E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to severe Crohn’s disease |
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E.1.1.1 | Medical condition in easily understood language |
Crohn's disease (an inflammatory disease of the intestines) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10011403 |
E.1.2 | Term | Crohn's disease aggravated |
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 objective of the study is to evaluate the proportion of subjects with clinical response (defined as a decrease from Baseline of at least 100 points in the total CDAI score) or in clinical remission (defined as a total CDAI score of ≤150) following 8 weeks of treatment with OKZ, relative to placebo, in subjects with moderate to severe CD. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the number of subjects with clinical response (defined as a decrease from Baseline of at least 100 points in the total CDAI score)
• To evaluate the number of subjects in clinical remission (defined as a total CDAI score of ≤150)
• To evaluate changes in CDAI over time
• To evaluate the safety and tolerability of OKZ therapy
• To assess the impact of OKZ on subjects’ health-related quality of life as assessed by the IBDQ |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. An Independent Ethics Committee (IEC) approved written Informed Consent form is signed and dated by the subject.
2. Subject is considered reliable and capable of adhering to the protocol (eg, able to understand and complete diaries), visit schedule, and medication intake, according to the judgment of the Investigator.
3. Subject is male or female, 18 to 65 years of age at Screening.
4. Body mass index between 18 and 35kg/m2.
5. Diagnosis of CD (colonic localization) confirmed (at least 12 weeks prior to Screening) by either radiological or endoscopic evidence and/or histological examination.
6. Colonoscopy performed prior to first IMP administration (Week 0) with evidence of active CD and presence of ulceration but with no clinical suspicion of dysplasia or malignancy (colonoscopy to be performed after informed consent has been received, and all other Screening assessments have been completed).
7. Active inflammation indicated by CRP level ≥ 5mg/L at Screening.
8. Moderately to severely active CD (CDAI score: 220 to 450, inclusive) at Baseline.
9. Chest x-ray must have been performed within the last 6 months prior to Screening and must rule out active or old TB infection. Positive radiographic findings consistent with active or old TB infection may include apical lung fibrosis, pleural thickening, calcified lung nodules, calcified hilar lymph nodes, and pericardial calcification. Suspected radiographic findings must be documented with clinical interpretation by the treating physician or medical expert.
10. Subject must meet all concomitant medication criteria summarized in Table 6:1(page 24 in the protocol) before Baseline (Week 0).
a) If subjects discontinue the medication prior to Baseline a washout period of at least 2 weeks is required, or longer as detailed in the table.
b) Corticosteroid equivalent doses are summarized in Appendix 18.1.(see protocol page 65)
Notes: Nonsteroidal anti-inflammatory drugs and COX inhibitors are prohibited during the study. Low dose
aspirin (up to 100mg/day) for cardiovascular protection and acetaminophen (as required) are permitted.
11. Female subjects must be either postmenopausal for at least 1 year, surgically incapable of childbearing, or effectively practicing an acceptable method of contraception (either oral/parenteral/implantable hormonal contraceptives, intrauterine device or barrier and
spermicide). Abstinence alone is not an acceptable method. Subjects must agree to use at least 2 forms of adequate contraception during the study and for 6 months (24 weeks) (or longer if required by local regulations) after the last dose of study treatment. Male
subjects must agree to ensure they or their female partner(s) use adequate contraception during the study and for at least 12 weeks (or longer if required by local regulations) after the subject receives the last dose of IMP.
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E.4 | Principal exclusion criteria |
General Criteria:
1. Subject has a history of chronic alcohol abuse or drug abuse within the last year.
2. Subject has any medical or psychiatric condition (according to the Diagnostic and Statistical Manual of Mental Disorders [DSM-IV-TR] criteria) that could jeopardize or would compromise the subject’s ability to participate in this study.
3. Subject has participated in another study of an IMP, or a medical device, within the last 3 months or 5 half-lives, which ever is longer, or is currently participating in another
study of an IMP or a medical device.
4. Female subjects who are breastfeeding, pregnant, or plan to become pregnant during the study or within 24 weeks following the last dose of the IMP.
Disease Specific Criteria:
5. Subject has a diagnosis of ulcerative colitis or indeterminant colitis as determined by the
Investigator.
6. Subject has obstructive strictures with clinical evidence of partial or completeobstruction.
7. Subject has an active fistula (fistula secreting spontaneously or by gentle pressure).
8. In subjects with non-secreting fistula, abscesses need to be ruled out according to local practice (eg, ultrasound, endoscopic ultrasound, or magnetic resonance imaging).
9. Subject has evidence of an intra-abdominal or peri-rectal infection or abscess.
10. Subject has a history of diverticulitis or symptomatic diverticulosis.
11. Subject has had more than one bowel resection, or has had a bowel resection within the 12 months prior to Screening.
12. Subject has current status or any history of bowel perforation prior to Screening.
13. Subject has ostomy or ileoanal pouch.
14. Subject has short bowel syndrome with clinical evidence of malabsorption.
Prior/Concomitant Medication Criteria:
15. Subject is currently receiving total parenteral nutrition.
16. Subject has any prior exposure to natalizumab (Tysabri®).
17. Subject has any prior exposure to anti-IL-6 agents (eg, TCZ).
18. Subject is receiving continuous dosing with narcotic analgesics or Vitamin K antagonists (eg, phenprocoumon, acenocoumarol, warfarin).
19. Subject has had previous exposure to OKZ in a clinical study.
20. Subject is receiving or has received any live (includes attenuated) vaccination within the 8 weeks prior to Baseline (Week 0) (eg, inactivated influenza and pneumococcal vaccines are allowed but nasal influenza vaccination is not permitted).
21. Subject has any condition that requires additional immunosuppressants during the study.
Laboratory Test Criteria:
22. Subject has positive stool cultures for enteric pathogens during Screening.
23. Subject has clinically significant laboratory abnormalities
Safety Criteria:
24. Currently known active TB or clinical signs and symptoms consistent with pulmonary or extra-pulmonary TB infection and active TB can not be ruled out at the time of randomization.
25. Subject has a positive PPD test result at Screening (induration of 5mm or greater), unless the subject has been adequately treated and that there are no residual findings.
26. Subject receiving concomitant treatment for latent TB during the study.
27. Subject has concurrent acute or chronic viral hepatitis B or C or known human immunodeficiency virus (HIV) infection.
28. Subject has a known history of, or current clinically active infection with, Histoplasma, Coccidiodes, Paracoccidioides, Pneumocystis, nontuberculous mycobacteria, Blastomyces, or Aspergillus.
29. Subject has a history of chronic or recurrent infections.
30. Subject has a history of an infected joint prosthesis at any time with that prosthesis still in situ.
31. Subject has a high risk of infection.
32. Subject has a history of a lymphoproliferative disorder, including lymphoma or current signs and symptoms suggestive of lymphoproliferative disease.
33. Subject has a concurrent malignancy or a history of malignancy.
34. Subject has Class III or IV congestive heart failure as per the New York Heart Association (NYHA) 1997 criteria.
35. Subject has a history of, or suspected, demyelinating disease of the central nervous system.
36. Subject has a transplanted organ (except corneal transplant).
37. Subject has had major surgery (including joint surgery) within 12 weeks prior to Baseline, or surgery is planned during the study.
38. Subject has a current or recent history, as determined by the Investigator, of severe, progressive, and/or uncontrolled renal, hepatic, hematological, endocrine, pulmonary, cardiac, or neurological disease.
39. Subject has any other condition which, in the Investigator’s judgment, would make the
subject unsuitable for inclusion in the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects with clinical response (defined as a decrease from Baseline of at least 100 points in the total CDAI score) or in clinical remission (defined as a total CDAI score of ≤150) at Week 8. |
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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) |
Efficacy end points:
The proportion of subjects with clinical response (defined as a decrease from Baseline of
at least 100 points in the total CDAI score) over time
• The proportion of subjects in clinical remission (defined as a total CDAI score of ≤150) over time
• Mean change from Baseline in CDAI score over time
• Mean change from Baseline in IBDQ score over time
• The proportion of subjects with IBDQ response (defined as an increase in the IBDQ total
score ≥16 points from Baseline)
• The proportion of subjects in IBDQ remission (defined as an IBDQ total score ≥170 points)
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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 | 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) | 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 | No |
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 | Yes |
E.8.2.3.1 | Comparator description |
Olokizumab 120 mg OR 240 mg every two weeks OR 120 mg + loading dose 480 mg at week 0 |
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E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 63 |
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 |
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E.8.7 | Trial has a data monitoring committee | No |
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 date of the last visit of the last subject in the study (Safety Follow-Up Visit; Week 18 for subjects completing 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 | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |