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 remissio

Phase 4

Completed

Conditions: Inflammatory Bowel disease: ulcerative colitis and Crohn's disease
10017943
10003816

Registration Number: NL-OMON43635

Lead Sponsor: Santeon

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 182

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 remission defined as:
a. Crohn*s disease: HBI score <5 and a fecal calprotectin <250 mg/g.
b. Ulcerative colitis: total Mayo score of <=2 and 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.

Exclusion Criteria

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-γ 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.
f. 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.

Study & Design

Study Type: Observational invasive

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Efficacy of Infliximab-Biosimilar and Infliximab will be assessed by evaluation<br /><br>of the duration of clinical remission and the relapse rate for each diagnosis<br /><br>seperately.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- Evaluation of adverse effects and overall safety of Infliximab-biosimilar in<br /><br>comparison with Infliximab-innovator up to 30 weeks.<br /><br>- Evaluation of pharmacokinetics of Infliximab-biosimilar in comparison with<br /><br>Infliximab-innovator up to 30 weeks.<br /><br>This will be done by evaluating the following secondary endpoints;<br /><br>• SIBDQ scores<br /><br>• Pharmacokinetic evaluation (trough levels)<br /><br>and<br /><br>• Adverse and serious adverse events<br /><br>• Assessment and monitoring of TB signs and symptoms.<br /><br>• Physical Examination findings<br /><br>• Clinical laboratory analyses, including calprotectin.</p><br>