Guselkumab for Crohn's Disease

(FUZION CD Trial)

Recruiting at 159 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Janssen-Cilag Ltd.

Disqualifiers: Severe luminal disease, Rectovaginal fistulas, Stenosis, Stoma, Lupus, 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: 24 weeks

280 Participants Needed

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. ^{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 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. ^{6 7 8 9 10}

Research Team

Janssen-Cilag Ltd. Clinical Trial

Principal Investigator

Janssen-Cilag Ltd.

Eligibility 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

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

Treatment Details

Interventions

• Guselkumab

Trial Overview 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.

Participant Groups

Group I: Group 3: Placebo Experimental Treatment 2 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: Guselkumab Experimental Treatment 2 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: Guselkumab Experimental Treatment 2 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

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

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]

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]

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]

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]

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]

Adalimumab, a monoclonal antibody targeting tumor necrosis factor, has been shown to effectively induce clinical response and remission in patients with moderate-to-severe Crohn's disease, based on recent evaluations.

The safety profile of adalimumab appears comparable to other similar treatments, but further long-term studies are necessary to fully assess its efficacy and safety in Crohn's disease management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adalimumab for the treatment of Crohn's disease. Papadakis, KA.[2010]

References

1. 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]

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

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

3. 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]

4. 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]

5. England pubmed.ncbi.nlm.nih.gov

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

6. Spain pubmed.ncbi.nlm.nih.gov

Medical management of Crohn's disease. [2019]

7. England pubmed.ncbi.nlm.nih.gov

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

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

Adalimumab for the treatment of Crohn's disease. [2010]