E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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] - Digestive System Diseases [C06] |
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 |
1. To evaluate the efficacy of TAK-018 in reducing endoscopic recurrence of intestinal inflammation in postoperative subjects with CD after planned laparoscopic ileocecal resection with primary anastomosis.
2. To assess the safety and tolerability of TAK-018 in postoperative subjects with CD after planned laparoscopic ileocecal resection with primary anastomosis |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of TAK-018 on intestinal inflammation based on endoscopic recurrence and serial fecal calprotectin measures.
To characterize the pharmacokinetics (PK) of TAK-018 in postoperative subjects with CD after planned laparoscopic ileocecal resection with primary anastomosis. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. In the opinion of the investigator, the subject is capable of understanding and complying with protocol requirements
2. Subject signs and dates a written informed consent form (ICF), and any required privacy authorization before performance of any study-related procedures not part of standard medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
3. Male or female subject aged ≥18 years or local legal age at signing of ICF.
4. Subject must have a documented diagnosis of CD confirmed by endoscopic biopsy before resection or by tissue obtained at resection.
5. Subject is planned to undergo a laparoscopic ileocecal resection with primary anastomosis within 72 hours before randomization (D1). Confirmation that no active disease has been left behind after resection will be based on surgeon’s documentation in the operative report.
6. Subject with postoperative discontinuation of all concomitant medications specifically related to the treatment of CD. This includes anti-TNF-alpha and anti-integrin therapy, anti-IL 12/23, thiopurines and other
immunomodulators, steroids, 5-aminosalicylates, and prophylactic use of antibiotics for the prevention of postoperative recurrence such as metronidazole.
7. Subject has resumed oral intake and is capable of swallowing tablets within 72 hours after surgery.
8. Female subject who is:
- Postmenopausal for at least 1 year before signing of the informed consent, OR
- Surgically sterile, OR
- If she is of childbearing potential, agrees to practice 1 highly effective method of contraception (specified in protocol Section 9.3.17) and 1 additional effective (barrier) method at the same time, from the time of signing the informed consent through 40 days after the last dose of study drug, OR
- Agrees to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)
Male subject, even if surgically sterilized (ie, status postvasectomy), who:
- Agrees to practice effective barrier contraception (specified in Section 9.3.17) during the entire study treatment period and through 100 days after the last dose of study drug, OR
- Agrees to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)
9. Subject with suitable venous access for the study-required blood sampling, including PK sampling. |
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E.4 | Principal exclusion criteria |
1. Subject has active perianal CD.
2. Subject has had >3 previous surgical procedures for CD.
3. Subject has macroscopically active CD that was not resected at the time of surgery as documented in the surgeon's operative report.
4. Subject with a small bowel resection that exceeds 100 cm or ta subject who is considered at risk of short bowel syndrome by the surgeon or investigator.
5. Subject has any significant intraoperative or postoperative complications such as anastomotic leak, surgical site infection, or inability to tolerate oral intake.
6. Subject is unable or unwilling to undergo or has contraindications to ileocolonoscopic procedures as assessed by the investigator.
7. Subject has inadequate renal or hepatic function postsurgery and before randomization based on the following laboratory parameters:
- Total bilirubin >1.5× the institutional upper limit of normal (ULN) unless subject has known Gilbert’s syndrome that can explain the elevation of bilirubin.
OR
- Serum alanine aminotransferase (ALT) >3× the institutional ULN. OR
- Creatinine >1.5× the institutional or central laboratory ULN or estimated creatinine clearance <50 mL/minute/1/73 m2 for subjects with serum creatinine concentrations above the institutional or central laboratory limits.
8. Subject has any unstable or uncontrolled cardiovascular, pulmonary, hepatic, renal, genitourinary, coagulation, immunological, endocrine/metabolic, neurologic, active substance abuse, psychiatric or other medical disorder not related to the subject’s primary disease that, in the opinion of the investigator, would confound the study results, compromise subject safety, or interfere with completion of the study.
9. Subject has active or latent tuberculosis, regardless of treatment history, as evidenced by any of the following: history of tuberculosis, OR positive QuantiFERON test or 2 successive indeterminate QuantiFERON tests, OR a tuberculin skin test reaction ≥10 mm (≥5 mm in subjects receiving the equivalent of >15 mg/day prednisone).
10. Subject has chronic hepatitis B (hepatitis B surface antigen positive, or positive for both hepatitis B surface antibody and hepatitis B core antibody but negative for hepatitis B surface antigen) or hepatitis C infection (evident by viral replication by polymerase chain reaction) within 30 days of randomization.
11. Subject has a history of HIV or tests positive for HIV at screening.
12. If female, the subject is pregnant, lactating or breastfeeding, or intending to become pregnant before, during, or within 40 days after last dose of the study drug; or intending to donate ova during such time period.
13. If male, the subject intends to donate sperm during this study or for 100 days thereafter.
14. Subject has a current diagnosis of biliary obstruction.
15. Subject demonstrates significant undernutrition at the time of screening (body mass index <18.5 kg/m2, and weight loss >15% within 6 months, and serum albumin <3 g/dL)
16. A subject who, in the opinion of the investigator, is unwilling or unlikely to comply with the
requirements of the study.
17. Subject has participated in another clinical study within the past 30 days before completing informed consent or has received any investigational compound within 30 days before screening.
18. Subject has received TAK-018 (previously known as EB8018) in a previous clinical study.
19. Subject is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.
20. Subject has a history of hypersensitivity or allergies to TAK-018, including any excipients contained in the study drug formulation.
21. Subject has a history of drug abuse (defined as any illicit drug use or history of alcohol abuse) within the past 12 months.
22. Subject takes or is required to take excluded medications listed in protocol section 8.3. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. The percentage of subjects with endoscopic recurrence of CD at W26. Endoscopic recurrence is defined as Rutgeerts score ≥i2 (i2, i3, i4;) 2. The percentage of subjects who experience treatment-emergent adverse events (TEAEs), defined as AEs that begin or worsen after the first dose of study treatment regardless of relationship to study drug, SAEs, and/or clinically significant changes in vital signs, standard laboratory tests and procedures (eg, clinical chemistry, hematology, urinalysis). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. At Week 26
2. From the administration of the first dose of study drug till the study end |
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E.5.2 | Secondary end point(s) |
1. The percentage of subjects with fecal calprotectin (FCP) >135 μg/g at Week 3 (W3), Week 6 (W6), Week 12 (W12), Week 18 (W18), Week 26 (W26), and Week 30 (W30).
2. Observed plasma trough concentrations of TAK-018. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. At week 3 (W3), week 6 (W6), week 12 (W12), week 18 (W18), week 26 (W26) and week 30 (W30).
2. at week 3 (W3) |
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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 | Yes |
E.6.3 | Therapy | No |
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 | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | 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 | 19 |
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 |
Austria |
France |
Germany |
Netherlands |
United Kingdom |
United States |
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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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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 | 8 |
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 |