Guselkumab for Crohn's Disease
(REASON Trial)
Recruiting in Palo Alto (17 mi)
+41 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Janssen-Cilag Ltd.
Disqualifiers: Bowel resection, Abscess, Stoma, others
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?The purpose of this study is to evaluate the efficacy of guselkumab in healing of all layers of the digestive tract (transmural healing) with the help of a score called Magnetic Resonance Index of Activity (MaRIA) based on a scan at Week 48.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. However, it mentions that participants should have shown an inadequate response or intolerance to conventional or advanced therapies for Crohn's disease.
Is Guselkumab safe for use in humans?
Guselkumab, also known as Tremfya or CNTO1959, has been studied for safety in treating moderate-severe Crohn's disease and other conditions. Research shows that it is generally well tolerated, with most side effects being mild, indicating a good safety profile.
12345How does the drug Guselkumab differ from other treatments for Crohn's disease?
Guselkumab is unique because it targets a specific part of the immune system involved in inflammation, which is different from the commonly used treatments for Crohn's disease that often target tumor necrosis factor (TNF). This novel approach may offer an alternative for patients who do not respond well to existing therapies.
678910Eligibility Criteria
This trial is for individuals with Crohn's disease of at least 3 months, showing active symptoms and poor response or intolerance to certain therapies. Participants must have a specific level of disease activity measured by stool frequency or abdominal pain and confirmed transmural activity in the digestive tract.Inclusion Criteria
I have had Crohn's disease affecting my colon or small intestine for at least 3 months.
My Crohn's disease is active, with significant symptoms.
I have active inflammation in my intestines shown by an MRI.
+1 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive guselkumab 200 mg IV at weeks 0, 4, and 8, followed by SC doses every 4 or 8 weeks up to week 96
96 weeks
In-person visits at weeks 0, 4, 8, and every 4-8 weeks thereafter
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Open-label extension (optional)
Participants may opt into continuation of treatment long-term
Long-term
Participant Groups
The study tests Guselkumab's ability to heal all layers of the digestive tract in Crohn's patients. Effectiveness will be measured using a special MRI-based score (MaRIA) at Week 48 to assess transmural healing.
1Treatment groups
Experimental Treatment
Group I: GuselkumabExperimental Treatment1 Intervention
Participants will receive guselkumab 200 milligram (mg) intravenously (IV) at week 0, 4 and 8. Afterwards, participants will be alternately assigned at study level to 2 dose cohorts, high dose (200 mg subcutaneous (SC) every 4 weeks (Q4W) starting at week 12) through week 92 or low dose (100 mg SC every 8 weeks (Q8W) starting at week 16) through week 88. Starting at Week 24, participants in the low-dose cohort will be permitted to escalate to the 200 mg SC Q4W regimen if they are symptomatic and at the discretion of the investigator.
Guselkumab is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Tremfya for:
- Moderate to severe plaque psoriasis
- Psoriatic arthritis
- Moderately to severely active ulcerative colitis
🇪🇺 Approved in European Union as Tremfya for:
- Moderate to severe plaque psoriasis
- Psoriatic arthritis
- Moderately to severely active ulcerative colitis
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Western University & London Health Sciences CentreLondon, Canada
Loading ...
Who Is Running the Clinical Trial?
Janssen-Cilag Ltd.Lead Sponsor
References
[Adalimumab for the treatment of Crohn's disease - consensus paper of the Working Group "chronic inflammatory bowel diseases" of the Austrian Society for Gastroenterology and Hepatology]. [2015]The advent of anti-TNF alpha antibodies has clearly improved the outcome of patients with Crohn's disease. With adalimumab, the first fully human, monoclonal anti-TNF alpha antibody, which can be administered subcutaneously by means of a pen, became available in 2007. In Europe adalimumab is approved for the treatment of severe, active Crohn's disease, in patients who have not responded despite a full and adequate course of therapy with a corticosteroid and/or an immunosuppressant; or who are intolerant to or have medical contraindications for such therapies. Adalimumab is clinically efficacious both in patients with Crohn's disease naïve to previous exposure to anti-TNF alpha antibodies and in those previously exposed with a rapid onset of action and a confirmed maintenance performance over 3 years. A reduction in the rate of hospitalisation and an improvement of health-related quality of life are associated with this treatment. The safety profile of adalimumab is comparable to those of other TNF alpha inhibitors. Due to low immunogenicity, allergic reactions are rare. A careful screening of patients before and during treatment with adalimumab is of key importance. The presented therapy guidelines based on existing evidence are aimed to assist in the efficient and safe use of adalimumab in the treatment of Crohn's disease.
Adverse events in IBD therapy: the 2018 update. [2019]Crohn's disease and ulcerative colitis affect an increasing number of patients, and utilization of immune suppressant and biologic therapies is also increasing. These agents are linked to adverse events ranging from mild nuisance symptoms to potentially life-threatening complications including infections and malignancies. Areas covered: This review provides an updated discussion on adverse events associated with immunomodulator, anti-TNF-α, anti-integrin, and anti-IL 12/IL-23 antibody therapies. In addition, we review the risk profile of the currently widely available infliximab biosimilar medication. Expert commentary: Providers should engage in risk-benefit discussion with information specific to each medication discussed, and consider individualized risk factors when selecting therapeutic agents. Drug monitoring and shared decision-making results in more personalized medical management of inflammatory bowel disease.
A dose escalating, placebo controlled, double blind, single dose and multidose, safety and tolerability study of fontolizumab, a humanised anti-interferon gamma antibody, in patients with moderate to severe Crohn's disease. [2022]This study was designed to evaluate the safety of fontolizumab, a humanised anti-interferon gamma antibody, in patients with moderate to severe Crohn's disease (CD).
Adalimumab safety in global clinical trials of patients with Crohn's disease. [2022]Adalimumab, a fully human anti-tumor necrosis factor (anti-TNF) monoclonal antibody, is approved for the treatment of Crohn's disease (CD) in adults. We evaluated the overall safety profile of adalimumab in global clinical trials in patients with CD. Patients who participated in these trials, which included randomized induction and maintenance trials, Phase IIIb trials, and open-label extension studies, had moderately to severely active CD and were evaluated for safety at regular intervals.
The Efficacy and Safety of Biologic Drugs in the Treatment of Moderate-Severe Crohn's Disease: A Systematic Review. [2023]Conventional therapy is the most commonly used treatment for Crohn's disease (CD), but it does not always achieve disease control, which is why the use of biologic drugs is increasing. The aim of this study was to analyze the efficacy and safety of biologic drugs in adult patients diagnosed with moderate-severe CD. An intensive search was performed in PubMed, Web of Science and Medline to collect phase 2 or 3 clinical trials published between 2018 and 2023 that were randomized, placebo-controlled and double-blind trials analyzing the efficacy and safety of biologic drugs in adult patients diagnosed with CD. This systematic review was conducted according to the PRISMA statement. Thirteen clinical trials evaluating eight biologic drugs were included. Upadacitinib, vedolizumab, adalimumab, guselkumab, mirikizumab, ustekinumab and risankizumab showed statistically significant efficacy across different clinical, endoscopic, histological, genetic, biomarker or quality-of-life parameters. However, PF-00547659 only showed statistically significant results for the CDAI-70 at week 12. In terms of safety, the incidence and severity of adverse effects were analyzed, with all drugs being well tolerated and presenting a good safety profile since most adverse effects were mild. Biologic drugs can be considered an effective and safe option for the treatment of moderate-severe CD in adult patients with an inadequate response or intolerance to conventional therapy.
IBD: Adalimumab for ulcerative colitis— is the glass half empty or half full? [2021]Antibodies that target tumor necrosis factor are effective at inducing and maintaining remission in both Crohn's disease (infliximab, adalimumab and certolizumab) and ulcerative colitis (infliximab). The results of a randomized controlled trial of adalimumab for inducing remission in moderately to severely active ulcerative colitis have now been published.
Medical management of Crohn's disease. [2019]Crohn's disease is a chronic inflammatory bowel disease of unknown etiology. Sulfasalazine and the newer 5-aminosalicylates remain the first agents of choice to treat mild to moderate disease and often are effective at high doses as maintenance therapies. Corticosteroids are often required to treat more moderate to severe disease activity, although approximately one-third of patients become steroid-dependent after a steroid-induced remission. Corticosteroids have proven ineffective in maintaining remission and side effects resulting from prolonged exposure preclude their long-term use. Azathioprine and 6-mercaptopurine are effective in the setting of steroid dependence and steroid resistance, as well as for the treatment of perianal and fistulizing complications unresponsive to antibiotics. Crohn's disease commonly recurs following surgical resection, and there is expanding evidence that postoperative prophylaxis with certain antibiotics (e.g., metronidazole), aminosalicylates or immunomodulators may be beneficial in the prevention of disease recurrence following resection. Cyclosporin may benefit patients with severe Crohn's disease or refractory fistulas. Recent trials of newer immunosuppressive agents commonly employed in transplant recipients and ongoing development of a new class of "biologic" agents targeting specific sites in the immunoinflammatory cascade, are expanding the pharmacological armamentarium available to treat certain patients.
The state of the art on treatment of Crohn's disease. [2019]Crohn's disease (CD) is a chronic, progressive, and destructive disease of the gastrointestinal tract. Although its incidence appears to be stable or decreasing in most countries in the North America and Europe, the incidence is rising rapidly in Asian countries. Immunomodulators and biologics are increasingly used to avoid long-term bowel damage and subsequent disability. Therapeutic drug monitoring facilitates optimizing thiopurines and anti-TNFs use. New biologic agents targeting various pathological pathways of CD are blooming in recent years, and the high cost of biologics and expiration of patents for several biologic agents have driven the utility of biosimilars for CD treatment. Here, the literature regarding the efficacy, safety, and withdrawal of the drugs, as well as the evolution of therapeutic targets will be reviewed.
Systematic Review and Network Meta-Analysis: Comparative Efficacy and Safety of Biosimilars, Biologics and JAK1 Inhibitors for Active Crohn Disease. [2021]Background: Crohn disease (CD) is a chronic inflammatory disease that affects quality of life. There are several drugs available for the treatment of CD, but their relative efficacy is unknown due to a lack of high-quality head-to-head randomized controlled trials. Aim: To perform a mixed comparison of the efficacy and safety of biosimilars, biologics and JAK1 inhibitors for CD. Methods: We searched PubMed, Web of Science, embase and the Cochrane Library for randomized controlled trials (RCTs) up to Dec. 28, 2020. Only RCTs that compared the efficacy or safety of biosimilars, biologics and JAK1 inhibitors with placebo or another active agent for CD were included in the comparative analysis. Efficacy outcomes were the induction of remission, maintenance of remission and steroid-free remission, and safety outcomes were serious adverse events (AEs) and infections. The Bayesian method was utilized to compare the treatments. The registration number is CRD42020187807. Results: Twenty-eight studies and 29 RCTs were identified in our systematic review. The network meta-analysis demonstrated that infliximab and adalimumab were superior to certolizumab pegol (OR 2.44, 95% CI 1.35-4.97; OR 2.96, 95% CI 1.57-5.40, respectively) and tofacitinib (OR 2.55, 95% CI 1.27-5.97; OR 3.10, 95% CI 1.47-6.52, respectively) and revealed the superiority of CT-P13 compared with placebo (OR 2.90, 95% CI 1.31-7.59) for the induction of remission. Infliximab (OR 7.49, 95% CI 1.85-34.77), adalimumab (OR 10.76, 95% CI 2.61-52.35), certolizumab pegol (OR 4.41, 95% CI 1.10-21.08), vedolizumab (OR 4.99, 95% CI 1.19-25.54) and CT-P13 (OR 10.93, 95% CI 2.10-64.37) were superior to filgotinib for the maintenance of remission. Moreover, infliximab (OR 3.80, 95% CI 1.49-10.23), adalimumab (OR 4.86, 95% CI 1.43-16.95), vedolizumab (OR 2.48, 95% CI 1.21-6.52) and CT-P13 (OR 5.15, 95% CI 1.05-27.58) were superior to placebo for steroid-free remission. Among all treatments, adalimumab ranked highest for the induction of remission, and CT-P13 ranked highest for the maintenance of remission and steroid-free remission. Conclusion: CT-P13 was more efficacious than numerous biological agents and JAK1 inhibitors and should be recommended for the treatment of CD. Further head-to-head RCTs are warranted to compare these drugs.
gp130 blockade to NOD off Crohn's disease. [2021]In a recent publication, Nayar et al. uncover specific inflammatory cell populations associated with Crohn's disease (CD) pathogenesis, and a gp130-STAT3 signaling axis linked to disease in anti-TNF antibody treatment-refractory patients. Therefore, gp130 blockade might represent a potential CD therapy approach, perhaps in conjunction with existing anti-TNF treatment regimes.