| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10011401 |
| E.1.2 | Term | Crohn's disease |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective of this study will be to compare the efficacy of infliximab with that of placebo in the prevention of clinical recurrence of CD through Week 76, defined as a composite endpoint that requires endoscopic confirmation of recurrence, in patients who are at an increased risk of active CD recurrence following ileocolonic resection. |
|
| E.2.2 | Secondary objectives of the trial |
| The major secondary objective will be to compare the efficacy of infliximab with that of placebo in the prevention of endoscopic recurrence of CD through Week 76, defined as a Rutgeerts score ≥ i2 either at the anastomosis or elsewhere in the gastrointestinal [GI] tract, in patients who are at an increased risk of active CD recurrence following ileocolonic resection. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1.Man or woman 18 years of age or older
2.Are considered eligible according to the following TB screening criteria:
a. Have no history of latent or active TB prior to screening. An exception is made for patients with a history of latent TB and documentation of having completed appropriate treatment for latent TB within 3 years prior to the first administration of study agent. It is the responsibility of the investigator to verify the adequacy of previous antituberculous treatment and provide appropriate documentation.
b. Have no signs or symptoms suggestive of active TB upon medical history and/or physical examination.
c. Have no recent close contact with a person with active TB or, if there has been such contact, will be referred to a physician specializing in TB to undergo additional evaluation and, if warranted, receive appropriate treatment for latent TB prior to or simultaneously with the first administration of study agent.
4.Have undergone an ileocolonic surgical resection (i.e. an intestinal resection with an ileocolonic anastomosis).
5.Patients must also be at an increased risk of recurrence of active CD, as defined by at least ONE of the following:
a.The qualifying surgery was the patient’s second intra-abdominal operation for CD in the past 10 years
b.The qualifying surgery was the patient’s third (or more) intra-abdominal operation for CD
c.The qualifying surgery was performed for a penetrating complication of CD (i.e. an intra-abdominal abscess, internal fistula, sinus tracts or intestinal perforation)
d.The patient has any history of perianal fistulizing CD provided that this has not been active in the 3 months prior to study start
e.The patient is a cigarette smoker (defined as currently smoking and having smoked an average of at least 10 cigarettes a day for the past year or more) and has been unable or unwilling to quit smoking despite counseling to stop smoking
6.Patients must meet the following criteria with respect to prior treatment with an anti-TNF agent:
a.Started an anti-TNF agent for the first time within 1 year prior to surgery and received the last dose of the anti-TNF agent within 4 months or less of having surgery
AND
b.Have not previously discontinued any anti-TNF agent as a result of tolerability issues
OR
c.Be naïve to treatment with an anti-TNF agent
7.Are able to adhere to the following concomitant medication requirements:
a.Patients who are receiving treatment with an immunomodulator (AZA, 6-MP, or MTX) prior to surgery may continue on this medication but must be on a stable dose by 4 weeks after their surgery and should remain on that dose for the duration of the study, unless discontinuation or a dose decrease is warranted for safety or tolerability reasons. Patients who are not taking an immunomodulator prior to surgery should not initiate an immunomodulator after surgery or at any time during the study. Patients may have discontinued immunomodulators at any time prior to the start of the study.
b.Patients taking 5-ASA compounds prior to surgery may continue on these medications but must be on a stable dose by 4 weeks after their surgery and should remain on that dose for the duration of the study, unless discontinuation or a dose decrease is warranted for safety or tolerability reasons. Patients who are not taking 5-ASA compounds prior to surgery should not initiate 5-ASA compounds after surgery or at any time during the study. Patients may have discontinued 5-ASA compounds at any time prior to the start of the study.
d.Antibiotics for the treatment of CD are not allowed in this study. Antibiotics for other indications must be discontinued by Week 2 of the study. Subsequent use of antibiotics is permitted only for reasons other than CD (e.g., urinary tract infections), and then only for a maximum course of 14 days per course of antibiotics.
8.Have a baseline CDAI < 200.
9. Are able to adhere to the study visit schedule (see the Time and Events Schedule) and other protocol requirements
10. Women of childbearing potential and all men must be using adequate birth control measures (e.g., abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, or surgical sterilization) throughout the study and must continue such precautions for 6 months after receiving the last study agent infusion.
11. The screening laboratory tests must meet the following criteria:
a. Hemoglobin > 8.0 g/dL
b. White blood cell (WBC) count > 3.0 x 109 cells/L
c. Neutrophils > 1.5 x 109 cells/L
d. Platelets > 100 x 109 cells/L
12 . Are capable of providing written informed consent. Prior to performing any study-related procedures, patients must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study. |
|
| E.4 | Principal exclusion criteria |
1. Have a history of latent or active granulomatous infection, including histoplasmosis or coccidioidomycosis, prior to screening. Refer to inclusion criterion 2 for information regarding eligibility with a history of latent TB 2. Have had a Bacille Calmette-Guerin (BCG) vaccination within 12 months of screening 3. Have a chest radiograph within 3 months prior to the first infusion of study agent that shows a clinically significant abnormality, such as a malignancy or infection, or any abnormalities suggestive of TB 4. Have had a nontuberculous mycobacterial infection or opportunistic infection within 6 months prior to screening 5. Have initial and repeat indeterminate QuantiFERON-TB Gold test results 6. Are considered ineligible according to the TB eligibility assessment, screening and early detection of reactivation rules 7. Have macroscopically active CD which was not resected at the time of surgery 8. Have had any active perianal disease in the past 3 months (except skin tags) or have had any draining fistula within the past 3 months 9. Have evidence of active CD in regions beyond the site of surgery in the GI tract within 1 year of the time of enrollment 10. Do not meet the criteria for being at an increased risk of postoperative recurrence of active CD as outlined in the inclusion criteria. 11. Have an ostomy or stoma 12. Have a qualifying surgery with postoperative complications such as, but not limited to, postoperative intra-abdominal abscess, wound dehiscense, anastomotic leak, the need for a second operation, pulmonary embolus, or serious infection. 13. Have documented short bowel syndrome (more than 100 cm in total of small bowel resected) 14. Are pregnant, nursing, or planning pregnancy (both men and women) during the trial or within the 6-month period thereafter 15. Have shown a previous immediate hypersensitivity response, including anaphylaxis, to an immunoglobulin product (plasma-derived or recombinant, e.g., monoclonal antibody) 16. Have a known allergy to murine proteins or other chimeric proteins 17. Have received within 3 months prior to screening or are expected to receive any live viral (e.g., small-pox) or live bacterial vaccinations during the trial or up to 3 months after the last administration of study agent 18. Have evidence of an active infection at the time of randomization or have had a serious infection not related to CD within 6 months prior to screening 19. Have had a Clostridium difficile (C. difficile) infection within the past 4 months 20. Have or have had an opportunistic infection (e.g., herpes zoster [shingles], cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria other than TB) within 6 months prior to screening 21. Have current active hepatitis B or a history of hepatitis C infection 22. Have documented or suspected human immunodeficiency virus (HIV) infection 23. Have current signs or symptoms of or a history of systemic lupus erythematosus; severe, progressive, or uncontrolled renal, hepatic, hematologic, endocrine, pulmonary, cardiac, neurologic, or cerebral diseases 24. Have a transplanted organ (with the exception of a corneal transplant performed > 3 months prior to screening) 25. Have a history of lymphoproliferative disease including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy of unusual size or location (e.g., nodes in the posterior triangle of the neck, intraclavicular, epitrochlear, or periaortic areas), or splenomegaly 26. Have any known malignancy or history of malignancy within the 5-year period prior to screening (with the exception of squamous or basal cell carcinoma of the skin that has been completely excised without evidence of recurrence) 27. Have multiple sclerosis or other central demyelinating disorder 28. Have had a chronic or recurrent infectious disease including but not limited to chronic renal infection; chronic chest infection (e.g., bronchiectasis); sinusitis; recurrent urinary tract infection (recurrent pyelonephritis or chronic nonremitting cystitis); open, draining, or infected skin wound or ulcer 29. Have any condition that, in the opinion of the investigator, would compromise the well-being of the patient or the study or prevent the patient from meeting or performing study requirements.
30. Have used any investigational drug within 30 days prior to screening, or within 5 half-lives of the investigational agent, whichever is longer 31.Are currently participating in another investigative trial using an investigational agent, procedure, or medical device during participation in this trial 32. Have a history of substance abuse within the previous 3 years, history of noncompliance to medical regimens, or other condition/circumstance that could interfere with the patient’s adherence to protocol requirements 33. Have a concomitant diagnosis or any history of congestive heart failure |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary endpoint is clinical recurrence of CD through Week 76. Clinical recurrence is a composite endpoint defined by the following:
• A ≥ 70-point increase from baseline in CDAI; and
• A CDAI score of ≥ 200; and
• Evidence of endoscopic recurrence. Endoscopic recurrence is defined as a Rutgeerts score of ≥ i2 at the anastomotic site or its equivalent elsewhere in the GI tract.
Patients who meet the criteria for clinical recurrence at Week 76 or at any timepoint prior to Week 76 will be considered to have clinical recurrence through Week 76. Patients who initiate a prohibited CD-related medication or have a prohibited use of a CD medication prior to Week 76 will be considered to have had clinical recurrence. Patients who have surgery for CD prior to Week 76 will be considered to have had clinical recurrence.
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 100 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| The study is considered completed with the last visit of the last patient participating in the study. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| E.8.9.2 | In all countries concerned by the trial months | 2 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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