Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

BIOTIPRA: BIOmarker-guided Treatment Decisions In Psoriatic and Rheumatoid Arthritis (BIOTIPRA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03853395
Recruitment Status : Recruiting
First Posted : February 25, 2019
Last Update Posted : November 13, 2020
Sponsor:
Information provided by (Responsible Party):
Dr. James Bluett, University of Manchester

Brief Summary:

TNFi drugs remain the most prescribed first-line biologics for patients with rheumatoid arthritis (RA) and Psoriatic Arthritis (PsA). However, up to 40% of RA patients fail to respond to TNFi treatment. One explanation of non-response is the development of anti-drug antibodies and low drug levels.

Studies have consistently shown that:

  1. Drug levels of monoclonal antibodies (e.g. adalimumab/certolizumab) and the presence of anti-drug antibodies in samples taken at 3 and 6 months correlate with 12 month response.
  2. Non-responders and those who develop anti-drug antibodies are less likely to receive concomitant methotrexate or, if they do receive it, are on lower doses than responder groups.

However, it has not been proven that knowing that a patient has low drug levels or anti-drug antibodies improves the outcome; neither has it been shown that introducing or increasing the dose of methotrexate would reduce the formation of anti-drug antibodies, thereby improving outcome. Observational data has revealed that RA non-responders, who exhibit adequate serum drug levels and no detectable anti-drug antibodies, have lower probability of response to another agent with the same mechanism of action (MOA). RA and PsA non-responders, who have low detectable serum trough levels and detectable anti-drug antibodies, may benefit in switching to a less immunogenic drug. The next essential step, therefore, is to prove that introducing these tests improves clinical outcome.

The proposed trial is a clinical feasibility trial with the aim to ensure a realistic assessment and capability to conduct the full clinical trial. Participants with RA or PsA, commencing adalimumab or certolizumab will be randomised to determine whether providing test results on trough drug levels and anti-drug antibodies at 4 weeks, 3 and 6 months to clinicians caring for patients with RA or PsA (n=15 patients) starting treatment with adalimumab/certolizumab, improves the course of disease activity, compared to standard care (n=15 patients). Clinicians will be provided with feedback and a treatment algorithm. The feasibility of the study will be assessed by a number of factors including evaluation of recruitment, attrition, data completeness and process evaluation.


Condition or disease Intervention/treatment Phase
Arthritis, Rheumatoid Arthritis, Psoriatic Diagnostic Test: Tests for drug levels and anti-drug antibodies Not Applicable

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: BIOmarker-guided Treatment Decisions In Psoriatic and Rheumatoid Arthritis: A Feasibility Study
Actual Study Start Date : May 31, 2019
Estimated Primary Completion Date : July 2022
Estimated Study Completion Date : August 2023


Arm Intervention/treatment
Active Comparator: Control Arm
Participants on this arm of the study will provide trough blood samples and complete participant questionnaires. Their research teams will return clinical information about them to the University of Manchester. Clinicians for this group of participants will not receive blood results (about drug levels or anti-drug antibodies) or treatment advice from the University of Manchester about their participant.
Diagnostic Test: Tests for drug levels and anti-drug antibodies
Measurement of drug levels and anti-drug antibodies will be undertaken using commercially available enzyme-linked immunosorbent assays (ELISAs) and/or radioimmunoassays

Experimental: Experimental Arm
Participants on this arm of the study will provide trough blood samples and complete participant questionnaires. Their research teams will return clinical information about them to the University of Manchester. Clinicians for this group of participants will receive blood results (about drug levels or anti-drug antibodies) or treatment advice from the University of Manchester about their participant. They will be able to act accordingly.
Diagnostic Test: Tests for drug levels and anti-drug antibodies
Measurement of drug levels and anti-drug antibodies will be undertaken using commercially available enzyme-linked immunosorbent assays (ELISAs) and/or radioimmunoassays




Primary Outcome Measures :
  1. 1. Power for full randomised controlled trial: Change in Disease Activity Score (DAS)-28 over 12 months [ Time Frame: through study completion, an average of 1 year ]
  2. 2. Process evaluation: Patient/care-giver opinion of measuring adalimumab/certolizumab drug levels and anti-drug antibodies with feedback using a specially adapted questionnaire [ Time Frame: through study completion, an average of 1 year ]
  3. 3. Process evaluation: Patient and care-giver opinion of process of research, including outcome measures measured by a specially adapted questionnaire [ Time Frame: through study completion, an average of 1 year ]
  4. 4. Process evaluation: fidelity and quality of trial implementation and success of recruitment strategy [ Time Frame: through study completion, an average of 1 year ]
    A mixed-methods process evaluation will explore the fidelity and quality of implementation through evaluation of missing and non-missing responses. To inform the decision to proceed to a full clinical trial evaluation will take place measuring intervention fidelity; recruitment time; uptake; patient acceptability; withdrawal rate; effect size; affordability; study period required; time required for drug measurement and patient perspectives.


Secondary Outcome Measures :
  1. 1. Change in Health Assessment Questionnaire (HAQ) measurement [ Time Frame: through study completion, an average of 1 year ]
  2. 2. Change in Short Form 36 (SF-36) [ Time Frame: through study completion, an average of 1 year ]
  3. 3. Change in SF-36 vitality subscale [ Time Frame: through study completion, an average of 1 year ]
  4. 4. Health Assessment Questionnaire Disability Index at 12 months [ Time Frame: through study completion, an average of 1 year ]
  5. 5. Change in pain Visual Analog Scale (VAS) [ Time Frame: through study completion, an average of 1 year ]
  6. 6. Percentage of patients with increase in MTX dose [ Time Frame: through study completion, an average of 1 year ]
  7. 7. Percentage of patients with reduction of anti-drug antibody formation [ Time Frame: through study completion, an average of 1 year ]
  8. 8. Percentage of patients who stop TNFi and experience disease flare within 12 months of recruitment [ Time Frame: through study completion, an average of 1 year ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with RA or PsA about to start therapy with adalimumab or certolizumab (n = 30 total)
  2. Age 18 and over, male or female
  3. Willing to take part in the study
  4. Patients who are taking part in either the BRAGGSS or OUTPASS study -

Exclusion Criteria:

  1. Patients unwilling or unable to take part in the study
  2. Pregnant women or nursing (breast feeding) mothers.
  3. Planned pregnancy within next 12 months.
  4. Scheduled surgery in the next 12 months or other pre-planned reasons for treatment discontinuation in the next 12 months.
  5. Contraindication to adalimumab or certolizumab according to the summary of product characteristics -

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03853395


Locations
Layout table for location information
United Kingdom
Centre for Musculoskeletal Research Not yet recruiting
Manchester, England, United Kingdom, M13 9PT
Contact: Sarah L Ashton, BSc    +44 (0)161 306 0539    sarah.ashton-2@manchester.ac.uk   
Contact: Rebecca Pad    +44 (0)7785695470    rebecca.pad@manchester.acuk   
Principal Investigator: James Bluett         
Hampshire Hospitals NHS Foundation Trust Recruiting
Basingstoke, Hampshire, United Kingdom, RG24 9NA
Contact: Chris Graver    01256 314002    Christine.Graver@hhft.nhs.uk   
Midlands Partnership NHS Foundation Trust Not yet recruiting
Stafford, Staffordshire, United Kingdom, ST16 3AG
Contact: Chantel-lea Grocott    01785 783180    chantel-lea.grocott@mpft.nhs.uk   
Leicester Royal Infirmary Recruiting
Leicester, United Kingdom, LE1 5WW
Contact: Louise Boyles    0116 2586772    louise.m.boyles@uhl-tr.nhs.uk   
Homerton University Hospital NHS Foundation Trust Recruiting
London, United Kingdom, E9 6SR
Contact: Cate Holbrook    0208 510 7412    catherine.holbrook@nhs.net   
Manchester University Hospitals NHS Foundation Trust Recruiting
Manchester, United Kingdom, M13 9WL
Contact: JoAnn Nicolson    0161 701 8538    JoAnn.Nicholson@mft.nhs.uk   
Northern Care Alliance NHS Group Recruiting
Manchester, United Kingdom, M5 5AP
Contact: Lorraine Lock    0161 778 2634    Lorraine.lock@pat.nhs.uk   
Torbay and South Devon NHS Foundation Trust Active, not recruiting
Torquay, United Kingdom, TQ2 7AA
Royal Wolverhampton NHS Trust Not yet recruiting
Wolverhampton, United Kingdom, WV10 0QP
Contact: Julie Edwards       julie.edwards26@nhs.net   
Sponsors and Collaborators
University of Manchester
Layout table for additonal information
Responsible Party: Dr. James Bluett, Chief Investigator, University of Manchester
ClinicalTrials.gov Identifier: NCT03853395    
Other Study ID Numbers: NHS001481
First Posted: February 25, 2019    Key Record Dates
Last Update Posted: November 13, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No person identifiable information (PII, as defined by the GDPR) will be made available to other researchers. Other bone fide may access other information upon request to Dr. James Bluett.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Arthritis
Arthritis, Rheumatoid
Arthritis, Psoriatic
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Spondylarthropathies
Spondylarthritis
Spondylitis
Spinal Diseases
Bone Diseases
Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases
Antibodies
Immunologic Factors
Physiological Effects of Drugs