Etanercept in Rheumatoid Arthritis and Vascular Inflammation

NCT02109289 | Terminated Phase 4

• 1 other identifier: Inno-6032
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

The primary goal of this preliminary project is to study the effect of etanercept, a medicine approved by Health Canada for the treatment of rheumatoid arthritis, on the inflammation of certain blood vessels. In particular, the inflammation of the aorta and the carotid arteries will be studied. This study's goal is to determine if etanercept (that blocks TNF (tissue necrosis factor) alpha) could have an effect on blood vessel inflammation. As well, the information from this study will be used to determine the number of patients to recruit in a future study. This study will evaluate the effect of etanercept on 10 patients with rheumatoid arthritis at one rheumatology clinic in Montreal. The 10 patients will be recruited at the Montreal Rheumatology Institute (Institut de Rhumatologie de Montréal) and the images of the blood vessels taken at a medical imaging center will be analyzed by the Montreal Heart Institute. To evaluate vascular inflammation subjects will undergo a PET scan (Positron Emission Tomography).

Conditions

Rheumatoid Arthritis; Vascular Inflammation

Keywords

Anti-Tumor necrosis factor alpha; 18-FluoroDeoxyGlucose Positron Emission Tomography; High-sensitivity C- Reactive protein

Outcome Measures

Primary Outcomes (1)

• Target to background ratio (TBR) from the ascending aorta

  Change from baseline in target (atherosclerotic plaque) to background (blood) ratio (TBR) from the ascending aorta.

  16 weeks

Secondary Outcomes (7)

• TBR from the mean of both carotid arteries

  16 Weeks

• High Sensitivity C-reactive protein (hsCRP)

  16 weeks

• Count of swollen and tender joints

  16 weeks

• Correlation of TBR from the ascending aorta with hsCRP

  16 weeks

• Correlation of TBR from the mean of both carotid arteries with hsCRP

  16 weeks

Other Outcomes (3)

• Duration of recruitment and recruitment rate

  Day 0

• Screen failure rate

  Day 0

• Attrition rate

  Week 16

Study Arms (1)

Methotrexate and Etanercept

EXPERIMENTAL

Patients already taking Methotrexate prior to the study will continue taking 15 mg weekly and start Etanercept 50 mg every week for 16 weeks

Drug: etanercept

Interventions

etanercept DRUG

Etanercept is a tumor necrosis factor antagonist

Also known as: Enbrel

Methotrexate and Etanercept

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient is 18 to 80 years of age, inclusive.
• Patient's weight at screening is a maximum of 180 kg.
• Patient has a clinical diagnosis of active RA for at least 3 months defined as:
• joints with active synovitis OR
• joint with active synovitis and a high sensitivity C-reactive protein higher than the upper limit.
• Patient with active synovitis despite treatment for at least 3 months with a dose of methotrexate of at least 15 mg per week.
• Patient is eligible to receive etanercept according to Canadian Product Monograph.
• Medications used to control angina, hypertension, serum lipids and any medication that can have an effect on inflammation must be on a stable dose for at least 8 weeks before baseline.
• Patient with an ascending aorta atherosclerotic plaque inflammation target-to-background ratio of 1.6 or more as determined by 18-FDG uptake measured by PET scanning at pre-enrolment.
• Female patients of childbearing potential must have a negative serum pregnancy test at the Screening visit.
• Unless patient or patient's partner is in a menopausal state for at least a year, surgically sterile (hysterectomy, bilateral oophorectomy, tubal ligation or vasectomy), clinically diagnosed infertile, having a same-sex partner or abstinent,female of childbearing potential or male patient (or his female partner of childbearing potential) is willing to use effective contraceptive method for at least 30 days before Day 0 and at least 4 weeks after the last study drug administration. Effective contraceptive methods are:
• Barrier methods such as condom, sponge or diaphragm combined with spermicide in foam, gel or cream
• Hormonal contraception (oral, intramuscular, implant or transdermal) which include Depo-Provera, Evra and Nuvaring. Oral contraceptives must have been taken at a stable dose for at least 90 days before study start
• Intrauterine device (IUD).
• If result not available in the last 6 months: Patient will be evaluated for latent TB infection with a PPD (Purified Protein Derivative (Mantoux test)) or a Quantiferon Gold test and CXR (chest x-ray).

You may not qualify if:

• Patient has a history of an allergic reaction or significant sensitivity to constituents of study drug (etanercept), including latex (a component of the pre-filled syringe).
• Patient has chronic or recurrent infection or history of listeriosis, histoplasmosis or any other invasive fungal or mycobacterial infections, treated or untreated Tuberculosis (TB), persistent chronic infections, or recent active infections requiring hospitalization or treatment with intravenous anti-infectives drug within 30 days prior to the Day 0 visit or oral anti-infectives within 14 days prior to the Day 0 visit.
• Patient used any non-biological investigational agents within 30 days or 5 half-lives prior to Day 0 visit (whichever is longer).
• Patient who has used any biological therapy for the treatment of RA less than 3 months (90 days) or 5 half-lives prior to Day 0 visit (whichever is longer) or patient has received Anakinra/Kineret within the last 2 weeks prior to the Day 0 visit or is likely to receive Anakinra/Kineret during the course of the study.
• Patient has used a non-biological systemic therapy for the treatment of RA less than 30 days before Day 0, other than methotrexate.
• Patient is taking or requires oral or injectable corticosteroids at a dose equivalent to more than 5 mg of prednisone daily within 30 days of Day 0 and during the study. Inhaled corticosteroids for stable medical conditions are allowed. Patients taking oral or injectable corticosteroids must be on a stable dose for at least 3 months before Day 0.
• Patient for whom the treating physician is planning to change the dose of methotrexate or oral corticosteroids during the study.
• Patient has used a systemic immunosuppressor (eg. Azathioprine, 6-mercaptopurine) less than 30 days before Day 0.
• Patient who has another musculoskeletal disease that could interfere with or prevent with joint examination
• Patient who had a myocardial infarction or hospitalization for a cardiac condition within the past 12 weeks.
• Patient has a pacemaker or a defibrillator.
• Patient who has a history of acute coronary syndrome, percutaneous coronary intervention, coronary artery dilatation bypass graft, coronary revascularization, carotid endarterectomy, stent installation or carotid revascularization within 12 weeks of baseline.
• Patient for whom a change in medical treatment for angina, serum lipids, hypertension or any other medication that can have a significant effect on inflammation is planned for the duration of the study.
• Patient with active or chronic Hepatitis B and /or Hepatitis C.
• Patient has a known sero-positivity for HIV virus or with or at risk of sepsis syndrome or history of any other immunosuppressive disease.

Sponsors & Collaborators

• Innovaderm Research Inc.: lead

Study Sites (1)

Institut de rhumatologie de Montreal

Montreal, Quebec, H2L 1S6, Canada

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Etanercept

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Immunoglobulin Constant Regions; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins

Study Officials

• Boulos Haraoui, MD

  Institut de Rhumatologie de Montreal

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2014
• First Posted: April 9, 2014
• Study Start: April 1, 2014
• Primary Completion: November 1, 2016
• Study Completion: November 1, 2016
• Last Updated: February 7, 2017

Record last verified: 2017-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)