Clinical trial NCT04062695: Tofacitinib for Reduction of Spinal Inflammation in Patients With Psoriatic ArthritiS PresenTing With Axial InvOlvement
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Psoriatic Arthritis
Spondylitis
Sacroilitis
Keywords: Psoriatic Arthritis
Sacroiliitis
Spondylitis
MRI
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
First posted: 2019-08-20
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Placebo controlled parallel group for 12 weeks followed by 12 weeks open label
Primary purpose: TREATMENT

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).

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.

Eligibility 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

Primary outcomes:
measure: MRI Berlin Score
timeFrame: Week 12 vs Baseline
Secondary outcomes:
measure: The Assessment of Spondyloarthritis International Society (ASAS) response criteria
timeFrame: Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12
measure: Responses in ASAS Health Index
timeFrame: Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12
measure: Responses in ASDAS
timeFrame: Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12
measure: Responses in BASDAI
timeFrame: Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12
measure: Responses in BASFI
timeFrame: Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12
measure: Responses in BASMI(lin)
timeFrame: Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12
measure: Responses in HAQ-DI
timeFrame: Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12
measure: Responses in Patient Global Score
timeFrame: Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12
measure: Responses in Physician Global Score
timeFrame: Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12
measure: Responses in DAPSA
timeFrame: Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12
measure: Responses in PASI
timeFrame: Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12
measure: Responses in MASES
timeFrame: Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12
measure: Response in CRP
timeFrame: Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12
measure: Response in ESR
timeFrame: Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12
measure: MRI Berlin Score
timeFrame: Week 24 vs Baseline, Week 24 vs Week 12
Other outcomes:
Locations:
city: Berlin-Steglitz
country: Germany
facility: Rheumatol Schwerpunktpraxis
city: Berlin
country: Germany
facility: Charite University, Rheumatology CCM
city: Berlin
country: Germany
facility: Praxis für Rheumatologie
city: Berlin
country: Germany
facility: Charite University - Dept. Rheumatology CBF
city: Düsseldorf
country: Germany
facility: Uniklinik, Forschungszentrum Rheumatologie
city: Ehringshausen
country: Germany
facility: Praxis Dilltal
city: Erlangen
country: Germany
facility: Uniklinikum, Med. Klinik 3
city: Frankfurt/Main
country: Germany
facility: CIRI Zentrum f innovative Diagnsotik und Therapie
city: Freiburg
country: Germany
facility: Uniklinikum, Dept. Rheumatologie
city: Hamburg
country: Germany
facility: Hamburger Rheumaforschungszentrum
city: Herne
country: Germany
facility: Rheumazentrum Ruhrgebiet
city: Kiel
country: Germany
facility: Uniklinik, Rheumatologie
city: Köln
country: Germany
facility: University Cologne, Dept. Rheumatology
city: Ludwigshafen
country: Germany
facility: Klinikum Ludwigshafen, Rheumatologie
city: Magdeburg
country: Germany
facility: Rheumapraxis Dr. Sieburg
city: Magdeburg
country: Germany
facility: Inst. f Präventive Medizin & Klinische Forschung
city: Mainz
country: Germany
facility: Uniklinikum, I. Med. Klinik
city: München
country: Germany
facility: Praxis Prof. Kellner
city: Wuppertal
country: Germany
facility: KH St. Josef, Dept. Rheumatology
Study officials:
affiliation: Charite University, Dept. Rheumatology CBF
name: Denis Poddubnyy, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.