A Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Certolizumab Pegol in Combination With Methotrexate in the Treatment of Disease Modifying Antirheumatic Drugs (DMARD)-naïve Adults With Early Active Rheumatoid Arthritis

Rheumatoid Arthritis Clinical Trial

— C-early  

Official title:

A Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Certolizumab Pegol in Combination With Methotrexate for Inducing and Sustaining Clinical Response in the Treatment of DMARD-Naïve Adults With Early Active Rheumatoid Arthritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01519791
• Other study ID #: RA0055 Period 1
• Secondary ID: 2011-001729-25
• Status: Completed
• Phase: Phase 3
• Start date: January 2012
• Est. completion date: September 2015

Study information

• Verified date: March 2018
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is intended to evaluate the efficacy and safety of Certolizumab Pegol (CZP) in combination with Methotrexate (MTX) for inducing and sustaining clinical response in the treatment of Disease Modifying Antirheumatic Drug (DMARD)-naïve adults with early active Rheumatoid Arthritis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 880
• Est. completion date: September 2015
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subjects must have a time since diagnosis of adult-onset Rheumatoid Arthritis (RA) less than 1 year as defined by the 2010 ACR/EULAR classification criteria from Screening Visit

• Positive Rheumatoid Factor (RF) and/or positive anticyclic Citrullinated Peptide Antibody (anti-CCP)

• Active RA disease

• DMARD-naïve

• Subject is naïve to RA related biologics

Exclusion Criteria:

• A diagnosis of any other inflammatory Arthritis

• History of infected joint prosthesis, or other significant infection and other serious medical condition

• Known Tuberculosis (TB) disease or high risk of acquiring TB infection

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Biological:
• Certolizumab Pegol
Prefilled syringes containing an injectable volume of 1 ml of solution for injection CZP for single use at a dosage strength of 200 mg/ml. Injections will be given subcutaneously. CZP 400 mg at Baseline, Week 2 and Week 4, followed by a maintenance dose of 200 mg every 2 Weeks until Week 50.

Other:
• Placebo
2 syringes Placebo at Baseline, Week 2 and Week 4, followed by 1 syringe Placebo every 2 Weeks.

Biological:
• Methotrexate
The MTX treatment is to be initiated at a dose of 10 mg per Week (oral tablets at the strength of 2.5 mg/tablet). The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8. Patients who could not tolerate = 15 mg/week MTX by Week 8 were withdrawn while the maximum tolerated dose per patient (optimized dose) was maintained to Week 52.

Locations

Country	Name	City	State
Argentina	276	Buenos Aires
Argentina	284	Rosario
Argentina	279	San Juan
Argentina	291	Tucuman
Australia	6	Coffs Harbour	New South Wales
Australia	5	Fitzroy	Victoria
Australia	4	Geelong	Victoria
Australia	2	Herson	Queensland
Australia	3	Malvern	Victoria
Australia	1	Maroochydore	Queensland
Australia	7	Perth	Western Australia
Australia	8	Woodville South	South Australia
Austria	50	Wien
Belgium	51	Brussels
Belgium	126	Gilly
Belgium	36	Kortrijk
Belgium	65	Yvoir
Canada	235	Hamilton	Ontario
Canada	240	Kelowna	British Columbia
Canada	188	Montreal	Quebec
Canada	194	Trois-rivieres	Quebec
Colombia	303	Barranquilla
Colombia	272	Bogota
Colombia	293	Bogota
Colombia	299	Bogota
Colombia	297	Bucaramanga
Colombia	288	Chia
Colombia	271	Medellin
Colombia	298	Medellin
Czechia	108	Brno
Czechia	124	Bruntal
Czechia	38	Hradec Kralove
Czechia	37	Praha
France	16	Le Kremlin Bicetre
France	85	Le Mans
France	88	Montpellier Cedex 5
France	34	Orleans
France	79	Strasbourg
Germany	52	Bad Doberan
Germany	17	Bayreuth
Germany	113	Berlin
Germany	120	Berlin
Germany	89	Erfurt
Germany	70	Frankfurt
Germany	71	Hamburg
Germany	81	Hildesheim
Germany	127	Lingen
Germany	61	München
Germany	53	Planegg
Germany	132	Ratingen
Germany	49	Rendsburg
Germany	69	Rheine
Germany	114	Würzburg
Germany	59	Zerbst
Hungary	18	Budapest
Hungary	21	Budapest
Hungary	86	Eger
Hungary	131	Szolnok
Hungary	110	Szombathely
Hungary	19	Veszprem
Ireland	33	Cork
Ireland	54	Dublin
Ireland	32	Limerick
Italy	115	Ferrara
Italy	122	Milano
Italy	40	Reggio Emilia
Italy	72	Roma
Italy	41	Verona
Mexico	281	Durango
Mexico	286	Guadalajara
Mexico	302	Merida
Mexico	292	Mexico City
Mexico	280	Monterrey
Mexico	294	San Luis Potosi
Monaco	78	Monaco
Netherlands	42	Leiden
Poland	128	Bydgoszcz
Poland	67	Elblag
Poland	99	Krakow
Poland	92	Poznan
Poland	74	Torun
Poland	100	Warszawa
Poland	44	Wroclaw
Romania	58	Brasov
Romania	111	Bucharest
Romania	22	Bucharest
Romania	25	Bucharest
Romania	26	Bucharest
Romania	24	Iasi
Romania	57	Lasi
Spain	93	Coruna
Spain	47	Madrid
Spain	63	Santiago de Compostela
Sweden	76	Göteborg
Sweden	82	Huddinge
Sweden	106	Lund
Sweden	123	Malmö
Sweden	77	Stockholm
Sweden	75	Uppsala
Switzerland	118	Fribourg
Switzerland	68	St. Gallen
United Kingdom	125	Cannock
United Kingdom	105	Dudley
United Kingdom	56	Leeds
United Kingdom	121	London
United Kingdom	27	London
United Kingdom	80	Sheffield
United Kingdom	119	York
United States	207	Albuquerque	New Mexico
United States	217	Allen	Texas
United States	185	Amarillo	Texas
United States	161	Austin	Texas
United States	195	Bethlehem	Pennsylvania
United States	209	Birmingham	Alabama
United States	176	Brooklyn	New York
United States	215	Cedar Rapids	Iowa
United States	189	Charleston	South Carolina
United States	183	Clarksburg	West Virginia
United States	228	Clifton	New Jersey
United States	226	Coeur d'Alene	Idaho
United States	205	Columbia	South Carolina
United States	178	Corpus Christi	Texas
United States	160	Covina	California
United States	162	Dallas	Texas
United States	167	Duncansville	Pennsylvania
United States	236	Durham	North Carolina
United States	198	Eagan	Minnesota
United States	190	Fort Lauderdale	Florida
United States	174	Glendale	Wisconsin
United States	247	Glendale	Arizona
United States	177	Hagerstown	Maryland
United States	257	Hemet	California
United States	204	Hendersonville	Tennessee
United States	184	Houston	Texas
United States	206	Houston	Texas
United States	223	Houston	Texas
United States	170	Huntsville	Alabama
United States	196	Jupiter	Florida
United States	199	Kalamazoo	Michigan
United States	233	Kennewick	Washington
United States	238	Lake Mary	Florida
United States	229	Lebanon	New Hampshire
United States	181	Lincoln	Nebraska
United States	159	Los Angeles	California
United States	158	Mesquite	Texas
United States	232	Miami	Florida
United States	245	Middleburg Heights	Ohio
United States	180	Mobile	Alabama
United States	213	Naples	Florida
United States	175	Nassau Bay	Texas
United States	214	Ocala	Florida
United States	241	Oklahoma City	Oklahoma
United States	237	Orange Park	Florida
United States	255	Orlando	Florida
United States	163	Palm Harbor	Florida
United States	165	Paradise Valley	Arizona
United States	234	Paradise Valley	Arizona
United States	243	Phoenix	Arizona
United States	242	Plainview	New York
United States	249	Plano	Texas
United States	166	Plantation	Florida
United States	186	Portland	Oregon
United States	256	Reno	Nevada
United States	227	Rochester	New York
United States	179	Saint Louis	Missouri
United States	197	San Antonio	Texas
United States	201	San Leandro	California
United States	192	Sarasota	Florida
United States	224	South Bend	Indiana
United States	244	Springfield	Illinois
United States	251	Tucson	Arizona
United States	203	Tupelo	Mississippi
United States	202	Upland	California
United States	200	Vero Beach	Florida
United States	172	Whittier	California
United States	191	Wichita	Kansas
United States	210	Wichita	Kansas
United States	168	Wyomissing	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
UCB Pharma SA

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Canada,  Colombia,  Czechia,  France,  Germany,  Hungary,  Ireland,  Italy,  Mexico,  Monaco,  Netherlands,  Poland,  Romania,  Spain,  Sweden,  Switzerland,  United Kingdom, 

References & Publications (2)

Emery P, Bingham CO 3rd, Burmester GR, Bykerk VP, Furst DE, Mariette X, van der Heijde D, van Vollenhoven R, Arendt C, Mountian I, Purcaru O, Tatla D, VanLunen B, Weinblatt ME. Certolizumab pegol in combination with dose-optimised methotrexate in DMARD-na — View Citation

Weinblatt ME, Bingham CO 3rd, Burmester GR, Bykerk VP, Furst DE, Mariette X, van der Heijde D, van Vollenhoven R, VanLunen B, Ecoffet C, Cioffi C, Emery P. A Phase III Study Evaluating Continuation, Tapering, and Withdrawal of Certolizumab Pegol After One — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Subjects in Sustained Remission at Week 52	Sustained remission is defined as a Disease Activity Score [Erythrocyte Sedimentation Rate] (DAS28[ESR]) < 2.6 at both Weeks 40 and 52.; DAS28[ESR] is calculated using the Tender Joint Count (TJC), Swollen Joint Count (SJC) Erythrocyte Sedimentation Rate (ESR in mm/hour), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm) using the following formula: 0.56 x v(TJC) + 0.28 x v(SJC) + 0.70 x lognat (ESR) + 0.014 x PtGADA, where 28 joints are examined and a lower score indicates less disease activity.	Week 52
Secondary	Percentage of Subjects in Sustained Low Disease Activity (LDA) at Week 52	Sustained LDA is defined as a Disease Activity Score [Erythrocyte Sedimentation Rate] (DAS28[ESR]) = 3.2 at both Weeks 40 and 52.	Week 52
Secondary	Change From Baseline in Modified Total Sharp Score (mTSS) to Week 52	Van der Heijde modified Total Sharp Score (mTSS) is a methodology to assess the degree of joint damage by quantifying the extent of bone erosions and joint space narrowing for 44 and 42 joints, respectively. The mTSS ranges from 0 to 448, with higher scores representing greater damage.	From Baseline (Week 0) to Week 52
Secondary	Percentage of Subjects With Radiographic Non-progression From Baseline to Week 52	Radiographic non-progression is defined as change in mTSS = 0.5.	From Baseline (Week 0) to Week 52
Secondary	Change From Baseline in the Joint Erosion Score to Week 52	Erosions were assessed in 16 locations per hand and 6 joints per foot. Erosions for each hand location were scored from 0 to 5, with 0 indicating no erosion. Scores 1 to 5 may have included combinations of discrete erosion(s) and/or large erosions. Erosions for each foot joint were scored from 0 to 10, with 0 indicating no erosions.; The maximum possible erosion score for all 32-hand joints was 160. The maximum possible erosion score for all 12 feet joints was 120. Thus, the maximum possible total erosion score for hands and feet was 280.	From Baseline (Week 0) to Week 52
Secondary	Change From Baseline in the Joint Narrowing Score to Week 52	Joint space narrowing (JSN) was assessed in 15 locations per hand and 6 locations per foot. Joint space narrowing for each location was scored from 0 to 4, with 0 indicating no narrowing. The maximum possible score for JSN in all 30 hand joints was 120. The maximum possible score for JSN in all 12 feet joints was 48. Thus, the maximum possible total JSN score for Hands and feet was 168.	From Baseline (Week 0) to Week 52
Secondary	Percentage of Subjects Meeting the American College of Rheumatology 20 % Response Criteria (ACR20) at Week 52	The assessments are based on a 20 % or greater improvement from Baseline in the number of tender joints, a 20 % or more improvement in the number of swollen joints, and a 20% or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP).	From Baseline (Week 0) to Week 52
Secondary	Percentage of Subjects Meeting the American College of Rheumatology 50 % Response Criteria (ACR50) at Week 52	The assessments are based on a 50 % or greater improvement from Baseline in the number of tender joints, a 50 %, or more improvement in the number of swollen joints, and a 50 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP).	From Baseline (Week 0) to Week 52
Secondary	Percentage of Subjects Meeting the American College of Rheumatology 70 % Response Criteria (ACR70) at Week 52	The assessments are based on a 70 % or greater improvement from Baseline in the number of tender joints, a 70 %, or more improvement in the number of swollen joints, and a 70 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP).	From Baseline (Week 0) to Week 52
Secondary	Percentage of Subjects Meeting the 2011 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) Remission Criteria at Week 52	The ACR/EULAR 2011 remission criteria is defined as: Tender Joint Count (TJC) = 1, Swollen Joint Count (SJC) = 1, C-reactive protein (CRP) = 1 mg/dl and Patient's Global Assessment of Disease Activity (PtGADA) = 1.	Week 52
Secondary	Percentage of Subjects With Clinical Disease Activity Index (CDAI) = 2.8 at Week 52	CDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm), and Physician's Global Assessment of Disease Activity - Visual Analog Scale (PhGADA-VAS in mm). 28 joints are examined where a lower score indicates less disease activity.	Week 52
Secondary	Percentage of Subjects With Simplified Disease Activity Index (SDAI) = 3.3 at Week 52	SDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm), Physician's Global Assessment of Disease Activity - Visual Analog Scale (PhGADA-VAS in mm) and C-Reactive Protein (CRP in mg/L). 28 joints are examined where a lower score indicates less disease activity.	Week 52
Secondary	Percentage of Subjects With Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) < 2.6 at Week 52	DAS28[ESR] is calculated using the Tender Joint Count (TJC), Swollen Joint Count (SJC) Erythrocyte Sedimentation Rate (ESR in mm/hour), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm) using the following formula: 0.56 x v(TJC) + 0.28 x v(SJC) + 0.70 x lognat (ESR) + 0.014 x PtGADA, where 28 joints are examined and a lower score indicates less disease activity.	Week 52
Secondary	Percentage of Subjects Meeting the 2011 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) Remission Criteria Simplified for Clinical Practice at Week 52	The 2011 ACR/EULAR remission criteria simplified for clinical practice is defined as: Tender Joint Count (TJC) = 1, Swollen Joint Count (SJC) = 1 and Patient's Global Assessment of Disease Activity (PtGADA) = 1.	Week 52
Secondary	Percentage of Subjects Achieving a Good or Moderate European League Against Rheumatism (EULAR) Response at Week 52	Good response is defined as: DAS28[ESR] = 3.2 and decrease from Baseline by > 1.2; moderate response is defined as achievement of one of the following: DAS28[ESR] = 3.2 and decrease from Baseline > 0.6 and = 1.2; DAS28[ESR] > 3.2 and = 5.1 and decrease from Baseline > 0.6; DAS28[ESR] > 5.1 and decrease from Baseline >1.2.	From Baseline (Week 0) to Week 52
Secondary	Change From Baseline in Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) to Week 52	DAS28[ESR] is calculated using the Tender Joint Count (TJC), Swollen Joint Count (SJC) Erythrocyte Sedimentation Rate (ESR in mm/hour), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm) using the following formula: 0.56 x v(TJC) + 0.28 x v(SJC) + 0.70 x lognat (ESR) + 0.014 x PtGADA, where 28 joints are examined and a lower score indicates less disease activity. A negative value in DAS28[ESR] change from Baseline indicates an improvement from Baseline.	From Baseline (Week 0) to Week 52
Secondary	Change From Baseline in Clinical Disease Activity Index (CDAI) to Week 52	CDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm), and Physician's Global Assessment of Disease Activity - Visual Analog Scale (PhGADA-VAS in mm). 28 joints are examined where a lower score indicates less disease activity.; The CDAI score ranges from 0 to 76, with a negative value in CDAI change from Baseline indicating an improvement from Baseline.	From Baseline (Week 0) to Week 52
Secondary	Change From Baseline in Simplified Disease Activity Index (SDAI) to Week 52	SDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm), Physician's Global Assessment of Disease Activity - Visual Analog Scale (PhGADA-VAS in mm) and C-Reactive Protein (CRP in mg/L). 28 joints are examined where a lower score indicates less disease activity.; The SDAI score ranges from 0 to 86, with a negative value in SDAI change from Baseline indicating an improvement from Baseline.	From Baseline (Week 0) to Week 52
Secondary	Percentage of Subjects With a Health Assessment Questionnaire- Disability Index (HAQ-DI) = 0.5 at Week 52	Normative physical function is defined as HAQ-DI score = 0.5. The domains of the HAQ-DI are dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities.; The total score ranges from 0 to 3 with lower scores meaning lower disability.	Week 52
Secondary	Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) to Week 52	The domains of the HAQ-DI are dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities.; The total score ranges from 0 (no difficulty) to 3 (unable to do) with lower scores meaning lower disability.; A negative value in HAQ-DI change from Baseline indicates an improvement from Baseline.	From Baseline (Week 0) to Week 52
Secondary	Change From Baseline in the Bristol Rheumatoid Arthritis Fatigue- Multidimensional Questionnaire (BRAF-MDQ) Total Score to Week 52	BRAF-MDQ total score ranges from 0 to 70 (with higher scores indicating worse fatigue).; A negative value in BRAF-MDQ change from Baseline indicates an improvement from Baseline.	From Baseline (Week 0) to Week 52
Secondary	Number of Work Days Missed (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52	Number of work days missed in the last month for employed subjects.	Week 52
Secondary	Number of Work Days With Reduced Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52	Number of work days with reduced productivity in the last month for employed subjects.	Week 52
Secondary	Interference With Work Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52	The Arthritis interference in the last month with work productivity is measured on a scale that ranges from 0 (no interference) to 10 (complete interference) for employed subjects.	Week 52
Secondary	Number of Days With no Household Work (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52	Number of days with no household work in the last month.	Week 52
Secondary	Number of Days With Reduced Household Work Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52	Number of days with reduced household work productivity in the last month.	Week 52
Secondary	Number of Days With Hired Outside Help (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52	Number of days with hired outside help in the last month.	Week 52
Secondary	Number of Days Missed of Family/Social/Leisure Activities (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52	Number of days missed of family/social/leisure activities in the last month.	Week 52
Secondary	Interference With Household Work Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52	The Arthritis interference in the last month with household work productivity is measured on a scale that ranges from 0 (no interference) to 10 (complete interference).	Week 52
Secondary	Percentage of Subjects Achieving Low Disease Activity (LDA) at Week 52	LDA is defined as achieving a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) = 3.2.	Week 52

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