ulcerative colitis. [2011]

6. England pubmed.ncbi.nlm.nih.gov

Rapid Changes in Laboratory Parameters and Early Response to Adalimumab: A Pooled Analysis From Patients With Ulcerative Colitis in Two Clinical Trials. [2020]

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

Article Topic: Positioning Ulcerative Colitis Therapies in 2022 and Beyond. [2022]

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

Adalimumab for Moderately to Severely Active Ulcerative Colitis: A Systematic Review and Meta-Analysis. [2018]

9. England pubmed.ncbi.nlm.nih.gov

The safety of non-biological treatments in Ulcerative Colitis. [2017]

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

Heterogeneity in Definitions of Endpoints for Clinical Trials of Ulcerative Colitis: A Systematic Review for Development of a Core Outcome Set. [2019]

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

Improving the efficiency of estimation in randomized trials of adaptive treatment strategies. [2007]

12. Germany pubmed.ncbi.nlm.nih.gov

Adaptive control of drug dosage regimens using maximum a posteriori probability Bayesian fitting. [2005]

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

C-learning: A new classification framework to estimate optimal dynamic treatment regimes. [2019]

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

Modeling antibiotic treatment in hospitals: A systematic approach shows benefits of combination therapy over cycling, mixing, and mono-drug therapies. [2019]

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

OptiDose: Computing the Individualized Optimal Drug Dosing Regimen Using Optimal Control. [2021]