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 |
Ulcerative Colitis is a type of inflammatory bowel disease that causes the lining of the large intestine (colon) to become inflamed (irritated and swollen) which may cause ulcers and bleeding. |
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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 | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045365 |
E.1.2 | Term | Ulcerative colitis |
E.1.2 | System Organ Class | 100000004856 |
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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 safety of long-term treatment with brazikumab in UC participants who previously completed or discontinued participation due to lack of efficacy after Week 10 in the lead-in Study D5272C00001 (Legacy #3151-201-008) |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Male or female participants who: 1. successfully completed or discontinued participation due to lack of efficacy after Week 10 in the lead-in Study D5272C00001. AND Meets 1 of the following criteria for successful completion or early termination from Study D5272C00001: (a) Participant completed Study D5272C00001, received scheduled study interventions, completed scheduled visits, and completed Week 54 assessments. (b) Participant discontinued participation due to lack of efficacy after Week 10 in Study D5272C00001, received scheduled study interventions, and completed Early Termination Visit assessments. 2. No known history of active TB or latent TB without completion of appropriate intervention. 3. Male participants willing to minimize the risk of inducing pregnancy for the duration of the clinical study and follow-up period. Nonsterilized men who are sexually active with a female partner of childbearing potential should use condom during treatment and for 18 weeks after the last dose of study intervention 4. Female participants of childbearing potential must have a negative urine pregnancy test prior to administration of study intervention and must agree to use a highly effective method of birth control (confirmed by the investigator) from randomization throughout the study duration and for at least 18 weeks after last dose of study intervention 5. Women not of childbearing potential are defined as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal. 6. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. 7. Written informed consent from the participant has been obtained prior to any study related procedures. 8. Written documentation has been obtained in accordance with the relevant country and local privacy requirements, where applicable (eg, Written Authorization for Use and Release of Health and Research Study Information [US sites] and written Data Protection consent [EU sites]). 9. Demonstration of adequate compliance with the study procedures in Study D5272C00001, in the opinion of the investigator and/or sponsor. 10. Willingness and ability to attend all study visits, comply with the study procedures, and be able to complete the study period. 11. Participant must be 18 to 80 years of age inclusive, at the time of signing the ICF. Complete inclusion criteria are in the study protocol |
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E.4 | Principal exclusion criteria |
1. Any participant with an unresolved AE from the lead-in study that, in the investigator’s opinion, would limit the participant’s ability to participate in or complete this study. Any unresolved AE related to an infection will require further discussion with the study medical monitor prior to enrollment. 2. Current diagnosis of fulminant colitis, CD or indeterminate colitis, presence of a fistula consistent with CD, primary sclerosing cholangitis, celiac disease, or toxic megacolon. Bile acid malabsorption and other conditions that may potentially confound assessments must be treated prior to baseline. 3. Organ or cell-based transplantation with the exception of corneal transplant. 4. Any other condition or finding that, in the investigator’s or sponsor’s opinion, would either confound proper interpretation of the study or expose a participant to unacceptable risk. 5. The following are exclusionary with regards to malignancy: a) Evidence of intestinal epithelial dysplasia on endoscopy, and this is confirmed on biopsy, the participant. b) Any diagnosis of malignancy that requires discontinuation of study intervention from lead-in study. c) Any new diagnosis of malignancy after completion of the lead-in study. d) Carcinoma in situ of the cervix, with apparent successful curative therapy within 12 months prior to Week 0. 6. Participant meets criteria for discontinuation of study intervention during prior lead-in study. 7. Chronic hepatitis B or C infection 8. Known history of primary immunodeficiency, splenectomy, or any underlying condition that predisposes the participant to infection, including HIV infection. 9. Prolonged QTcF interval or conditions leading to additional risk for QT prolongation. Participants with electrolyte abnormalities such as hypokalemia and hypomagnesemia that would increase the risk of QT prolongation are to be corrected prior to enrollment. 10. Clinically significant kidney disease including but not limited to: (a) Chronic kidney disease with an estimated glomerular filtration rate of less than 30 ml/min calculated by Modification of Diet in Renal Disease equation. 11. Participant requires additional immunosuppressive therapy (aside from permitted concomitant medication in the protocol), biological treatment or prohibited treatment 12. Participant received a prohibited medication during participation in the D5272C00001 study. 13. Participant received a Bacille Calmette-Guérin vaccination within 12 months of Week 0 or any other live vaccine < 4 weeks prior to Week 0, or is planning to receive any such vaccine over the course of the study. 14. Participant has received an investigational product after discontinuation from Study D5272C00001 and prior to enrolling in this study or participant is planning to receive an investigational drug (other than study intervention) or investigational device at any time during Study D5272C00002. 15. Participant who discontinued participation due to lack of efficacy after Week 10 in Study D5272C00001 and did not receive all 3 IV infusions of study interventions scheduled for Week 0 (Day 1), Week 2 (Day 15), and Week 6 (Day 43), and SC at Week 10 (Day 71) in accordance with the protocol for Study D5272C00001. 16. Participant who discontinued due to lack of efficacy after Week 10 in Study D5272C00001 but currently demonstrates clinical response and/or meets endoscopic Mayo Score of 0 or 1 prior to Week 54 in Study D5272C00001: Clinical Response defined as: Reduction in mMS ≥ 2 points from baseline AND ≥ 30% from baseline, AND a decrease in the rectal bleeding score ≥ 1 point from baseline or a score of 0 or 1, in Study D5272C00001. Note: Participants are encouraged to remain in the lead-in Study D5272C00001 if the participant is demonstrating evidence of clinical response. Participants should not early terminate that study due to lack of efficacy if this exclusion is met. 17. Abnormal laboratory results at screening as described in the protocol. 18. Females who are pregnant, breast feeding, or planning a pregnancy during the study OR females who are of childbearing potential and do not agree to use contraception. 19. Participant is directly or indirectly involved in the planning and/or conduct and administration of this study as study staff member, or employee of the sponsor, or the participant is a first-degree family member, significant other, or relative residing with one of the above persons involved directly or indirectly in the study; or the participant is enrolled in this study at another clinical study site. 20. Judgment that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements. 21. Previous enrollment in the present study. Complete exclusion criteria are in the study protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
- AEs - Clinical laboratory values - Vital signs -Physical exams - ECGs |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Across the 52-week treatment period for each primary endpoints |
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E.5.2 | Secondary end point(s) |
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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 | 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 | Yes |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 80 |
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 |
India |
Israel |
Japan |
Korea, Republic of |
Russian Federation |
South Africa |
Taiwan |
Ukraine |
United States |
Austria |
Czechia |
France |
Germany |
Hungary |
Italy |
Poland |
United Kingdom |
Spain |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 5 |