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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 8 August 2016
Main ID:  EUCTR2015-001954-14-NL
Date of registration: 25/08/2015
Prospective Registration: Yes
Primary sponsor: Santeon
Public title: "Efficacy and safety of Infliximab-biosimilar (Inflectra) compared to Infliximab-innovator (Remicade) in patients with inflammatory bowel disease in remission: the SIMILAR Trial”
Scientific title: SIMILAR Trial: Santeon InflixMab biosimILAr Research A randomized, controlled, double blind, phase 4 noninferiority trial to assess efficacy of Infliximab-biosimilar (Inflectra) compared to Infliximab-innovator (Remicade) in patients with inflammatory bowel disease in remission. - SIMILAR Trial: Santeon InflixMab biosimILAr Research
Date of first enrolment: 14/09/2015
Target sample size:
Recruitment status: Authorised-recruitment may be ongoing or finished
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-001954-14
Study type:  Interventional clinical trial of medicinal product
Study design:  Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2  
Phase:  Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes
Countries of recruitment
Netherlands
Contacts
Name: Principal Investigator   
Address:  Oosterparkstraat 9 1091 AC Amsterdam Netherlands
Telephone: +31205999111
Email: j.m.jansen@olvg.nl
Affiliation:  Onze Lieve Vrouwe Gasthuis
Name: Principal Investigator   
Address:  Oosterparkstraat 9 1091 AC Amsterdam Netherlands
Telephone: +31205999111
Email: j.m.jansen@olvg.nl
Affiliation:  Onze Lieve Vrouwe Gasthuis
Key inclusion & exclusion criteria
Inclusion criteria:
In order to be eligible to participate in this study, a subject must meet all of the following criteria:
1. Patient, male or female, is aged above 18 years.
2. Patient has an established diagnosis of ulcerative colitis or Crohn’s disease.
3. Patient has ulcerative colitis or Crohn’s disease in clinical and endoscopic remission defined as:
a. Crohn’s disease: HBI score <5 with a fecal calprotectin <250 mg/g.
b. Ulcerative colitis: total Mayo score of =2 with a fecal calprotectin <250 mg/g.
4. Patient is being treated with Infliximab 5mg/kg to 10mg/kg with stable dosing intervals between 6 to 10 weeks for at least 12 weeks.
5. Patient may receive one of the following treatments:
a. 5-aminosalicylates (no dosage changes for at least 8 weeks for inclusion)
b. Antibiotics
c. Azathioprine, 6-mercaptopurine (6-MP) or tioguanine (6-TG) (no dosage changes for at least 8 weeks for inclusion)
d. Methotrexate (MTX) (no dosage changes for at least 8 weeks for inclusion)
6. Patient has stable renal and hepatic function at time of screening, defined as:
a. Serum creatinine <1.5 x upper limit of normal (ULN) or an estimated creatinine clearance level >50mL/min
b. Serum alanine aminotransferase <2.5 x ULN
c. Serum aspartate aminotransferase <2.5 x ULN
d. Serum total bilirubin <2 x ULN
7. Patient has the following hematology laboratory test results at time of screening:
a. Hemoglobin =5.5mmol/l
b. White blood cell count: =3.5 x 109 cells/l
c. Neutrophil count: =1.5 x 109 cells/l
d. Platelet count: =100 x 109 cells/l
8. Patient is able to understand the intention, the nature and the possible risks of the study, to cooperate with the investigator and to understand given instructions.
9. Patient is informed about the intention and nature of the study including all possible risks and has given his written consent before inclusion.
10.
a. Female patients of child of childbearing potential agree to use 1 of the following medically acceptable methods of contraception during the course of the study and for 12 weeks following discontinuation of study drug (excluding women who are not of childbearing potential or who have been sterilized):Barrier contraceptives (male condom, female condom, or diaphragm with a spermicidal gel)
b. Hormonal contraceptives (implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings)
c. Intrauterine device.
Female patients who have been surgically sterilized for less than 6 months prior to the date of informed consent must agree to use 1 medically acceptable methods of contraception. Menopausal females must have experienced their last period more than 12 months prior to the date of informed consent to be classified as not of childbearing potential.
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 138
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 44

Exclusion criteria:
A potential subject who meets any of the following criteria will be excluded from participation in this study:

1. Patient has an allergy or hypersensitivity to one of the components of infliximab and/or immunoglobulin products, except hypersensitivity reactions which have a positive response to hydrocortisone and thereby are under control.
2. Patient has a history of tuberculosis (TB) or a current diagnosis of TB or other severe or chronic infection such as abscess, opportunistic infection or invasive fungal infection. Patients with a past history of a severe or chronic infection will not be excluded.
3. Patient has had recent exposure to persons with active TB. In that case screening for latent TB (defined as a positive result for interferon-? release assay (IGRA) with a negative examination of chest X-ray) will be performed. If there is sufficient documentation of prophylaxis or complete resolution following TB-treatment based on hospital-specific guidelines the patient can be enrolled. If the result of the IGRA is indeterminate at screening, 1 retest will be done. If the repeated IGRA result is indeterminate again, the patient will be excluded. Patients with a positive IGRA result and a negative examination of chest X-ray who has received at least the first 30 days of TB-therapy can be enrolled.
4. Patient who is taking any of the following concomitant medications or treatment:
a. Current use of corticosteroids (prednisone, prednisolone or budesonide).
b. Alkylating agents: current use or within 12 months to randomization
c. Live or live-attenuated vaccine within 8 weeks of randomization.
d. Any other biological treatments than infliximab.
e. Any planned abdominal surgery for IBD at the time of randomization and/or during the study period.
5. Patient has one or more of the following medical conditions:
a. Active entero-vesical, entero-retroperitoneal, entero-cutaneous and entero-vaginal fistula for within 6 months prior to screening. Entero-enteral fistulae without clinical significant symptoms upon investigator’s opinion and anal fistulae without draining problems are allowed.
b. Current short bowel syndrome.
c. History of any malignancy within the 5 years prior to randomization except cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma or completely excised and cured squamous carcinoma of the uterine cervix.
d. History of lymphoma or lymphoproliferative disease or bone marrow hyperplasia.
e. New York Heart Association (NYHA) class III or IV heart failure.
f. History of organ transplantation, including corneal graft/transplantation.
g. Ileostomy of colostomy.
6. Patient has had treatment with any other investigational device or medical product within 4 weeks of randomization or 5 half-lives, whichever is longer.
7. Female patient who is currently pregnant, breastfeeding, or planning to become pregnant or breastfeed within 12 weeks of the last dose of study drug.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Therapeutic area: Diseases [C] - Immune System Diseases [C20]
ulcerative colitis and Crohn’s disease
MedDRA version: 19.0 Level: PT Classification code 10011401 Term: Crohn's disease System Organ Class: 10017947 - Gastrointestinal disorders
MedDRA version: 19.0 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 10017947 - Gastrointestinal disorders
Intervention(s)

Trade Name: Inflectra 100 mg powder for concentrate for solution for infusion
Product Name: Inflectra 100 mg powder for concentrate for solution for infusion
Pharmaceutical Form: Powder for concentrate for solution for infusion

Trade Name: Remicade 100 mg powder for concentrate for solution for infusion.
Product Name: Remicade 100 mg powder for concentrate for solution for infusion.
Product Code: EMEA/H/C/000240
Pharmaceutical Form: Powder for concentrate for solution for infusion

Primary Outcome(s)
Main Objective: The objective of this study is to compare the efficacy of Infliximab-biosimilar to Infliximab-innovator and to demonstrate its noninferiority up to 30 weeks, in patients with ulcerative colitis or Crohn’s disease in remission under treatment with infliximab for at least 12 weeks.
Primary end point(s): Relapse rate:
The primary endpoint relapse is in CD defined as a SES-CD score >2 and in UC as a Mayo endoscopy score of =2. In patients with only small bowel involvement a MRI will used to evaluate disease activity. If an exacerbation, and therefore a relapse is proven by colonoscopy or MRI, dose escalation or change of treatment will be considered as is standard care. A colonoscopy will be performed in case of worsening of symptoms in combination with a fecal calprotectin >250 mg/g. Worsening of symptoms is defined in CD as an increase in HBI of = 4 points from baseline and a minimum HBI score of 7 points and in UC as an increase in partial Mayo score of = 3 points from baseline and a minimum partial Mayo score of = 5 points.
Secondary Objective: - Evaluation of adverse effects and overall safety of Infliximab-biosimilar in comparison with Infliximab-innovator up to 30 weeks.
- Evaluation of pharmacokinetics of Infliximab-biosimilar in comparison with Infliximab-innovator up to 30 weeks.
Timepoint(s) of evaluation of this end point: Patiënts will be evaluated for the primary end point up to 30 weeks after randomisation.
Secondary Outcome(s)
Secondary end point(s): Secondary efficacy endpoints
• SIBDQ scores
• Pharmacokinetic evaluation

Secondary safety endpoints
• Adverse and serious adverse events
• Assessment and monitoring of TB signs and symptoms.
• Physical Examination findings
• Clinical laboratory analyses, including calprotectin.
Timepoint(s) of evaluation of this end point: Evaluation at screening:
Clinical laboratory analyses, latent TB screening, HBI/Mayo scores, SIBDQ, Physical Examination, Vital signs and Weight, Calprotectin,

Evaluation at the first and last study drug administration and in case of relapse:
Immunogenicity testing
Pharmacokinetic blood sampling

Evaluation at each visit from (and including) baseline to (and including) end of study at 30 weeks. The visits will be carried out according to the patient’s pre-randomization innovator infliximab treatment schedule, i.e. ranging from every 6 to 10 weeks.
Physical Examination
Vital signs and Weight
Adverse and serious adverse events
Hypersensitivity testing
TB clinical monitoring
Secondary ID(s)
NCT02452151
Source(s) of Monetary Support
Santeon
Secondary Sponsor(s)
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
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