Infliximab for Aneurysms

Overseen By Daniel L Cooke, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of California, San Francisco

Must not be taking: Anti-TNF, Biologics

Disqualifiers: Active infection, TB, HIV, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

8 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests infliximab, administered through an IV, to determine its effectiveness for a type of brain aneurysm that surgery cannot treat. These aneurysms, known as dolichoectactic vertebrobasilar (DVB) aneurysms, can cause serious issues like strokes or pressure on the brainstem. The trial seeks a non-surgical treatment option for individuals with these aneurysms. Suitable candidates have a DVB aneurysm that surgery cannot address. As a Phase 1, Phase 2 trial, it focuses on understanding the treatment's effects and measuring its effectiveness in an initial group, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial requires that you have not used an anti-TNF or other biologic medication in the past 12 months. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.

Is there any evidence suggesting that infliximab is likely to be safe for humans?

Research shows that infliximab, a medication used to reduce inflammation, has undergone safety studies in people with various conditions. One study on giant cell arteritis tested infliximab for safety and effectiveness. Although specific side effects were not detailed, these studies aim to ensure the treatment's safety for patients. Infliximab has been carefully tested to identify any major issues when used by patients.

The FDA has approved infliximab for treating other inflammatory conditions, such as certain types of arthritis and inflammatory bowel disease, suggesting that patients generally tolerate the drug well. However, like any medication, it carries some risk of side effects.

In summary, infliximab has been studied for safety and is used for other conditions, indicating it is reasonably safe. However, discussing personal risks with healthcare providers before starting any new treatment is always important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for aneurysms, which often involve surgical intervention or blood pressure management, infliximab offers a unique approach by targeting inflammation. Infliximab is a monoclonal antibody that specifically inhibits tumor necrosis factor-alpha (TNF-alpha), a protein involved in inflammatory processes. Researchers are excited about infliximab because it could potentially reduce aneurysm growth by addressing the underlying inflammation, offering a non-surgical option that could be less invasive and more targeted than current treatments.

What evidence suggests that infliximab might be an effective treatment for DVB aneurysms?

Research has shown that infliximab, the treatment under study in this trial, might slow aneurysm growth and repair damage. One study found that patients receiving infliximab experienced slower aneurysm growth compared to those not receiving the treatment. Infliximab reduces inflammation, a major factor in aneurysm growth. It has also effectively treated other inflammatory conditions, such as Giant Cell Arteritis, a type of blood vessel inflammation. Although further research is needed, these early results suggest that infliximab could be promising for treating DVB aneurysms. ^{1 2 6 7 8}

Who Is on the Research Team?

Daniel L Cooke, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for adults over 18 with a specific type of aneurysm in the brain's arteries that can't be treated with surgery or other common methods. Participants must not have severe kidney issues, recent drug abuse, certain infections like HIV or TB, or liver problems. Women who could get pregnant must use effective contraception and not be breastfeeding.

Inclusion Criteria

I have a complex aneurysm in my brain that cannot be treated with surgery or through the blood vessels.

I am over 18 years old.

Exclusion Criteria

I have not had serious infections or needed strong antibiotics in the last month.

I have a positive TB test but haven't completed or am not undergoing treatment for latent TB.

I have had a positive TB test but no treatment or preventive measures for TB.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive infliximab intravenously at specified intervals for a total of 12 months

12 months

Visits at 0, 3, 7 weeks, then every 8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

MR imaging at 0, 12, and 24 months

What Are the Treatments Tested in This Trial?

Interventions

• Infliximab

Trial Overview

The trial tests Infliximab therapy on patients with dolichoectactic vertebrobasilar aneurysms to prevent stroke and brainstem compression. It seeks alternatives to surgical treatments which are often not viable for these patients.

How Is the Trial Designed?

Group I: Infliximab treatment Experimental Treatment 1 Intervention

Administer infliximab intravenously to patients with DVB aneurysms (3 mg/kg at 0, 3 and 7 weeks, then at 8-week intervals x 7) for a total of 12-months. Patients will undergo MR imaging at 0, 12, and 24-month time points.

Infliximab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Remicade for:

• Ankylosing Spondylitis
• Crohn's Disease
• Ulcerative Colitis
• Psoriatic Arthritis
• Rheumatoid Arthritis
• Plaque Psoriasis

Approved in United States as Remicade for:

• Ankylosing Spondylitis
• Crohn's Disease
• Ulcerative Colitis
• Psoriatic Arthritis
• Rheumatoid Arthritis
• Plaque Psoriasis

Approved in Canada as Remicade for:

• Ankylosing Spondylitis
• Crohn's Disease
• Ulcerative Colitis
• Psoriatic Arthritis
• Rheumatoid Arthritis
• Plaque Psoriasis

Approved in Japan as Remicade for:

• Ankylosing Spondylitis
• Crohn's Disease
• Ulcerative Colitis
• Psoriatic Arthritis
• Rheumatoid Arthritis
• Plaque Psoriasis

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Published Research Related to This Trial

Infliximab, an anti-TNF-alpha monoclonal antibody, was studied in 771 patients for Crohn's disease and rheumatoid arthritis, showing an acceptable safety profile with only 17% experiencing acute infusion reactions compared to 7% in the placebo group.

While infliximab was associated with a higher overall rate of infections (26% vs. 16% for placebo), there was no increased risk of serious infections or difference in mortality rates, indicating it is generally safe for use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long term safety of infliximab. Schaible, TF.[2019]

In a study of 650 biologic-naïve patients with moderate to severe rheumatoid arthritis, the biosimilar PF-06438179/GP1111 showed similar efficacy to the reference infliximab (Remicade®) at week 14, with ACR20 response rates of 62.7% and 64.1%, respectively, indicating that the biosimilar is an effective alternative.

Both PF-06438179/GP1111 and infliximab-EU had comparable safety profiles and immunogenicity rates, with no significant differences in adverse effects or antibody development, suggesting that the biosimilar is as safe as the reference product.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized controlled trial comparing PF-06438179/GP1111 (an infliximab biosimilar) and infliximab reference product for treatment of moderate to severe active rheumatoid arthritis despite methotrexate therapy. Cohen, SB., Alten, R., Kameda, H., et al.[2019]

A survey of 96 gastroenterologists revealed that while 86% frequently use infliximab, only 48% prescribe immunomodulators beforehand, indicating a potential gap in optimal treatment practices.

Many gastroenterologists underestimated the risks of serious adverse effects associated with infliximab, such as serious infections and malignancies, highlighting the need for improved education on treatment protocols and side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prescribing patterns and awareness of adverse effects of infliximab: a health survey of gastroenterologists. Donovan, M., Lunney, K., Carter-Pokras, O., et al.[2018]

Infliximab is an effective treatment for moderately to severely active Crohn disease and rheumatoid arthritis, showing rapid onset of action and disease-modifying activity, particularly in patients who have not responded to other treatments.

While generally well tolerated, infliximab carries risks such as reactivation of tuberculosis and worsening of certain conditions, necessitating careful use in high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spotlight on infliximab in Crohn disease and rheumatoid arthritis. Siddiqui, MA., Scott, LJ.[2018]

Infliximab is an effective treatment for moderately to severely active Crohn's disease and rheumatoid arthritis, showing rapid onset of action and disease-modifying activity, particularly in patients who have not responded to other treatments.

While generally well tolerated, infliximab carries risks such as reactivation of tuberculosis and worsening of certain conditions, necessitating careful use in high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infliximab: a review of its use in Crohn's disease and rheumatoid arthritis. Siddiqui, MA., Scott, LJ.[2018]

Citations

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This meta-analysis investigates the efficacy of infliximab in reducing vascular damage, suppressing inflammation, and promoting mucosal healing

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Study Details | NCT02638701 | Infliximab Therapy for ...

Our primary outcome for assessing the effectiveness of the infliximab treatment will be the reduction in aneurysm volume over the treatment course based on ...

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Long-Term Clinical Outcomes After Switching from ...

Following a switch from Remicade to CT-P13, 82% of IBD patients continued treatment through 1 year. Disease activity scores and inflammatory markers remained ...

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The purpose of this study is to evaluate the safety and efficacy (effectiveness) of Infliximab (Remicade) in patients with Giant Cell Arteritis. Infliximab ( ...

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Compared with untreated patients, treatment with infliximab showed a trend toward lower aneurysm growth and was associated with reversal of ...

6.

ahajournals.org

ahajournals.org/doi/10.1161/SVIN.123.000890?doi=10.1161/SVIN.123.000890

A Preliminary Study of Anti‐TNFα Therapy for Symptomatic ...

Compared with untreated patients, treatment with infliximab showed a trend toward lower aneurysm growth and was associated with reversal of ...

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a randomised, multicentre comparative effectiveness trial

10–20% of children have recurrence of fever after initial therapy and are at increased risk of coronary artery aneurysms. A second infusion of ...

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Potential of Disease-Modifying Anti-Rheumatic Drugs to Limit ...

These results were particularly influenced by one study that reported larger aneurysms in IL-1β-deficient mice. Further investigation suggested that an ...