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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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011401 |
E.1.2 | Term | Crohn's disease |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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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 |
The primary objectives are:
- To evaluate clinical remission for the 2 SC maintenance regimens of ustekinumab in subjects with moderately to severely active Crohn’s disease induced into clinical response with ustekinumab in the induction studies, CNTO1275CRD3001 and CNTO1275CRD3002.
- To evaluate the safety of 2 SC maintenance regimens of ustekinumab in subjects with moderately to severely active Crohn’s disease. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are:
- To evaluate the efficacy of ustekinumab in maintaining clinical response in subjects induced into clinical response.
- To evaluate the efficacy of ustekinumab in maintaining clinical remission in subjects induced into clinical remission.
- To evaluate the efficacy of ustekinumab in achieving corticosteroid free remission. To evaluate the pharmacokinetics, immunogenicity, and pharmacodynamics of Ustekinumab therapy, including changes in C-reactive protein (CRP), fecal calprotectin, fecal lactoferrin, and other pharmacodynamic biomarkers.
- To evaluate the effect of ustekinumab on health related quality of life. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Have received study agent at Week 0 in study CNTO1275CRD3001 or CNTO1275CRD3002 and completed the Week 8 CDAI score evaluation.
2. Be able to complete the Week 0 visit in study CNTO1275CRD3003 within 4 days of the Week 8 visit in study CNTO1275CRD3001 or CNTO1275CRD3002. At the discretion of the investigator, the window may be extended to 8 days to allow appropriate treatment and/or recovery of nonserious infections (eg, acute upper respiratory tract infection, simple urinary tract infection).
3. Be able and willing to adhere to the study visit schedule and comply with other protocol requirements
4. Be capable of providing informed consent, which must be obtained prior to any study-related procedures |
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E.4 | Principal exclusion criteria |
1. Had any of the following changes to their concomitant medications due to Crohn’s disease (ie, lack of efficacy) since Week 0 of studies CNTO1275CRD3001 and CNTO1275CRD3002
a. Increase in physician-prescribed daily dose of oral corticosteroids of more than 5 mg or more of prednisone (or equivalent increase in prednisone-equivalent dose of other corticosteroids),
b. Initiation of oral budesonide or increase in daily dose
c. Initiation of parenteral, and oral corticosteroids for Crohn’s disease, except for dose equivalent substitutions among oral corticosteroids
d. Initiation or increased physician-prescribed daily dose of methotrexate (MTX), 6-MP, or azathioprine (AZA), except for dose equivalent substitutions
2. Initiated a protocol prohibited medication since Week 0 of studies CNTO1275CRD3001 and CNTO1275CRD3002:
a. Immune suppressing immunomodulatory agents other than 6-MP/AZA or MTX (including but not limited to 6-TG, cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil)
b. Immunosuppressant biologic agents (including but not limited to TNF-antagonists, natalizumab, abatacept, commercial ustekinumab)
c. Experimental Crohn’s disease medications (including but not limited to thalidomide, briakinumab, vedolizumab, traficet, AMG-827)
3. Underwent a Crohn’s disease related surgery since Week 0 of induction study CNTO1275CRD3001 or CNTO1275CRD3002. Seton placement and recent cutaneous and perianal abscesses which have been drained and adequately treated at least 3 weeks prior to receiving baseline study agent are not exclusionary provided that there is no anticipated need for any further surgery
4. Subjects from countries with high multidrug-resistant TB burden (eg, South Africa, Bulgaria, and the Russian Federation) diagnosed with latent TB during induction study CNTO1275CRD3001 or CNTO1275CRD3002, or any subject who has discontinued or is noncompliant with appropriate therapy for the treatment of latent TB.
5. Are diagnosed with any medical condition (or signs or symptoms thereof) which would have precluded enrollment in induction studies CNTO1275CRD3001 and CNTO1275CRD3002. This includes any lymphoproliferative disorder or malignancy (other than basal cell carcinoma of the skin), opportunistic or other significant infection, or other severe, progressive, or uncontrolled medical (eg renal, hepatic, hematological, endocrine, pulmonary, cardiac, neurologic, or autoimmune) or psychiatric disease, including recent significant instability in a previous condition.
6. Have signs and symptoms of latent or active granulomatous infection, including TB, histoplasmosis, or coccidioidomycosis.
7. Is a woman who is pregnant, or breast-feeding, or planning to become pregnant or is a man who plans to father a child while enrolled in this study or within 20 weeks after the last dose of study agent. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint analysis and the major secondary endpoint analyses will include only subjects in clinical response to ustekinumab at Week 8 from 1 of the induction studies (CNTO1275CRD3001 or CNTO1275CRD3002) who were randomized at Week 0 of this study into 1 of the maintenance regimens.
The primary endpoint is clinical remission at Week 44, where clinical remission is defined as a CDAI score of < 150 points. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
The major secondary endpoints in order of importance are:
1. Clinical response at Week 44.
2. Clinical remission at Week 44 among subjects in clinical remission to ustekinumab at Week 0.
3. Corticosteroid-free remission at Week 44.
4. Clinical remission at Week 44 in the subset of subjects who were refractory or intolerant to TNF-antagonist therapy (ie, subjects from induction study CNTO1275CRD3001). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.11 | Pharmacogenomic | Yes |
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.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 113 |
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 | No |
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 |
Australia |
Brazil |
Canada |
Croatia |
European Union |
Iceland |
Israel |
Japan |
Korea, Republic of |
New Zealand |
Russian Federation |
Serbia |
South Africa |
United States |
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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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The end of the study is defined as the completion of the final safety follow-up visit for the last subject after his or her last SC administration of study agent in the study extension phase of the study. |
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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 | 8 |
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 | 8 |
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 |