Infliximab treatment for dolichoectatic vertebrobasilar aneurysms

Infliximab Therapy for Dolichoectactic Vertebrobasilar Aneurysms

This trial will test whether infliximab, a TNFα blocker, can slow aneurysm growth or reduce complications in adults with dolichoectatic vertebrobasilar aneurysms who are not candidates for surgery.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 8 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of California, San Francisco (Academic / other)
• Drugs / interventions: rituximab, tocilizumab, infliximab
• Locations: 1 site (San Francisco, California)
• Trial ID: NCT02638701 on ClinicalTrials.gov

What this trial studies

This Phase 1/2 interventional trial at UCSF gives infliximab infusions to adults with dolichoectatic vertebrobasilar (DVB) aneurysms that cannot be treated microsurgically or endovascularly. Because DVB aneurysms are fusiform and often too large for clipping or coiling, participants will be followed with periodic brain imaging, neurological exams, and laboratory monitoring to track aneurysm size, ischemic or hemorrhagic events, and treatment safety. Key eligibility criteria include age over 18 and aneurysm anatomy not amenable to intervention, while exclusions include recent biologic therapy, positive tuberculosis testing, or significant blood, liver, or kidney abnormalities. The trial is small and primarily focused on safety, tolerability, and early signals of efficacy for a condition with very limited treatment options.

Who should consider this trial

Good fit: Adults (over 18) with vertebral and/or basilar dolichoectatic aneurysms that are not amenable to microsurgical or endovascular treatment and who meet laboratory and infection-screening criteria are ideal candidates.

Not a fit: Patients who recently received anti-TNF or other biologic agents, have active or latent tuberculosis, or have severe blood, liver, or kidney abnormalities are excluded and unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, infliximab could provide the first effective medical treatment to slow or halt growth and reduce stroke or brainstem compression risk in patients with DVB aneurysms who cannot undergo surgery.

How similar studies have performed: Preclinical studies show TNFα inhibition can prevent aneurysm growth and human data support vascular anti-inflammatory effects of infliximab, but using infliximab for DVB aneurysms is a novel and largely untested clinical approach.

Eligibility criteria

Inclusion Criteria:

1. Vertebral and/or basilar artery dolichoectactic aneurysm not amenable to microsurgical or endovascular treatment.
2. Age greater than 18 years at time of first study drug administration.

Exclusion Criteria:

1. Use of an anti-TNF or other biologic medication (Including but not limited to abatacept, rituximab, or tocilizumab) within the previous 12 months.
2. The following laboratory parameters at the Screening visit: Neutropenia (absolute neutrophil count \< 1,500/microliter; Thrombocytopenia (platelets \< 100,000/ • Anemia (hemoglobin \< 8 g/dL); Greater than or equal to 3 times the upper limit of normal (ULN) for either of the following liver function tests (LFTs): aspartate transaminase (AST) or alanine transaminase (ALT); Renal insufficiency (serum creatinine\> 2.0 mg/dL)
3. Purified protein derivative (PPD) test of \> 5 mm induration regardless of prior BacilleCalmette Guerin vaccine administration or positive QuantiFERON®-TB Gold In-Tube Test (QFT-G\_IT) without documentation of completed treatment or evidence of ongoing treatment of latent tuberculosis (TB) for 30 days. Subjects with active TB infection are excluded.
4. History of positive PPD, positive QuantiFERON®-TB Gold In-Tube Test (QFT-G\_IT), or chest x-ray findings indicative of prior TB infection, without documentation of either treatment for TB infection or chemoprophylaxis for TB exposure
5. Presence of open leg ulcers
6. Chronic or persistent infection including but not limited to human immunodeficiency virus \[HIV\], untreated hepatitis B, listeriosis, TB, or other opportunistic infection). Patients with hepatitis C but without evidence of cirrhosis or significant hepatic dysfunction will be considered for inclusion on a case-by-case basis as will patients with chronic hepatitis B on anti-viral therapy.
7. Active infection or severe infections requiring hospitalization or treatment with intravenous (IV) antibiotics, IV antivirals, or IV antifungals within 30 days prior to randomization, or oral antibiotics, oral antivirals, or oral antifungals within 14 days prior to randomization
8. Receipt of a live vaccine within 4 weeks prior to randomization
9. History of malignancy within the past 5 years other than treated localized carcinoma in situ of the cervix or adequately treated non-metastatic squamous or basal cell skin carcinoma
10. Any medical condition, which, in the opinion of the investigator, would put the subject at risk by participation in the protocol
11. Women of childbearing potential who are sexually active and who do not agree to practice one of the following methods of contraception during the duration of the study: condoms, sponge, foams, jellies, diaphragm or intrauterine device; oral or parenteral contraceptives for 2 months prior to study product administration; a vasectomized partner; abstinence.
12. Pregnant (all women of childbearing potential must have a negative serum pregnancy test) or breastfeeding
13. Any investigational agent within the earlier of 4 weeks or 5 half-lives prior to randomization
14. History of drug or alcohol abuse within 6 months prior to randomization
15. Known allergy or hypersensitivity to any study products
16. Any psychiatric disorder that prevents the subject from providing informed consent
17. Inability or unwillingness to follow the protocol.
18. Unable to undergo MR imaging.

Where this trial is running

San Francisco, California

• UCSF Medical Center — San Francisco, California, United States (Recruiting)

Study contacts

• Principal investigator: Daniel L Cooke, MD — University of California, San Francisco
• Study coordinator: Daniel L Cooke, MD

Conditions Aneurysm; Stroke; Vasculitis; Tumor Necrosis Factor-alpha