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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02659150
• Date of registration: 21/12/2015
• Prospective Registration: Yes
• Primary sponsor: Massachusetts General Hospital
• Public title: Effect of Subcutaneous ACTEMRA on Inflamed Atherosclerotic Plaques in Patients With Rheumatoid Arthritis
• Scientific title: A Multicenter, Open-Label, Proof-of-Activity Study of the Effect of Subcutaneous ACTEMRA on Inflamed Atherosclerotic Plaques in Patients With Rheumatoid Arthritis
• Date of first enrolment: May 18, 2016
• Target sample size: 21
• Recruitment status: Unknown status
• URL: https://clinicaltrials.gov/show/NCT02659150
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 4

Contacts

• Name: Ahmed Tawakol, MD
• Affiliation: Massachusetts General Hospital

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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

Exclusion Criteria:

- 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

Exclusions for General Safety:

- 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.

- Positive QuantiFERON TB test , history of tuberculosis, or active TB infection without
at least 4 weeks of adequate therapy for TB.

- Active infection with EBV as defined by EBV viral load = 10,000 copies per mL of whole
blood.

- Active infection with CMV as defined by CMV viral load = 10,000 copies per mL of whole
blood.

- Any of the following hematologic abnormalities, confirmed by repeat tests:

- White blood count <3,000/µL or >14,000/µL;

- Lymphocyte count <500/µL;

- Platelet count <100,000 /µL;

- Hemoglobin <8.0 g/dL; or

- Neutrophil count <2,000 cells/µL.

- Any major episode of infection requiring hospitalization or treatment with IV
antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to
screening.

- Primary or secondary immunodeficiency (history of or currently active) unless related
to primary disease under investigation.

- Any medical or psychological condition that in the opinion of the principal
investigator would interfere with safe completion of the trial.

- History of other malignancy within 5 years prior to screening, except for
appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or
Stage I uterine cancer.

- Pregnant women or nursing (breast feeding) mothers.

- Patients with reproductive potential not willing to use an effective method of
contraception.

- History of alcohol, drug or chemical abuse within 1 year prior to screening.

- Neuropathies or other conditions that might interfere with pain evaluation unless
related to primary disease under investigation.

- Rheumatic autoimmune disease other than RA, including SLE, MCTD, scleroderma,
polymyositis, or significant systemic involvement secondary to RA (e.g., vasculitis,
pulmonary fibrosis or Felty's Syndrome). Secondary Sjogrens syndrome with RA is
allowable.

- Prior history of, or current inflammatory joint disease other than RA (e.g., gout,
Lyme disease, seronegative spondyloarthropathy including reactive arthritis, psoriatic
arthritis, arthropathy of inflammatory bowel disease).

- Relatively significant radiation exposure over th


Age minimum: 50 Years
Age maximum: 75 Years
Gender: Female

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis

Intervention(s)

Drug: tocilizumab

Primary Outcome(s)

Change in arterial FDG uptake (on FDG PET) from baseline to post-treatment [Time Frame: 13-18 weeks]

Secondary Outcome(s)

change in FDG uptake within joints [Time Frame: 13-18 weeks]

fMRI signal in amygdala [Time Frame: 13-18 weeks]

LDL [Time Frame: 13-18 weeks]

Change in arterial FDG uptake within atherosclerotic plaque in carotid/aortic arteries, from baseline to post-treatment [Time Frame: 13-18 weeks]

Secondary ID(s)

ML29520

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Brigham and Women's Hospital