Clinical trial NCT00152386: A Placebo Controlled Study to Assess Efficacy and Safety of Certolizumab Pegol in the Treatment of Rheumatoid Arthritis
Official title: A Phase III Multicentre, Double Blind, Placebo-controlled, Parallel Group 52-week Study to Assess the Efficacy and Safety of 2 Dose Regimens of Lyophilised CDP870 as Additional Medication to Methotrexate in the Treatment of Signs and Symptoms and Preventing Structural Damage in Patients With Active Rheumatoid Arthritis Who Have an Incomplete Response to Methotrexate
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid Arthritis, CDP870
Certolizumab pegol, Cimzia
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2005-09-09
Enrollment: 950
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Patients will be assigned to one of three treatment groups. Study medication is administered over a 52 week study duration.


Eligibility criteria: Inclusion Criteria:

* Male and female, aged at least 18 years old at the Screening visit.
* A clear chest X-ray within 3 months prior to Baseline visit.
* A diagnosis of adult-onset RA (of at least six months duration but not longer than 15 years prior to Screening) as defined by the 1987 American College of Rheumatology classification criteria.
* Active RA disease at Screening and Baseline as defined by:

  * ≥9 tender joints.
  * ≥9 swollen joints. and fulfilling 1 of the following 2 criteria:
  * ≥30 mm/hour ESR (Westergren), or
  * CRP \>15 mg/L.
* Must have received a stable dose of MTX with or without folic acid for at least 3 months prior to Baseline visit. The minimum dose is 10 mg MTX weekly.
* Patient must be willing to attend for a Week 52 X-ray of the hands and feet even if they are no longer receiving study treatment but have not withdrawn their informed consent.

Exclusion Criteria:

* A diagnosis of any other inflammatory arthritis e.g., psoriatic arthritis or ankylosing spondylitis.
* A secondary, non-inflammatory type of arthritis (e.g. OA or fibromyalgia) that in the Investigator's opinion is symptomatic enough to interfere with evaluation of the effect of CDP870 on the patient's primary diagnosis of RA.
* A history of an infected joint prosthesis at any time with prosthesis still in situ.
* Does not meet exclusionary concomitant medication criteria.
* A history of a lymphoproliferative disorder including lymphoma or signs and symptoms suggestive of lymphoproliferative disease at any time.
* Patients at a high risk of infection in the Investigator's opinion (e.g. leg ulcers, indwelling urinary catheter and persistent or recurrent chest infections).

Primary outcomes:
measure: To assess the efficacy of CDP870 in combination with Methotrexate in the treatment of Rheumatoid Arthritis and prevention of structural damage by measuring the ACR20 response at week 24 and change from Baseline
Secondary outcomes:
measure: Change from Baseline in mTSS at week 24, Change from Baseline in HAQ-DI at weeks 24 and 52, ACR20 responder rate at week 52, ACR50 and ACR70 responder rate at weeks 24 and 52
Other outcomes:
Locations:
city: Huntsville
country: United States
state: Alabama
city: Paradise Valley
country: United States
state: Arizona
city: La Jolla
country: United States
state: California
city: San Diego
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Danbury
country: United States
state: Connecticut
city: Washington
country: United States
state: District of Columbia
city: Aventura
country: United States
state: Florida
city: Ocala
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Sarasota
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Coeur d'Alene
country: United States
state: Idaho
city: Springfield
country: United States
state: Illinois
city: Wichita
country: United States
state: Kansas
city: Wheaton
country: United States
state: Maryland
city: Saint Louis
country: United States
state: Missouri
city: Lincoln
country: United States
state: Nebraska
city: Charlotte
country: United States
state: North Carolina
city: Cleveland
country: United States
state: Ohio
city: Dayton
country: United States
state: Ohio
city: Duncansville
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Austin
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Capital Federal
country: Argentina
city: Cordoba
country: Argentina
city: Camperdown
country: Australia
city: Coffs Harbour
country: Australia
city: Cotton Tree
country: Australia
city: Malvern
country: Australia
city: Shenton Park
country: Australia
city: Victoria Park
country: Australia
city: Westmead
country: Australia
city: Wooloongabba
country: Australia
city: Antwerpen
country: Belgium
city: Brussels
country: Belgium
city: Liege
country: Belgium
city: Merksem
country: Belgium
city: Sijsele
country: Belgium
city: Pleven
country: Bulgaria
city: Sofia
country: Bulgaria
city: Stara Zagora
country: Bulgaria
city: Varna
country: Bulgaria
city: Courtice
country: Canada
city: Hamilton
country: Canada
city: Kitchener
country: Canada
city: London
country: Canada
city: Mississauga
country: Canada
city: Montreal
country: Canada
city: Newmarket
country: Canada
city: Point Claire
country: Canada
city: Sainte Foy
country: Canada
city: Toronto
country: Canada
city: Winnipeg
country: Canada
city: Valdivia
country: Chile
state: Las Condes
city: Santiago
country: Chile
state: Santiago Centro
city: Santiago de Chile
country: Chile
city: Santiago
country: Chile
city: Temuco
country: Chile
city: Rijeka
country: Croatia
city: Brno Bohunice
country: Czechia
city: Brno
country: Czechia
city: Ostrava Trebovice
country: Czechia
city: Plzen
country: Czechia
city: Prague 2
country: Czechia
city: Praha 5
country: Czechia
city: Praha
country: Czechia
city: Uherske Hradiste
country: Czechia
city: Zlin
country: Czechia
city: Afula
country: Israel
city: Haifa
country: Israel
city: Ramat Gan
country: Israel
city: Tel Aviv
country: Israel
city: Riga
country: Latvia
city: Moscow
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Ivano-Frankivsk
country: Ukraine
Study officials:
affiliation: UCB Pharma
name: UCB Clinical Trial Call Center
role: STUDY_DIRECTOR
References:
citation: Keystone E, Heijde Dv, Mason D Jr, Landewe R, Vollenhoven RV, Combe B, Emery P, Strand V, Mease P, Desai C, Pavelka K. Certolizumab pegol plus methotrexate is significantly more effective than placebo plus methotrexate in active rheumatoid arthritis: findings of a fifty-two-week, phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Arthritis Rheum. 2008 Nov;58(11):3319-29. doi: 10.1002/art.23964.
citation: van Vollenhoven RF, Felson D, Strand V, Weinblatt ME, Luijtens K, Keystone EC. American College of Rheumatology hybrid analysis of certolizumab pegol plus methotrexate in patients with active rheumatoid arthritis: data from a 52-week phase III trial. Arthritis Care Res (Hoboken). 2011 Jan;63(1):128-34. doi: 10.1002/acr.20331.
citation: Hazes JM, Taylor P, Strand V, Purcaru O, Coteur G, Mease P. Physical function improvements and relief from fatigue and pain are associated with increased productivity at work and at home in rheumatoid arthritis patients treated with certolizumab pegol. Rheumatology (Oxford). 2010 Oct;49(10):1900-10. doi: 10.1093/rheumatology/keq109. Epub 2010 Jun 14.
citation: Pincus T, Furer V, Keystone E, Yazici Y, Bergman MJ, Luijtens K. RAPID3 (Routine Assessment of Patient Index Data 3) severity categories and response criteria: Similar results to DAS28 (Disease Activity Score) and CDAI (Clinical Disease Activity Index) in the RAPID 1 (Rheumatoid Arthritis Prevention of Structural Damage) clinical trial of certolizumab pegol. Arthritis Care Res (Hoboken). 2011 Aug;63(8):1142-9. doi: 10.1002/acr.20481.
citation: Curtis JR, Chen L, Luijtens K, Navarro-Millan I, Goel N, Gervitz L, Weinblatt M. Dose escalation of certolizumab pegol from 200 mg to 400 mg every other week provides no additional efficacy in rheumatoid arthritis: an analysis of individual patient-level data. Arthritis Rheum. 2011 Aug;63(8):2203-8. doi: 10.1002/art.30387.
citation: Keystone EC, Curtis JR, Fleischmann RM, Furst DE, Khanna D, Smolen JS, Mease PJ, Schiff MH, Coteur G, Davies O, Combe B. Rapid improvement in the signs and symptoms of rheumatoid arthritis following certolizumab pegol treatment predicts better longterm outcomes: post-hoc analysis of a randomized controlled trial. J Rheumatol. 2011 Jun;38(6):990-6. doi: 10.3899/jrheum.100935. Epub 2011 Mar 1.
citation: Curtis JR, Luijtens K, Kavanaugh A. Predicting future response to certolizumab pegol in rheumatoid arthritis patients: features at 12 weeks associated with low disease activity at 1 year. Arthritis Care Res (Hoboken). 2012 May;64(5):658-67. doi: 10.1002/acr.21600.
citation: Paul S, Marotte H, Kavanaugh A, Goupille P, Kvien TK, de Longueville M, Mulleman D, Sandborn WJ, Vande Casteele N. Exposure-Response Relationship of Certolizumab Pegol and Achievement of Low Disease Activity and Remission in Patients With Rheumatoid Arthritis. Clin Transl Sci. 2020 Jul;13(4):743-751. doi: 10.1111/cts.12760. Epub 2020 Apr 1.
citation: Curtis JR, Winthrop K, O'Brien C, Ndlovu MN, de Longueville M, Haraoui B. Use of a baseline risk score to identify the risk of serious infectious events in patients with rheumatoid arthritis during certolizumab pegol treatment. Arthritis Res Ther. 2017 Dec 15;19(1):276. doi: 10.1186/s13075-017-1466-y.
citation: Combe B, Furst DE, Keystone EC, van der Heijde D, Luijtens K, Ionescu L, Goel N, Emery P. Certolizumab Pegol Efficacy Across Methotrexate Regimens: A Pre-Specified Analysis of Two Phase III Trials. Arthritis Care Res (Hoboken). 2016 Mar;68(3):299-307. doi: 10.1002/acr.22676.
citation: van der Heijde D, Keystone EC, Curtis JR, Landewe RB, Schiff MH, Khanna D, Kvien TK, Ionescu L, Gervitz LM, Davies OR, Luijtens K, Furst DE. Timing and magnitude of initial change in disease activity score 28 predicts the likelihood of achieving low disease activity at 1 year in rheumatoid arthritis patients treated with certolizumab pegol: a post-hoc analysis of the RAPID 1 trial. J Rheumatol. 2012 Jul;39(7):1326-33. doi: 10.3899/jrheum.111171. Epub 2012 May 15.
citation: Strand V, Mease P, Burmester GR, Nikai E, Coteur G, van Vollenhoven R, Combe B, Keystone EC, Kavanaugh A. Rapid and sustained improvements in health-related quality of life, fatigue, and other patient-reported outcomes in rheumatoid arthritis patients treated with certolizumab pegol plus methotrexate over 1 year: results from the RAPID 1 randomized controlled trial. Arthritis Res Ther. 2009;11(6):R170. doi: 10.1186/ar2859. Epub 2009 Nov 12.
citation: Kavanaugh A, Smolen JS, Emery P, Purcaru O, Keystone E, Richard L, Strand V, van Vollenhoven RF. Effect of certolizumab pegol with methotrexate on home and work place productivity and social activities in patients with active rheumatoid arthritis. Arthritis Rheum. 2009 Nov 15;61(11):1592-600. doi: 10.1002/art.24828.