Clinical trial NCT03631225: The Effect of Guided Care With Vectra Compared to Treatment as Usual in Patients With Rheumatoid Arthritis
Official title: Vectra InVolved Informed Decision Outcome Study (VIVID): A Prospective Randomized Controlled Trial Evaluating the Effect of Guided Care With Vectra Compared to Treatment as Usual in Patients With Rheumatoid Arthritis
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Rheumatoid Arthritis (RA)
Keywords: Rheumatoid Arthritis
Vectra
Radiographic Projections
Lead sponsor: Sequenom, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Laboratory Corporation of America
First posted: 2018-08-15
Enrollment: 1500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients diagnosed with active rheumatoid arthritis at pre-determined clinical sites

Brief summary: The goal of treating patients diagnosed with rheumatoid arthritis (RA) is to achieve remission or low disease activity and thereby prevent joint damage, loss of physical function, and disability. Optimal management requires regular assessment of disease activity, with treatment changes made as needed for optimal efficacy. Vectra is a blood serum test that looks at 12 biomarkers and produces a score on a scale of 1 to 100. The Vectra score has been shown to be the strongest predictor of risk for progression of disease. There is opportunity to gain more information about the utility of Vectra in a real-world clinical setting. This study will, therefore, evaluate the utility of Vectra for guiding treatment decisions and improving RA-related outcomes in comparison with usual care, which will not include Vectra testing. This study will enable a direct evaluation of the clinical benefit associated with using Vectra to guide treatment decisions in patients with RA.

Detailed description: Disease activity in RA can be assessed by physical examination, patient-reported outcomes (PROs) or laboratory tests. Joints counts and PROs are partly or entirely subjective. Their ability to support clinical assessment is limited in certain settings, including for RA patients with common comorbidities, such fibromyalgia, obesity, or depression, or with clinically uncertain inflammatory burden. It can be difficult to assess the origin of ongoing pain in such patients using clinical assessment alone. The two blood tests routinely used to assess RA disease activity, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), are objective but are in the normal range in more than half of RA patients with active disease, which reduces their negative predictive value and greatly limits their utility. These clinical and laboratory measures are variously combined in composite scores of RA disease activity, such as the 28-joint count Disease Activity Score (DAS28) or the Clinical Disease Activity Index (CDAI) which are not widely used in the US outside of clinical trials because complete, formal joint counts are time-consuming and composite scores pose logistic challenges in a busy clinic setting.

Radiographic progression (RP) is a validated endpoint accepted by the FDA for clinical trials that reflects RA-related damage to joints. It is associated with long-term disability. Optimal care requires that the risk of progression be reduced. Quantitative scoring of RP is performed only for clinical trials and is not used for assessing RP risk in clinical practice. Rheumatologists are generally not trained to score radiographs and they are very time-consuming to score, typically taking 20 or more minutes per patient for a skilled reader. However, they are a valuable scientific endpoint in that they serve as a valid proxy for long term damage and associated RA-related disability. Conventional clinical and laboratory-based measures of RA disease activity are weak predictors of RP, including among patients in clinical remission, where progression can still occur. Thus, an objective, convenient measure that reflects pathologically meaningful disease activity and predicts risk for progression is needed for optimal management of RA.

The multi-biomarker disease activity (MBDA) test, Vectra®, is an objective tool that combines serum concentrations of 12 biomarkers in a validated algorithm to produce a score on a scale of 1 to 100. The MBDA test was subsequently adjusted to account for the effects of age, sex, and leptin (a surrogate for adiposity) in patients with rheumatoid arthritis (RA). The Vectra score has been shown to be the strongest predictor of risk for RP, compared with conventional disease activity measures, including DAS28-CRP, CRP and the swollen joint count. In multivariate analyses, it was the only disease activity measure to independently predict RP. High Vectra scores (\>44) are associated with greatest risk for progression and low and moderate scores with very low risk. Across multiple studies, Vectra has a negative predictive value for progression of 93-97%, and in a meta-analysis, the relative risk for progression with a high Vectra score (5.1) is substantially greater than with a high DAS28-CRP (1.4) or high CRP (1.6). The predictive value of Vectra exists even when the Vectra score and clinical measures are discordant, which means that patients with high DAS28-CRP have little risk for RP when Vectra score is low and, conversely, patients with low DAS28-CRP have high risk for RP when Vectra score is high.

Thus, reducing high Vectra scores should be a primary goal of therapy, regardless of the level of clinical disease activity, and using Vectra scores to guide therapy should be an effective way to prevent radiographic progression. A recent prospective study of daily and diurnal variation in Vectra score established that the minimally important difference (MID) in Vectra score - i.e., the magnitude of change in Vectra score that is needed to be confident that it reflects real biologic change and is not due only to random variation - is greater than or equal to 8 Vectra units. Accordingly, a threshold of 8 can be used in guidances for using Vectra to evaluate treatment response.

The primary objective is to compare the clinical response from baseline to 12 months among patients with RA receiving Vectra-Guided care versus those receiving usual care.

The secondary objectives of this study are to:

* Evaluate the rate of radiographic progression from baseline to year 1 among patients with RA whose care is guided by Vectra relative to those receiving usual care.
* Evaluate changes in Vectra score from baseline to 6 months and baseline to year 1 among patients with RA whose care is guided by Vectra DA relative to those receiving usual care.
* Evaluate clinical response from baseline to 1 year among patients with RA receiving Vectra-guided care relative to those receiving usual care.

Eligibility criteria: Inclusion Criteria:

* ≥ 18 years old at screening visit
* Diagnosed with RA according to 1987 or 2010 criteria of the American College of Rheumatology
* At the time of the pre-baseline visit, patient has a CDAI score of \>10
* Currently taking one or more non-biologic or biologic DMARD at screening and for at least the 3 months prior to screening
* Visit at time of screening scheduled as part of routine care
* Subject and/or physician willing to consider treatment change at screening
* No expectation of imminent treatment change at screening or baseline visit

Exclusion Criteria:

* Currently taking an anti-IL-6R drug (tocilizumab, sarilumab)
* Any contraindication, administrative barrier, or financial limitation (e.g. no insurance coverage) that makes it impossible for subject to receive at least one new biologic or JAKi therapy for RA
* Active infection
* History of malignancy within the past 5 years or any evidence of persistent malignancy, except fully excised basal cell or squamous cell carcinomas of the skin, or cervical carcinoma in situ that has been treated or excised in a curative procedure
* Current enrollment in another clinical trial
* Any condition or circumstance that makes it likely the patient will not be able to complete the trial

Primary outcomes:
measure: ACR20 response at 12 months
timeFrame: Baseline visit to 12 months
Secondary outcomes:
measure: Radiographic progression at 1 year
timeFrame: Baseline to 12 months (1 year)
measure: Change in Vectra score
timeFrame: Baseline to 6 months, and baseline and 12 months (1 year)
measure: ACR20 response at 6 months
timeFrame: Baseline to 12 months (1 year)
Other outcomes:
measure: Exploring a change in the definition of non-progression less than or equal to 5
timeFrame: Baseline to 12 months (1 year)
measure: Exploring a change in the definition of non-progression less than or equal to 3
timeFrame: Baseline to 12 months (1 year)
measure: Change in physical function measured by HAQ-D1
timeFrame: Baseline to 12 months (1 year)
measure: Change in clinical disease activity measured by Patient Reported Outcomes Measurement Information System (PROMIS)
timeFrame: Baseline to 12 months (1 year)
measure: Change in physical function measured by PROMIS
timeFrame: Baseline to 12 months (1 year)
measure: Change in clinical disease activity measured by RAPID3
timeFrame: Baseline to 12 months (1 year)
measure: Change in clinical disease activity measured by CDAI
timeFrame: Baseline to 12 months (1 year)
measure: Change in clinical disease activity measured by SDAI
timeFrame: Baseline to 12 months (1 year)
measure: Change in clinical disease activity measured by DAS28-CRP
timeFrame: Baseline to 12 months (1 year)
measure: The frequency of changes in RA medications [non-biologic, biologic, or targeted synthetic disease modifying anti-rheumatic drugs (DMARDs)]
timeFrame: Baseline to 12 months (1 year)
Locations:
city: La Mesa
country: United States
facility: Bio Solutions Clinical Research
state: California
city: Murrieta
country: United States
facility: Brigid Freyne, MD
state: California
city: Orange
country: United States
facility: J. Lee MD Medical Corp
state: California
city: Lewes
country: United States
facility: Delaware Arthritis
state: Delaware
city: Aventura
country: United States
facility: AARDS Research, Inc.
state: Florida
city: Clearwater
country: United States
facility: Robert W. Levin, MD, PA
state: Florida
city: Miami
country: United States
facility: Artemisa Analytics
state: Florida
city: Orlando
country: United States
facility: Rheumatology Associates of Central Florida, P.A.
state: Florida
city: South Miami
country: United States
facility: Clin-Med Research & Development, LLC
state: Florida
city: Lake Charles
country: United States
facility: Accurate Clinical Research
state: Louisiana
city: Monroe
country: United States
facility: Arthritis and Diabetes Clinic, Inc.
state: Louisiana
city: Tupelo
country: United States
facility: North Mississippi Medical Center
state: Mississippi
city: Springfield
country: United States
facility: Clinvest Research, LLC.
state: Missouri
city: Smithtown
country: United States
facility: Rheumatology Associates of Long Island
state: New York
city: Middleburg Heights
country: United States
facility: Paramount Medical Research & Consulting, LLC
state: Ohio
city: Wheelersburg
country: United States
facility: Southern Ohio Rheumatology Inc.
state: Ohio
city: Bethlehem
country: United States
facility: East Penn Rheumatology Associates, P.C.
state: Pennsylvania
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research
state: Pennsylvania
city: Wexford
country: United States
facility: Advanced Rheumatology & Arthritis Research Center, PC
state: Pennsylvania
city: Wyomissing
country: United States
facility: PA Regional Center for Arthritis and Osteoporosis Research
state: Pennsylvania
city: Myrtle Beach
country: United States
facility: Carolina Health Specialists
state: South Carolina
city: Baytown
country: United States
facility: Accurate Clinical Research
state: Texas
city: Cypress
country: United States
facility: Pioneer Research Solutions, Inc
state: Texas
city: Houston
country: United States
facility: Accurate Clinical Research
state: Texas
city: Sherman
country: United States
facility: CardioVoyage
state: Texas
city: Chesapeake
country: United States
facility: Center for Arthritis and Rheumatic Diseases, P.C.
state: Virginia
city: Manassas
country: United States
facility: Arthritis and Osteoporosis Center of Northern Virginia
state: Virginia
city: Suffolk
country: United States
facility: Center for Arthritis and Rheumatic Diseases., P.C.
state: Virginia
city: Spokane
country: United States
facility: Arthritis Northwest, PLLC
state: Washington
city: Franklin
country: United States
facility: Aurora Rheumatology and Immunotherapy Center
state: Wisconsin
Study officials:
affiliation: Consultant
name: Elena Hitraya, MD
role: STUDY_DIRECTOR
affiliation: University of Alabama at Birmingham
name: Jeffrey R. Curtis, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: