Effect of Subcutaneous ACTEMRA on Inflamed Atherosclerotic Plaques in Patients With Rheumatoid Arthritis

NCT02659150 | Terminated Phase 4 Results FDA Drug

• 1 other identifier: ML29520
• Study Type: interventional
• Target: 16
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to test the hypothesis that anti-IL-6 therapy is effective for reducing plaque inflammation as measured by fluorine-2-deoxy-D-glucose positron emission tomography (FDG-PET) in patients with rheumatoid arthritis (RA) who are synthetic disease-modifying antirheumatic drugs (dMARD) inadequate responders and are naive to biologic therapy.

Conditions

Rheumatoid Arthritis

Keywords

tocilizumab; subcutaneous injection; rheumatoid arthritis; plaque inflammation; atherosclerotic plaque; joint inflammation; FDG-PET; PET-MR; ACTEMRA

Outcome Measures

Primary Outcomes (1)

• Change in Arterial Inflammation in the Carotids

  The change in the target-to-background ratio of FDG uptake of the carotid, measured on PET-MR imaging before vs after 12 weeks of tocilizumab treatment. FDG uptake is calculated as Target to background values (TBR) . TBR, in turn, is calculated as the mean arterial standardized uptake value (SUV) divided by background blood pool SUV.

  Baseline and 13-18 weeks follow-up

Secondary Outcomes (5)

• Association Between Change in Arterial Inflammation and Change in Articular Inflammation

  Baseline and 13-18 weeks follow-up

• Change in Target to Background Ratio Within Carotid Artery Plaques

  Baseline and 13-18 weeks follow-up

• Association Between Change in Arterial Inflammation and Change in LDL

  Baseline and 13-18 weeks follow-up

• Association Between Change in Arterial Inflammation and Change in CRP

  Baseline and 13-18 weeks follow-up

• Correlation Between Change in BOLD Signals in the Amygdala and Anterior Cingulate Cortex With Atherosclerotic Plaque FDG Uptake

  Baseline to 13-18 weeks follow-up

Study Arms (1)

Open-Label tocilizumab

OTHER

tocilizumab will be given to rheumatoid arthritis patients at a dose of 162 mg subcutaneously a week

Drug: tocilizumab

Interventions

tocilizumab DRUG

subjects will be treated with 162mg of weekly subcutaneous tocilizumab in an open-label manner, this will be done addition to MTX or monotherapy. On subsequent weeks after the first dose of tocilizumab, subjects will be instructed to inject the full amount of syringe according to the directions provided in the Instructions For Use (IFU).

Also known as: ACTEMRA

Open-Label tocilizumab

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults aged 50-75
• Diagnosis of RA according to the revised 1987 American College of Rheumatology (ACR; formerly American Rheumatism Association), criteria.
• Patients who have had an inadequate response to non-biologic disease-modifying anti-rheumatic drug (DMARD) and are naïve to biologic agents.
• Presence of plaque inflammation, identified during secondary screening, defined as a target to baseline (TBR ratio) ≥ 1.7 in the carotid artery or ascending aorta.
• Not wheelchair or bedbound.
• At screening, active RA consisting of ≥4 swollen joints (28 joint count) and ≥ 4 tender joints (28 joint count) and any one of the following criteria:
• Erythrocyte sedimentation rate (ESR) (Westergren) ≥ upper limit normal
• CRP ≥ upper limit normal
• If using other non-biologic DMARDS, (ex: methotrexate, sulfasalazine, hydroxychloroquine, azathioprine, cyclosporine, leflunomide), patient must demonstrate inadequate response, be on stable dose(s) for at least 4 weeks prior to baseline visit. For methotrexate: patients must be on methotrexate for at least 3 months with 4 weeks stable dose, and will stay on stable dose during the study.
• taking corticosteroids, must be on stable doses of oral corticosteroids (≤ 10mg/day prednisone or equivalent) for at least 4 weeks prior to the baseline visit. Dose should remain stable throughout the study.
• Any investigational treatment not mentioned elsewhere must be discontinued for 4 weeks or 5 half lives, whichever is longer, prior to the baseline visit. Exposure to any investigational biologics should be discussed with the Sponsor.
• Signed informed consent (and informed assent of minor, if applicable).
• Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for twelve months after completion of treatment.
• Subject has provided written informed consent

You may not qualify if:

• Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization.
• Treatment with any investigational agent within 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of screening.
• Previous treatment with any cell-depleting therapies, including investigational agents or approved therapies, some examples include: CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19 and anti-CD20.
• Treatment with intravenous gamma globulin, plasmapheresis or Prosorba column within 6 months of baseline.
• Immunization with a live/attenuated vaccine within 4 weeks prior to baseline.
• Previous treatment with TCZ or other biologics (an exception to this criterion may be granted for single dose exposure upon application to the PI on a case-by-case basis).
• Any previous treatment with alkylating agents such as chlorambucil, or with total lymphoid irradiation.
• Currently taking a statin
• An intra-articular injection of steroids within 6 weeks of imaging
• History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies.
• Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (include uncontrolled diabetes mellitus) or gastrointestinal disease (including complicated diverticulitis, ulcerative colitis, Crohn's disease, or other symptomatic lower GI conditions that might predispose to perforations.)
• Diagnosis of liver disease or elevated hepatic enzymes, as defined by ALT, AST, or both \> 1.5 x the upper limit of age-determined normal (ULN) or total bilirubin \> ULN.
• Serum creatinine \> 1.6 mg/dL (141 µmol/L) in female patients and \> 1.9 mg/dL (168 µmol/L) in male patients. Patients with serum creatinine values exceeding limits may be eligible for the study if their estimated glomerular filtration rates (GFR) are \>30
• Any history of recent serious bacterial, viral, fungal, mycobacterial or other opportunistic infections.
• Have serologic evidence of current or past HIV, Hepatitis B, or Hepatitis C.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Brigham and Women's Hospital: collaborator
• Genentech, Inc.: collaborator

MeSH Terms

Conditions

Arthritis, Rheumatoid; Plaque, Atherosclerotic; Arthritis

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Ahmed Tawakol, MD
• Organization: Massachusetts General Hospital

atawakol@mgh.harvard.edu

617-724-3699

Study Officials

• Ahmed Tawakol, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Nuclear Cardiology

Study Record Dates

• First Submitted: December 21, 2015
• First Posted: January 20, 2016
• Study Start: May 18, 2016
• Primary Completion: November 16, 2019
• Study Completion: November 16, 2019
• Last Updated: February 23, 2021
• Results First Posted: February 23, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share