Guselkumab for Crohn's Disease

(REASON Trial)

Recruiting at 66 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Janssen-Cilag Ltd.

Disqualifiers: Bowel resection, Abscess, Stoma, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 96 weeks

112 Participants Needed

Trial Summary

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. ^{1 2 3 4 5}

How 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. ^{6 7 8 9 10}

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.

Research Team

Janssen Cilag Ltd. Clinical trial

Principal Investigator

Janssen-Cilag Ltd.

Eligibility 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.

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

Treatment Details

Interventions

• Guselkumab

Trial Overview 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.

Participant Groups

Group I: Guselkumab Experimental Treatment 1 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

Who Is Running the Clinical Trial?

Janssen-Cilag Ltd.

Lead Sponsor

Trials

100

Recruited

49,200+

Joaquin Duato

Janssen-Cilag Ltd.

Chief Executive Officer since 2022

MBA from ESADE Business School

Biljana Naumovic

Janssen-Cilag Ltd.

Chief Medical Officer since 2019

MD from Belgrade University Medical School

Findings from Research

Adalimumab, a fully human monoclonal anti-TNF alpha antibody, has been shown to be clinically effective in treating severe, active Crohn's disease, providing rapid action and maintaining efficacy over 3 years in both treatment-naïve and previously treated patients.

The treatment is associated with a reduction in hospitalization rates and improved quality of life, while its safety profile is comparable to other TNF alpha inhibitors, with low immunogenicity and rare allergic reactions, highlighting the importance of careful patient screening during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[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]. Reinisch, W., Haas, T., Kaser, A., et al.[2015]

Immunosuppressant and biologic therapies for Crohn's disease and ulcerative colitis can lead to a range of adverse events, from mild symptoms to serious complications like infections and cancers, highlighting the importance of careful monitoring.

The review emphasizes the need for healthcare providers to engage in personalized risk-benefit discussions with patients regarding these therapies, considering individual risk factors to optimize treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in IBD therapy: the 2018 update. Quezada, SM., McLean, LP., Cross, RK.[2019]

Fontolizumab, an anti-interferon gamma antibody, was generally well tolerated in a study of 45 patients with moderate to severe Crohn's disease, with only mild adverse effects reported at higher doses.

While no significant differences in clinical activity were observed between fontolizumab and placebo, the highest dose (4.0 mg/kg) showed a notable reduction in Crohn's disease severity and inflammation markers, suggesting potential biological activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Reinisch, W., Hommes, DW., Van Assche, G., et al.[2022]

In a review of safety data from 3160 patients with Crohn's disease treated with adalimumab over 3401.9 patient-years, serious infections were the most common adverse events, with intraabdominal abscesses being the most frequent.

The standardized mortality rate for patients treated with adalimumab was lower than that reported in a meta-analysis of Crohn's disease patients, indicating a favorable safety profile similar to other TNF antagonists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adalimumab safety in global clinical trials of patients with Crohn's disease. Colombel, JF., Sandborn, WJ., Panaccione, R., et al.[2022]

A systematic review of 13 clinical trials involving biologic drugs for moderate-severe Crohn's disease showed that most drugs, including upadacitinib and vedolizumab, demonstrated significant efficacy across various health parameters.

All biologic drugs analyzed were well tolerated, with most adverse effects being mild, indicating a good safety profile for patients who do not respond adequately to conventional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Efficacy and Safety of Biologic Drugs in the Treatment of Moderate-Severe Crohn's Disease: A Systematic Review. Avedillo-Salas, A., Corral-Cativiela, S., Fanlo-Villacampa, A., et al.[2023]

Antibodies targeting tumor necrosis factor, such as adalimumab, have been shown to effectively induce and maintain remission in patients with ulcerative colitis and Crohn's disease.

A recent randomized controlled trial specifically demonstrated the efficacy of adalimumab in inducing remission in patients with moderately to severely active ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IBD: Adalimumab for ulcerative colitis— is the glass half empty or half full? Armuzzi, A., Pugliese, D.[2021]

Sulfasalazine and 5-aminosalicylates are the first-line treatments for mild to moderate Crohn's disease, while corticosteroids are used for more severe cases but can lead to steroid dependence and have significant side effects.

Newer treatments, including immunomodulators and biologic agents, are being developed to address steroid resistance and prevent disease recurrence after surgery, expanding the options for managing Crohn's disease effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medical management of Crohn's disease. Stein, RB., Hanauer, SB.[2019]

Immunomodulators and biologics are increasingly used to treat Crohn's disease (CD) to prevent long-term bowel damage, with therapeutic drug monitoring helping to optimize their use.

The rise of new biologic agents and the introduction of biosimilars are important developments in CD treatment, especially given the high costs of biologics and the expiration of patents for some existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The state of the art on treatment of Crohn's disease. Shi, HY., Ng, SC.[2019]

A systematic review of 28 studies found that infliximab and adalimumab were more effective than certolizumab pegol and tofacitinib for inducing and maintaining remission in Crohn's disease, highlighting their superior efficacy.

CT-P13 (a biosimilar of infliximab) was shown to be more effective than several biological agents and JAK1 inhibitors for both inducing remission and maintaining steroid-free remission, suggesting it should be recommended for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review and Network Meta-Analysis: Comparative Efficacy and Safety of Biosimilars, Biologics and JAK1 Inhibitors for Active Crohn Disease. Wu, G., Yang, Y., Liu, M., et al.[2021]

Nayar et al. identified specific inflammatory cell populations that play a role in the development of Crohn's disease (CD), highlighting the importance of understanding these cells in disease management.

The study suggests that targeting the gp130-STAT3 signaling pathway could be a promising new treatment strategy for patients with CD who do not respond to anti-TNF antibody therapies, potentially enhancing existing treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

gp130 blockade to NOD off Crohn's disease. Mukherjee, T., Philpott, DJ.[2021]

References

1. Germany pubmed.ncbi.nlm.nih.gov

[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]

2. England pubmed.ncbi.nlm.nih.gov

Adverse events in IBD therapy: the 2018 update. [2019]

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

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]

4. England pubmed.ncbi.nlm.nih.gov

Adalimumab safety in global clinical trials of patients with Crohn's disease. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

The Efficacy and Safety of Biologic Drugs in the Treatment of Moderate-Severe Crohn's Disease: A Systematic Review. [2023]

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

IBD: Adalimumab for ulcerative colitis— is the glass half empty or half full? [2021]

7. Spain pubmed.ncbi.nlm.nih.gov

Medical management of Crohn's disease. [2019]

8. Japan pubmed.ncbi.nlm.nih.gov

The state of the art on treatment of Crohn's disease. [2019]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Systematic Review and Network Meta-Analysis: Comparative Efficacy and Safety of Biosimilars, Biologics and JAK1 Inhibitors for Active Crohn Disease. [2021]

10. England pubmed.ncbi.nlm.nih.gov

gp130 blockade to NOD off Crohn's disease. [2021]