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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Spondylitis; Psoriatic Arthritis; Sacroilitis
• Intervention / Treatment: Drug: Tofacitinib 5 MG Oral Tablet [Xeljanz]; Drug: Placebo oral tablet

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.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Fabian N Proft, MD; Phone Number: 514582 +49-30-450; Email: fabian.proft@charite.de
• Study Contact Backup: Name: Bianca Mandt, SN; Phone Number: 2303 +49-30-8445; Email: bianca.mandt@charite.de

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Recruiting
    • Charite University, Rheumatology CCM
    • Contact: Sandra Hermann, Dr
  • Berlin, Germany, 12163
    • Recruiting
    • Praxis für Rheumatologie
    • Contact: Kirsten Karberg, Dr
  • Berlin, Germany, 12203
    • Recruiting
    • Charite University - Dept. Rheumatology CBF
    • Contact: Deni Poddubnyy, Prof
  • Berlin-Steglitz, Germany, 12161
    • Recruiting
    • Rheumatol Schwerpunktpraxis
    • Contact: Jan Brandt-Jürgens, PD Dr
  • Düsseldorf, Germany, 40225
    • Recruiting
    • Uniklinik, Forschungszentrum Rheumatologie
    • Contact: Philipp Severin, Dr
  • Ehringshausen, Germany, 35630
    • Recruiting
    • Praxis Dilltal
    • Contact: Mirko Steinmüller, Dr
  • Erlangen, Germany, 91054
    • Recruiting
    • Uniklinikum, Med. Klinik 3
    • Contact: Andreas Ramming, Dr
  • Frankfurt/Main, Germany, 60590
    • Recruiting
    • CIRI Zentrum f innovative Diagnsotik und Therapie
    • Contact: Frank Behrens, Dr
  • Freiburg, Germany, 79106
    • Recruiting
    • Uniklinikum, Dept. Rheumatologie
    • Contact: Stephanie Finzel, Dr
  • Hamburg, Germany, 22391
    • Recruiting
    • Hamburger Rheumaforschungszentrum
    • Contact: Hauke Heintz, Dr
  • Herne, Germany, 44649
    • Recruiting
    • Rheumazentrum Ruhrgebiet
    • Contact: Uta Kiltz, PD
  • Kiel, Germany, 24105
    • Recruiting
    • Uniklinik, Rheumatologie
    • Contact: Bimba Hoyer, Prof
  • Köln, Germany, 50937
    • Recruiting
    • University Cologne, Dept. Rheumatology
    • Contact: David Kofler, PD
  • Ludwigshafen, Germany, 67063
    • Recruiting
    • Klinikum Ludwigshafen, Rheumatologie
    • Contact: Raoul Bergner, Prof
  • Magdeburg, Germany, 39104
    • Recruiting
    • Rheumapraxis Dr. Sieburg
    • Contact: Maren Sieburg, Dr
  • Magdeburg, Germany, 39110
    • Recruiting
    • Inst. f Präventive Medizin & Klinische Forschung
    • Contact: Rüdiger Möricke, Prof
  • Mainz, Germany, 55131
    • Recruiting
    • Uniklinikum, I. Med. Klinik
    • Contact: Andreas Schwarting, Prof
  • München, Germany, 80935
    • Recruiting
    • Praxis Prof. Kellner
    • Contact: Herbert Kellner, Prof
  • Wuppertal, Germany, 42105
    • Recruiting
    • KH St. Josef, Dept. Rheumatology
    • Contact: Astrid Thiele, Dr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Tofacitinib; 5 mg oral BID	Drug: Tofacitinib 5 MG Oral Tablet [Xeljanz]; verum tablets; Other Names: Xeljanz
Placebo Comparator: Placebo; matching Placebo BID	Drug: Placebo oral tablet; tablets containing placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRI Berlin Score	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).	Week 12 vs Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Assessment of Spondyloarthritis International Society (ASAS) response criteria	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).	Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12
Responses in ASAS Health Index	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).	Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12
Responses in ASDAS	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.	Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12
Responses in BASDAI	Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Calculated score from 6 questions VAS; range 0-10, the higher the worse.	Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12
Responses in BASFI	Bath Ankylosing Spondylitis Functional Index (BASFI). Mean of 10 questions VAS, range 0-10; higher value = more impaired function.	Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12
Responses in BASMI(lin)	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.	Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12
Responses in HAQ-DI	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.	Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12
Responses in Patient Global Score	Patient Global Score of overall disease activity - VAS 0-10 (higher = worse)	Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12
Responses in Physician Global Score	Physician Global Score of overall disease activity - VAS 0-10 (higher = worse).	Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12
Responses in DAPSA	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).	Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12
Responses in PASI	Psoriasis Area and Severity Index (PASI) - description of skin involvement regarding scaling, redness, thickness and body surface area. Range 0-72.	Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12
Responses in MASES	Maastricht Ankylosing Spondylitis Enthesitis Score (MASES;Heuft-Dorenbosch Ann Rheum Dis 2003). Assessing 13 clinical enthesial sites (yes / no). Range 0-13.	Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12
Response in CRP	C-reactive protein (CRP, mg per litre)	Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12
Response in ESR	Erythrocyte Sedimentation Rate (ESR, mm per 1 hour)	Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12
MRI Berlin Score	Improvement of the Berlin MRI score (description see primary outcome) for sacroiliac joints and spine	Week 24 vs Baseline, Week 24 vs Week 12

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Investigators: Principal Investigator: Denis Poddubnyy, Prof, Charite University, Dept. Rheumatology CBF

Publications and helpful links

General Publications

• Proft F, Torgutalp M, Muche B, Rios Rodriguez V, Verba M, Poddubnyy D. Efficacy of tofacitinib in reduction of inflammation detected on MRI in patients with Psoriatic ArthritiS presenTing with axial involvement (PASTOR): protocol of a randomised, double-blind, placebo-controlled, multicentre trial. BMJ Open. 2021 Nov 16;11(11):e048647. doi: 10.1136/bmjopen-2021-048647.

Study record dates

Study Major Dates

• Study Start (Actual): August 4, 2020
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: May 14, 2019
• First Submitted That Met QC Criteria: August 19, 2019
• First Posted (Actual): August 20, 2019

Study Record Updates

• Last Update Posted (Actual): July 26, 2022
• Last Update Submitted That Met QC Criteria: July 23, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: MRI; Psoriatic Arthritis; Sacroiliitis; Spondylitis
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Infections; Joint Diseases; Musculoskeletal Diseases; Skin Diseases, Papulosquamous; Spinal Diseases; Bone Diseases; Spondylarthropathies; Psoriasis; Bone Diseases, Infectious; Arthritis; Inflammation; Arthritis, Psoriatic; Spondylitis; Spondylarthritis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Tofacitinib
• Other Study ID Numbers: PASTOR2018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• 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