U3P study - Upadacitinib in Psoriatic Arthritis Pain Processing

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitaetsklinikum Erlangen AöR

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

24 Mar 2022 → 22 Jan 2025

Decision date (initial)

2024-03-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-512669-15-00

EudraCT number

2020-005518-16

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

To describe early and long term central nervous system (CNS) pain response due to blood oxygenation level dependent (BOLD) signal changes in fMRI of the brain to upadacitinib treatment in psoriatic arthritis

Conditions and MedDRA coding

Psoriatic arthritis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Patients fulfilling CASPAR criteria for PsA
2. Subjects must have active hand joint involvement (at least one swollen/tender joint)
3. Indication for systemic treatment
4. Subjects who failed to respond to or are intolerant to at least one csDMARD
5. Subjects who were not exposed to more than one bDMARD before; for bDMARDs the wash-out period should be at least three times the half-life of the bDMARD concerned
6. Eligibility for the treatment with Upadacitinib according to the EU label
7. Glucocorticoids less than 10mg/day will be allowed
8. Must understand and voluntarily sign an informed consent form including written consent for data protection
9. Adults aged ≥ 18 years and <65 years at time of consent
10. Must be able to adhere to the study visit schedule and other protocol requirements
11. Male subjects (including those who have had a vasectomy) must agree to use barrier contraception (latex condoms) when engaging in reproductive sexual activity with females of childbearing potential (FCBP) while on study medication and for at least 28 days after taking the last dose of study medication
12. Females of childbearing potential (FCBP) must have a negative urine pregnancy test at baseline and must be willing to use one highly-effective form of birth control when engaging in reproductive sexual activity while on study medication and for at least 28 days after taking the last dose of study medication

Exclusion criteria 23

1. Prior exposure to any Janus kinase (JAK) inhibitor
2. Investigational study drug within 4 weeks (or 5 half-lives, whichever is longer) prior to enrollment
3. ANC < 1.000/mm3, ALC < 500/mm3 or hemoglobin < 8g/dl
4. Any contraindication to perform MRI
5. Anti-CCP- Antibody positivity
6. Any other autoimmune or inflammatory disease such as SLE, PSS, MCTD, Behcet disease, vasculitis or autoimmune hepatitis
7. malignancy risk factors (e.g. current malignancy or history of malignancy)
8. Any severe active infection, e.g. hepatitis B or C, SARS-CoV 2 (COVID 19), or active tuberculosis as defined by a positive Quantiferon TB-test. If presence of latent tuberculosis is established then treatment according to local guidelines must have been initiated prior to enrollment
9. Have a known history of serious infections (e.g., hepatitis, pneumonia, or pyelonephritis) in the previous 3 months
10. Immunocompromised patients
11. Uncontrolled severe concomitant disease
12. Pregnant or lactating females
13. Known hypersensitivity to upadacitinib or any other drug components
14. Requirement for immunization with live vaccine during the trial period or within 4 weeks preceding baseline
15. History of venous thrombosis or pulmonary embolism, inherited coagulation disorder, planned major surgery, immobilisation
16. History of atherosclerotic cardiovascular disease or other cardiovascular risk factors
17. Current of past long-time smokers
18. Clinically significant cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, neurologic, gastrointestinal, immunologic, or other major diseases
19. Evidence of severe renal dysfunction defined as: eGFR < 30 ml/min/1,73 m2 (calculated using the CKD-EPI formula) at screening (Visit 1)
20. Abnormal liver function tests such as GOT (AST), GPT (ALT), alkaline phosphatase or bilirubin. The investigator should be guided by the following criteria: o GOT, GPT, alkaline phosphatase: any single parameter may not exceed 3x upper limit of normal (ULN). A single parameter elevated up to and including 3x ULN should be re-checked once more as soon as possible. o Total bilirubin: if total bilirubin concentration is increased above 2x ULN, total bilirubin should be differentiated into direct and indirect reacting bilirubin. In any case, serum bilirubin should not exceed the value of 1,6mg/dl (exemption: the diagnose of gilbert´s syndrome has already been established or based on higher levels of unconjugated bilirubin without either signs of other liver problems or red blood cell breakdown can be made)
21. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
22. Patients who are younger than 18 years or are incapable to understand the aim, importance and consequences of the study and to give legal informed consent
23. Have a history of alcohol or substance abuse within the preceding 6 months that, in the opinion of the investigator, may increase the risks associated with study participation or study agent administration, or may interfere with interpretation of results

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. BOLD signal voxel count at week 1 and week 12 compared to baseline

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaetsklinikum Erlangen AöR

Sponsor organisation

Universitaetsklinikum Erlangen AöR

Address

Maximiliansplatz 2, Innenstadt Innenstadt

City

Erlangen

Postcode

91054

Country

Germany

Scientific contact point

Organisation

Universitaetsklinikum Erlangen AöR

Contact name

Klinik für Rheumatologie und Immunologie

Public contact point

Organisation

Universitaetsklinikum Erlangen AöR

Contact name

Klinik für Rheumatologie und Immunologie

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications