Comparing the effectiveness of tofacitinib extended release (XR) chronotherapy, morning versus evening dosing, in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients from a patient’s, clinical as well as a translational point of view.

• Register: EUCTR
• Last refreshed on: 3 February 2025
• Main ID: EUCTR2021-004131-84-NL
• Date of registration: 08/09/2021
• Prospective Registration: Yes
• Primary sponsor: Erasmus Medical Center
• Public title: Comparing the effectiveness of tofacitinib extended release (XR) chronotherapy, morning versus evening dosing, in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients from a patient’s, clinical as well as a translational point of view.
• Scientific title: Chronotherapy in Inflammatory Arthritis (ChronIA trial): a randomized controlled trial comparing the effectiveness of morning and evening dosing of tofacitinib extended-release - ChronIA trial
• Date of first enrolment: 14/02/2022
• Target sample size: 84
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2021-004131-84
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Netherlands

Contacts

• Name: Pascal H.P. de Jong
• Affiliation: Erasmus Medical Center

• Name: Pascal H.P. de Jong
• Affiliation: Erasmus Medical Center

Key inclusion & exclusion criteria

Inclusion criteria:
In order to be eligible to participate in this study, a subject must meet all of the following criteria:
- RA or PsA, , according to respectively the ACR/EULAR 2010 criteria for RA and CASPAR criteria
- Active disease, respectively defined as a DAS>2.4 or DAPSA>14
- Age =18 years
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 64
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion criteria:
- Current or previous treatment of arthritis with tsDMARD(s)
- Prednisone (or equivalent) usage at a dose of >7.5mg
- Work in shifts
- (Relative) contraindications for study medication:
a. Evidence of ongoing infectious or malignant process obtained within 3 months prior to screening and evaluated by a qualified health care professional.
b. Pregnant or nursing (lactating) women.
c. Female participants of child bearing potential and male participants whose partner is of child bearing potential who are not willing to ensure that they or their partner use effective contraception during the trial and for 3 months thereafter as in standard practice.
d. History of clinically significant liver disease or liver injury as indicated by abnormal liver function tests (LFT) such as aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT), alanine aminotransferase/ serum glutamic pyruvic transaminase (ALT/SGPT), alkaline phosphatase, or serum bilirubin. The Investigator should be guided by the following criteria: Any single parameter may not exceed 2 x upper limit of normal (ULN). A single parameter elevated up to and including 2 x ULN should be re-checked once more as soon as possible, and in all cases, at least prior to enrolment/randomization, to rule out laboratory error.
e. History of renal trauma, glomerulonephritis, or subjects with one kidney only, or a glomerular filtration rate (GFR) < 30 ml/min.
f. Other underlying metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal conditions which in the opinion of the Investigator immunocompromises the patient and/or places the patient at unacceptable risk for participation in an immunomodulatory therapy.
g. Use of powerful CYP3A4 inhibitors (e.g. ketoconazole, fluconazole, tacrolimus and ciclosporin)
- Unable to understand, speak and write in Dutch.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Rheumatoid arthritis or psoriatic arthritis according to respectively 2010 criteria or CASPAR criteria
MedDRA version: 23.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
MedDRA version: 21.0 Level: LLT Classification code 10037160 Term: Psoriatic arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Intervention(s)

Trade Name: Xeljanz XR
Product Name: Tofacitinib XR
Product Code: EMEA/H/C/004214
Pharmaceutical Form: Tablet

Primary Outcome(s)

Primary end point(s): The primary outcome is the difference in self-reported disease activity, measured with the Routine Assessment of Patient Index Data 3 (RAPID-3), between morning and evening dosing of tofacitinib XR after 3 months of treatment.

Main Objective: The primary outcome is the difference in self-reported disease activity, measured with the Routine Assessment of Patient Index Data 3 (RAPID-3), between morning and evening dosing of tofacitinib XR after 3 months of treatment.

Secondary Objective: Secondary endpoints are: (self-reported) disease activity (states); morning stiffness; general health; fatigue; pain; sleep; functional ability; quality of life; worker productivity; treatment satisfaction; and compliance. In addition, we will investigate whether the expression of circadian clock genes and microbiota composition change over time and whether these changes correlate with treatment response.

Timepoint(s) of evaluation of this end point: Patients will be assessed at baseline and after 1, 3 and 6 months of treatment. At each visit patients will fill out online questionnaires and are seen by the research nurse, who calculates the DAS or DAPSA depending on the diagnosis.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Patients will be assessed at baseline and after 1, 3 and 6 months of treatment. At each visit patients will fill out online questionnaires and are seen by the research nurse, who calculates the DAS or DAPSA depending on the diagnosis. Additional blood and faecal samples will be taken at baseline (T0), 1 month (T1, only blood), 3 months (T3) and 6 months (T6). Finally, patients will wear an actigraph unit, a wristwatch-like package, on the wrist 2-times for 2 weeks at home. The actigraph will be picked up by the patient in the hospital 2 weeks prior to the visit.

Secondary end point(s): Secondary endpoints are: (self-reported) disease activity (states); morning stiffness; general health; fatigue; pain; sleep; functional ability; quality of life; worker productivity; treatment satisfaction; and compliance. In addition, we will investigate whether the expression of circadian clock genes and microbiota composition change over time and whether these changes correlate with treatment response.

Secondary ID(s)

ChronIA001

Source(s) of Monetary Support

Pfizer B.V.

Ethics review

Status: Approved
Approval date: 14/02/2022
Contact: