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Stand UP to Rheumatoid Arthritis (SUPRA) (SUPRA)

Primary Purpose

Rheumatoid Arthritis

Status
Recruiting
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
TNFi
Anti-IL6
JAKi
Sponsored by
Marie Hudson, MD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Rheumatoid Arthritis focused on measuring Rheumatoid arthritis, Pragmatic trials, Feasibility

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age ≥ 18 years;
  • Arthritis that fulfills the 2010 ACR/EULAR classification criteria for RA;
  • Failure to standard conventional synthetic DMARDs and eligible for second-line b/tsDMARDs (Sub-study 1) or failure to at least one TNF inhibitor and eligible for third-line b/tsDMARDs (Sub-study 2).

Exclusion Criteria:

  • Prior b/tsDMARDs for Sub-study 1 or prior b/tsDMARDs other than TNF inhibitors for Sub-study 2;
  • Contraindication to b/tsDMARD therapy, such as active infection or untreated latent TB, current malignancy, severe organ dysfunction, history of VTE (unless anticoagulated), high risk of cardiovascular disease, pregnancy/lactation;
  • Overlap with another inflammatory disease requiring specific immunosuppressive therapy, such as lupus nephritis;
  • Unable to provide consent or complete forms (alone or with assistance) in English or French

Sites / Locations

  • Sir Mortimer B. Davis Jewish General HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Active Comparator

Active Comparator

Active Comparator

Arm Label

Sub-study 1 TNFi

Sub-study 1 Anti-IL6

Sub-study 2 Anti-IL6

Sub-study 2 JAKi

Arm Description

TNFi - any sub-cutaneous (sc) formulation, namely etanercept (receptor fusion protein), adalimumab (monoclonal antibody), golimumab (monoclonal antibody), or certolizumab (pegylated fragment of a monoclonal antibody)

Anti-IL6 receptor monoclonal antibodies - tocilizumab or sarilumab

Anti-IL6 receptor monoclonal antibodies - tocilizumab or sarilumab

JAKi - tofacitinib (JAK1/3 inhibitor), baricitinib (JAK 1/2 inhibitor) or upadacitinib (JAK1 inhibitor)

Outcomes

Primary Outcome Measures

Rate of recruitment at two RA referral centers over 12 months
Feasibility outcome
Prompt access to drugs
Feasibility outcome
Proportion of participants adhering to the allocated treatment
Feasibility outcome
Proportion of eligible patients who are invited to participate by their physician
Physician acceptability outcome
Proportion of eligible patients who accept to participate
Patient acceptability outcome
Proportion of patients reaching SDAI <= 3.3
Exploratory outcome
Proportion of patients reaching DAS28 LDA state
Exploratory outcome
Patient-reported outcomes (function, health-related quality of life, fatigue)
Exploratory outcome

Secondary Outcome Measures

Full Information

First Posted
February 26, 2022
Last Updated
February 2, 2023
Sponsor
Marie Hudson, MD
Collaborators
McGill University Health Centre/Research Institute of the McGill University Health Centre, Montreal General Hospital, Lady Davis Institute
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1. Study Identification

Unique Protocol Identification Number
NCT05305066
Brief Title
Stand UP to Rheumatoid Arthritis (SUPRA)
Acronym
SUPRA
Official Title
Innovative Trial Designs, Multi-omics and Advanced Computational Prediction to Transform Clinical Care in RA
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 1, 2023 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Marie Hudson, MD
Collaborators
McGill University Health Centre/Research Institute of the McGill University Health Centre, Montreal General Hospital, Lady Davis Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Rheumatoid arthritis is a disabling arthritis that affects young women disproportionately. Although the physicians have some excellent treatments, they do not know which treatment is best for which patient. The investigators want to find ways to identify the right drug for the right patient at the right time. This is what personalized medicine is all about.
Detailed Description
Rheumatoid arthritis (RA) is a complex, chronic disease of the immune system characterized by disfiguring and disabling arthritis. It affects predominantly women (3:1 ratio with men) and has its peak onset during their most productive years (ages 30-50). RA is associated with serious morbidity (including impaired fertility and pregnancy outcomes, disability, and depression) and premature mortality (particularly from cardiovascular and infectious causes). The Arthritis Alliance of Canada estimates that the cost of RA will exceed $30 billion in Canada in 2040. First-line treatment of RA consists of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) with methotrexate considered as the gold standard. Yet, only 30% of patients will achieve adequate response to methotrexate and the majority will need additional treatment. The development of new biologic and targeted synthetic DMARDs (b/tsDMARDs) in the 20th century has transformed the treatment of RA. Anti-tumour necrosis factor (TNF)-α molecules were the first clinically successful biologic therapies for RA. Drugs targeting other signaling pathways (JAK-STAT, which work downstream of interferons), inflammatory cytokines (IL-6), as well as B cells and T cells have now also become available. Molecules with novel targets (eg. GM-CSF, CD40L) are in clinical trials. Although hailed as 'game-changers' in patient care, the inconvenient truth is that even though nine different b/tsDMARDs are currently available to treat RA, 30% of patients will fail any particular drug. Moreover, physicians have no reliable way of predicting response and guiding treatment decisions. Clinical and genetic predictors have been the subject of intense research but these factors explain only a small portion of the observed variance in treatment response. Using the current trial-and-error approach, patients can cycle through multiple drugs before finally attaining disease control. This means months or years of suboptimal disease control and considerable losses in many domains including physical and emotional well-being, family and social networks, and occupational attainment. The lack of a personalized approach is particularly detrimental in RA because there is a narrow ''window of opportunity'' in the first 3-6 months of onset to control disease and optimize long term outcomes. In addition, failure to personalize treatment may also result in wasted spending on ineffective drugs, that cost up to $20,000 per patient per year, and exposing patients to unnecessary risks of adverse events, in particular serious infections. There is a critical need to 1) transform the current 'trial-and-error' treatment paradigm, 2) explore novel predictors of b/tsDMARD response in RA and, 3) harness the power of advanced analytical strategies to personalize treatment decision-making and optimize outcomes in RA. The investigators propose a multi-pronged solution that combines innovative trial designs, multi-omics and advanced computational prediction to transform clinical care in RA. The investigators propose to develop a new model of care and investigate new avenues, including sex and gender, diet, gut bacteria and environmental exposures, to make treatment decisions. The investigators will also use new methods of analyzing complex information. The highly talented research team has what is needed to transform the care of people living with RA. In preparation for a full-scale study, the investigators propose this feasibility study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
Rheumatoid arthritis, Pragmatic trials, Feasibility

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Two separate sub-studies will be conducted: Sub-study 1: Subjects who have failed conventional DMARDS will be randomised to receive therapy with TNFi or anti-IL6 using covariate adaptive randomization. Sub-study 2: Subjects who have failed TNFi will be randomised to receive therapy with anti-IL6 or JAKi using covariate adaptive randomization.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
75 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Sub-study 1 TNFi
Arm Type
Active Comparator
Arm Description
TNFi - any sub-cutaneous (sc) formulation, namely etanercept (receptor fusion protein), adalimumab (monoclonal antibody), golimumab (monoclonal antibody), or certolizumab (pegylated fragment of a monoclonal antibody)
Arm Title
Sub-study 1 Anti-IL6
Arm Type
Active Comparator
Arm Description
Anti-IL6 receptor monoclonal antibodies - tocilizumab or sarilumab
Arm Title
Sub-study 2 Anti-IL6
Arm Type
Active Comparator
Arm Description
Anti-IL6 receptor monoclonal antibodies - tocilizumab or sarilumab
Arm Title
Sub-study 2 JAKi
Arm Type
Active Comparator
Arm Description
JAKi - tofacitinib (JAK1/3 inhibitor), baricitinib (JAK 1/2 inhibitor) or upadacitinib (JAK1 inhibitor)
Intervention Type
Drug
Intervention Name(s)
TNFi
Other Intervention Name(s)
Etanercept, Adalimumab, Golimumab, Certolizumab
Intervention Description
TNFi - any sub-cutaneous (sc) formulation, namely etanercept (receptor fusion protein) 50 mg sc per week, adalimumab (monoclonal antibody) 40 mg sc every 2 weeks, golimumab (monoclonal antibody) 50 mg sc every month, or certolizumab (pegylated fragment of a monoclonal antibody) 400 mg sc at week 0, 2 and 4, and then 200 mg sc every 2 weeks or 400 mg sc every 4 weeks.
Intervention Type
Drug
Intervention Name(s)
Anti-IL6
Other Intervention Name(s)
Tocilizumab, Sarilumab
Intervention Description
Anti-IL6 receptor monoclonal antibodies - tocilizumab (if weight <100 kg: 162 mg SC every other week, followed by an increase to weekly based on clinical response; if weight ≥100 kg: 162 mg SC weekly) or sarilumab (200 mg SC once every 2 weeks)
Intervention Type
Drug
Intervention Name(s)
JAKi
Other Intervention Name(s)
Tofacitinib, Upadacitinib, Baricitinib
Intervention Description
JAKi - tofacitinib (JAK1/3 inhibitor) 5 mg po bid, baricitinib 2 mg po qd (JAK 1/2 inhibitor) or upadacitinib 15 mg po qd (JAK1 inhibitor)
Primary Outcome Measure Information:
Title
Rate of recruitment at two RA referral centers over 12 months
Description
Feasibility outcome
Time Frame
12 months
Title
Prompt access to drugs
Description
Feasibility outcome
Time Frame
4 weeks
Title
Proportion of participants adhering to the allocated treatment
Description
Feasibility outcome
Time Frame
24 months
Title
Proportion of eligible patients who are invited to participate by their physician
Description
Physician acceptability outcome
Time Frame
12 months
Title
Proportion of eligible patients who accept to participate
Description
Patient acceptability outcome
Time Frame
12 months
Title
Proportion of patients reaching SDAI <= 3.3
Description
Exploratory outcome
Time Frame
24 months
Title
Proportion of patients reaching DAS28 LDA state
Description
Exploratory outcome
Time Frame
24 months
Title
Patient-reported outcomes (function, health-related quality of life, fatigue)
Description
Exploratory outcome
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥ 18 years; Arthritis that fulfills the 2010 ACR/EULAR classification criteria for RA; Failure to standard conventional synthetic DMARDs and eligible for second-line b/tsDMARDs (Sub-study 1) or failure to at least one TNF inhibitor and eligible for third-line b/tsDMARDs (Sub-study 2). Exclusion Criteria: Prior b/tsDMARDs for Sub-study 1 or prior b/tsDMARDs other than TNF inhibitors for Sub-study 2; Contraindication to b/tsDMARD therapy, such as active infection or untreated latent TB, current malignancy, severe organ dysfunction, history of VTE (unless anticoagulated), high risk of cardiovascular disease, pregnancy/lactation; Overlap with another inflammatory disease requiring specific immunosuppressive therapy, such as lupus nephritis; Unable to provide consent or complete forms (alone or with assistance) in English or French
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Marie Hudson, MD
Phone
514-340-8222
Ext
23476
Email
marie.hudson@mcgill.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marie Hudson, MD
Organizational Affiliation
Sir Mortimer B. Davis - Jewish General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sir Mortimer B. Davis Jewish General Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marie Hudson, MD MPH
Phone
1-514-340-8222
Ext
23476
Email
marie.hudson@mcgill.ca

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Participants' study information and biological samples may be shared with researchers at this institution or other institutions for genetic, immunological, and other analyses (e.g. microbiome sequencing, biomarkers analyses, etc.).
IPD Sharing Time Frame
After 2025, for 3 years
IPD Sharing Access Criteria
The sharing of these samples will be done under specific research agreements; the samples and the data will be coded and confidentiality strictly protected.
Citations:
PubMed Identifier
25956159
Citation
Loudon K, Treweek S, Sullivan F, Donnan P, Thorpe KE, Zwarenstein M. The PRECIS-2 tool: designing trials that are fit for purpose. BMJ. 2015 May 8;350:h2147. doi: 10.1136/bmj.h2147. No abstract available.
Results Reference
background

Learn more about this trial

Stand UP to Rheumatoid Arthritis (SUPRA)

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