A Phase IIIb multicentre, open label induction and double blind comparison of two maintenance schedules evaluating clinical benefit and tolerability of certolizumab pegol, a PEGylated Fab' fragment of humanized antibody to tumor necrosis factor (TNF) over 26 weeks in patients suffering from Crohn’s Disease with prior loss of response or intolerance to infliximab.

• Register: EUCTR
• Last refreshed on: 3 April 2012
• Main ID: EUCTR2005-004104-37-AT
• Date of registration: 04/04/2006
• Prospective Registration: Yes
• Primary sponsor: UCB S.A.
• Public title: A Phase IIIb multicentre, open label induction and double blind comparison of two maintenance schedules evaluating clinical benefit and tolerability of certolizumab pegol, a PEGylated Fab' fragment of humanized antibody to tumor necrosis factor (TNF) over 26 weeks in patients suffering from Crohn’s Disease with prior loss of response or intolerance to infliximab.
• Scientific title: A Phase IIIb multicentre, open label induction and double blind comparison of two maintenance schedules evaluating clinical benefit and tolerability of certolizumab pegol, a PEGylated Fab' fragment of humanized antibody to tumor necrosis factor (TNF) over 26 weeks in patients suffering from Crohn’s Disease with prior loss of response or intolerance to infliximab.
• Date of first enrolment: 24/05/2006
• Target sample size: 600
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-004104-37
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Austria, Belgium, Germany, Italy, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Adult men and women = 18 years

Patient suffering from Crohn’s disease with a CDAI score between 220 and 450, scored over the 7 days prior to the first study treatment dose.

Patients must have been treated and must have responded to infliximab (estimated by the Investigator and documented by the patient’s medical file) but are no longer responding or have developed intolerability due to acute or delayed infusion reactions.

Loss of response is defined as: No response or lack of improvement/ worsening of the clinical symptoms (liquid stools, abdominal pain, fever, drainage of existing fistulas or development of new fistulas, rectal bleeding, changing or introduction of new anti diarrheic medication) after two consecutive infusions of infliximab of at least 5mg/kg with a maximum interval of 8 weeks evaluated two weeks after the last infusion.

Acute infusion reactions to infliximab include at least one of the following signs or symptoms during or within 2 hours of the infliximab infusion:- hypotension- urticaria- flushing- facial or hand edema,- throat tightness, oral cavity or lip edema- headache- shortness of breath.

Delayed infusion reactions to infliximab are defined as at least two of the following four signs or symptoms occurring within 1-14 days following the infliximab infusion:- rash- fever (more than 100° F (38° C)- polyarthralgias- myalgias.

Patients able to understand the information provided to them and to give written informed consent.

Female patient either postmenopausal for at least one year, surgically incapable of childbearing, or effectively practicing an acceptable method of contraception (oral or parenteral hormonal contraceptives; intrauterine device; barrier and spermicide. Abstinence is not an acceptable method). Patients must agree to use adequate contraception during the study and for 12 weeks after the last dose of CDP870.

Concomitant medications5-ASA or antibiotics (stable for 4 weeks prior screening), corticosteroids equivalent to or less than 30 mg prednisone per day (stable dose for 2 weeks), azathioprine and 6-mercaptopurine or methotrexate (stable dose for 8 weeks) are allowed at Baseline and during the study. Tapering of the dose of steroids is allowed after week 8 starting with 5 mg weekly if the dose higher than 20mg/ daily and with 2.5 mg weekly onward until the complete discontinuation of steroids. The patients taking 20mg/day or less will start directly to taper with 2,5 mg weekly.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Crohn’s Disease Related:

Symptomatic obstructive intestinal strictures. Bowel resection within 4 weeks of starting the study medication. Fistula abscess present at screening. Current total parenteral nutrition. Short bowel syndrome. Positive stool laboratory results for enteric pathogens. Antibiotic treatment for non- Crohn’s related infections within 3 weeks prior to screening

Medical History Exclusion:
- Ulcerative colitis.
- Lactating and / or pregnant female patients. Female patients of childbearing age who are NOT practicing (in the Investigator’s opinion) effective birth control. All female patients must test negative on a serum pregnancy test before study entry and negative on urine testing immediately before every CDP870 administration.
- A history of chronic infection, recent serious or life-threatening infection (within 6 months, including herpes zoster), or any current sign or symptom that may indicate an infection (e.g. fever, cough).
- A history of tuberculosis or positive chest X-ray for tuberculosis or positive (defined as positive induration per local medical practice) PPD skin test.
- 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 (e.g. leg ulcers, indwelling urinary catheter and persistent or recurrent chest infections).
- Patients with known concurrent viral hepatitis or known positivity to HBe-Ag, HBV DNA, HBV DNA polymerase, HCVRNA, anti HCV antibodies with decompensated liver function will not be enrolled in the study·
- Receipt of any vaccination (live or attenuated) within 8 weeks prior to Baseline. (Influenza and Pneumococcal vaccines are allowed).
- Concurrent malignancy or a history of malignancy (other than carcinoma of the cervix or basal cell carcinoma successfully treated more than five years prior to screening).·
- Current or recent history of severe, progressive, and/or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, or cerebral disease.
- Known human immunodeficiency virus (HIV) infection.
- New York Heart Association (NYHA) class III-IV congestive heart failure requiring medical treatment.
- A history of, or suspected, demyelinating disease of the central nervous system (e.g. multiple sclerosis or optic neuritis).·
- A history of an adverse reaction to polyethylene glycol (PEG) or a protein medicinal product.
- Any other condition, which in the Investigator’s judgment would make the patient unsuitable for inclusion in the study

Previous clinical trials and previous biological therapy exclusion:
- Receipt of any experimental biological or non-biological therapy within or outside a clinical trial in the 3 months prior to Baseline visit.
- Patients treated with infliximab within 12 weeks prior to screening.
- Previous treatment with a biological therapy for CD (including CDP870) that resulted in a severe hypersensitivity reaction, an anaphylactic reaction or lack of response**Patients having experienced severe or anaphylactic reactions only will not be enrolled

Concomitant medications exclusion criteria
- 5-ASA or antibiotics (stable for 4 weeks prior screening), corticosteroids equivalent to or less than 30 mg prednisone per day (stable dose for 2 weeks), azathioprine and 6-mercaptopurine or methotrexate (stable dose for 8 weeks) are allowed at Baseline and during the study.
- Any modifi

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients with Crohn's Disease with prior loss of response or intolerance to infliximab
Classification code 10011401

Intervention(s)

Product Name: certolizumab pegol
Product Code: CDP870
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: certolizumab pegol
Current Sponsor code: CDP870
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: range
Concentration number: 150-+/- 15
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Secondary Objective: - To assess and compare the clinical efficacy of subcutaneous certolizumab pegol 400mg maintenance therapy administered Q4W or Q2W over 26 weeks in patients with Crohn’s disease who responded to certolizumab pegol induction therapy.

- To assess the clinical efficacy of subcutaneous certolizumab pegol 400 mg as induction and two regimens of maintenance therapy on patient reported outcome scores.

- To evaluate tolerability and safety of certolizumab pegol induction and maintenance therapy in patients who have previously received and responded to infliximab, but who no longer have a sustained response and/ or have tolerance to infliximab.

- To evaluate the effect of certolizumab pegol induction and maintenance therapy on plasma CRP levels.

Primary end point(s): Response rate with response defined as at least 100 point decrease of CDAI score from baseline at week 6.

Main Objective: To assess the clinical efficacy of subcutaneous certolizumab pegol 400mg at week 6, following administration at 0,2 and 4 weeks for the treatment of signs and symptoms of active Crohn’s disease (CDAI between 220 and 450 inclusive: scored over 7 days before the first administration of the study drug) in patients who have previously received and responded to infliximab, but who no longer have a sustained response and/ or tolerance to infliximab.

Secondary ID(s)

2005-004104-37-BE

C87042