Clinical trial NCT00993668: Assessing the Use of Certolizumab Pegol in Adult Subjects With Rheumatoid Arthritis on the Antibody Response When Receiving Influenza Virus and Pneumococcal Vaccines
Official title: A Phase 4, Randomized, Single-blind, Placebo-controlled, Multicenter Study to Evaluate the Immunogenicity of Pneumococcal and Influenza Vaccines in Adult Subjects With Rheumatoid Arthritis Receiving Certolizumab Pegol or Placebo
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Rheumatoid Arthritis
Keywords: influenza
vaccine
pneumococcal vaccine
certolizumab pegol
Cimzia
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2009-10-12
Enrollment: 224
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: The purpose of this trial is to assess the affect of Certolizumab Pegol (CZP) treatment on antibody response to T cell-independent and T cell-dependent immunizations using pneumococcal and influenza vaccines, respectively.


Eligibility criteria: Inclusion Criteria:

* Subjects must be at least 18 years old at the screening visit
* Subjects must be able to understand the information provided to them and to give written informed consent, and be able and willing to comply with the study requirements
* Female subjects must be either postmenopausal for at least 1 year, surgically incapable of childbearing, or effectively practicing an acceptable method of contraception (either oral/parenteral/implantable hormonal contraceptives, intrauterine device or barrier and spermicide. Abstinence only is not an acceptable method. Subjects must agree to use adequate contraception during the study and for 10 weeks after the last dose of CZP. Male subjects must agree to ensure they or their female partner(s) use adequate contraception during the study and for 10 weeks after the subject receives their last dose of CZP
* Subjects must have a diagnosis of adult-onset Rheumatoid Arthritis (RA) of at least 6-months duration as defined by the 1987 American College of Rheumatology (ACR) classification criteria
* Subjects must have active RA disease as defined by: ≥ 4 tender joints (28 joint count) at Screening and Week 0; and ≥ 4 swollen joints (28 joint count) at Screening and Week 0

Exclusion Criteria:

* Subjects who have a diagnosis of any other inflammatory arthritis (eg., psoriatic arthritis or ankylosing spondylitis)
* Subjects who have a history of an infected joint prosthesis at any time with that prosthesis still in situ
* Subjects must be free of defined prohibited medication and biological therapy
* Subjects who have received any experimental nonbiological therapy, within or outside of a clinical trial in the 3 months prior to Week 0
* Subjects who have received any experimental biological agent in the past 3 months or within 5 half-lives prior to Week 0 (whichever is longer)
* Subjects who have received previous treatment with biological response modifier therapy for RA that resulted in a severe hypersensitivity reaction or an anaphylactic reaction.
* Subjects with a history of pneumococcal or influenza infection in the last 3 months
* Subjects with a history of pneumococcal vaccination in the last 5 years
* Subjects with a history of influenza vaccination within the last 6 months
* Female subjects who are breast-feeding, pregnant, or plan to become pregnant during the trial or within 3 months following last dose of study drug
* Subjects with a history of chronic or recurrent infections (more than 3 episodes requiring antibiotics/antivirals during the preceding year), recent serious or life-threatening infection within 6 months (including herpes zoster), or any current sign or symptom that may indicate an infection
* Subjects who have had a splenectomy
* Subjects who have had a hypersensitivity reaction to previous pneumococcal or influenza vaccination
* Subjects who have a known hypersensitivity to eggs and egg products or to other components of the vaccine
* Subjects with a history of Guillain-Barre syndrome
* Subjects with a history of tuberculosis, active tuberculosis, positive chest x-ray for tuberculosis, or positive purified protein derivative (PPD) skin test (defined as induration of ≥5 mm). Subjects who are not candidates for PPD testing due to prior severe reaction to the PPD test or a history of PPD positivity must undergo an Elispot test instead for tuberculosis evaluation. Subjects testing positive via the PPD or having an indeterminate or positive Elispot test, or for which latent tuberculosis cannot be ruled out, may be enrolled in the study provided that they are treated (eg., isoniazid for 9 months) and that their treatment has been initiated at least 4 weeks prior to the first administration of CZP
* Subjects at high risk of infection (eg., presence of leg ulcers or an indwelling urinary catheter, persistent or recurrent chest infections, bedridden or wheelchair bound subjects)
* Subjects with a history of a lymphoproliferative disorder including lymphoma or signs and symptoms suggestive of lymphoproliferative disease
* Subjects with known concurrent acute or chronic viral hepatitis B or C or positive hepatitis B surface antigen (HBs-Ag) or hepatitis C virus antibody (HCV-Ab)
* Subjects with known human immunodeficiency virus (HIV) infection
* Subjects receiving any live or attenuated vaccination within 12 weeks prior to Week 0
* Concurrent malignancy or a history of malignancy (other than carcinoma of the cervix or basal cell carcinoma successfully treated more than 5 years prior to screening)
* Subjects with Class III or Class IV congestive heart failure according to the New York Heart Association (NYHA) 1964 classification criteria
* Subjects with a history of, or suspected, demyelinating disease of the central nervous system (eg., multiple sclerosis or optic neuritis)
* Subjects with a current or recent history of severe, progressive, and/or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological or cerebral disease
* Subjects with any other condition (eg., clinically significant laboratory values) which in the Investigator's judgement would make the subject unsuitable for inclusion in the study
* Subjects with a history of an adverse reaction to polyethylene glycol (PEG)

Primary outcomes:
measure: Percentage of Subjects Without Baseline Protective Titers Achieving a ≥ 2-fold Titer Increase in ≥ 3 of 6 Pneumococcal Antigens (6B, 9V, 14, 18C, 19F, and 23F) at Week 6.
timeFrame: Baseline, End of single blind period (Week 6)
measure: Percentage of Subjects Without Baseline Protective Titers Achieving a ≥ 4-fold Titer Increase in ≥ 2 of 3 Influenza Antigens (2009/2010 Composition) at Week 6.
timeFrame: Baseline, End of single blind period (Week 6)
Secondary outcomes:
measure: Percentage of All Subjects Achieving a ≥ 2-fold Titer Increase in ≥ 3 of 6 Pneumococcal Antigens (6B, 9V, 14, 18C, 19F, and 23F) at Week 6.
timeFrame: End of single blind period (Week 6)
measure: Percentage of All Subjects Achieving a ≥ 4-fold Titer Increase in ≥ 2 of 3 Influenza Antigens (2009/2010 Composition) at Week 6.
timeFrame: End of single blind period (Week 6)
measure: Percentage of Subjects With no Previous Protective Pneumococcal Antibody Titers at Baseline With Protective Pneumococcal Antibody Titers (≥1.6 µg/ml in ≥ 3 of 6 of the Pneumococcal Antigens) at Week 6.
timeFrame: Baseline, End of single blind period (Week 6)
measure: Percentage of Subjects With no Previous Protective Influenza Antibody Titers at Baseline With Protective Influenza Antibody Titers (≥1:40 in ≥ 2 of 3 Influenza Antigens) at Week 6.
timeFrame: Baseline, End of single blind period (week 6)
measure: Percentage of All Subjects With Protective Pneumococcal Antibody Titers (≥1.6 µg/ml in ≥ 3 of 6 of the Pneumococcal Antigens) at Week 6.
timeFrame: End of single blind period (Week 6)
measure: Percentage of All Subjects With Protective Influenza Antibody Titers (≥1:40 in ≥ 2 of 3 Influenza Antigens) at Week 6.
timeFrame: End of single blind period (Week 6)
measure: Percentage of Subjects Without Baseline Protective Titers Achieving a ≥ 2-fold Titer Increase in ≥ 3 of 6 Pneumococcal Antigens at Week 6 by Concomitant Methotrexate (MTX) Use.
timeFrame: Baseline, End of single blind period (Week 6)
measure: Percentage of Subjects Without Baseline Protective Titers Achieving a ≥ 4-fold Titer Increase in ≥ 2 of 3 Influenza Antigens at Week 6 by Concomitant MTX Use.
timeFrame: Baseline, End of single blind period (Week 6)
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Huntsville
country: United States
state: Alabama
city: Tuscaloosa
country: United States
state: Alabama
city: Peoria
country: United States
state: Arizona
city: Scottsdale
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Los Angeles
country: United States
state: California
city: Palm Desert
country: United States
state: California
city: Santa Maria
country: United States
state: California
city: Santa Monica
country: United States
state: California
city: Aventura
country: United States
state: Florida
city: Fort Lauderdale
country: United States
state: Florida
city: Melbourne
country: United States
state: Florida
city: Orange Park
country: United States
state: Florida
city: Palm Harbor
country: United States
state: Florida
city: Venice
country: United States
state: Florida
city: Vero Beach
country: United States
state: Florida
city: Zephyrhills
country: United States
state: Florida
city: Idaho Falls
country: United States
state: Idaho
city: Meridian
country: United States
state: Idaho
city: Cedar Rapids
country: United States
state: Iowa
city: Kalamazoo
country: United States
state: Michigan
city: Lansing
country: United States
state: Michigan
city: Hattiesburg
country: United States
state: Mississippi
city: Florissant
country: United States
state: Missouri
city: Reno
country: United States
state: Nevada
city: Brooklyn
country: United States
state: New York
city: Smithtown
country: United States
state: New York
city: Syracuse
country: United States
state: New York
city: Asheville
country: United States
state: North Carolina
city: Charlotte
country: United States
state: North Carolina
city: Middleburg Heights
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Duncansville
country: United States
state: Pennsylvania
city: Erie
country: United States
state: Pennsylvania
city: West Reading
country: United States
state: Pennsylvania
city: Myrtle Beach
country: United States
state: South Carolina
city: Orangeburg
country: United States
state: South Carolina
city: San Antonio
country: United States
state: Texas
city: Seattle
country: United States
state: Washington
city: Oak Creek
country: United States
state: Wisconsin
Study officials:
affiliation: +1-877-822-9493 (UCB)
name: UCB Clinical Trial Call Center
role: STUDY_DIRECTOR
References:
citation: Kivitz AJ, Schechtman J, Texter M, Fichtner A, de Longueville M, Chartash EK. Vaccine responses in patients with rheumatoid arthritis treated with certolizumab pegol: results from a single-blind randomized phase IV trial. J Rheumatol. 2014 Apr;41(4):648-57. doi: 10.3899/jrheum.130945. Epub 2014 Mar 1.