Study to Assess the Short- and Long-term Efficacy of Certolizumab Pegol Plus Methotrexate Compared to Adalimumab Plus Methotrexate in Subjects With Moderate to Severe Rheumatoid Arthritis (RA) Inadequately Responding to Methotrexate

Rheumatoid Arthritis Clinical Trial

Official title:

A Multicenter, Single-blind, Randomized Parallel-group Study to Assess the Short- and Long-term Efficacy of Certolizumab Pegol Plus Methotrexate Compared to Adalimumab Plus Methotrexate in Subjects With Moderate to Severe Rheumatoid Arthritis Responding Inadequately to Methotrexate

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01500278
• Other study ID #: RA0077
• Secondary ID: 2011-002067-20
• Status: Completed
• Phase: Phase 4
• Start date: December 2011
• Est. completion date: January 2016

Study information

• Verified date: July 2017
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is conducted to evaluate the short (12 Weeks) and long term (104 Weeks) efficacy of Certolizumab Pegol compared with Adalimumab both in combination with Methotrexate (MTX) in the treatment of moderate to severe Rheumatoid Arthritis (RA) that is not responding adequately to MTX.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 915
• Est. completion date: January 2016
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subject must have a diagnosis of Rheumatoid Arthritis (RA) at Screening, as defined by the 2010 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria (Aletaha D et al, 2010)

• Subject must have a positive Rheumatoid Factor (RF) and/or a positive anti-Cyclic Citrullinated Peptide antibody (anti-CCP) as determined by the central laboratory at Screening

• Subject must have moderate to severe RA disease at Screening and Baseline defined as:

1. Screening (all criteria required)

• = 4 swollen joints (of 28 prespecified joints)

• Disease Activity Score [Erythrocyte Sedimentation Rate] (DAS28[ESR]) > 3.2

• C-Reactive Protein (CRP) concentration = 10 mg/L (or 1.0 mg/dL) or Erythrocyte Sedimentation Rate (ESR) (Westergren) = 28 mm/hr

2. Baseline (both criteria required)

• = 4 swollen joints (of 28 prespecified joints)

• Disease Activity Score [Erythrocyte Sedimentation Rate] (DAS28[ESR]) > 3.2

• Subject must have inadequately responded previously to Methotrexate (MTX)

• Subject is using MTX 15 to 25 mg/week orally or subcutaneously at Screening and has used the same MTX regimen for a minimum of 28 days prior to Baseline

Exclusion Criteria:

• Subject has previously received any biological Disease Modifying Antirheumatic Drug (DMARD) or has received treatment with cyclophosphamide, chlorambucil, Janus Kinase, phosphodiesterase 4 inhibitors or investigational agents such as spleen tyrosine kinase

• Diagnosis of any other inflammatory arthritis

• Infected with Tuberculosis (TB) or high risk of acquiring TB infection

• Subjects with concurrent acute or chronic viral hepatitis B or C infection

• Subjects with a history of chronic or recurrent infections or subjects at high risk of infection

• Use of prohibited medications like nonbiological DMARDs (excluding MTX), biological DMARDs excluding study medications, experimental therapy, IA hyaluronic acid

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Biological:
• Certolizumab Pegol (CZP)
Active substance: an injectable volume of 1 ml solution for injection CZP Pharmaceutical form: prefilled syringes CZP Concentration: 200 mg/ml CZP Route of Administration: injections will be given subcutaneously: loading dose of CZP 400 mg at Baseline, and Weeks 2 and 4, followed by a maintenance dose of 200 mg every 2 weeks through Week 102 or withdrawal.
• Adalimumab (ADA)
Active substance: an injectable volume of 0.8 ml solution for injection ADA Pharmaceutical form: prefilled syringes ADA Concentration: 40 mg/0.8 ml ADA Route of Administration: injections will be given subcutaneously. ADA 40 mg plus an injection with Placebo (to preserve blind) at Baseline, and Weeks 2 and 4, followed by ADA 40 mg every 2 weeks through Week 102 or withdrawal.

Drug:
• Methotrexate (MTX)
Active substance: Methotrexate Pharmaceutical form: oral tablet Concentration: 15-25 mg/week Route of Administration: MTX orally

Locations

Country	Name	City	State
Australia	6	Camperdown	New South Wales
Australia	7	Clayton	Victoria
Australia	8	Fitzroy	Victoria
Australia	4	Hobart	Tasmania
Australia	5	Kogarah	New South Wales
Australia	1	Malvern	Victoria
Australia	2	Maroochydore	Queensland
Australia	3	Subiaco	Western Australia
Austria	85	Stockerau
Austria	22	Wien
Bulgaria	18	Pleven
Bulgaria	35	Plovdiv
Bulgaria	21	Sofia
Bulgaria	29	Sofia
Bulgaria	34	Sofia
Bulgaria	46	Sofia
Canada	221	Barrie
Canada	179	Edmonton	Alberta
Canada	183	Halifax	Nova Scotia
Canada	172	Hamilton	Ontario
Canada	174	Hamilton	Ontario
Canada	177	Ottawa	Ontario
Canada	206	Ottawa	Ontario
Canada	171	Quebec
Canada	218	Rimouski	Quebec
Canada	169	Sainte Foy	Quebec
Canada	175	St. Catharines	Ontario
Canada	168	St. John's	Newfoundland and Labrador
Canada	176	St. John's	Newfoundland and Labrador
Czechia	103	Brno
Czechia	61	Hradec Kralove
Czechia	58	Plzen
Czechia	49	Praha
Czechia	40	Uherske Hradiste
France	89	Brest
France	70	Le Mans
France	62	Lyon
France	72	Montpellier Cedex 5
France	90	Orleans
France	105	Toulouse Cedex 9
Germany	56	Berlin
Germany	47	Fulda
Germany	17	Hamburg
Germany	31	Heidelberg
Germany	37	Herne
Germany	64	Köln
Germany	63	Osnabrück
Germany	11	Ratingen
Germany	66	Rheine
Germany	48	Rostock
Germany	71	Traunstein
Germany	44	Zerbst
Greece	94	Heraklion
Greece	95	Larisa
Hungary	13	Budapest
Hungary	42	Budapest
Hungary	68	Gyula
Hungary	100	Kistarcsa
Hungary	43	Szeged
Hungary	33	Veszprem
Ireland	23	Dublin
Ireland	51	Dublin
Ireland	20	Limerick
Italy	80	Bergamo
Italy	38	Genova
Italy	88	Genova
Italy	79	Magenta
Italy	98	Napoli
Italy	67	Prato
Italy	36	Roma
Italy	39	Verona
Mexico	194	Chihuahua
Mexico	195	Chihuahua
Mexico	193	Guadalajara
Mexico	192	Monterrey
Mexico	191	San Luis Potosi
Monaco	60	Monaco
Poland	107	Bydgoszcz
Poland	106	Poznan
Poland	113	Warszawa
Poland	115	Warszawa
Poland	108	Wroclaw
Portugal	69	Coimbra
Portugal	76	Lisboa
Portugal	27	Lisbon
Portugal	14	Ponte De Lima
Portugal	81	Porto
Romania	54	Bacau
Romania	74	Braila
Romania	24	Bucharest
Romania	25	Bucharest
Romania	28	Bucharest
Romania	32	Bucharest
Romania	57	Bucharest
Romania	12	Cluj-Napoca
Romania	96	Galati
Romania	26	Iasi
Spain	16	A Coruna
Spain	52	A Coruna
Spain	30	Madrid
Spain	83	Madrid
Spain	82	Sabadell
Spain	65	Vigo
Switzerland	53	St. Gallen
Switzerland	50	Zürich
United Kingdom	86	Ashford
United Kingdom	78	Brighton
United Kingdom	59	Leeds
United Kingdom	19	London
United Kingdom	77	Poole
United Kingdom	55	Sheffield
United Kingdom	73	Upton
United Kingdom	99	Wigan
United States	154	Albany	New York
United States	205	Albuquerque	New Mexico
United States	211	Arlington	Virginia
United States	138	Austin	Texas
United States	142	Aventura	Florida
United States	178	Baltimore	Maryland
United States	137	Battle Creek	Michigan
United States	164	Bethlehem	Pennsylvania
United States	141	Birmingham	Alabama
United States	136	Brooklyn	New York
United States	210	Charleston	South Carolina
United States	140	Cincinnati	Ohio
United States	163	Clarksburg	West Virginia
United States	145	Coeur d'Alene	Idaho
United States	151	Corpus Christi	Texas
United States	147	Covina	California
United States	131	Dallas	Texas
United States	146	Dallas	Texas
United States	213	Dallas	Texas
United States	153	Detroit	Michigan
United States	132	Duncansville	Pennsylvania
United States	204	Eagan	Minnesota
United States	216	Fort Lauderdale	Florida
United States	161	Fullerton	California
United States	162	Gainesville	Florida
United States	215	Glendale	Wisconsin
United States	152	Hot Springs	Arkansas
United States	166	Houston	Texas
United States	212	Houston	Texas
United States	133	Jackson	Tennessee
United States	160	Knoxville	Tennessee
United States	217	La Mesa	California
United States	155	Lansing	Michigan
United States	220	Lewes	Delaware
United States	134	Lexington	Kentucky
United States	149	Los Angeles	California
United States	202	Maywood	Illinois
United States	144	Menifee	California
United States	187	Myrtle Beach	South Carolina
United States	184	Oklahoma City	Oklahoma
United States	135	Omaha	Nebraska
United States	203	Orangeburg	South Carolina
United States	219	Orchard Park	New York
United States	207	Plainview	New York
United States	170	Reno	Nevada
United States	180	Rochester	Minnesota
United States	185	Roseville	California
United States	208	Sacramento	California
United States	143	Saint Louis Park	Minnesota
United States	139	San Antonio	Texas
United States	157	Spokane	Washington
United States	181	Sugar Land	Texas
United States	167	Syracuse	New York
United States	201	Teaneck	New Jersey
United States	159	Tucson	Arizona
United States	214	Tuscaloosa	Alabama
United States	189	Van Nuys	California
United States	209	Vero Beach	Florida
United States	165	Victoria	Texas
United States	150	Voorhees	New Jersey
United States	148	Whittier	California
United States	190	Wyomissing	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
UCB Pharma SA	Parexel

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Bulgaria,  Canada,  Czechia,  France,  Germany,  Greece,  Hungary,  Ireland,  Italy,  Mexico,  Monaco,  Poland,  Portugal,  Romania,  Spain,  Switzerland,  United Kingdom, 

References & Publications (1)

Smolen JS, Burmester GR, Combe B, Curtis JR, Hall S, Haraoui B, van Vollenhoven R, Cioffi C, Ecoffet C, Gervitz L, Ionescu L, Peterson L, Fleischmann R. Head-to-head comparison of certolizumab pegol versus adalimumab in rheumatoid arthritis: 2-year effica — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Subjects Who Met the American College of Rheumatology 20 % (ACR20) Criteria at Week 12	Subjects who met the ACR20 criteria were those subjects with at least 20% improvement from Baseline for Tender Joint Count (TJC), Swollen Joint Count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGA-VAS).	Week 12
Primary	Percentage of Subjects Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) = 3.2 at Week 104	DAS28 [ESR] was 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 Patient Global Assessment of Arthritis, where 28 joints were examined and a lower score indicates less disease activity.	Week 104
Secondary	Percentage of Week 12 Responders Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) = 3.2 at Week 104	DAS28 [ESR] was 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 Patient Global Assessment of Arthritis, where 28 joints were examined and a lower score indicates less disease activity.; The definition of Week 12 responders was DAS28[ESR] Low Disease Activity (LDA) (ie = 3.2) or an improvement of = 1.2 in DAS28[ESR] relative to Baseline.	Week 104
Secondary	Percentage of Subjects Who Met the American College of Rheumatology 20 % (ACR20) Criteria at Week 6	Subjects who met the ACR20 criteria were those subjects with at least 20% improvement from Baseline for Tender Joint Count (TJC), Swollen Joint Count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGA-VAS).	Week 6
Secondary	Percentage of Subjects Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) = 3.2 at Week 6	DAS28 [ESR] was 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 Patient Global Assessment of Arthritis, where 28 joints were examined and a lower score indicates less disease activity.	Week 6
Secondary	Percentage of Subjects Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) = 3.2 at Week 12	DAS28 [ESR] was 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 Patient Global Assessment of Arthritis, where 28 joints were examined and a lower score indicates less disease activity.	Week 12
Secondary	Percentage of Subjects With a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) = 3.2 at Week 104, in Subjects Responding at Both Week 6 and Week 12	DAS28 [ESR] was 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 Patient Global Assessment of Arthritis, where 28 joints were examined and a lower score indicates less disease activity.; The definition of Week 6/12 responders was DAS28[ESR] Low Disease Activity (LDA) (ie = 3.2) or an improvement of = 1.2 in DAS28[ESR] relative to Baseline.	Week 104
Secondary	Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 104	HAQ-DI was derived based on the mean of individual scores in 8 categories of daily living actives (using 20 questions). Each question was scored 0-3 (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, and 3 = unable to do), and the total HAQ-DI was scored on the scale of 0-3 as well. Change from Baseline was computed as the value at Week 104 minus the Baseline value. A negative value in Change from Baseline indicates an improvement.	From Baseline to Week 104
Secondary	Kaplan-Meier Estimates of Proportion of Subjects Who Discontinued After Response at Week 12	Response at Week 12 means that a subject had either a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) = 3.2 at Week 12 or had a reduction of DAS28 [ESR] = 1.2 from Baseline to Week 12. Kaplan-Meier Estimates of Proportion of Subjects Discontinued are presented per study week (days relative to Week 12 visit).	From Week 12 up to Week 104

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