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Tofacitinib for Reduction of Spinal Inflammation in Patients With Psoriatic ArthritiS PresenTing With Axial InvOlvement (PASTOR)

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ClinicalTrials.gov Identifier: NCT04062695
Recruitment Status : Recruiting
First Posted : August 20, 2019
Last Update Posted : September 3, 2020
Sponsor:
Information provided by (Responsible Party):
Denis Poddubnyy, Charite University, Berlin, Germany

Brief Summary:
To evaluate the efficacy of Tofacitinib in reducing inflammation in the sacroiliac joints and spine on magnetic resonance imaging (MRI) in patients with active Psoriatic Arthritis (PsA) with axial Involvement (BASDAI [Bath Ankylosing Spondylitis Disease Activity Index] ≥ 4 and total backpain ≥ 4 despite treatment with NSAIDs plus evidence of active inflammation in the sacroiliac joints or spine on MRI).

Condition or disease Intervention/treatment Phase
Psoriatic Arthritis Spondylitis Sacroilitis Drug: Tofacitinib 5 MG Oral Tablet [Xeljanz] Drug: Placebo oral tablet Phase 2

Detailed Description:

This study is a prospective, randomized, double-blind, placebo-controlled, multicenter study to investigate the efficacy of Tofacitinib in reducing inflammation in the sacroiliac joints and in the spine on MRI in patients with active axial PsA.

Eligible patients (n=80) will be randomized 1:1 to receive either Tofacitinib 5mg orally twice daily or placebo for a 12-week period. After week 12, all patients will receive Tofacitinib 5mg orally twice daily for another 12 weeks. The study duration will include a 6-week screening period, a 24-week treatment period and a safety follow-up period of 4 weeks. Patients will be closely monitored throughout the study on a total of 11 visits. Safety data will be collected in the form of adverse events, vital parameters, physical examinations, and laboratory parameters throughout the study.

The baseline MRI of the whole spine and sacroiliac (SI) joints will be performed within the 6-week screening period to confirm the presence of active inflammation (bone marrow edema) compatible with Spondyloarthritis (will be assessed by a central reader), at week 12 to evaluate the primary study endpoint, and at week 24 to evaluate the secondary endpoint.

The primary study endpoint will be an improvement of the total Berlin MRI score for sacroiliac joints and spine at week 12 as compared to baseline.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Placebo controlled parallel group for 12 weeks followed by 12 weeks open label
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Efficacy of Tofacitinib in Reduction of Inflammation Detected on MRI in Patients With Psoriatic ArthritiS PresenTing With Axial InvOlvement - a Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial
Actual Study Start Date : August 4, 2020
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : June 2022


Arm Intervention/treatment
Active Comparator: Tofacitinib
5 mg oral BID
Drug: Tofacitinib 5 MG Oral Tablet [Xeljanz]
verum tablets
Other Name: Xeljanz

Placebo Comparator: Placebo
matching Placebo BID
Drug: Placebo oral tablet
tablets containing placebo




Primary Outcome Measures :
  1. MRI Berlin Score [ Time Frame: Week 12 vs Baseline ]
    Improvement of the Berlin MRI score for sacroiliac joints and spine. Scoring includes spinal inflammation (Lucas C et al, J Rheumatol 2007): 23 vertebral units with semiquantitative range of inflammation between 0 to 3 (min. score = 0, max. score = 69, the higher the worse). Additionally, inflammation of the sacroiliac joints is scored (Hermann KG, Rheumatologe 2004; scoring each quadrant between 0 and 4, max. score 16, the higher, the worse).


Secondary Outcome Measures :
  1. The Assessment of Spondyloarthritis International Society (ASAS) response criteria [ Time Frame: Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 ]
    Assessment of Spondyloarthritis International Society Response Criteria (Anderson JJ, Arthritis Rheum 2001): change in percent of at least 3 of 4 subcores (Patient Global VAS, Pain VAS, BASFI and BASDAI questions 5&6).

  2. Responses in ASAS Health Index [ Time Frame: Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 ]
    Assessment of Spondyloarthritis International Society ASAS Health Index (Kiltz U, Ann Rheum Dis 2015). Consisting of 17 questions answered, calculated in percent (100 % = best spondylarthritis related health).

  3. Responses in ASDAS [ Time Frame: Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 ]
    Ankylosing Spondylitis Disease Activity Score (ASDAS) combining 3 questions VAS (back pain, peripheral pain and morning stiffness) with CRP or ESR; formulas used as described in Lucas C, Ann Rheum Dis 2009. Values <1.3 inactive disease, <2.1 low disease activity, 2.1-3.5 high disease activity, >3.5 very high disease activity.

  4. Responses in BASDAI [ Time Frame: Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 ]
    Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Calculated score from 6 questions VAS; range 0-10, the higher the worse.

  5. Responses in BASFI [ Time Frame: Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 ]
    Bath Ankylosing Spondylitis Functional Index (BASFI). Mean of 10 questions VAS, range 0-10; higher value = more impaired function.

  6. Responses in BASMI(lin) [ Time Frame: Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 ]
    Bath Ankylosing Spondylitis Metrology Index - linear score (BASMI; van der Heijde Ann Rheum Dis 2008). Measuring Schober´s test (cm), intermalleolar distance (cm), cervical rotation (degree), lateral lumbar flexion (cm) and tragus-to-wall-distance (cm) and calculate the score as reported in the citation.

  7. Responses in HAQ-DI [ Time Frame: Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 ]
    Health assessment questionnaire disability index (HAQ-DI; Princus T, Arthritis Rheum 1983) measuring influence of arthritis on quality of life. Patient questionnaire recalculated in scores 0 to 3, higher = worse.

  8. Responses in Patient Global Score [ Time Frame: Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 ]
    Patient Global Score of overall disease activity - VAS 0-10 (higher = worse)

  9. Responses in Physician Global Score [ Time Frame: Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 ]
    Physician Global Score of overall disease activity - VAS 0-10 (higher = worse).

  10. Responses in DAPSA [ Time Frame: Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 ]
    Disease Activity in PSoriatic Arthritis (DAPSA; Schoels M, Arthritis Rheum 2010); calculated by summing swollen joint count (max. 66) + tender joint count (max. 68) + patient pain VAS + patient global assessments VAS + CRP. Value ranges 0 to >28 (the higher, the worse).

  11. Responses in PASI [ Time Frame: Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 ]
    Psoriasis Area and Severity Index (PASI) - description of skin involvement regarding scaling, redness, thickness and body surface area. Range 0-72.

  12. Responses in MASES [ Time Frame: Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 ]
    Maastricht Ankylosing Spondylitis Enthesitis Score (MASES;Heuft-Dorenbosch Ann Rheum Dis 2003). Assessing 13 clinical enthesial sites (yes / no). Range 0-13.

  13. Response in CRP [ Time Frame: Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 ]
    C-reactive protein (CRP, mg per litre)

  14. Response in ESR [ Time Frame: Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 ]
    Erythrocyte Sedimentation Rate (ESR, mm per 1 hour)

  15. MRI Berlin Score [ Time Frame: Week 24 vs Baseline, Week 24 vs Week 12 ]
    Improvement of the Berlin MRI score (description see primary outcome) for sacroiliac joints and spine



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

Inclusion Criteria:

  • Psoriatic Arthritis fulfilling ClASsification for Psoriatic ARthritis (CASPAR) criteria
  • chronic back pain > 3 months
  • BASDAI value ≥ 4 and backpain ≥ 4 / 10 VAS
  • presence of active inflammation in Screening MRI of sacroiliac joints and / or spine (central reading)
  • history of inadequate response to ≥ 2 NSAIDs or intolerance / contraindications

Exclusion Criteria:

  • active current infection, severe infections in the last 3 months
  • history of recurrent Herpes zoster or disseminated Herpes simplex
  • immunodeficiency
  • chronic Hepatitis B, C or HIV infection
  • women: pregnant or lactating (have to practice reliable method of contraception)
  • other severe diseases conflicting with a clinical study, contraindications for MRI

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): NCT04062695


Contacts
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Contact: Fabian N Proft, MD +49-30-450 ext 514582 fabian.proft@charite.de
Contact: Bianca Mandt, SN +49-30-8445 ext 2303 bianca.mandt@charite.de

Locations
Show Show 19 study locations
Sponsors and Collaborators
Charite University, Berlin, Germany
Investigators
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Principal Investigator: Denis Poddubnyy, Prof Charite University, Dept. Rheumatology CBF
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Responsible Party: Denis Poddubnyy, Prof. Dr. Denis Poddubnyy, Charite University, Berlin, Germany
ClinicalTrials.gov Identifier: NCT04062695    
Other Study ID Numbers: PASTOR2018
First Posted: August 20, 2019    Key Record Dates
Last Update Posted: September 3, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Denis Poddubnyy, Charite University, Berlin, Germany:
Psoriatic Arthritis
Sacroiliitis
Spondylitis
MRI
Additional relevant MeSH terms:
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Spondylitis
Arthritis
Arthritis, Psoriatic
Inflammation
Joint Diseases
Musculoskeletal Diseases
Pathologic Processes
Bone Diseases, Infectious
Infection
Bone Diseases
Spinal Diseases
Spondylarthropathies
Spondylarthritis
Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases
Tofacitinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action