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Trial registered on ANZCTR


Registration number
ACTRN12622000032752
Ethics application status
Approved
Date submitted
30/11/2021
Date registered
14/01/2022
Date last updated
30/11/2023
Date data sharing statement initially provided
14/01/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
A phase 4, single-arm, open-label treatment, descriptive study of upadacitinib effectiveness assessed by magnetic resonance imaging (MRI) changes in the hand/wrist and clinical response outcomes in participants with rheumatoid arthritis on methotrexate and who are biologic naïve.
Scientific title
A phase 4, single-arm, open-label treatment, descriptive study of upadacitinib effectiveness assessed by magnetic resonance imaging (MRI) changes in the hand/wrist and clinical response outcomes in participants with rheumatoid arthritis on methotrexate and who are biologic naïve.
Secondary ID [1] 305936 0
Protocol number: ER-AV-UPARA-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
rheumatoid arthritis 324528 0
Condition category
Condition code
Inflammatory and Immune System 321995 321995 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Upadacitinib 15mg oral tablet, once per day for 24 weeks of treatment. No dose modifications will be made. Single-arm and open-label.

Compliance will be checked using compliance calculations throughout the trial at clinic visits.
Intervention code [1] 322328 0
Treatment: Drugs
Comparator / control treatment
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 329752 0
To describe the MRI findings using RAMRIS score in the chosen hand/wrist in participants with rheumatoid arthritis on a stable background of methotrexate who are starting upadacitinib treatment.
Timepoint [1] 329752 0
MRI findings (synovitis, tenosynovitis, osteitis) in the chosen hand/wrist from screening to the MRI findings in the chosen hand/wrist at weeks 2, 6, 12 and 24 in patients with rheumatoid arthritis on a stable background of methotrexate who are starting upadacitinib treatment. The improvement beyond the smallest detectable difference (SDD), which is calculated on the intra-observer reliability score, is regarded as true change and will be stated as raw scores.
Secondary outcome [1] 403661 0
To describe the change in the number of tender joints in participants with rheumatoid arthritis on a stable background of methotrexate who are starting upadacitinib treatment.

This will be assessed by in-person tender joint count examination by qualified staff staff.
Timepoint [1] 403661 0
To describe the change in tender joints from baseline to the number of tender joints at weeks 2, 6, 12 and 24 in patients with rheumatoid arthritis on a stable background of methotrexate who are starting upadacitinib treatment.
Secondary outcome [2] 404207 0
To describe the change in the number of swollen joints in participants with rheumatoid arthritis on a stable background of methotrexate who are starting upadacitinib treatment.

This will be assessed by in-person swollen joint count examination by qualified staff staff.
Timepoint [2] 404207 0
To describe the change in swollen joints from baseline to the number of swollen joints at weeks 2, 6, 12 and 24 in patients with rheumatoid arthritis on a stable background of methotrexate who are starting upadacitinib treatment.
Secondary outcome [3] 404208 0
To describe the change in participant reported outcomes Patient Global Assessment (PtGA), Disability of the Arm Shoulder and Hand (DASH), European Quality of life Five Dimension (EQ-5D), Short Form Survey (SF-36), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Health Assessment Questionnaire (HAQ) responses in participants with rheumatoid arthritis on a stable background of methotrexate who are starting upadacitinib treatment.

this will be composite outcomes. The scales assessed are quality of life and function.
Timepoint [3] 404208 0
To describe the change in participant reported outcomes Patient Global Assessment (PtGA), Disability of the Arm Shoulder and Hand (DASH), European Quality of life Five Dimension (EQ-5D), Short Form Survey (SF-36), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Health Assessment Questionnaire (HAQ) responses from baseline to the responses at weeks 2, 6, 12 and 24 in patients with rheumatoid arthritis on a stable background of methotrexate who are starting upadacitinib treatment.
Secondary outcome [4] 404209 0
To describe the change in Physician Global Assessment in participants with rheumatoid arthritis on a stable background of methotrexate who are starting upadacitinib treatment.
Timepoint [4] 404209 0
To describe the change in Physician Global Assessment responses from baseline to the Physician Global Assessment responses at weeks 2, 6, 12 and 24 in patients with rheumatoid arthritis on a stable background of methotrexate who are starting upadacitinib treatment.
Secondary outcome [5] 404210 0
To describe the change in Disease Activity Score 28 (C-Reactive Protein) in participants with rheumatoid arthritis on a stable background of methotrexate who are starting upadacitinib treatment.
Timepoint [5] 404210 0
To describe the change in Disease Activity Score 28 (C-Reactive Protein) result from baseline to the Disease Activity Score 28 (C-Reactive Protein) results at weeks 2, 6, 12 and 24 in patients with rheumatoid arthritis on a stable background of methotrexate who are starting upadacitinib treatment.

Eligibility
Key inclusion criteria
1 Male or female adult participants greater than or equal to 18years of age who can give informed consent, able to understand English and willing and able to complete the study activities and has been assessed by a Rheumatologist as suitable to commence upadacitinib as part of their rheumatoid arthritis management and will commence this treatment at baseline.
2 Clinically defined active rheumatoid arthritis despite methotrexate use (with or without other DMARDs), where active rheumatoid arthritis is defined as a DAS28-CRP greater than or equal to 3.2 at screening.
3 Clinically active synovitis (defined by synovitis sum score of greater than or equal to 3) of the chosen hand or wrist on MRI at screening, as determined by the MRI reader.
4 The methotrexate dose must be less than or equal to 25mg per week and the participant must also be on folic acid supplement according to local standard of care. The methotrexate dose must have been stable for greater than or equal to 3 months prior to baseline.
5 If the participant is on a DMARD in addition to methotrexate at the time of screening (allowed but not required), the dose must have been stable for greater than or equal to 3 months prior to baseline and remain stable throughout the duration of the trial.
Note: the combination of leflunomide and methotrexate is allowed but with a cap of no more than 2 trial participants using this combination.
6 Non-steroidal anti-inflammatory drug (NSAID) medications are allowed but the participant is not required to be using these medications. If NSAIDs are being taken at the time of screening, the dose must have been stable for greater than or equal to 10 days prior to baseline and remain stable throughout the duration of the trial.
7 Prednisolone or equivalent is allowed but the participant is not required to be using this medication. If prednisolone (or equivalent) is being taken at the time of screening, the prednisolone dose must be less than or equal to10mg per day (or equivalent) and the dose must have been stable for greater than or equal to 2 weeks prior to baseline and remain stable throughout the duration of the trial.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Negative MRI of the chosen hand/wrist (i.e. no signs of active clinical synovitis defined as synovitis sum wrist and MCP score less than 3) at screening as determined by the central MRI reader.
2. Inability to have MRI with gadolinium due to either claustrophobia or other contraindications to MRI with gadolinium.
3. Screening eGFR less than 60 mL/min/1.73m2
4. Any prior use of biologic treatment or targeted synthetic DMARD (JAK inhibitor).
5. Use of any intra-articular corticosteroid use in the previous 3 months in the chosen hand/wrist.
6. Any prior joint surgery in the chosen hand/wrist.
7. If the participant is a female of child-bearing potential: Currently pregnant or breastfeeding or plan to become pregnant or breastfeed during the course of the study. The participant must use contraception throughout treatment and for four weeks after the last dose.
Females who are not of child-bearing potential (post-menopausal women, permanently sterile) are not required to use contraception.
Same sex relationships are not required to use contraception.
8. Recent infection requiring intravenous antibiotics in the previous three months.
9. Any history of malignancy in the participant’s lifetime. Adequately treated squamous cell carcinoma, basal cell carcinoma and carcinoma in situ of the cervix are acceptable.
10. Live vaccines in the previous three months or plans to receive a live vaccine while on study (inactivated vaccines are acceptable).
11. Contraindication to use of upadacitinib.
12. Active Tuberculosis (TB) as determined by local QuantiFERON gold and local chest x-ray. If latent TB is diagnosed, the participant may be enrolled into the study providing treatment for latent TB according to local standard of care is initiated prior to the first dose of upadacitinib. If results are available from a chest x-ray and/or QuantiFERON gold within the three months prior to baseline, there is no need to repeat and these results can be used to assess eligibility.
13. Positive Hepatitis B, Hepatitis C or HIV laboratory tests. If results are available from Hepatitis B, Hepatitis C or HIV laboratory tests within the three months prior to baseline, there is no need to repeat and these results can be used to assess eligibility.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
The total of 30 participants was chosen based off the number of participants required in a similar trial.
As a descriptive study, most aspects will be considered in qualitative terms rather than by statistical analysis.

Recruitment
Recruitment status
Stopped early
Data analysis
No data analysis planned
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
Stopped early due to updated upadacitinib label and challenges in patient recruitment
Date of first participant enrolment
Anticipated
20/05/2022
Actual
1/06/2022
Date of last participant enrolment
Anticipated
28/04/2023
Actual
13/12/2022
Date of last data collection
Anticipated
30/10/2023
Actual
23/05/2023
Sample size
Target
30
Accrual to date
Final
7
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 21243 0
Emeritus Research - Camberwell
Recruitment hospital [2] 21244 0
Emeritus Research - Botany - Botany
Recruitment postcode(s) [1] 36116 0
3124 - Camberwell
Recruitment postcode(s) [2] 36117 0
2019 - Botany

Funding & Sponsors
Funding source category [1] 310275 0
Commercial sector/Industry
Name [1] 310275 0
AbbVie Pty Ltd
Country [1] 310275 0
Australia
Primary sponsor type
Other
Name
Emeritus Research Pty Ltd
Address
Level 2, 1180 Toorak Road
Camberwell VIC 3124
Country
Australia
Secondary sponsor category [1] 311380 0
None
Name [1] 311380 0
Address [1] 311380 0
Country [1] 311380 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309946 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 309946 0
123 Glen Osmond Road
Eastwood SA 5063
Ethics committee country [1] 309946 0
Australia
Date submitted for ethics approval [1] 309946 0
30/11/2021
Approval date [1] 309946 0
10/02/2022
Ethics approval number [1] 309946 0
2021-11-1335

Summary
Brief summary
The aim is to assess at what timepoints any relevant MRI changes are seen with upadacitinib use; which aspects of rheumatoid involvement respond earliest; and if this precedes the timepoints when other clinical RA outcome measures change. Clinical response to treatment will involve assessing response to treatment on MRI of the participant’s most affected hand/wrist (as determined by Investigator assessment by examination at screening). This trial will observe improvements in MRI tenosynovitis, synovitis and osteitis, and evaluate the time to improvement/resolution of these MRI features, as well as clinical outcome measures such as inflammatory markers and joint count assessments. In addition, participant reported outcomes (PROs) will be completed to assess the overall disease activity levels as reported by the participant. The PROs chosen include the conventional PROs EQ-5D, SF-36, FACIT-F and PtGA as these are well-established PROs that have demonstrated validity and reliability in assessing disease state, as well as a specific upper limb function PRO, the DASH. The DASH, which was developed by the Institute for Work & Health4, specifically assesses hand function and is therefore relevant to the objectives of the study.
This trial is novel in nature as it looks are earlier MRI timepoints than what has been completed in earlier clinical trials and also compares the MRI findings to PRO data captured at the same timepoint, which has also not been completed in earlier trials.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 115942 0
Prof Stephen Hall
Address 115942 0
Level 2, 1180 Toorak Road
Camberwell VIC 3124
Country 115942 0
Australia
Phone 115942 0
+61 395096166
Fax 115942 0
Email 115942 0
[email protected]
Contact person for public queries
Name 115943 0
Stephen Hall
Address 115943 0
Level 2, 1180 Toorak Road
Camberwell VIC 3124
Country 115943 0
Australia
Phone 115943 0
+61 395096166
Fax 115943 0
Email 115943 0
[email protected]
Contact person for scientific queries
Name 115944 0
Stephen Hall
Address 115944 0
Level 2, 1180 Toorak Road
Camberwell VIC 3124
Country 115944 0
Australia
Phone 115944 0
+61 395096166
Fax 115944 0
Email 115944 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No de-identified data will be shared.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.