AzTrials
AzTrials

Rheumatoid ArthritisPhase 4PULMORANCT04311567

Effects of Tofacitinib vs Methotrexate on Rheumatoid Arthritis Interstitial Lung Disease

A Phase 4 study testing Tofacitinib and Methotrexate in people with Rheumatoid Arthritis and Interstitial Lung Disease Due to Systemic Disease (Disorder), run by Vastra Gotaland Region at 3 sites in Sweden.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

Pulmonary abnormalities are present in up to 60% of patients with early rheumatoid arthritis (RA), and up to 10% of the patients will develop clinical interstitial lung disease (ILD). Recent data indicate that inhibition of Janus kinase is beneficial for this extra-articular manifestation. Read more about this study

Who is it for?
Ages 18 to 80 years
What is being tested?
Tofacitinib and Methotrexate
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
3 sitesSweden
Study dates
7 Nov 2020to 26 Mar 2024
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosis of seropositive (i.e., presence of RF and/or anti-CCP antibodies) rheumatoid arthritis (RA) according to the ACR/EULAR 2010 criteria within 24 months.
  • No previous treatment with disease modifying anti-rheumatic drugs (DMARDs). History of prednisone use is allowed but should have been discontinued 2 weeks before baseline measurement.
  • Active disease with ≥2 painful and ≥2 swollen joints in 66/68 joints and CRP ≥2.0 mg/L
  • Aged 18-80 years
  • The subject has given written consent to participate in the study.

Who cannot join

  • Current active inflammatory joint disease other than RA.
  • Significant and/or uncontrolled cardiac, pulmonary disease, nervous system, renal, hepatic, endocrine or gastrointestinal disorders or severe RA which in the investigator's opinion would preclude patient participation.
  • Malignancy within the past 5 years, except for successfully treated cervical carcinoma in situ, basal cell and squamous cell carcinoma of the skin, with no evidence of recurrence or metastatic disease for at least 3 years.
  • Primary or secondary immunodeficiency (history of, or currently active), including known history of HIV infection.
  • Pregnant or lactating women.
  • For subjects in part II the following exclusion criteria also apply:
Show all 17Show fewer
  • Women of childbearing potential not willing or able to use highly effective methods of birth control per ICH M3 (R2) for 28 days prior and 3 months after end of study.
  • Active infection (excluding fungal infections of nail beds) requiring i.v. anti-infectives within 4 weeks, or oral anti-infectives within 2 weeks prior to baseline.
  • Positive tests for hepatitis B (HBsAg or HBV DNA),hepatitis C serology or SARS-CoV2
  • History of herpes zoster infection during last 10 years.
  • History or risk of venous thromboembolism or diverticulitis.
  • Positive tuberculosis history and/or positive Quantiferon test.
  • Hemoglobin <90 g/L.
  • Absolute neutrophil count < 1500 cells/uL.
  • ASAT or ALAT >2.0 times the upper limit of normal.
  • High or very high risk (≥ 5%) of cardiovascular death within 10 years by SCOREx1,5.
  • Multiple incidental solid/subsolid lung nodules of size ≥6 mm, single incidental solid lung nodules ≥8 mm.

Trial locations and contacts

3 sites in 1 country.

Sweden3 sites
  • Clinical Rheumatology Research Center, The Sahlgrenska University Hospital

    Gothenburg, Västra Götaland County, 41345

  • Skåne University Hospital, Department of Rheumatology

    Lund, Skåne County, 20502

  • Karolinska University Hospital, Department of Rheumatology

    Stockholm, 17176

Other trials in Sweden

About this study

Official title: Effects of Tofacitinib vs Methotrexate on Clinical and Molecular Disease Activity Markers in Joints and Lungs in Early Rheumatoid Arthritis (PULMORA) - A Randomized, Controlled, Open-label, Assessor-blinded, Phase IV Trial

Pulmonary abnormalities are present in up to 60% of patients with early rheumatoid arthritis (RA), and up to 10% of the patients will develop clinical interstitial lung disease (ILD). Recent data indicate that inhibition of Janus kinase is beneficial for this extra-articular manifestation. Our goal is to determine whether tofacitinib is an effective and safe treatment, compared to standard-of-care methotrexate, for subclinical and clinical ILD in patients with early RA. The study also explores disease mechanisms in lungs and joints, to identify potential biomarkers for diagnosis, prognosis, and response to treatment of RA-ILD.

Read the detailed description

Study objectives:

Primary objective: Effects of tofacitinib compared to that of methotrexate on interstitial pulmonary abnormalities at 24 weeks.

Secondary objectives: Effects of tofacitinib compared to that of methotrexate on pulmonary abnormalities and function, RA disease activity and remission rates and patient reported outcome measures at different time points. Frequency of adverse events.

Exploratory objectives: Effects of tofacitinib compared to that of methotrexate on cellular and molecular activity profiles of clinical samples from joints and lungs.

Study design:

A randomized, actively controlled, open-label, assessor-blinded, multicenter 48 weeks phase IV trial. The study design includes an optional sub-study collecting tissue samples using ultrasound-guided synovial biopsies, bronchoalveolar lavage and Particles in Exhaled Air (PExA).

Study population and intervention:

Patients with early untreated RA with active and seropositive disease will be eligible for screening and the performance of high-resolution computed tomography (HRCT). Subjects with pulmonary abnormalities suggestive of RA-ILD will be randomized (1:1) to tofacitinib 5 mg BID (group 1) or standard-of-care methotrexate 20 mg weekly (group 2) for 48 weeks. All patients receive prednisone with tapering for 6 weeks. Patients with incomplete response at 24 weeks will escalate to combination therapy with tofacitinib+methotrexate (group 3). Intra-articular injections of cortisone will be allowed during the study.

145 subjects will be included and screened (part 1), and approximately 48 subjects will be randomized to active treatment (part 2).

Being tested
Tofacitinib, Methotrexate
Keywords
Rheumatoid arthritis, Interstitial lung disease, Janus Kinase inhibition, tofacitinib, methotrexate
Medical subject headings
Arthritis, Rheumatoid, Lung Diseases, Interstitial

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TofacitinibDrug

    Also called Xeljanz

    Open-label tofacitinib for 48 weeks. All subjects (both arms) receive prednisone starting at 20 mg QD with tapering for 6 weeks. Patients with incomplete response at 24 weeks will escalate to combination therapy with tofacitinib 5 mg BID + methotrexate 20 mg weekly up to week 48.

  • MethotrexateDrug

    Also called metotrexat

    Open-label methotrexate for 48 weeks. All subjects (both arms) receive prednisone starting at 20 mg QD with tapering for 6 weeks. Patients with incomplete response at 24 weeks will escalate to combination therapy with tofacitinib 5 mg BID + methotrexate 20 mg weekly up to week 48.

Study groups in NCT04311567
Study groupRoleWhat they receive
TofacitinibExperimentalOral tablet tofacitinib 5 mg BID for 48 weeks
Receives: Drug: Tofacitinib
MethotrexateActive comparatorOral tablet methotrexate 2.5 mg: 8 tablets in one dose (=20 mg) once weekly for 48 weeks
Receives: Drug: Methotrexate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in total interstitial disease score of pulmonary abnormalities by HRCT

    Total interstitial disease score will be calculated as the mean of six (anatomical levels) interstitial disease scores. Each level's interstitial disease score will be calculated as the sum of the extent of five different parenchymal patterns (Ground glass, reticulations, honey-combing, consolidations and emphysema) measured as percentage of pattern area to total lung area at a specified anatomical level.

    Measured: Baseline and 24 weeks

Secondary outcomes (14)
  1. Change in extent of parenchymal lung disease by HRCT pattern

    The extent of the separate parenchymal pattern (Ground glass/reticulations/honey-combing/consolidations/emphysema) by HRCT measured as percentage of pattern area to total lung area at six different anatomical level.

    Measured: Baseline and 24 weeks

  2. Change in extent of parenchymal lung disease by HRCT pattern

    The extent of the separate parenchymal pattern (Ground glass/reticulations/honey-combing/consolidations/emphysema) by HRCT measured as percentage of pattern area to total lung area at six different anatomical level.

    Measured: Baseline and 48 weeks

  3. Change in Forced Vital Capacity (FVC)

    FVC will be measured by spirometry. The proportion of patients with FVC 24wks ≤ FVC baseline will also be calculated.

    Measured: Baseline and 24 weeks

  4. Change in Diffusion Capacity of Carbon Monoxide (DLCO)

    DLCO will be measured according to standard protocol and corrected for haemoglobulin level.

    Diffusion capacity divided by alveolar volume (DLCO/VA) will also be calculated.

    Measured: Baseline and 24 weeks

  5. Change in walking distance (meters)

    6-minutes walking test Diffusion capacity divided by alveolar volume (DLCO/VA) will also be calculated.

    Measured: Baseline and 24 weeks

  6. Change in blood oxygen saturation (SpO2) after 6-minutes walking

    6-minutes walking test with pulse oximetry recording Diffusion capacity divided by alveolar volume (DLCO/VA) will also be calculated.

    Measured: Baseline and 24 weeks

  7. Patient reported outcome of breathing and airway symptoms

    Patient reported outcomes of breathing and airway symptoms will be evaluated using Saint George's Respiratory Questionnaire.

    Measured: baseline, 24 and 48 weeks

  8. Disease activity score of rheumatoid arthritis (DAS28-CRP)

    DAS28-CRP will be calculated as follows: 0.56*√(TJC28) +0.28*√(SJC28)+0.014*PaGH+0.36*ln(CRP+1)+0.96.

    TJC = number of tender joints of 28, SJC= number of swollen joints of 28, CRP=c-reactive protein level and PaGH=Patient reported global impact of disease on health on a VAS scale (0-100)

    Measured: baseline, 12, 24 and 48 weeks

  9. Patient reported health assessment of physical function (HAQ index)

    Patient reported function assessed by a validated questionnaire HAQ = health assessment questionnaire. The assessment gives a value/index between 0 - 3.0.

    Measured: baseline, 24 and 48 weeks

  10. Proportion of patients in rheumatoid arthritis DAS remission

    DAS28 remission is defined as DAS28<2.6.

    Measured: 24 and 48 weeks

  11. Frequency of adverse events (AE)

    Number of AE per category and serious AE will be calculated for the different treatment groups

    Measured: baseline, 24 and 48 weeks

  12. Patient reported global disease activity

    Patient reported global impact of disease on health on a VAS scale (0-100 mm)

    Measured: baseline, 12, 24 and 48 weeks

  13. Proportion of patients in rheumatoid arthritis ACR-EULAR Boolean remission

    Boolean RA remission is defined as: SJC, TJC, PaGH and CRP, all ≤1. TJC = number of tender joints of 28, SJC= number of swollen joints of 28 and PaGH=Patient reported global impact of disease on health on a VAS scale (0-10)

    Measured: 24 and 48 weeks

  14. Clinical disease activity score of rheumatoid arthritis (CDAI)

    Clinical disease activity score of rheumatoid arthritis (CDAI) is calculated as follows: SJC + TJC + PaGH + PhGH.

    TJC = number of tender joints of 28, SJC= number of swollen joints of 28, PaGH=Patient reported global impact of disease on health on a VAS scale (0-10) and PhGH=physician assessment of global impact of disease on health of patient on a VAS scale (0-10). CDAI ranges from 0 - 76.

    Measured: baseline, 12, 24 and 48 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Mar 2020
  2. Study start7 Nov 2020
  3. Primary completion30 Nov 2023
  4. Study completion26 Mar 2024

Why it stopped: Low recruitment due to the pandemic and high screening failure rate in particular because of low prevalence of interstitial abnormalities at diagnosis in Sweden.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
A study in two parts: 1. Screening with HRCT. Patients will be stratified based on the the findings to: cohort A, with pulmonary abnormalities; and cohort B, with normal findings (who will end further participation in the main trial). 2. Randomization of cohort A to 48 weeks of active treatment. Parallel group design from baseline to week 24.
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04311567
Sponsor's protocol ID
EudraCT 2019-004179-38
Acronym
PULMORA
Status last verified
Apr 2022
First submitted
5 Mar 2020
Last updated
23 May 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Tofacitinib and Methotrexate in people with Rheumatoid Arthritis and Interstitial Lung Disease Due to Systemic Disease (Disorder), run by Vastra Gotaland Region at 3 sites in Sweden.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 23 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Low recruitment due to the pandemic and high screening failure rate in particular because of low prevalence of interstitial abnormalities at diagnosis in Sweden.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in total interstitial disease score of pulmonary abnormalities by HRCT (time frame: Baseline and 24 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 May 2024.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in