NCT02281552

A Study To Evaluate The Safety And Efficacy Of Tofacitinib Modified Release Tablets Compared To Tofacitinib Immediate Release Tablets In Adult Patients With Rheumatoid Arthritis

Completed Phase 3 Results posted Last updated 12 October 2018

What this trial tests

Phase 3 trial testing Tofacitinib in Rheumatoid Arthritis in 209 participants. Completed in 15 March 2017.

Timeline

18 November 2014

Primary endpoint
15 March 2017

15 March 2017

Quick facts

Lead sponsor	Pfizer
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	209
Start date	18 November 2014
Primary completion	15 March 2017
Estimated completion	15 March 2017
Sites	36 locations across Japan

Drugs / interventions tested

• Tofacitinib (tofacitinib) — full drug profile →
• Tofacitinib (tofacitinib) — full drug profile →

Conditions studied

• Rheumatoid Arthritis — all drugs for Rheumatoid Arthritis →

Sponsor

Pfizer — full company profile →

Who can join

20 and older, any sex, with Rheumatoid Arthritis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Disease Activity Score in 28 Joints Using 4 Variables (DAS28-4) (C-Reactive Protein [CRP]) at Week 12 Primary · Baseline, Week 12

DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (CRP) was calculated from swollen joint count (SJC) and tender/painful joint count (TJC) using 28 joints count, CRP (milligrams per liter \[mg/L\]) and patient global assessment of disease activity on a 100 millimeter (mm) visual analog scale (VAS: scores ranging from 0 mm \[very well\] to 100 mm \[extremely bad\], higher scores indicate worse health condition). Total DAS28-4 (CRP) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (CRP) \[less t

Group	Value	95% CI
Tofacitinib Modified Release (MR)	-2.43	± 0.09
Tofacitinib Immediate Release (IR)	-2.85	± 0.09

Change From Baseline in Disease Activity Score in 28 Joints Using 4 Variables (DAS28-4) (Erythrocyte Sedimentation Rate [ESR]) at Week 12 Secondary · Baseline, Week 12

DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, ESR (millimeters per hour \[mm/hr\]) and patient global assessment of disease activity on a 100 mm visual analog scale (VAS: scores ranging from 0 mm \[very well\] to 100 mm \[extremely bad\], higher scores indicate worse health condition). Total DAS28-4 (ESR) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (ESR) \<=3.2 implied low disease activity and \>3.2 to \<=5.1 implied moderat

Group	Value	95% CI
Tofacitinib Modified Release (MR)	-2.50	± 0.09
Tofacitinib Immediate Release (IR)	-2.86	± 0.09

Number of Participants Achieving an American College of Rheumatology 20 Percent [%] (ACR20) Response at Week 12 Secondary · Week 12

Participants with 20% improvement in 68-tender and 66-swollen joint counts and 20% improvement in at least 3 of the 5 measures: patient's global assessment of arthritis, physician global assessment of arthritis, patient's assessment of arthritis pain, health assessment questionnaire-disability index(HAQ-DI) and CRP. Patient's global assessment of arthritis: participant assessed arthritis by 100 mm VAS, score: 0 mm (no arthritis) to 100 mm (extreme arthritis), higher score implied more arthritis. Physician global assessment of arthritis: physician judged participants arthritis by 100 mm VAS, sc

Group	Value	95% CI
Tofacitinib Modified Release (MR)	87
Tofacitinib Immediate Release (IR)	83

Number of Participants Achieving an American College of Rheumatology 50% (ACR50) Response at Week 12 Secondary · Week 12

Participants with 50% improvement in 68-tender and 66-swollen joint counts and 50% improvement in at least 3 of the 5 measures: patient's global assessment of arthritis, physician global assessment of arthritis, patient's assessment of arthritis pain, health assessment questionnaire-disability index(HAQ-DI) and CRP. Patient's global assessment of arthritis: participant assessed arthritis by 100 mm VAS, score: 0 mm (no arthritis) to 100 mm (extreme arthritis), higher score implied more arthritis. Physician global assessment of arthritis: physician judged participants arthritis by 100 mm VAS, sc

Group	Value	95% CI
Tofacitinib Modified Release (MR)	70
Tofacitinib Immediate Release (IR)	71

Number of Participants Achieving an American College of Rheumatology 70% (ACR70) Response at Week 12 Secondary · Week 12

Participants with 70% improvement in 68-tender and 66-swollen joint counts and 70% improvement in at least 3 of the 5 measures: patient's global assessment of arthritis, physician global assessment of arthritis, patient's assessment of arthritis pain, health assessment questionnaire-disability index(HAQ-DI) and CRP. Patient's global assessment of arthritis: participant assessed arthritis by 100 mm VAS, score: 0 mm (no arthritis) to 100 mm (extreme arthritis), higher score implied more arthritis. Physician global assessment of arthritis: physician judged participants arthritis by 100 mm VAS, sc

Group	Value	95% CI
Tofacitinib Modified Release (MR)	32
Tofacitinib Immediate Release (IR)	48

Number of Participants With DAS Remission (DAS28-4-CRP <2.6) at Week 12 Secondary · Week 12

DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (CRP) was calculated from SJC and TJC using 28 joints count, CRP (mg/L) and patient global assessment of disease activity on a 100 mm visual analog scale (VAS: scores ranging from 0 mm \[very well\] to 100 mm \[extremely bad\], higher scores indicate worse health condition). Total DAS28-4 (CRP) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (CRP) \<=3.2 implied low disease activity and \>3.2 to \<=5.1 implied moderate disease activity, \>5.1

Group	Value	95% CI
Tofacitinib Modified Release (MR)	52
Tofacitinib Immediate Release (IR)	72

Number of Participants With DAS Remission (DAS28-4-ESR <2.6) at Week 12 Secondary · Week 12

DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, ESR (mm/hr) and patient global assessment of disease activity on a 100 mm visual analog scale (VAS: scores ranging from 0 mm \[very well\] to 100 mm \[extremely bad\], higher scores indicate worse health condition). Total DAS28-4 (ESR) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (ESR) \<= 3.2 implied low disease activity and \>3.2 to \<=5.1 implied moderate disease activity, \>5.

Group	Value	95% CI
Tofacitinib Modified Release (MR)	18
Tofacitinib Immediate Release (IR)	36

Number of Participants With Low Disease Activity (DAS28-4-CRP <=3.2) at Week 12 Secondary · Week 12

DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (CRP) was calculated from SJC and TJC using 28 joints count, CRP (mg/L) and patient global assessment of disease activity on a 100 mm visual analog scale (VAS: scores ranging from 0 mm \[very well\] to 100 mm \[extremely bad\], higher scores indicate worse health condition). Total DAS28-4 (CRP) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (CRP) \<=3.2 implied low disease activity and \>3.2 to \<=5.1 implied moderate disease activity, \>5.1

Group	Value	95% CI
Tofacitinib Modified Release (MR)	76
Tofacitinib Immediate Release (IR)	82

Number of Participants With Low Disease Activity (DAS28-4-ESR <=3.2) at Week 12 Secondary · Week 12

DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, ESR (mm/hr) and patient global assessment of disease activity on a 100 mm visual analog scale (VAS: scores ranging from 0 mm \[very well\] to 100 mm \[extremely bad\], higher scores indicate worse health condition). Total DAS28-4 (ESR) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (ESR) \<=3.2 implied low disease activity and \>3.2 to \<=5.1 implied moderate disease activity, \>5.1

Group	Value	95% CI
Tofacitinib Modified Release (MR)	44
Tofacitinib Immediate Release (IR)	63

Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12 Secondary · Baseline, Week 12

HAQ-DI assesses the degree of difficulty a participant has experienced during the past week in 8 categories of daily living activities: dressing/grooming; arising; eating; walking; reach; grip; hygiene; and other activities over past week. Each activity category consisted of 2-3 items. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0 (least difficulty) and 3 (extreme difficulty), where higher scor

Group	Value	95% CI
Tofacitinib Modified Release (MR)	-0.44	± 0.04
Tofacitinib Immediate Release (IR)	-0.46	± 0.04

Number of Participants Achieving an Improvement of at Least 0.22 Units in Health Assessment Questionnaire (HAQ Scores) at Week 12 Secondary · Week 12

HAQ-DI assesses the degree of difficulty a participant has experienced during the past week in 8 categories of daily living activities: dressing/grooming; arising; eating; walking; reach; grip; hygiene; and other activities over past week. Each activity category consisted of 2-3 items. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0 (least difficulty) and 3 (extreme difficulty), where higher scor

Group	Value	95% CI
Tofacitinib Modified Release (MR)	65
Tofacitinib Immediate Release (IR)	60

Change From Baseline in the Short Form 36 (SF-36) Health Survey Domain Scores at Week 12 Secondary · Baseline, Week 12

SF-36 is a participant reported standardized survey designed to assess generic health related quality of life. It consisted of 36 items evaluating 8 aspects of functional health and well-being: physical functioning, role physical, bodily pain, social functioning, mental health, role emotional, vitality, and general health. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Scores of 8 health aspects were aggregated to derive the two component scores (physical component scores \[PCS\], mental componen

Physical Functioning

Group	Value	95% CI
Tofacitinib Modified Release (MR)	5.54	± 0.67
Tofacitinib Immediate Release (IR)	6.29	± 0.68

Role Physical

Group	Value	95% CI
Tofacitinib Modified Release (MR)	6.51	± 0.81
Tofacitinib Immediate Release (IR)	6.97	± 0.83

Bodily Pain

Group	Value	95% CI
Tofacitinib Modified Release (MR)	9.41	± 0.77
Tofacitinib Immediate Release (IR)	11.92	± 0.78

General Health

Group	Value	95% CI
Tofacitinib Modified Release (MR)	4.53	± 0.52
Tofacitinib Immediate Release (IR)	4.72	± 0.53

Vitality

Group	Value	95% CI
Tofacitinib Modified Release (MR)	8.07	± 0.75
Tofacitinib Immediate Release (IR)	8.20	± 0.76

Social Function

Group	Value	95% CI
Tofacitinib Modified Release (MR)	4.26	± 0.63
Tofacitinib Immediate Release (IR)	5.06	± 0.64

Role Emotional

Group	Value	95% CI
Tofacitinib Modified Release (MR)	7.23	± 0.86
Tofacitinib Immediate Release (IR)	6.56	± 0.87

Mental Health

Group	Value	95% CI
Tofacitinib Modified Release (MR)	4.46	± 0.80
Tofacitinib Immediate Release (IR)	5.26	± 0.81

Adverse events — posted to ClinicalTrials.gov

Time frame: From baseline up to 12 weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Tofacitinib Modified Release (MR)

Serious: 5/104 (5%)

Deaths: 0/104

Tofacitinib Immediate Release (IR)

Serious: 4/105 (4%)

Deaths: 0/105

Serious adverse events (7 terms)

Reaction	System	Tofacitinib Modified Relea…	Tofacitinib Immediate Rele…
Pneumocystis jirovecii pneumonia	Infections and infestations	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Pneumonia	Infections and infestations	—	—
Pneumonia bacterial	Infections and infestations	—	—
Femoral neck fracture	Injury, poisoning and procedural complications	—	—
Rectal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	—	—

Other adverse events (1 terms — click to expand)

Reaction	System	Tofacitinib Modified Relea…	Tofacitinib Immediate Rele…
Nasopharyngitis	Infections and infestations	—	—

Most-reported serious reactions: Pneumocystis jirovecii pneumonia, Anaemia, Pneumonia, Pneumonia bacterial, Femoral neck fracture, Rectal cancer, Interstitial lung disease.

Data from ClinicalTrials.gov NCT02281552 adverse events section.

Sponsor's own description

This is a 12 week study that will evaluate the efficacy and safety of the 11 mg tofacitinib modified release tablet taken once a day in patients with rheumatoid arthritis who continue taking methotrexate. Results for the modified release tablets will be compared to the efficacy and safety of the 5 mg tofacitinib immediate release tablets taken twice a day in patients with rheumatoid arthritis who continue taking methotrexate.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Signal Transducer and Activator of Transcription (STATs) Proteins in Cancer and Inflammation: Functions and Therapeutic Implication.
   Loh CY, Arya A, Naema AF, Wong WF, et al · · 2019 · cited 241× · PMID 30847297 · DOI 10.3389/fonc.2019.00048
2. Malignancy risk with tofacitinib versus TNF inhibitors in rheumatoid arthritis: results from the open-label, randomised controlled ORAL Surveillance trial.
   Curtis JR, Yamaoka K, Chen YH, Bhatt DL, et al · · 2023 · cited 103× · PMID 36600185 · DOI 10.1136/ard-2022-222543
3. Identification of two tofacitinib subpopulations with different relative risk versus TNF inhibitors: an analysis of the open label, randomised controlled study ORAL Surveillance.
   Kristensen LE, Danese S, Yndestad A, Wang C, et al · · 2023 · cited 89× · PMID 36931693 · DOI 10.1136/ard-2022-223715
4. Impact of cardiovascular risk enrichment on incidence of major adverse cardiovascular events in the tofacitinib rheumatoid arthritis clinical programme.
   Dougados M, Charles-Schoeman C, Szekanecz Z, Giles JT, et al · · 2023 · cited 13× · PMID 36720582 · DOI 10.1136/ard-2022-223406
5. Modified- versus immediate-release tofacitinib in Japanese rheumatoid arthritis patients: a randomized, phase III, non-inferiority study.
   Tanaka Y, Sugiyama N, Toyoizumi S, Lukic T, et al · · 2019 · cited 12× · PMID 30137547 · DOI 10.1093/rheumatology/key250
6. Fracture in clinical studies of tofacitinib in rheumatoid arthritis.
   Hansen KE, Mortezavi M, Nagy E, Wang C, et al · · 2022 · cited 9× · PMID 36601090 · DOI 10.1177/1759720x221142346
7. Influenza Adverse Events in Patients with Rheumatoid Arthritis, Ulcerative Colitis, or Psoriatic Arthritis in the Tofacitinib Clinical Development Programs.
   Winthrop KL, Yndestad A, Henrohn D, Danese S, et al · · 2023 · cited 6× · PMID 36526796 · DOI 10.1007/s40744-022-00507-z
8. Risk Stratification of Patients with Psoriatic Arthritis and Ankylosing Spondylitis for Treatment with Tofacitinib: A Review of Current Clinical Data.
   Kristensen LE, Deodhar A, Leung YY, Vranic I, et al · · 2024 · cited 5× · PMID 38696034 · DOI 10.1007/s40744-024-00662-5