E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderately to Severely Active Crohn’s Disease |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10011401 |
E.1.2 | Term | Crohn's disease |
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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 |
To evaluate the efficacy of ustekinumab in inducing clinical response. To evaluate the safety of ustekinumab. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of ustekinumab in inducing clinical remission, fistula response, and mucosal healing. To obtain data to support selection of a maintenance dose regimen for continued clinical development. To explore the pharmacokinetics and pharmacodynamics of ustekinumab therapy. To evaluate the efficacy of ustekinumab in achieving delayed clinical response. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacogenomic analyses of blood samples and mucosal biopsy samples. For further details reference is made to the main study protocol (section 8.2) |
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E.3 | Principal inclusion criteria |
- Have Crohn’s disease or fistulizing Crohn’s disease of at least 3 months’ duration, with colitis, ileitis, or ileocolitis, confirmed by radiography and/or endoscopy. - Have active disease, defined as a baseline CDAI score of ≥ 220 and ≤ 450. - Have received infliximab, adalimumab, or certolizumab pegol at a dose approved for the treatment of Crohn’s disease and: a. Did not respond initially (ie, primary nonresponders). or b. Responded initially but then lost response with continued therapy (ie, secondary nonresponders). or c. Were intolerant to the medication. - Are men or women who are ≥ 18 years of age at time of consent. - Adhere to the following concomitant medication requirements relative to the first study agent administration at baseline (Week 0). a. 5-ASA compounds. b. Oral corticosteroids (eg, prednisone, budesonide) c. Crohn’s disease-specific antibiotics d. Immunomodulators: -Women of childbearing potential and all men must be using adequate birth control measures - Have the capacity to understand and sign an informed consent form. - Be able to adhere to the study visit schedule and other protocol requirements. - Have screening laboratory test results within the following parameters: - Hemoglobin > 8.5 g/dL - WBCs ≥ 3.5 x 103/µL - Neutrophils ≥ 1.5 x 103/µL - Platelets ≥ 100 x 103/µL - Serum creatinine < 1.5 mg/dL - AST and ALT concentrations must be within 2 times the ULN range for the laboratory conducting the test. - Direct (conjugated) bilirubin < 2.0 mg/dL. - Are considered eligible according to the following TB screening criteria: a. Have no history of latent or active TB prior to screening. b. Have no signs or symptoms suggestive of active TB upon medical history and/or physical examination. c. Have had 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. d. Within 2 months prior to the first administration of study agent, either have negative diagnostic TB test results (defined as a negative QuantiFERON-TB Gold In-Tube test), or have a newly identified positive diagnostic TB test result (defined as a positive QuantiFERON-TB Gold In-Tube test) during screening in which active TB has been ruled out and for which appropriate treatment for latent TB has been initiated either prior to or simultaneously with the first administration of study agent. e. Have a chest radiograph (both posterior-anterior and lateral views), taken within 3 months prior to the first administration of study agent and read by a qualified radiologist, with no evidence of current active TB or old inactive TB. |
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E.4 | Principal exclusion criteria |
- Have complications of Crohn’s disease such as strictures, stenoses, short gut syndrome, or any other manifestation that might require surgery, could preclude the use of the CDAI to assess response to therapy, or would possibly confound the evaluation of benefit from treatment with ustekinumab. - Have any current or prior abscesses, unless they have been drained and treated at least 6 weeks prior to baseline and are not anticipated to require surgery. Subjects with active fistulas may be included if there is no anticipation of a need for surgery and there are currently no abscesses present. - Have had any kind of bowel resection, diversion, or placement of a stoma within months or any other intra-abdominal surgery within 3 months prior to screening. - Have received treatment with total parenteral nutrition (TPN) within 2 weeks of screening. - Have a stool culture or other examination positive for an enteric pathogen, including Clostridium difficile toxin, in the last 4 months unless a repeat examination is negative and there are no signs of ongoing infection with that pathogen. - Are pregnant, nursing, or planning pregnancy (both men and women) while enrolled in the study, or within 20 weeks after receiving the last dose of study agent. - Have used any therapeutic agent targeted at reducing IL-12 or IL-23, including but not limited to, ustekinumab (CNTO 1275) and ABT-874. - Have used any investigational drug within the previous 4 weeks or 5 times the half-life of the investigational agent prior to the first administration of study agent, whichever is longer. - Have used any TNF antagonist ≤ 8 weeks prior to the first administration of study agent or any other biologic ≤ 12 weeks prior to the first administration of study agent or within 5 times the half-life of the biologic prior to the first administration of study agent, whichever is longer. - Have received natalizumab, efalizumab, or agents that deplete B or T cells within 12 months of screening, or, if after receiving these agents, evidence is available at screening of persistent depletion of the targeted lymphocyte population. - Have used apheresis (eg, Ada column apheresis) ≤ 2 weeks prior to screening. - Have received any live bacterial or viral vaccination ≤ 12 weeks prior to Week 0. Subjects must agree not to receive a live virus or bacterial vaccination during the study or up to 12 months after the last administration of study agent. - Have had a Bacille Calmette-Guérin (BCG) vaccination within 12 months of screening. Subject must agree not to receive a BCG vaccination during the study or up to 12 months after the last study agent administration. - Have a history of, or ongoing, chronic or recurrent infectious disease. - Have current signs or symptoms of infection or history of serious infection. - Have evidence of a herpes zoster infection ≤ 8 weeks of screening. - Have a history of latent or active granulomatous infection. - Have evidence of current active infection. - Have or ever have had a nontuberculous mycobacterial infection or serious opportunistic infection. - Are known to be infected with human immunodeficiency virus, hepatitis B, or hepatitis C. - Have severe, progressive, or uncontrolled renal, hepatic, hematological, endocrine, pulmonary, cardiac, neurologic, cerebral, or psychiatric disease, or signs and symptoms thereof. - Have a transplanted organ (with exception of a corneal transplant > 12 weeks prior to screening) or have ever received stem cell therapy (eg, Prochymal). - Have a known history of lymphoproliferative disease, including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy and/or splenomegaly. - Have any known malignancy or have a history of malignancy. - Are known to have had a substance abuse (drug or alcohol) problem within the previous 12 months.
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E.5 End points |
E.5.1 | Primary end point(s) |
Clinical response at Week 6 |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 70 |
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 |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |