Guselkumab for Crohn's Disease
(FUZION CD Trial)
Recruiting in Palo Alto (17 mi)
+158 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Janssen-Cilag Ltd.
Disqualifiers: Severe luminal disease, Rectovaginal fistulas, Stenosis, Stoma, Lupus, others
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?This trial tests a medicine called guselkumab on adults with severe Crohn's disease who haven't responded to other treatments. The study will last over two years and will check both how well the medicine works and its safety. Guselkumab is already approved for treating other conditions like plaque psoriasis and psoriatic arthritis.
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants should have previously tried certain advanced drug therapies for Crohn's disease, which might imply some changes to your current treatment plan.
Is Guselkumab safe for use in humans?
Guselkumab, also known as Tremfya or CNTO1959, has been studied for safety in treating 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 protein involved in the immune response, which is different from other treatments like corticosteroids or anti-TNF drugs that have broader effects. This targeted approach may offer a new option for patients who do not respond well to existing therapies.
678910Eligibility Criteria
This trial is for individuals with Crohn's disease who've had it for at least 3 months and have at least one active draining perianal fistula. They must be new to biologic treatments or not responding well to current therapies. People with severe luminal disease, rectovaginal fistulas, ongoing infections, or complications that could need surgery can't join.Inclusion Criteria
I have at least one active draining fistula due to Crohn's disease, confirmed by MRI.
I have been diagnosed with Crohn's disease for at least 3 months.
I have Crohn's Disease and haven't responded well to standard or biologic treatments.
Exclusion Criteria
I have or had complications related to perianal disease.
I have a long-term or recurring infection.
Any medical contraindications preventing study participation
+2 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive guselkumab or placebo with IV infusion followed by subcutaneous administration. Non-responders may switch doses at Week 24.
24 weeks
Regular visits for administration and monitoring
Follow-up
Participants are monitored for safety and effectiveness after treatment, with assessments up to Week 48.
24 weeks
Periodic visits for assessments
Long-Term Extension (LTE)
Participants who are eligible and willing may continue to receive guselkumab in an open-label extension.
Long-term
Participant Groups
The study is testing the effectiveness of a drug called Guselkumab in treating fistulizing, perianal Crohn's disease compared to a placebo. It aims to see if this medication can help manage symptoms better than no treatment.
3Treatment groups
Experimental Treatment
Group I: Group 3: PlaceboExperimental Treatment2 Interventions
Participants will receive placebo IV infusion followed by placebo SC. At Week 24, placebo non-responders will continue to receive guselkumab Dose 4 followed by guselkumab Dose 2 SC. Participants will receive matching placebo to maintain the blind. Participants who are eligible and willing to continue guselkumab may enter the LTE period and continue to receive guselkumab.
Group II: Group 2: GuselkumabExperimental Treatment2 Interventions
Participants will receive guselkumab Dose 1 IV infusion followed by Dose 3 SC. Participants will receive matching placebo to maintain the blind. At Week 24, guselkumab Dose 3 SC non-responders will switch to receive guselkumab dose 2 SC. Participants who are eligible and willing to continue guselkumab may enter the LTE period and continue to receive guselkumab.
Group III: Group 1: GuselkumabExperimental Treatment2 Interventions
Participants will receive guselkumab Dose 1 intravenous (IV) infusion followed by Dose 2 subcutaneously (SC). Participants will receive matching placebo to maintain the blind. Participants who are eligible and willing to continue guselkumab may enter the Long-Term Extension (LTE) period and continue to receive guselkumab.
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:
University of California San Diego Medical CenterLa Jolla, CA
University of Alberta- Ziedler Ledcor CentreEdmonton, Canada
Gastro OneGermantown, TN
AdventHealth Medical Group Blood & Marrow Transplant at OrlandoOrlando, FL
More Trial Locations
Loading ...
Who Is Running the Clinical Trial?
Janssen-Cilag Ltd.Lead Sponsor
References
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.
[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.
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.
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.
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.
Adalimumab for the treatment of Crohn's disease. [2010]Crohn's disease is a chronic inflammatory intestinal disorder characterized by chronic, recurrent, often granulomatous inflammation affecting any part of the intestines, but most frequently involving the small bowel and colon. The development of novel biologic agents targeting tumor necrosis factor has revolutionized the treatment of patients with moderate-to-severe Crohn's disease. Adalimumab, a fully human anti-tumor necrosis factor monoclonal antibody, has recently been evaluated for Crohn's disease and was found to be effective for induction of clinical response and remission in patients with active inflammatory disease. Preliminary experience also indicates that adalimumab is useful in patients with prior intolerance or loss of response to infliximab. The rate of adverse events is comparable to other tumor necrosis factor antagonists in rheumatoid arthritis, but longer studies are needed to evaluate both the long-term efficacy and safety of adalimumab in the treatment of Crohn's disease.