Ulcerative Colitis
Conditions
Keywords
Ulcerative Colitis, Japanese, subcutaneously
Brief summary
This is a multi-centre, randomised, double-blind, placebo controlled, parallel group, Phase II study to evaluate efficacy and safety of 3 doses of MEDI7183, in Japanese subjects with moderate to severe UC
Interventions
DRUGMEDI7183 low dose
MEDI7183 will be administered by SC on Day 1, Week 2, 4, and 8
DRUGMEDI7183 medium dose
MEDI7183 will be administered by SC on Day 1, Week 2, 4, and 8
DRUGMEDI7183 high dose
MEDI7183 will be administered by SC on Day 1, and placebo for MEDI7183 at Week 2, 4, and 8
DRUGMatching Placebo
Placebo will be administered by SC on Day 1, Week 2,4, and 8
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Provision of informed consent prior to any study specific procedures * Diagnosis of UC established by clinical and endoscopic evidence and corroborated by a histopathology report * Moderate to severe active UC as defined by a total Mayo score of 6 to 12 with rectosigmoidoscopy score ≥ 2 during screening period * Demonstrated an inadequate response to, loss of response to, or intolerance to at least one of immunomodulators or Anti- TNF-α agents. etc.
Exclusion criteria
* Disease limited to the rectum * Toxic megacolon * Crohn's Disease * History of subtotal colectomy with ileorectostomy or colectomy with ileoanal pouch, Koch pouch, or ileostomy for UC * Planned bowel surgery within 12 weeks from Visit 2 * Stool positive for C. difficile toxin at screening * Primary Sclerosing Cholangitis * History of gastrointestinal surgery within 8 weeks of Visit 2 * Any uncontrolled or clinically significant systemic disease * Condition or disease that, in the opinion of the investigator would pose a risk to subject safety or interfere with study evaluation, procedures or completion * Subjects with positive HBsAg, HBsAb, HBcAb or HCVAb serology at screening etc
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Remission at Week 8 | 8 weeks | Remission at Week 8 was defined as a total Mayo score 2 points or smaller, and with no individual subscore more than 1 point. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Response at Week 8 | 8 weeks | Response at Week 8 was assessed by total Mayo score. Response was defined as decrease 3 points or more and 30 percents in total Mayo score compared to baseline, and with an accompanying decrease in the subscore for rectal bleeding of 1 point or more, or with an absolute subscore for rectal bleeding of 0 or 1. |
| Number of Participants With Mucosal Healing at Week 8 | 8 weeks | Mucosal healing was defined as an absolute Mayo subscore for rectosigmoidoscopy of 0 or 1. |
| Number of Participants With Response at Week 12 | 12 weeks | Response at Week 12 was assessed by Partial Mayo Score. Response was defined as reduction by 2 or more points and 25% in Partial Mayo Score compared to baseline. |
Countries
Japan
Participant flow
Recruitment details
In the protocol part, the number of enrolled participants was 44. This number means 44 participants who were assigned and received the treatment. In fact, 59 participants signed informed consent form. Out of the enrolled, 45 participants were assigned, and 1 out of the 45 participants discontinued the study without receiving any treatment.
Pre-assignment details
Out of the 59 enrolled participants, 14 participapatients were not assigned to any arm. Out of these 14 participants, 13 participants did not meet the eligibility criteria and 1 participants withdrew the informed consent.
Participants by arm
| Arm | Count |
|---|---|
| Placebo placebo double blind phase | 13 |
| MEDI7183 21 mg MEDI7183 21 mg double blind phase | 10 |
| MEDI7183 70 mg MEDI7183 70 mg double blind phase | 12 |
| MEDI7183 210 mg MEDI7183 210 mg double blind phase | 9 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 |
| Overall Study | Lack of Efficacy | 1 | 0 | 0 | 0 |
| Overall Study | overdose | 0 | 0 | 0 | 1 |
| Overall Study | Welfare recipient | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | MEDI7183 21 mg | MEDI7183 70 mg | MEDI7183 210 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 38.0 Years | 45.9 Years | 39.8 Years | 33.1 Years | 39.3 Years |
| any prior use of anti-TNF-a agents Number of participants who took the drug | 8 Participants | 5 Participants | 7 Participants | 6 Participants | 26 Participants |
| duration of Ulcerative Colitis | 5.41 years | 6.75 years | 5.43 years | 3.29 years | 5.28 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 13 Participants | 10 Participants | 12 Participants | 9 Participants | 44 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 5 Participants | 3 Participants | 4 Participants | 3 Participants | 15 Participants |
| Sex: Female, Male Male | 8 Participants | 7 Participants | 8 Participants | 6 Participants | 29 Participants |
| use of 5-aminosalicylates Number of participants who took the drug | 11 Participants | 10 Participants | 10 Participants | 8 Participants | 39 Participants |
| use of immunomodulators Number of participants who took the drug | 7 Participants | 3 Participants | 8 Participants | 5 Participants | 23 Participants |
| use of oral corticosteroids Number of paticipants who took the drug | 3 Participants | 1 Participants | 3 Participants | 2 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 10 | 0 / 12 | 0 / 9 |
| other Total, other adverse events | 9 / 13 | 6 / 10 | 6 / 12 | 3 / 9 |
| serious Total, serious adverse events | 0 / 13 | 1 / 10 | 0 / 12 | 1 / 9 |
Outcome results
Primary
Number of Participants With Remission at Week 8
Remission at Week 8 was defined as a total Mayo score 2 points or smaller, and with no individual subscore more than 1 point.
Time frame: 8 weeks
Population: All randomised participants who received at least one dose of investigational drug during the double-blind phase
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Remission at Week 8 | Number of participants with Remission | 0 Participants |
| MEDI7183 21 mg | Number of Participants With Remission at Week 8 | Number of participants with Remission | 1 Participants |
| MEDI7183 70 mg | Number of Participants With Remission at Week 8 | Number of participants with Remission | 2 Participants |
| MEDI7183 210 mg | Number of Participants With Remission at Week 8 | Number of participants with Remission | 1 Participants |
Secondary
Number of Participants With Mucosal Healing at Week 8
Mucosal healing was defined as an absolute Mayo subscore for rectosigmoidoscopy of 0 or 1.
Time frame: 8 weeks
Population: All randomised participants who received at least one dose of investigational drug during the double-blind phase
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Mucosal Healing at Week 8 | Number of participants with Mucosal healing | 4 Participants |
| MEDI7183 21 mg | Number of Participants With Mucosal Healing at Week 8 | Number of participants with Mucosal healing | 1 Participants |
| MEDI7183 70 mg | Number of Participants With Mucosal Healing at Week 8 | Number of participants with Mucosal healing | 4 Participants |
| MEDI7183 210 mg | Number of Participants With Mucosal Healing at Week 8 | Number of participants with Mucosal healing | 4 Participants |
Secondary
Number of Participants With Response at Week 12
Response at Week 12 was assessed by Partial Mayo Score. Response was defined as reduction by 2 or more points and 25% in Partial Mayo Score compared to baseline.
Time frame: 12 weeks
Population: All randomised participants who received at least one dose of investigational drug during the double-blind phase
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Response at Week 12 | Number of participants with Response | 6 Participants |
| MEDI7183 21 mg | Number of Participants With Response at Week 12 | Number of participants with Response | 3 Participants |
| MEDI7183 70 mg | Number of Participants With Response at Week 12 | Number of participants with Response | 6 Participants |
| MEDI7183 210 mg | Number of Participants With Response at Week 12 | Number of participants with Response | 6 Participants |
Secondary
Number of Participants With Response at Week 8
Response at Week 8 was assessed by total Mayo score. Response was defined as decrease 3 points or more and 30 percents in total Mayo score compared to baseline, and with an accompanying decrease in the subscore for rectal bleeding of 1 point or more, or with an absolute subscore for rectal bleeding of 0 or 1.
Time frame: 8 weeks
Population: All randomised participants who received at least one dose of investigational drug during the double-blind phase
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Response at Week 8 | Number of participants with Response | 7 Participants |
| MEDI7183 21 mg | Number of Participants With Response at Week 8 | Number of participants with Response | 3 Participants |
| MEDI7183 70 mg | Number of Participants With Response at Week 8 | Number of participants with Response | 6 Participants |
| MEDI7183 210 mg | Number of Participants With Response at Week 8 | Number of participants with Response | 6 Participants |