Cimzia (Certolizumab Pegol)
Company: UCB Inc.
Approval Status: Approved April 2008
Treatment for: Crohn's disease
Areas: Gastroenterology
| General Information | Clinical Results | Side Effects | Mechanism of Action | Literature References | Additional Information |
General Information
Cimzia is a humanized, pegylated tumor necrosis factor alpha (TNF-a) inhibitor. TNFa is a key pro-inflammatory cytokine with a central role in inflammatory processes.
Cimzia is specifically indicated for reducing signs and symptoms of Crohn’s disease and maintaining clinical response in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy.
Cimzia is supplied as a powder for reconstitution into a liquid formulation designed for subcutaneous administration. The recommended initial dose of the drug is 400 mg (given as two subcutaneous injections of 200 mg) initially, and at Weeks 2 and 4. In patients who obtain a clinical response, the recommended maintenance regimen is 400 mg every four weeks.
Clinical Results
FDA Approval
FDA approval of Cimzia was based on the results of two clinical
trials.
Study CD1
This randomized placebo-controlled study enrolled 662 subjects with
active Crohn’s disease. The subjects received Cimzia (400 mg
subcutaneously) or placebo administered at Weeks 0, 2, and 4 and
then every four weeks to Week 24. Assessments were done at Weeks 6
and 26. Clinical response was defined as at least a 100-point
reduction in CDAI score compared to baseline, and clinical
remission was defined as an absolute CDAI score of 150 points or
lower. At Week 6 the proportion of clinical responders was 35% in
the Cimzia group compared to 27% in the placebo group (p-value <
0.05). Clinical remission was seen in 22% of the Cimzia group and
17% of the placebo group; this did not reach statistical
significance. At Week 26 the proportion of clinical responders was
37% in the Cimzia arm and 27% in the placebo arm and clinical
remission was seen in 29% of the Cimzia arm and 18% of the placebo
arm (p-value < 0.05 for both endpoints).
Study CD2
All the subjects who entered this randomized treatment-withdrawal
study were initially treated with Cimzia 400 mg at Weeks 0, 2, and
4. They were subsequently assessed for clinical response at Week 6
(as defined by at least a 100-point reduction in CDAI score). At
Week 6, a group of 428 clinical responders were randomized to
receive either Cimzia 400 mg or placebo, every four weeks starting
at Week 8, as maintenance therapy through Week 24. Non-responders
were withdrawn from the study. Final evaluation was based on the
CDAI score at Week 26. At Week 26 the proportion of clinical
responders in the Cimzia 400 mg x3 + Placebo group was 36% compared
to 63% in the Cimzia 400 mg arm (p < 0.05). Clinical remission
was seen in 29% of the Cimzia/placebo arm and 48% in the Cimzia arm
(p < 0.05).
Ongoing Study Commitments
- UCB Pharma has agreed to conduct a study in pediatric patients,
"A Phase II Open-Label Multi-Center Study to Assess the Safety
and Effcacy ofCertolizumab pegol in Children and Adolescents with
Active Crohn's Disease" (Study CDP870-035). This study is
proposed to evaluate the pharmacokinetics, safety and clinical
response of pediatric patients, ages 6-17, with moderately to
severely active Crohn's disease to treatment with Cimzia.
Protocol Submission: September 2008
Study Start Date: June 2009
Final Report Submission: October 2013 - UCB Pharma has agreed to a long-term observational study in the
U.S. that wil include approximately 2000 Cimzia-treated Crohn's
disease patients and 2000 matched controls receiving other
treatments for Crohn's disease. Patients wil be monitored for
ten years.
Protocol Submission: September 2008
Study Start Date: February 2009
Final Report Submission: March 2020 - UCB has agreed to CDP870-033, an ongoing open-label trial to
assess the long-term safety of Cimzia in patients with Crohn's
disease who have previously completed trials CDP870-031 or
CDP870-032. The objectives of this trial include measurement of
pharmacokinetics and antibody response in Cimzia-treated patients.
Patient follow-up wil be extended to seven years from the start of
treatment.
Protocol Amendment Submission: October 2008
Trial Start Date: Ongoing
Final Report Submission: May 2013 - UCB Pharma has agreed to CDP870-034, an ongoing open-label
trial to assess the long-term safety of re-exposure to Cimzia after
a variable interval in patients with Crohn's disease who were
previously withdrawn from completed trials CDP870-031 or CDP870-032
due to an exacerbation of Crohn's disease. The objectives of
this trial include measurement of pharmacokinetics and antibody
response in Cimzia-treated patients. Patient follow-up wil be
extended to seven years from the start of treatment.
Protocol Amendment Submission: October 2008
Trial Start Date: Ongoing
Final Report Submission: May 2013 - UCB Pharma has agreed to CDP870-088, an open-label trial to
assess the long-term safety of Cimzia in patients with Crohn's
disease who have either completed trial CDP870-085 or were
withdrawn from CDP870-085 due to an exacerbation of Crohn's
disease. The objectives of this trial include measurement of
pharmacokinetics and antibody response in Cimzia-treated patients.
Patient follow-up wil be extended to five years from the start of
treatment.
Protocol Amendment Submission: October 2008
Trial Start Date: May 2008
Final Report Submission: May 2015 - UCB Pharma has agreed to a placebo-controlled trial designed to
assess the effects of Cimzia treatment on antibody responses to a B
cell-mediated immunization, using pneumococcal vaccine
immunization, and to a T cell-mediated immunization, using
influenza vaccine, in patients with active rheumatoid arthritis.
The study wil measure both antibody titers and rates of clinical
response in approximately 100 placebo- and 100 Cimzia-treated
patients who wil be given polyvalent pneumococcal polysaccharide
vaccine and influenza vaccine.
Protocol Submission: October 2008
Trial Start Date: October 2009
Final Report Submission: March 2011
Side Effects
Adverse events associated with the use of Cimzia may include, but are not limited to, the following:
- upper respiratory infection
- urinary tract infection
- arthralgia
- abdominal pain
- diarrhea
- intestinal obstruction
Mechanism of Action
Certolizumab pegol is a humanized, pegylated tumor necrosis factor alpha (TNF-a) inhibitor. TNFa is a key pro-inflammatory cytokine with a central role in inflammatory processes. Certolizumab pegol selectively neutralizes TNFa (IC90 of 4 ng/mL for inhibition of human TNFa in the in vitro L929 murine fibrosarcoma cytotoxicity assay) but does not neutralize lymphotoxin a (TNFß). Certolizumab pegol was shown to neutralize membrane-associated and soluble human TNFa in a dose-dependent manner.
Literature References
Rutgeerts P, Schreiber S, Feagan B, Keininger DL, O'Neil L, Fedorak RN; CDP870 Crohn's Disease Study Group Certolizumab pegol, a monthly subcutaneously administered Fc-free anti-TNFalpha, improves health-related quality of life in patients with moderate to severe Crohn's disease. International Journal of Colorectal Disease 2008 Mar;23(3):289-96
Sandborn WJ, Feagan BG, Stoinov S, Honiball PJ, Rutgeerts P, Mason D, Bloomfield R, Schreiber S; PRECISE 1 Study Investigators Certolizumab pegol for the treatment of Crohn's disease. The New England Journal of Medicine 2007 Jul 19;357(3):228-38
Schreiber S, Rutgeerts P, Fedorak RN, Khaliq-Kareemi M, Kamm MA, Boivin M, Bernstein CN, Staun M, Thomsen OØ, Innes A; CDP870 Crohn's Disease Study Group A randomized, placebo-controlled trial of certolizumab pegol (CDP870) for treatment of Crohn's disease. Gastroenterology 2005 Sep;129(3):807-18
Winter TA, Wright J, Ghosh S, Jahnsen J, Innes A, Round P Intravenous CDP870, a PEGylated Fab' fragment of a humanized antitumour necrosis factor antibody, in patients with moderate-to-severe Crohn's disease: an exploratory study. Alimentary Pharmacology & Therapeutics 2004 Dec;20(11-12):1337-46
Additional Information
For additional information regarding Cimzia or Crohn's disease, please visit the Cimzia web page.
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