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.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

30 Sep 2024 → ongoing

Decision date (initial)

2024-09-30

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Pfizer B.V.

External identifiers

EU CT number

2024-517865-17-01

EudraCT number

2021-004131-84

ISRCTN

ISRCTN68663074

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

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 objectives 13

1. (self-reported) disease activity (states)
2. morning stiffness
3. general health
4. fatigue
5. pain
6. sleep
7. functional ability
8. quality of life
9. worker productivity
10. treatment satisfaction
11. compliance
12. changes in expression of circadian clock genes
13. changes in microbiota composition

Conditions and MedDRA coding

Rheumatoid arthritis or psoriatic arthritis according to respectively 2010 criteria or CASPAR criteria

Regulatory references

Scientific advice from competent authorities

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Plan to share IPD

No

IPD plan description

Individual participant data are available upon reasonable request.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. RA or PsA, , according to respectively the ACR/EULAR 2010 criteria for RA and CASPAR criteria
2. Active disease, respectively defined as a DAS>2.4 or DAPSA>14
3. Age ≥18 years

Exclusion criteria 5

1. Current or previous treatment of arthritis with tsDMARD(s)
2. Prednisone (or equivalent) usage at a dose of >7.5mg
3. Work in shifts
4. (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)
5. Unable to understand, speak and write in Dutch.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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 endpoints 2

1. 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.
2. 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.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Sponsor organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Address

Dr. Molewaterplein 40

City

Rotterdam

Postcode

3015 GD

Country

Netherlands

Scientific contact point

Organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Contact name

Dr. Pascal H.P. de Jong

Public contact point

Organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Contact name

Dr. Pascal H.P. de Jong

Locations

1 EU/EEA country · 2 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

Documents 4 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