E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with Crohn's Disease |
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E.1.1.1 | Medical condition in easily understood language |
Inflammatory Bowel Disease |
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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 |
To assess the proof-of-concept efficacy and safety of oral BT-11 in inducing clinical remission and endoscopic response at Week 12 in subjects with moderately to severely active Crohn’s disease (CD). |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are to evaluate the following at Week 12: 1. The effects of BT-11 on disease activity as measured by symptoms, colonoscopy, histology, and biomarkers 2. Health-related quality of life 3. The pharmacokinetic (PK) parameters of BT-11
Exploratory Objectives The exploratory objectives of this study are to evaluate the following through Week 30: 1. The effects of BT-11 on disease activity measured by symptoms, colonoscopy, histology, and biomarkers 2. Health-related quality of life 3. The PK parameters of BT-11 4. Target engagement and mechanism of action 5. The association of drug exposure in colonic mucosal tissue biopsies with clinical, endoscopic, histopathologic, and molecular outcomes. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male and female subjects aged 18 to 75 years, inclusive. 2. Diagnosis of CD for at least 3 months prior to screening. 3. Moderately to severely active CD as defined by all of the following: a) CDAI score of 220-450. b) SES-CD ≥ 6 (≥ 4 for isolated ileitis) scored by a blinded central reader. 4. If subjects have previously received biologic therapy for CD (i.e., TNF-antagonists, vedolizumab, natalizumab, or ustekinumab), they must have a washout period of 8 weeks prior to randomization (or within 4 weeks prior to randomization, if no detectable drug levels confirmed by validated or commercial assay), and any previous failure (i.e., primary or secondary nonresponse) to biologic treatment is limited to only 1 class of biologic; prior exposure to biologics that have been discontinued for reasons other than nonresponse will not be limited. (Note: this inclusion criterion is only applicable until 75 subjects with prior exposure to biologic therapy have been randomized). 5. If subjects are receiving the following CD treatments, they must be on a stable dose for at least 1 month prior to randomization: 5-aminosalicylates (5-ASAs) (not exceeding 4.8 g per day) or oral corticosteroids (not exceeding prednisone 20 mg/day, budesonide 9 mg/day, or equivalent). 6. If subjects are receiving bile-salt sequestrant, they must be on a stable dose for at least 3 months prior to randomization. 7. If subjects are receiving any nonprohibited medications, they must agree to maintain stable doses of concomitant medications for CD for the duration of the trial. 8. Unlikely to conceive, as defined by 1 of the following: a) subject is a surgically sterilized female, b) subject is a postmenopausal female ≥ 45 years of age with clinical documentation of menopause (i.e., 12 months without menses), or c) subject is male or is a woman of childbearing potential (WOCBP), and agrees to abstain from heterosexual activity, use adequate hormonal contraception, or use double-barrier contraception for 2 weeks after the last study drug administration. 9. For WOCBP, subject must have a negative pregnancy test at screening and within 24 hours prior to the first dose of study medication. 10. Able to participate fully in all aspects of this clinical trial. 11. Written informed consent must be obtained and documented. |
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E.4 | Principal exclusion criteria |
1. A diagnosis of UC. 2. At imminent risk of ileocolectomy. 3. Subjects with known current complications of CD defined as any of the following: a) Symptomatic bowel stricture. b) Ostomy or ileoanal pouch. c) Impassable anal or rectal stenoses. d) Short gut syndrome. e) Other complications that might require surgery, or any other manifestation that precludes or confounds the assessment of response to therapy (CDAI and endoscopic evaluation). 4. Any recent (within 2 months) abscess, unless it has been drained and treated at least 6 weeks prior to randomization and are not anticipated to require surgery. Subjects with nondraining perianal fistulas may be included provided there is no anticipated need for surgery and there are currently no abscesses present. 5. Any history of bowel resection or diversion within 3 months prior to screening. 6. Treatment with total parenteral nutrition within 2 weeks of screening. 7. Treatment with an immunosuppressant (azathioprine, 6-mercaptopurine [6-MP], methotrexate) within 25 days prior to randomization. 8. Treatment with efalizumab, or agents that deplete B or T cells (rituximab, alemtuzumab, or visilizumab) within 6 months of screening, or if after receiving these agents at any time prior to the study, evidence is available at screening of persistent depletion of the targeted lymphocyte population. 9. Regular daily use of opioids for medical reasons within 3 months prior to randomization. 10. Treatment with rectal 5-ASA compounds or intravenous or rectal corticosteroids within 4 weeks prior to randomization. 11. Treatment with oral corticosteroids prednisone equivalent dose > 20 mg/day, or > 9 mg/day of budesonide, or any changes to dose within the 4 weeks prior to randomization. 12. Treatment with antibiotics for CD within 1 month prior to screening. 13. Treatment with any investigational or approved biologic for CD within 8 weeks prior to randomization (or within 4 weeks prior to randomization, if no detectable drug levels confirmed by validated or commercial assay). 14. Treatment with any investigational or approved nonbiologic therapies for CD within 4 weeks prior to randomization. 15. Use of apheresis (e.g., Adacolumn apheresis) ≤ 2 weeks prior to screening. 16. Current bacterial or parasitic pathogenic enteric infection, including Clostridioides difficile, known infection with hepatitis B or C virus, known infection with human immunodeficiency virus, infection requiring hospitalization or intravenous antimicrobial therapy, or opportunistic infection within 6 months prior to screening, any infection requiring antimicrobial therapy within 2 weeks prior to screening, history of more than 1 episode of herpes zoster or any episode of disseminated zoster. 17. Any live bacterial or viral vaccination within 12 weeks prior to randomization. Patients 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 drug. 18. Bacille Calmette–Guérin vaccination within 12 months of screening. 19. Current or previous colonic dysplasia, with the exception of completely resected adenomatous polyps. 20. Fecal microbiota transplantation within 1 month prior to screening. 21. A concurrent clinically significant, unstable, or uncontrolled cardiovascular, pulmonary, hepatic, renal, GI, genitourinary, hematological, coagulation, immunological, endocrine/metabolic, or other medical disorder. 22. Known primary or secondary immunodeficiency. 23. History of myocardial infarction, unstable angina, transient ischemic attack, decompensated heart failure requiring hospitalization, congestive heart failure (New York Heart Association [NYHA] Class 3 or 4), uncontrolled arrhythmias, cardiac revascularization, stroke, uncontrolled hypertension, or uncontrolled diabetes within 6 months of screening. 24. Clinically significant laboratory abnormalities at screening, as determined and documented by the investigator. 25. Pregnant or lactating females. 26. History of major surgery within 3 months prior to screening or planned major surgery during the study 27. History of malignant neoplasms or carcinoma in situ (except for basal cell or in situ squamous cell carcinomas of the skin that have been excised or resolved) within 5 years prior to screening 28. Current or recent history of alcohol dependence or illicit drug use. 29. Mental or legal incapacitation at the time of screening visit or a history of clinically significant psychiatric disorders 30. Unable to attend study visits or comply with procedures. 31. Concurrent participation in any other interventional study. 32. Received any investigational therapy within 30 days of initiation of study drug. 33. Previous exposure to BT-11. 34. Prior enrollment in the current study and had received study treatment. 35. Treatment with sirolimus within 4 weeks prior to randomization. 36. A positive COVID-19 test, or exposure to COVID-19 patients.
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E.5 End points |
E.5.1 | Primary end point(s) |
Co-primary endpoints: 1. Proportion of subjects achieving clinical remission at Week 12, defined by CDAI < 150; 2. Frequency and severity of AEs compared to placebo |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. At weeks R, 2, 6, 12 ,18, 24, 30 2. Record adverse events from the time of the signing of the informed consent until the end of the study |
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E.5.2 | Secondary end point(s) |
Key (ranked) secondary endpoints: 1. Proportion of subjects with an endoscopic response at Week 12, defined by a 50% reduction from baseline in the Simple Endoscopic Score for Crohn’s Disease (SES-CD) score 2. Endoscopic remission (SES-CD of 0-2 or SES-CD ≤ 4, a ≥ 2-point improvement from baseline, and no subscore > 1) at Week 12 3. Proportion of subjects achieving histologic remission (Geboes score < 2B.1 [with absence of neutrophils in lamina propria]) at Week 12 4. Clinical response (CDAI reduction from baseline ≥ 100 points or CDAI < 150) at Week 12 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Screening, Week 12, 30 2. Screening, Week 12, 30 3. Screening, Week 12, 30 4. Week R, 2, 6, 12 ,18, 24, 30
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
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 | 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 | 2 |
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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 105 |
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 |
Albania |
Belarus |
Bosnia and Herzegovina |
Georgia |
North Macedonia |
Moldova, Republic of |
Serbia |
Turkey |
Ukraine |
United States |
Austria |
Bulgaria |
Croatia |
Netherlands |
Poland |
Slovakia |
Spain |
Czechia |
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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-Study is defined as the end of the posttreatment safety follow-up visit, 2 weeks after the last dose of study drug at the end of the maintenance period (or after the last dose in the induction period for subjects who do not continue in the maintenance period). |
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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 | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 10 |