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?

Patients harboring dolichoectactic vertebrobasilar (DVB) aneurysms are at risk of suffering SAH, ischemic stroke, and/or brainstem compression and many patients are not offered invasive treatment due to the futility of existing surgical methods. Consequently, there is demand for development of medical therapy for DVB aneurysms

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 infliximab generally safe for humans?

Infliximab has been studied for conditions like Crohn's disease and rheumatoid arthritis, showing an acceptable safety profile. Common side effects include infusion reactions like headache and fever, and a higher rate of infections, but no increased risk of serious infections or death. Some rare neurological side effects have been reported, and a small percentage of patients may develop mild autoantibodies, which usually resolve after stopping the drug. ^{1 2 3 4 5}

How does the drug infliximab differ from other treatments for aneurysms?

Infliximab is unique because it is a monoclonal antibody that targets and neutralizes tumor necrosis factor-alpha (TNF-alpha), a protein involved in inflammation, which may play a role in aneurysm development. Unlike conventional treatments, infliximab offers a targeted approach by specifically addressing the inflammatory component of the disease. ^{6 7 8 9 10}

What data supports the effectiveness of the drug infliximab for treating aneurysms?

Infliximab has shown effectiveness in treating conditions like Crohn's disease and rheumatoid arthritis by reducing symptoms and slowing disease progression. It has also been used in patients with Takayasu arteritis, a condition affecting blood vessels, which may suggest potential benefits for vascular-related issues like aneurysms. ^{9 11 12 13 14}

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.

Any medical condition, which, in the opinion of the investigator, would put the subject at risk by participation in the protocol

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

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]

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]

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]

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]

Citations

1. England 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. [2019]

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

Effectiveness and safety of infliximab dose escalation in patients with refractory Takayasu arteritis: A real-life experience from a monocentric cohort. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Spotlight on infliximab in Crohn disease and rheumatoid arthritis. [2018]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Infliximab: a review of its use in Crohn's disease and rheumatoid arthritis. [2018]

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

Efficacy and safety of TNF-α antagonists and tocilizumab in Takayasu arteritis: multicentre retrospective study of 209 patients. [2022]

6. Canada pubmed.ncbi.nlm.nih.gov

Long term safety of infliximab. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Prescribing patterns and awareness of adverse effects of infliximab: a health survey of gastroenterologists. [2018]

8. Spain pubmed.ncbi.nlm.nih.gov

[Brachial plexitis and myelitis and herpes-zoster lumbar plexus disorder in patient treated with infliximab]. [2015]

9. Korea (South) pubmed.ncbi.nlm.nih.gov

Infliximab Treatment for Intravenous Immunoglobulin-resistant Kawasaki Disease: a Multicenter Study in Korea. [2020]

10. Japan pubmed.ncbi.nlm.nih.gov

[Anti TNF-α (infliximab) treatment for intravenous immunoglobulin (IVIG) resistance patients with acute Kawasaki disease the effects of anticytokine therapy]. [2015]

11. Turkey pubmed.ncbi.nlm.nih.gov

Ameliorating the effects of Adalimumab on rabbits with experimental cerebral vasospasm after subarachnoid hemorrhage. [2021]

12. Italy pubmed.ncbi.nlm.nih.gov

Refractory Takayasu's arteritis successfully treated with the human, monoclonal anti-tumor necrosis factor antibody adalimumab. [2015]

13. Germany pubmed.ncbi.nlm.nih.gov

Takayasu's arteritis progression on anti-TNF biologics: a case series. [2021]

14. Italy pubmed.ncbi.nlm.nih.gov

Refractory Takayasu arteritis successfully treated with infliximab. [2022]