Guselkumab for Crohn's Disease

(GALAXI Trial)

Recruiting at 679 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Janssen Research & Development, LLC

Disqualifiers: Ulcerative colitis, Symptomatic strictures, others

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

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

1409 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop your current medications, but it mentions that unstable doses of Crohn's disease therapy are not allowed. It's best to discuss your specific medications with the trial coordinators.

Is Guselkumab safe for humans?

Guselkumab has been studied for safety in treating moderate to severe Crohn's disease and other conditions. It is generally well tolerated, with most side effects being mild, making it a safe option for patients who do not respond well to conventional treatments. ^{1 2 3 4 5}

How is the drug Guselkumab different 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 that target tumor necrosis factor (TNF). This novel approach may offer an alternative for patients who do not respond well to existing TNF-targeting therapies. ^{6 7 8 9 10}

What is the purpose of this trial?

This trial is testing guselkumab, a medication that reduces inflammation, in patients with Crohn's disease. It aims to find the best dose and check its safety and effectiveness. The medication works by calming the immune system to reduce symptoms.

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

This trial is for individuals with moderate to severe Crohn's Disease, confirmed by specific tests and criteria. Participants should have had an inadequate response or intolerance to conventional or biologic therapies. They must not have ulcerative colitis, indeterminate colitis, or complications like symptomatic strictures. Women of childbearing potential need a negative pregnancy test.

Inclusion Criteria

Have screening laboratory test results within the protocol specified parameters

I have moderate to severe Crohn's disease based on specific health scores.

I am a woman who can have children and have tested negative for pregnancy.

Exclusion Criteria

Any medical contraindications preventing study participation

I have been diagnosed with ulcerative colitis or indeterminate colitis.

I haven't taken any Crohn's disease biologics or experimental treatments recently.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 2 Treatment (GALAXI 1)

Participants receive guselkumab or placebo with potential switch to ustekinumab, evaluated for safety and efficacy over 48 weeks

48 weeks

Phase 3 Treatment (GALAXI 2 and 3)

Participants receive guselkumab or placebo with potential switch to ustekinumab, evaluated for clinical and endoscopic efficacy over 48 weeks

48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-Term Extension (LTE)

Participants may opt into continuation of treatment long-term with guselkumab or ustekinumab

Treatment Details

Interventions

• Guselkumab
• Placebo
• Ustekinumab

Trial Overview The study is testing the effectiveness and safety of different doses of Guselkumab in treating Crohn's Disease compared to Ustekinumab and a placebo. It aims to assess both clinical outcomes (symptom relief) and endoscopic results (internal healing as seen through a scope).

Participant Groups

Group I: Phase 3 (GALAXI 2 and 3): Group 4 (Placebo/Ustekinumab) Experimental Treatment 2 Interventions

Participants will receive placebo administered by intravenous (IV) infusion. At Week 12, non-responders will receive active treatment (ustekinumab) administered by intravenous (IV) infusion followed by subcutaneous (SC) injection. Participants who are eligible and willing to continue placebo/ustekinumab may enter the LTE and continue to receive placebo/ustekinumab.

Group II: Phase 3 (GALAXI 2 and 3): Group 1 and Group 2 (Guselkumab) Experimental Treatment 1 Intervention

Participants will receive guselkumab by intravenous (IV) infusion, followed by guselkumab by subcutaneous (SC) injection. Participants who are eligible and willing to continue guselkumab may enter the LTE phase and continue to receive guselkumab.

Group III: Phase 2 (GALAXI 1): Group 5 (Placebo/Ustekinumab) Experimental Treatment 2 Interventions

Participants will receive placebo administered by intravenous (IV) infusion. At Week 12, non-responders will receive active treatment (Ustekinumab) administered by intravenous (IV) infusion followed by subcutaneous (SC) injection. Participants who are eligible and willing to continue placebo/ustekinumab may enter the LTE and continue to receive placebo/ustekinumab.

Group IV: Phase 2 (GALAXI 1): Group 3 (Guselkumab) Experimental Treatment 2 Interventions

Participants will receive guselkumab (Dose 4) by intravenous (IV) infusion, followed by guselkumab (Dose 5) by subcutaneous (SC) injection. Participants who are eligible and willing to continue guselkumab may enter the LTE phase and continue to receive guselkumab.

Group V: Phase 2 (GALAXI 1): Group 2 (Guselkumab) Experimental Treatment 2 Interventions

Participants will receive guselkumab (Dose 3) by intravenous (IV) infusion, followed by guselkumab (Dose 2) by subcutaneous (SC) injection. Participants who are eligible and willing to continue guselkumab may enter the LTE phase and continue to receive guselkumab.

Group VI: Phase 2 (GALAXI 1): Group 1 (Guselkumab) Experimental Treatment 2 Interventions

Participants will receive guselkumab (Dose 1) by intravenous (IV) infusion, followed by guselkumab (Dose 2) by subcutaneous (SC) injection. Participants who are eligible and willing to continue guselkumab may enter the Long-Term Extension (LTE) phase and continue to receive guselkumab.

Group VII: Phase 3 (GALAXI 2 and 3): Group 3 (Ustekinumab) Active Control 1 Intervention

Participants will receive ustekinumab by intravenous (IV) infusion, followed by subcutaneous (SC) injection. Participants who are eligible and willing to continue ustekinumab may enter the LTE phase and continue to receive ustekinumab.

Group VIII: Phase 2 (GALAXI 1): Group 4 (Ustekinumab) Active Control 1 Intervention

Participants will receive ustekinumab by intravenous (IV) infusion, followed by subcutaneous (SC) injection. Participants who are eligible and willing to continue ustekinumab may enter the LTE and continue to receive ustekinumab.

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 Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

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]

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]

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]

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]

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]

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. England pubmed.ncbi.nlm.nih.gov

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

5. 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]

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

Medical management of Crohn's disease. [2019]

7. Japan pubmed.ncbi.nlm.nih.gov

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

8. 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]

9. England pubmed.ncbi.nlm.nih.gov

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

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

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