Arthritis, Rheumatoid
Conditions
Brief summary
In this 12-month multi-center prospective, site-randomized, two-arm trial, approximately 318 biologic-naïve subjects with RA who are candidates for treatment intensification due to inadequate response to MTX monotherapy will be enrolled at up to 60 study sites.
Detailed description
To determine whether a strategy of Vectra DA guided care (Arm A), compared with usual care (Arm B), achieves non-inferior clinical outcomes while reducing the cost of treatment in patients with active RA and an inadequate response to MTX monotherapy.
Interventions
OTHERVectra DA
OTHERUsual Care
Sponsors
Crescendo Bioscience
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Subjects will be eligible to participate in the study if they meet all the following criteria: 1. Willing and able to sign an ICF 2. Age 18 to 80 years at enrollment 3. Meets the 2010 ACR/EULAR criteria and/or 1987 criteria for RA, as determined by a board-certified rheumatologist ≥3 months prior to enrollment 4. Received uninterrupted treatment with weekly MTX begun ≥3 months prior to enrollment, at a stable dose of ≥15 mg per week for at least 4 weeks prior to enrollment. A history of therapy with split dose oral MTX or parenteral MTX is acceptable only if the weekly MTX dose was always ≤20 mg/week during the 3 months prior to enrollment. 5. CDAI \>10 as assessed by the Investigator at screening 6. At least 3 swollen joints (SJC ≥3) and 3 tender joints (TJC ≥3) out of 28 joints as assessed by the Investigator at screening 7. Must be eligible for treatment intensification with non-biologic and biologic DMARDs 8. Documented evidence of seropositivity (RF and/or anti-CCP antibodies). Seronegative subjects are allowed if erosive disease attributable to RA is documented on X-rays.
Exclusion criteria
Subjects will be ineligible to participate in the study if they meet any of the following criteria: 1. Use of a non-biologic DMARD other than MTX within 3 months prior to enrollment 2. MTX administered SQ or as an oral split dose at \>20 mg/week any time during the 3 months prior to enrollment 3. Two or more DMARDs used in combination (i.e., concomitantly), including but not limited to: MTX, HCQ, SSZ, LEF, cyclosporine, azathioprine, gold or penicillamine any time prior to enrollment 4. Biologic DMARD or JAKi use any time prior to enrollment 5. Any contraindication to use of MTX, HCQ, LEF or biologic DMARDs 6. Opiate use during the 2 weeks prior to enrollment 7. Oral corticosteroids during the month prior to enrollment at a dosage \>10 mg/day prednisone (or equivalent) or at a non-stable dose ≤10 mg/day prednisone (or equivalent) 8. MTX intolerance prior to enrollment that limits its use 9. Inflammatory joint disease (other than RA) or any other systemic autoimmune disorder. (Osteoarthritis is not a basis for exclusion.) 10. Primary or secondary immunodeficiency 11. Active infection (excluding fungal infection of nail beds); or acute or chronic infection requiring hospitalization or treatment with parenteral systemic antibiotics within one month of enrollment or treatment with oral antibiotics within 2 weeks of enrollment 12. IA, intravenous or IM corticosteroids during the month prior to enrollment 13. Initiation or non-stable dosing of NSAIDs within 2 weeks prior to enrollment 14. Vectra DA testing within 3 months prior to enrollment 15. Live vaccine within 90 days of enrollment 16. Active substance abuse or psychiatric illness likely to interfere with protocol conduct 17. History of severe allergic or anaphylactic reaction to any monoclonal antibody therapy 18. Known infection with HIV (HIV testing will not be a requirement for trial entry); a past or current history of hepatitis B virus or hepatitis C virus infection 19. History of malignancy within the past five 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 20. Pregnancy or inadequate contraception in women of childbearing potential 21. Breast feeding or lactating 22. Medical, psychiatric, cognitive or other conditions that, in the opinion of the Investigator, may compromise the ability of the subject to understand the study information, to give informed consent, to comply with the trial protocol, or to complete the study 23. Presently enrolled in another clinical trial 24. Vectra DA score at screening that is outside the applicable range as required for subject enrollment Note: Screening for TB is not required for subjects participating in the study. If an Investigator is considering a subject for treatment with a biologic DMARD in the study, guidelines for TB screening need to be followed.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in DAS28 at Month 6 | Baseline to 6 months |
| Percentage of subjects using any biologic DMARD or JAK inhibitor to Month 6 | Baseline to 6 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of subjects with radiographic non-progression at 12 months | Baseline to 12 months | Radiographic non-progression will be defined as change in modified total Sharp score (ΔmTSS) ≤0.5 units from baseline to Month 12 |
| Percentage of subjects with ACR20 response at Month 6 | Baseline to 6 months | — |
| Total cost of RA-related treatment, in US dollars, at Month 12 | Baseline to 12 months | — |
| Total cost of RA-related treatment, in US dollars, at Month 6 | Baseline to 6 months | — |
| Change in HAQ-DI score at Month 6 | Baseline to 6 months | — |
Other
| Measure | Time frame |
|---|---|
| Change in HAQ-DI score at Month 12 | Baseline to 12 months |
| Percentage of subjects with SAE | Baseline to 12 months |
| Change in work productivity as measured by the WPS-RA at Month 6 | Baseline to 6 months |
| Change in work productivity as measured by the WPS-RA at Month 12 | Baseline to 12 months |
| Percentage of subjects with low disease activity (DAS28 <3.2) at Month 6 | Baseline to 6 months |
| Change in health related QOL as measured by SF-36 at Month 12 | Baseline to 12 months |
| Change in health related QOL as measured by EQ-5D-5L at Month 6 | Baseline to 6 months |
| Change in health related QOL as measured by EQ-5D-5L at Month 12 | Baseline to 12 months |
| Percentage of subjects Incremental cost-effectiveness ratio (ICER) in terms of cost per QALY gained at Month 12 | Baseline to 12 months |
| Change in health related QOL as measured by SF-36 at Month 6 | Baseline to 6 months |
| Percentage of subjects with low disease activity (DAS28 <3.2) at Month 12 | Baseline to 12 months |
| Percentage of subjects with EULAR response at Month 6 | Baseline to 6 months |
| Percentage of subjects with EULAR response at Month 12 | Baseline to 12 months |
| Percentage of subjects with ACR50 response at Month 6 | Baseline to 6 months |
| Percentage of subjects with ACR50 response at Month 12 | Baseline to 12 months |
| Change in mTSS at Month 12 | Baseline to 12 months |
Countries
United States
Contacts
Primary ContactDavid Chernoff, MD
Outcome results
None listed