Mechanistic Studies of B- and T-Cell Function in RA Patients Treated With TNF Antagonists, Tocilizumab, or Abatacept

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02353780
• Date of registration: 30/06/2013
• Prospective Registration: Yes
• Primary sponsor: Dr. Larry W. Moreland
• Public title: Mechanistic Studies of B- and T-Cell Function in RA Patients Treated With TNF Antagonists, Tocilizumab, or Abatacept MAZERATI
• Scientific title: Mechanistic Studies of B- and T-Cell Function in Rheumatoid Arthritis Patients Treated With TNF Antagonists, Tocilizumab, or Abatacept
• Date of first enrolment: March 2015
• Target sample size: 10
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT02353780
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Basic Science. Masking: Single (Outcomes Assessor).
• Phase: Phase 4

Countries of recruitment

United States

Contacts

• Name: Larry W. Moreland, MD
• Affiliation: University of Pittsburgh

Key inclusion & exclusion criteria

Inclusion Criteria:

- Diagnosis of RA by a physician as defined by the 1987 and/or 2010 ACR criteria.

- 18 years of age or less than or equal to 64 at the time of diagnosis of RA.

- RA Disease Activity CDAI > 10

- If using oral corticosteroids, must have been on stable dose (= 10 mg/day) for at
least 2 weeks prior to study drug initiation.

- PPD negative or if PPD positive documentation of therapy with INH for at least 1 month
prior to study initiation and negative chest x-ray.

- Must have been treated within the past year with either methotrexate (MTX),
leflunomide (LEF), hydrochloroquine (HCQ) and/or sulfasalazine (SSZ) for = 3 months.

- Prior or concurrent use of other oral DMARD therapy, including MTX, leflunomide, SSZ,
and HCQ, is permitted. Patients taking oral DMARDs must be on stable doses of DMARDs
for at least 4 weeks prior to study drug initiation. Subjects are not required to be
taking an oral DMARD.

Exclusion Criteria:

- Use of cyclophosphamide, penicillamine, cyclosporine A, tacrolimus or gold therapy is
not permitted in the 6 months prior to enrollment.

- Patients who are using or have used other biologic agents or tofacitinib concomitantly
or prior to this study

- History of active and/or chronic infection such as hepatitis, pneumonia,
pyelonephritis,herpetic infections or chronic skin infections and any active
opportunistic infection, including but not limited to evidence of active
cytomegalovirus, active Pneumocystis carinii, aspergillosis, histoplasmosis or
atypical mycobacterium infection.

- Active TB or evidence of latent TB (positive PPD skin test or a history of old or
latent TB on chest x-ray) without adequate therapy for TB.

- Pregnant or lactating women.

- Patients with current signs or symptoms of uncontrolled renal, gastrointestinal,
endocrine, pulmonary, cardiac, neurologic or cerebral disease.

- Diagnosis of liver disease or elevated hepatic enzymes, as defined by ALT, AST or both
>1.5 x the upper limit of normal (ULN) or total bilirubin > ULN.

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

1. White blood count < 3,000/µL or > 14,000/µL

2. Lymphocyte count <500/µL

3. Platelet count < 100,000/µL

4. Hemoglobin < 8.0 g/dL

5. Neutrophil count < 2,000 cells/µL

- Major surgery (including joint surgery) within 8 weeks prior to screening or planned
major surgery within 6 months following randomization.

- Immunization with a live/attenuated vaccine within 2 months prior to baseline or 3
months of last study visit.

- History of severe allergic or anaphylactic reactions to human, humanized, or murine
monoclonal antibodies

- 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

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

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



Age minimum: 18 Years
Age maximum: 64 Years
Gender: All

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis (RA)

Intervention(s)

Drug: Tocilizumab

Drug: Abatacept

Drug: TNF Antagonist (enbrel, humire, remicade, cimzia, symponi)

Primary Outcome(s)

Mechanistic Comparisons (Changes in Frequencies of Peripheral Blood Immune Cell Subsets Following Institution of a Subcutaneously Administered TNF Antagonist, Tocilizumab or Abatacept.) [Time Frame: 0 to 3 months]

Secondary Outcome(s)

DMARD Use [Time Frame: 3 month and 6 month]

Steroid Use [Time Frame: 3 month and 6 month]

Adherence [Time Frame: 3 month and 6 month]

Corticosteroid Use [Time Frame: 3 month and 6 month]

Reason for Discontinuation of Treatment [Time Frame: 3 month and 6 month]

Efficacy (CDAI) [Time Frame: 0 to 3 months]

Efficacy (DAS) [Time Frame: 3 month and 6 month]

Efficacy (EULAR) [Time Frame: 3 month and 6 month]

ACR20, 50, and 70 Response [Time Frame: 3 month and 6 month]

Secondary ID(s)

STUDY19040127

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Genentech, Inc.

Bristol-Myers Squibb

Results

• Results available: Yes
• Date Posted: 01/10/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02353780