E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Active Celiac Disease in subjects attempting a Gluten-Free Diet |
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E.1.1.1 | Medical condition in easily understood language |
celiac disease combined with gluten-free diet . When people with celiac disease eat gluten (a protein found in wheat, rye, and barley), their immune system attacks and damages the small intestine. |
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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 | 10009839 |
E.1.2 | Term | Coeliac 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 |
To evaluate the efficacy of TAK-062, as measured by the CDSD, for reducing celiac-related symptoms due to gluten exposure in subjects with CeD attempting to maintain a GFD in treated subjects versus placebo controls. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of TAK-062 for improvement of small intestine mucosal injury due to gluten exposure in subjects with CeD attempting to maintain a GFD in treated subjects versus placebo controls. To evaluate the safety and tolerability of TAK-062 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. The subject is able to provide written informed consent form to participate in the study before completing any study-related procedures. 2. In the opinion of the investigator, the subject is willing and fully capable of understanding and complying with study procedures including PRO compliance and restrictions defined in this protocol. 3. The subject has an adequate comprehension of a GFD assessed by completion of a knowledge test after viewing of educational materials. 4. The subject has at least 1 CeD-related GI symptom of moderate or greater severity, as measured by the CDSD, on at least 3 days out of any consecutive 7-day period during the screening period (Week -8 visit until Week -4 visit), felt by the investigator to be related to gluten exposure. The CeD-related symptoms may vary day-by-day as long as the severity of at least 1 symptom is moderate or greater. The subjects must meet symptom criteria to undergo EGD/VCE. 5. The subject has biopsy-confirmed CeD. 6. The subject has been attempting to maintain a GFD for at least 12 months as self-reported by the subject. 7. The subject has small intestinal villous atrophy on duodenal biopsy defined as Vh:Cd <3.0 at Week -4. 8. The subject is HLA-DQ2 and/or HLA-DQ8 positive. 9. The subject in Cohort 1 is aged 18 to 75 years, inclusive, at the time of signing the informed consent form. 10. The subject in Cohort 2 is aged 12 to 75 years, inclusive, at the time of signing the informed consent/pediatric assent forms. 11. The subject is in a good general state of health according to clinical history and physical examination, in the opinion of the investigator. 12. The subjects must have a body mass index (BMI) between 16 and 35, inclusive. 13. The subject is willing and able to continue any current dietary and/or medical regimens (including gastric acid suppression) in effect at the screening visit (Visit 1). There should be no changes to diet, medications (prescription or over-the-counter) or supplements during study participation. 14. A male subject who is nonsterilized* and sexually active with a female partner of childbearing potential* agrees to use highly effective method of contraception (eg, condom with or without spermicide)* from signing of informed consent/pediatric assent forms throughout the duration of the study and for 100 days after last dose of study drug. 15. A female subject of childbearing potential* who is sexually active with a nonsterilized* male partner agrees to use a highly effective method of contraception* from signing of informed consent/pediatric assent forms throughout the duration of the study and for 40 days after the last dose of study drug. |
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E.4 | Principal exclusion criteria |
1. The 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. 2. The subject has inadequate renal or hepatic function before randomization based on the following laboratory parameters: - Total bilirubin ≥1.5 × ULN unless the subject has known Gilbert’s syndrome that can explain the elevation of bilirubin, or - Serum alanine aminotransferase (ALT) ≥3 × ULN, or - Creatinine >1.5 × ULN. 3. The subject has the presence of other inflammatory GI disorders or systemic autoimmune diseases (including but not limited to the following: inflammatory bowel disease, eosinophilic esophagitis, gastroenteritis or colitis, microscopic colitis diagnosed at screening or requiring treatment in the 6 months before screening, scleroderma, psoriatic or rheumatoid arthritis,lupus) other than those noted below: - Thyroid disease that has been well-controlled for at least 6 months. - Well-controlled type 1 diabetes (glycosylated hemoglobin <8 and no hospitalization or emergency room visit in the last 12 months for hyperglycemia or hypoglycemia). 4. The subject has ongoing systemic immunosuppressant, systemic corticosteroid treatment, or treatment with systemic immunosuppressants or systemic corticosteroids in the 12 weeks before screening. - The subject is receiving immunosuppressive doses of corticosteroids: 3 mg per day or more of budesonide for more than 3 consecutive days within 3 months before screening, more than 20 mg of prednisone given daily or on alternative days for 2 weeks or more within 6 months before the first dose, any dose of oral or IV corticosteroids within 30 days of the first dose, or high-dose inhaled corticosteroids (>960 μg/d of beclomethasone dipropionate or equivalent), or other systemic immunosuppressive agents. 5. The subject has ongoing use of over-the-counter digestive enzymes or digestive supplements,other than lactase, including those for gluten digestion. Probiotics are allowable if they were started before screening and not discontinued or changed in dose or type during the study. 6. The subject has an inability to swallow the study drug tablet. 7. The subject has completed the CDSD on ≤75% of the days during Week -8 until randomization. 8. If more than 10% of planned enrollment in a cohort report a greater than 1 point improvement in PGIS during the SIGE run-in period (Week -2 through Day -1), further subjects showing this degree of improvement will be excluded from the cohort. 9. The subject has ongoing symptoms that are considered by the investigator to be due to other GI conditions, including irritable bowel syndrome and eosinophilic disorders. 10. The subject has active microscopic colitis requiring treatment in the 6 months before screening. - Microscopic colitis detected at screening if sigmoidoscopy is performed would exclude the subject. 11. The subject has known or suspected type 2 refractory CeD or ulcerative jejunitis. 12. The subject has ongoing chronic use (defined as >7 days continuous use) of a nonsteroidal anti-inflammatory drug aside from <100 mg aspirin, daily, for prophylactic use. 13. The subject has ongoing use, or use in the 3 months before screening, of medications known to cause villous abnormalities (eg, mycophenolate mofetil, angiotensin receptor blockers,colchicine). 14. The subject used treatments for GI symptoms including antiemetics, antidiarrheals, constipation agents other than fiber, antispasmodics and medical marijuana within 2 weeks of screening. 15. The subject has a known or suspected severe enteric infection (viral, bacterial, or parasitic) within 6 months before randomization. Severe enteric infection is defined as requiring emergency room visit or hospitalization or treatment with antibiotics or anti-infectives due to infection. Non-enteric viral infections, either resolved or well-controlled are not exclusionary. 16. The subject has received any investigational compound within 12 weeks (84 days) or 5 half-lives, whichever is longer, before enrollment into the study. 17. The subject has a contraindication to endoscopy with duodenal biopsy. -Contraindication to VCE (strictures, anastomoses, etc) is not an exclusion if the subject is able to complete the other aspects of the study. 18. The subject has additional food allergies (eg, almond, nuts) to nongluten ingredients in the SIGE bar study food or significant symptoms upon ingestion of the gluten-free SIGE bar during screening. 19. The subject has a history of intolerance, hypersensitivity, or idiosyncratic reaction to an aminoglycoside. 20. Changes or planned changes to the subject’s medications or diet that could affect the study between screening and the end of study visit.
see protocol for others criteria: 21 to 28 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in CDSD GI symptom severity score from baseline (Week -1, the last week of the run-in period) to Week 12. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Week -1, the last week of the run-in period to Week 12. |
|
E.5.2 | Secondary end point(s) |
Change in Vh:Cd from baseline (measured at Week -4) to Week 24. |
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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 | No |
E.8.2.4 | Number of treatment arms in the trial | 7 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 39 |
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 |
Canada |
United States |
France |
Poland |
Netherlands |
Spain |
Italy |
Belgium |
United Kingdom |
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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 | |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 6 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 6 |