Biologic Therapies for Crohn's Disease
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: University of Calgary
Must not be taking: TNF antagonists, Anti-integrins
Disqualifiers: Colonic dysplasia, Active infections, Recent surgery, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?There are currently three classes of biologic treatments approved in Canada for the management of moderate-to-severe Crohn's disease: anti-tumor necrosis factor \[TNF\] alpha, anti-integrin, and anti-interleukin \[IL\]-23 targeted agents. The purpose of this trial is to determine which of these three classes of biologics results in the highest percentage of patients with small bowel (ileal) Crohn's disease entering into endoscopic remission without needing corticosteroids at 1 year. Endoscopic remission means that the ulcers in the small bowel from Crohn's disease have healed. All treatments in this trial are approved by Health Canada. No experimental drugs will be included.
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications, but it mentions that participants must not use any medications that are prohibited by the study. It's best to discuss your current medications with the trial team to see if they are allowed.
What data supports the effectiveness of the drug Adalimumab for Crohn's disease?
Adalimumab is effective in inducing remission in patients with active Crohn's disease who had secondary failure to infliximab therapy, and it has been shown to maintain remission in both Crohn's disease and ulcerative colitis.
12345Is Vedolizumab safe for treating Crohn's disease?
Vedolizumab has been shown to be generally safe for treating Crohn's disease, with studies indicating a favorable safety profile and no evidence of serious conditions like PML (a rare brain infection) or reactivation of latent infections like TB (tuberculosis) or hepatitis B. However, some adverse events have been reported, and longer-term studies are needed to fully understand its safety.
678910How does the drug Vedolizumab differ from other treatments for Crohn's disease?
Vedolizumab is unique because it targets the α4β7 integrin, which helps control the movement of immune cells into the gut, making it effective for patients who do not respond to or cannot tolerate other treatments like anti-TNF drugs.
257911Eligibility Criteria
This trial is for adults over 18 with moderate-to-severe ileal Crohn's Disease who haven't been treated with biologics before. They should have a documented large ileal ulcer and be experiencing active symptoms. Pregnant or breastfeeding women, those with recent surgeries, infections like TB or COVID-19, or a history of certain complications are excluded.Inclusion Criteria
I had a colonoscopy showing a large ulcer in my ileum within the last 3 months.
Established CD diagnosis by conventional criteria
Written informed consent must be obtained and documented
+6 more
Exclusion Criteria
I am not currently on treatment for any serious infections.
I have an active hepatitis B, hepatitis C, or HIV infection.
I have been treated with specific immune system targeting drugs.
+11 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive biologic treatments (TNF antagonist, anti-integrin, or anti-IL23) according to standard of care
12 months
Visits at weeks 0, 2, 4, 6, 8, and every 8 weeks thereafter
Follow-up
Participants are monitored for safety and effectiveness after treatment, including assessments for endoscopic remission and biomarker levels
4 weeks
Evaluations at months 4, 8, and 12
Extension
Participants may continue treatment based on standard care and clinical outcomes
Ongoing
Participant Groups
The PATHFINDER trial is testing which class of approved biologic treatments (anti-TNF alpha, anti-integrin, anti-IL-23) best induces endoscopic remission in small bowel Crohn's disease at one year without steroids. Patients will receive Vedolizumab IV/SC, Risankizumab, Ustekinumab, Infliximab or Adalimumab.
3Treatment groups
Active Control
Group I: TNFα antagonistActive Control2 Interventions
Participants will receive either:
* Infliximab 5 mg/kg intravenously \[IV\] at weeks 0, 2, 6, then 5 mg/kg every 8 weeks; OR
* Adalimumab subcutaneously \[SC\] 160 mg at week 0, 80 mg at week 2, then 40 mg every 2 weeks
Group II: Anti-IL12/23 or anti-IL23Active Control2 Interventions
Participants will receive either:
* Ustekinumab \~6 mg/kg IV x1, then 90 mg SC every 8 weeks; OR
* Risankizumab 600 mg IV at weeks 0, 4, and 8, then 360 mg SC every 8 weeks
Group III: Anti-integrinActive Control2 Interventions
Participants will receive either:
* Vedolizumab 300 mg IV at weeks 0, 2, and 6, then every 8 weeks; OR
* Vedolizumab 300 mg IV at weeks 0 and 2, then 108 mg SC every 2 weeks
Adalimumab is already approved in European Union, United States, Canada, Japan for the following indications:
🇪🇺 Approved in European Union as Humira for:
- Rheumatoid arthritis
- Psoriatic arthritis
- Ankylosing spondylitis
- Crohn's disease
- Ulcerative colitis
- Plaque psoriasis
- Juvenile idiopathic arthritis
🇺🇸 Approved in United States as Humira for:
- Rheumatoid arthritis
- Psoriatic arthritis
- Ankylosing spondylitis
- Crohn's disease
- Ulcerative colitis
- Plaque psoriasis
- Juvenile idiopathic arthritis
- Hidradenitis suppurativa
🇨🇦 Approved in Canada as Humira for:
- Rheumatoid arthritis
- Psoriatic arthritis
- Ankylosing spondylitis
- Crohn's disease
- Ulcerative colitis
- Plaque psoriasis
- Juvenile idiopathic arthritis
🇯🇵 Approved in Japan as Humira for:
- Rheumatoid arthritis
- Psoriatic arthritis
- Ankylosing spondylitis
- Crohn's disease
- Ulcerative colitis
- Plaque psoriasis
- Juvenile idiopathic arthritis
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
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Who Is Running the Clinical Trial?
University of CalgaryLead Sponsor
Alimentiv Inc.Collaborator
References
Adalimumab maintenance therapy for Crohn's disease with intolerance or lost response to infliximab: an open-label study. [2015]Adalimumab is effective in inducing remission in patients with active Crohn's disease who had secondary failure to infliximab therapy.
Advances in biologic therapy for ulcerative colitis and Crohn's disease. [2019]The medical management of inflammatory bowel disease (IBD) has changed considerably since the advent of biologic treatments. In this review we offer a critical evaluation of controlled studies with biologic agents for the management of both Crohn's disease (CD) and ulcerative colitis (UC). Biologics under evaluation or approved for UC that are discussed include monoclonal antibodies to tumor necrosis factor ([TNF]) infliximab), inhibitors of adhesion molecules (MLN02 and alicaforsen), anti-CD3 antibodies (visilizumab), and anti-interleukin (IL)-2 receptor antibodies (daclizumab). Biologics under evaluation or approved for CD that are reviewed include three monoclonal antibodies to TNF (infliximab, adalimumab, and certolizumab pegol), monoclonal antibodies against IL-12, interferon-chi, and IL-6 receptors, inhibitors of adhesion molecules (natalizumab, alicaforsen), and growth factors. Only the chimeric monoclonal anti-TNF antibody infliximab is currently available worldwide. The potency of this agent in moderate-to-severe UC and CD has been one of the most important advances in the care of IBD in the past decade.
An indirect comparison of ustekinumab and vedolizumab in the therapy of TNF-failure Crohn's disease patients. [2019]An indirect comparison of ustekinumab versus vedolizumab in patients with active moderate-to-severe Crohn's disease who were nonresponsive or intolerant to previous TNF-antagonist therapy.
Adalimumab for Crohn's disease with intolerance or lost response to infliximab: a 3-year single-centre experience. [2022]Adalimumab is effective in inducing clinical remission in patients with Crohn's disease who lost response or became intolerant to infliximab.
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.
Assessment of the real-world safety profile of vedolizumab using the United States Food and Drug Administration adverse event reporting system. [2023]Vedolizumab is the first gut-selective integrin blocker indicated for patients with Crohn's disease (CD) and ulcerative colitis (UC). This study aimed to examine the adverse events (AEs) profile of vedolizumab compared to anti-tumor necrosis factors (anti-TNFs) indicated for CD and UC using the FDA Adverse Event Reporting System (FAERS) database. AE reports with vedolizumab (5/20/2014-6/30/2015) and CD/UC-indicated anti-TNF drugs (adalimumab, infliximab, certolizumab pegol, and golimumab, during 8/1/1998-6/30/2015) as primary suspects were extracted from the FAERS database. AEs associated with vedolizumab were compared for signals of disproportionate reporting against anti-TNF drugs and all other drugs (1969-6/30/2015), using the proportional reporting ratio (PRR) and the empirical Bayesian geometric mean (EBGM) algorithms. The search retrieved 499 reports for vedolizumab and 119,620 reports for anti-TNFs, with 35.9% and 32.1% of these, respectively, being serious AEs. With the PRR approach, vedolizumab-associated reports had signals for 22 groups of AEs (9 were associated with serious outcomes) relative to anti-TNFs and had 34 signals relative to all other drugs. Signals detected included those reported as warnings in prescribing information and new AEs related to cardiovascular disease. Due to the voluntary nature of FAERS, this finding should be considered hypothesis generating (rather than hypothesis testing). Longer-term observational studies are required to evaluate the safety of vedolizumab.
Vedolizumab as a Treatment for Crohn's Disease and Ulcerative Colitis. [2022]The management of Crohn's disease and ulcerative colitis has become increasingly complex. With the current utilization of immunosuppressive therapies earlier in the disease course for patients presenting with moderate to severe disease, there is a great need for additional biologic agents targeting inflammatory mediators other than anti-tumor necrosis factor-α (anti-TNF) agents. Although anti-TNF agents have positively impacted the treatment of inflammatory bowel disease, many patients can lose their response or develop intolerance to these agents over time through the formation of antidrug antibodies. Furthermore, a sizeable percentage of patients are primary nonresponders to anti-TNF drugs. Vedolizumab (Entyvio, Takeda Pharmaceuticals), a monoclonal antibody to the α4β7 integrin, inhibits gut lymphocyte trafficking and has been demonstrated to be an effective and safe agent for the treatment of both Crohn's disease and ulcerative colitis. This article reviews the clinical trial evidence and rationale for the use of vedolizumab in moderate to severe Crohn's disease and ulcerative colitis.
Vedolizumab in the treatment of Crohn's disease. [2016]Vedolizumab, a recent addition to the therapeutic armamentarium in Crohn's disease, is promising in efficacy, durability of remission and safety. It is the first gut selective biologic treatment, acting by targeting α4β7-integrin, a receptor expressed on activated lymphocytes and binding to MAdCAM1, a cell adhesion molecule selectively expressed in the circulatory system of the digestive tract, preventing trafficking of lymphocytes to the gut. The pivotal GEMINI studies have demonstrated the efficacy and safety of vedolizumab in achieving clinical response and clinical remission in patients with moderately to severely active CD who are naïve or have previously failed therapy with TNF-antagonists, immunomodulators or dependent on steroids. Vedolizumab had a favorable safety profile and specifically showed no evidence of PML, reactivation of latent TB or hepatitis B. Overall, the number of malignancies in the clinical trials was small; however, long-term exposure was limited. Vedolizumab can be given as a first-line therapy or following treatment failure, and was tolerated as part of combination therapy. More medications with similar and novel therapeutic mechanisms are anticipated in the coming years.
Vedolizumab: first global approval. [2021]Vedolizumab [Entyvio(®) (US, Europe)], a humanized monoclonal antibody α4β7 integrin receptor antagonist, has been developed by Millennium Pharmaceuticals (d/b/a Takeda Pharmaceuticals International) for the treatment of ulcerative colitis and Crohn's disease. Vedolizumab has received its first global approval for the treatment of ulcerative colitis and Crohn's disease in the US, for use in adult patients with moderate-to-severe disease who have had an inadequate response, loss of response or intolerance to one or more standard therapies (corticosteroids, immunomodulators or tumour necrosis factor-α inhibitor) or demonstrated dependence on corticosteroids. Vedolizumab has since been approved for ulcerative colitis and Crohn's disease in the EU, Norway, Iceland and Liechtenstein. This article summarizes the milestones in the development of vedolizumab leading to its first approval for the treatment of ulcerative colitis and Crohn's disease.
Influence of Drug Exposure on Vedolizumab-Induced Endoscopic Remission in Anti-Tumour Necrosis Factor [TNF] Naïve and Anti-TNF Exposed IBD Patients. [2021]Vedolizumab has demonstrated efficacy and safety in patients with Crohn's disease [CD] and ulcerative colitis [UC]. Endoscopic outcome data are limited, especially in anti-tumour necrosis factor [TNF] naïve patients. The present study compared endoscopic outcome in anti-TNF naïve and exposed patients, and explored if this was affected by drug exposure.
[Biologic therapies in chronic inflammatory bowel diseases]. [2016]Crohn's disease and ulcerative colitis are chronic inflammatory bowel diseases which can be difficult to control with conventional therapies. Thanks to a better knowledge of their physiopathology, new therapies aimed at specific targets of the inflammatory cascade were developed. Three monoclonal anti-TNF antibodies were produced. Infliximab and adalimumab, currently widely used, can induce sustained remission in Crohn's disease. Infliximab is also efficacious in UC. Certolizumab pegol provides good short term results; its long term efficacy, however, remains to be assessed by further clinical trials. Therapies targeting leucocyte trafficking (anti-integrine) have also been provided and are associated with good clinical responses in Crohn's disease. Natalizumab (anti-alpha4) is responsible for significant side effects and is no longer in use in gasrtoenterology in Europe whereas MLN02 (anti-alpha417) has a good profile in terms of efficacy and safety. Monoclonal anti bodies targeting other cytokines are under development, mainly ustekinumab which inhibits IL12 and IL23. Ustekinumab generates favourable clinical responses in Crohn's disease. The development of biologic therapies in inflammatory bowel disease has dramatically altered the course and management of these disorders.