Effects of Tofacitinib (CP-690,550) on Magnetic Resonance Imaging (MRI)- Assessed Joint Structure In Early Rheumatoid Arthritis (RA)

Rheumatoid Arthritis Clinical Trial

Official title:

An Exploratory Phase 2, Randomized, Double-blind, Multicenter Study To Assess The Effects Of Tofacitinib (Cp-690,550) On Magnetic Resonance Imaging Endpoints, In Methotrexate Naive Subjects With Early Active Rheumatoid Arthritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01164579
• Other study ID #: A3921068
• Secondary ID: 2010-020890-18
• Status: Completed
• Phase: Phase 2
• First received: July 15, 2010
• Last updated: April 21, 2015
• Start date: October 2010
• Est. completion date: November 2013

Study information

• Verified date: April 2015
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Evaluation of efficacy and safety of tofacitinib (CP-690,550) for the treatment of early rheumatoid arthritis in adult patients with moderate to severe disease who are methotrexate naïve. The efficacy will be evaluated by exploring the effects on joint structure assessed by magnetic resonance imaging, x-rays and by standard clinical assessment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 109
• Est. completion date: November 2013
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult patients with moderate to severe early rheumatoid arthritis (< 2 years) who are methotrexate and biologic disease modifying antirheumatic drug naive.

Exclusion Criteria:

• Pregnant or lactating patients;

• Patients with renal or hepatic impairment or other severe or progressing disease;

• Patients with contraindication to magnetic resonance imaging with gadolinium contrast.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Tasocitinib plus Methotrexate
Tofacitinib (CP 690,550) 10 mg BID, tablets + methotrexate (MTX) 10 mg/wk to 20 mg/wk, titrated over 2 months
• Tofacitinib plus placebo methotrexate
Tofacitinib (CP-90,550) 10 mg BID, tablets. Placebo to match methotrexate (MTX) capsules titrated as in Treatment Arm 1.
• Placebo tofacitinib plus Methotrexate
Methotrexate (MTX) 10 mg/wk to 20 mg/wk, capsules, titrated over 2 months. Placebo in tablets to match tofacitinib

Locations

Country	Name	City	State
Argentina	Consultorios Reumatologicos Pampa	Buenos Aires
Argentina	OMI - Organización Médica de Investigación	Buenos Aires
Argentina	Saint Dennis Medical Group S.A.	Buenos Aires
Chile	Consulta Privada Dr. Juan Ignacio Vargas	Osorno	X Region
Chile	Hospital Base Valdivia	Valdivia	Region XIV
Croatia	University Hospital Centre Split,Department for Internal Medicine, Division of Clinical Rheumatology	Split
Croatia	General Hospital Sveti Duh	Zagreb
Czech Republic	ARTMEDI UPD s r.o.	Hostivice
Czech Republic	Nemocnice na Frantisku	Praha 1
Czech Republic	Nemocnice na Frantisku s poliklinikou	Praha 1
Czech Republic	DC Mediscan	Praha 11 - Chodov
Czech Republic	Revmatologicky ustav	Praha 2
Czech Republic	Uherskohradistska nemocnice, a.s.	Uherske Hradiste
Czech Republic	Nemocnice Atlas, a.s.	Zlin
Czech Republic	PV-Medical s.r.o.	Zlin
Hungary	Drug Research Center Kft.	Balatonfured
Hungary	Orszagos Reumatologiai es Fizioterapias Intezet	Budapest
Hungary	Synexus Magyarorszag Kft.	Budapest
Hungary	Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum, Reumatologiai Tanszek	Debrecen
Hungary	Petz Aladar Megyei Oktato Korhaz/Reumatologiai es Mozgasszervi Rehabilitacios Centrum	Gyor
Mexico	Hospital Angeles Mocel	Chapultepec
Mexico	Investigacion y Biomedicina de Chihuahua S.C	Chihuahua
Mexico	Centro de Investigacion y Tratamiento Reumatologico S.C.	Mexico	D. F.
Mexico	Centro de Investigacion y Tratamiento Reumatologico SC	Mexico	Distrito Federal
Mexico	Hospital Angeles Mocel	Mexico	D.f.
Mexico	Hospital Angeles Mocel	Mexico D.F.
Mexico	Centro de Alta Especialidad en Reumatologia e Investigacion del Potosi S.C.	San Luis Potosi
Poland	Niepubliczny Zaklad Opieki Zdrowotnej Centrum Osteoporozy i Chorob Kostno-Stawowych J.	Bialystok
Poland	Prywatna Praktyka Lekarska Prof. UM dr hab. med. Pawel Hrycaj	Poznan
Poland	Nzoz "Nasz Lekarz"	Torun
Puerto Rico	Mindful Medical Research	San Juan
Puerto Rico	San Juan Arthritis & Research Center	San Juan
United States	Office of John P. Lavery, MD, PA	Allen	Texas
United States	ArthroCare, Arthritis Care & Research, PC	Gilbert	Arizona
United States	Talbert Medical Group	Huntington Beach	California
United States	Oklahoma Medical Research Foundation	Oklahoma City	Oklahoma
United States	Millennium Research	Ormond Beach	Florida
United States	DMI Research, Inc.	Pinellas Park	Florida
United States	St. Petersburg Arthritis Center	St. Petersburg	Florida
United States	Inland Rheumatology Clinical Trials, Inc.	Upland	California

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Argentina,  Chile,  Croatia,  Czech Republic,  Hungary,  Mexico,  Poland,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline to Month 3 in Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) Wrist and Metacarpophalangeal (MCP) Synovitis	Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the first through fifth MCP joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 24. A negative value in synovitis change from Baseline score indicates an improvement.	Month 3	No
Primary	Change From Baseline to Month 6 in OMERACT RAMRIS Wrist and MCP Bone Marrow Edema	Bone edema was assessed at 25 anatomic locations: 15 in 1 wrist and 10 in attached hand. Bone edema was defined as a lesion within the trabecular bone, with ill-defined margins and signal characteristics consistent with increased water content. Each bone was scored separately; the scale was 0-3 based on the proportion of bone with edema, as follows 0: no edema; 1: 1-33% of bone edematous; 2: 34-66% of bone edematous; 3: 67-100%. OMERACT RAMRIS total bone edema score for hands/wrists was sum of the individual scores for each location. Thus the maximum score per hand/wrist was 75 (range 0-75). Increasing score=greater severity.	Month 6	No
Secondary	Change From Baseline to Months 1, 6, and 12 in OMERACT RAMRIS Wrist and MCP Synovitis	Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the first through fifth MCP joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 24. A negative value in synovitis change from Baseline score indicates an improvement.	Months 1, 6, and 12	No
Secondary	Change From Baseline to Months 1, 3, and 12 in OMERACT RAMRIS Bone Marrow Edema in Wrist and MCP	Bone edema was assessed at 25 anatomic locations: 15 in 1 wrist and 10 in attached hand. Bone edema was defined as a lesion within the trabecular bone, with ill-defined margins and signal characteristics consistent with increased water content. Each bone was scored separately; the scale was 0â€"3 based on the proportion of bone with edema, as follows 0: no edema; 1: 1â€"33% of bone edematous; 2: 34â€"66% of bone edematous; 3: 67â€"100%. OMERACT RAMRIS total bone edema score for hands/wrists was sum of the individual scores for each location. Thus the maximum score per hand/wrist was 75 (range 0-75). Increasing score=greater severity.	Months 1, 3, and 12	No
Secondary	Change From Baseline to Months 1, 3, 6, and 12 in OMERACT RAMRIS Wrist and MCP Erosions	Bone erosion assessed at 25 anatomic locations: 15 in 1 wrist and 10 in attached hand. Each site was scored in 1.0 increments from 0 (no damage) to 10 (severe damage), indicating erosion (each unit=10% bone loss) of original articular bone. OMERACT RAMRIS total erosion score for hands/wrists was sum of the individual scores for each location. Thus the maximum score per hand/wrist is 250 (range 0-250). Increasing score=greater severity.	Months 1, 3, 6, and 12	No
Secondary	Modified Total Sharp Score (mTSS) at Months 6 and 12	Modified TSS is a measure of change in joint health. TSS is defined as joint space narrowing score (range 0 [no narrowing] to 168 [high narrowing]) plus (+) erosion score (range is from 0 [no erosion] to 280 [high erosion]). The modified TSS range is from 0 (no damage) to 448 (bad joint status). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.	Months 6 and 12	No
Secondary	Change From Baseline to Months 6 and 12 in mTSS	Modified TSS is a measure of change in joint health. TSS is defined as joint space narrowing score (range 0 [no narrowing] to 168 [high narrowing]) + erosion score (range is from 0 [no erosion] to 280 [high erosion]). The modified TSS range is from 0 (no damage) to 448 (bad joint status). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.	Months 6 and 12	No
Secondary	Joint Space Narrowing (JSN) Scores at Months 6 and 12	JSN score (a component of the modified TSS) is a measure of change in joint health. JSN score range is 0 (no narrowing) to 168 (high narrowing). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.	Months 6 and 12	No
Secondary	Change From Baseline to Months 6 and 12 in JSN Scores	JSN score (a component of the modified TSS) is a measure of change in joint health. JSN score range is 0 (no narrowing) to 168 (high narrowing). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.	Months 6 and 12	No
Secondary	Erosion Scores at Months 6 and 12	Erosion score (a component of the modified TSS) is a measure of change in joint health. Erosion score range is from 0 (no erosion) to 280 (high erosion). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.	Months 6 and 12	No
Secondary	Change From Baseline to Months 6 and 12 in Erosion Score	Erosion score (a component of the modified TSS) is a measure of change in joint health. Erosion score range is from 0 (no erosion) to 280 (high erosion). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.	Months 6 and 12	No
Secondary	Percentage of Participants With an American College of Rheumatology (ACR) 20 Percent (%) Improvement (ACR20) Response	ACR20 response: greater than or equal to (≥)20% improvement in tender joint count; ≥20% improvement in swollen joint count; and ≥20% improvement in at least 3 of 5 remaining ACR core measures: Participant's Assessment of Pain; Participant's Global Assessment of Disease Activity; Physician Global Assessment of Disease Activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and C-Reactive Protein (CRP).	Months 1, 2, 3, 6, 9, and 12	No
Secondary	Percentage of Participants With an ACR 50% Improvement (ACR50) Response	ACR50 response: ≥ 50% improvement in tender or swollen joint counts and 50% improvement in 3 of the following 5 criteria: 1) Physician's Global Assessment of Disease Activity, 2) Participant's Assessment of disease activity, 3) Paricipant's Assessment of Pain, 4) Participant's assessment of functional disability via a HAQ, and 5) CRP at each visit.	Months 1, 2, 3, 6, 9, and 12	No
Secondary	Percentage of Participants With an ACR 70% Improvement (ACR70) Response	ACR70 response: ≥70% improvement in tender or swollen joint counts and 70% improvement in 3 of the following 5 criteria: 1) Physician's Global Assessment of Disease Activity, 2) Participant's Assessment of Disease Activity, 3) Participant's Assessment of Pain, 4) Participant's Assessment of Functional Disability via a HAQ, and 5) CRP at each visit.	Months 1, 2, 3, 6, 9, and 12	No
Secondary	Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP])	DAS28-3 (CRP) was calculated from the swollen joint count and tender joint count using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (CRP) less than or equal to (≤)3.2 implied low disease activity and greater than (>)3.2 to 5.1 implied moderate to high disease activity, and DAS28-3 (CRP) less than (<)2.6 = remission.	Baseline and Months 1, 2, 3, 6, 9, and 12	No
Secondary	Change From Baseline in DAS28-3 (CRP)	DAS28-3 (CRP) was calculated from the swollen joint count and tender joint count using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity.	Months 1, 2, 3, 6, 9, and 12	No
Secondary	Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR])	DAS28-4 (ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (millimeters per hour [mm/hour]) and Participant Global Assessment of disease activity (participant rated arthritis activity assessment). Total score range: 0 to 9.4; higher score=more disease activity. DAS28-4 (ESR) ≤3.2 implied low disease activity and >3.2 to 5.1 implied moderate to high disease activity, and DAS28-4 (ESR) <2.6 = remission.	Baseline and Months 1, 2, 3, 6, 9, and 12	No
Secondary	Change From Baseline in DAS28-4 (ESR)	DAS28-4 (ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (millimeters per hour [mm/hour]) and Participant Global Assessment of disease activity (participant rated arthritis activity assessment). Total score range: 0 to 9.4; higher score=more disease activity.	Months 1, 2, 3, 6, 9, and 12	No
Secondary	Percentage of Participants With DAS28-3 (CRP) Response (Good or Moderate Improvement)	DAS28-3(CRP) was calculated from the swollen joint count and tender joint count using 28-joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28 categorical responses define a good (absolute: <3.2 or >1.2 improvement from baseline [BL]), moderate (absolute: 3.2-5.1 or 0.6-1.2 change from BL), or no response (absolute: >5.1 or <0.6 change from BL).	Months 1, 2, 3, 6, 9, and 12	No
Secondary	Percentage of Participants With DAS28-3 (CRP) Score ≤3.2	DAS28-3(CRP) was calculated from the swollen joint count and tender joint count using 28-joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3(CRP) ≤3.2 implied low disease activity.	Months 1, 2, 3, 6, 9, and 12	No
Secondary	Percentage of Participants With DAS28-3 (CRP) Score <2.6	DAS28-3(CRP) was calculated from the swollen joint count and tender joint count using 28-joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3(CRP) <2.6 implied remission.	Months 1, 2, 3, 6, 9, and 12	No
Secondary	Percentage of Participants With DAS28-4 (ESR) Response (Good or Moderate Improvement)	DAS28-4(ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (mm/hour) and Participant's Global Assessment of Disease Activity (participant rated arthritis activity assessment). Total score range: 0 to 9.4, higher score=more disease activity. DAS28 categorical responses define a good (absolute: <3.2 or >1.2 improvement from BL), moderate (absolute: 3.2-5.1 or 0.6-1.2 change from BL), or no response (absolute: >5.1 or <0.6 change from BL).	Months 1, 2, 3, 6, 9, and 12	No
Secondary	Percentage of Participants With DAS28-4 (ESR) ≤3.2	DAS28-4(ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (mm/hour) and Participant's Global Assessment of Disease Activity (participant rated arthritis activity assessment). Total score range: 0 to 9.4, higher score=more disease activity. DAS28-4(ESR) ≤3.2 implied low disease activity.	Months 1, 2, 3, 6, 9, and 12	No
Secondary	Percentage of Participants With DAS28-4 (ESR) <2.6	DAS28-4(ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (mm/hour) and Participant's Global Assessment of Disease Activity (participant rated arthritis activity assessment). Total score range: 0 to 9.4, higher score=more disease activity. DAS28-4(ESR) <2.6 implied remission.	Months 1, 2, 3, 6, 9, and 12	No

External Links

•   To obtain contact information for a study center near you, click here.