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

Psoriatic Arthritis Clinical Trial

— PASTOR  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04062695
• Other study ID #: PASTOR2018
• Status: Recruiting
• Phase: Phase 2
• Start date: August 4, 2020
• Est. completion date: December 2023

Study information

• Verified date: July 2022
• Source: Charite University, Berlin, Germany
• Contact: Fabian N Proft, MD
• Phone: +49-30-450
• Email: fabian.proft[@]charite.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: December 2023
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Psoriatic
• Inflammation
• Psoriatic Arthritis
• Sacroilitis
• Spondylarthritis
• Spondylitis

Intervention

Drug:
• Tofacitinib 5 MG Oral Tablet [Xeljanz]
verum tablets
• Placebo oral tablet
tablets containing placebo

Locations

Country	Name	City	State
Germany	Charite University - Dept. Rheumatology CBF	Berlin
Germany	Charite University, Rheumatology CCM	Berlin
Germany	Praxis für Rheumatologie	Berlin
Germany	Rheumatol Schwerpunktpraxis	Berlin-Steglitz
Germany	Uniklinik, Forschungszentrum Rheumatologie	Düsseldorf
Germany	Praxis Dilltal	Ehringshausen
Germany	Uniklinikum, Med. Klinik 3	Erlangen
Germany	CIRI Zentrum f innovative Diagnsotik und Therapie	Frankfurt/Main
Germany	Uniklinikum, Dept. Rheumatologie	Freiburg
Germany	Hamburger Rheumaforschungszentrum	Hamburg
Germany	Rheumazentrum Ruhrgebiet	Herne
Germany	Uniklinik, Rheumatologie	Kiel
Germany	University Cologne, Dept. Rheumatology	Köln
Germany	Klinikum Ludwigshafen, Rheumatologie	Ludwigshafen
Germany	Inst. f Präventive Medizin & Klinische Forschung	Magdeburg
Germany	Rheumapraxis Dr. Sieburg	Magdeburg
Germany	Uniklinikum, I. Med. Klinik	Mainz
Germany	Praxis Prof. Kellner	München
Germany	KH St. Josef, Dept. Rheumatology	Wuppertal

Sponsors (1)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Response in CRP	C-reactive protein (CRP, mg per litre)	Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12
Secondary	Response in ESR	Erythrocyte Sedimentation Rate (ESR, mm per 1 hour)	Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12
Secondary	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