Ulcerative Colitis, Active Moderate, Ulcerative Colitis, Active Severe
Conditions
Keywords
IBD, UC, Colitis, Ulcerative Colitis
Brief summary
This is a randomized, double blind, placebo-controlled, parallel group multi-center study in adult participants with active moderate to severe UC.
Interventions
BIOLOGICALBertilimumab
IV infusion over 30 minutes, at Day 0, Day 14 and Day 28
BIOLOGICALPlacebo
IV infusion over 30 minutes, at Day 0, Day 14 and Day 28
Sponsors
Immune Pharmaceuticals
Alexion Pharmaceuticals, Inc.
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 70 Years
Healthy volunteers
No
Inclusion criteria
1. Males or females, 18 to 70 years of age inclusive. 2. Diagnosed with active moderate to severe UC per standard diagnostic criteria for a minimum of 3 months: * Mayo score of 6-12 (inclusive) at the Screening Visit * Endoscopic evidence of active mucosal disease, as assessed by flexible sigmoidoscopy, with an Endoscopic Finding Sub-score of ≥2 (assessed centrally) * Rectal Bleeding Sub-score of ≥1 * Physician's Global Assessment (PGA) Sub-score of ≥2. 3. Levels of eotaxin-1 in biopsied colon tissue of ≥100 pg/mg protein. 4. Adequate cardiac, renal and hepatic function as determined by the Investigator and demonstrated by screening laboratory evaluations and physical examination results; these findings must all be within normal limits or judged not clinically significant by the Investigator.
Exclusion criteria
1. History of colonic or rectal surgery other than hemorrhoidal surgery or appendectomy. 2. Currently receiving total parenteral nutrition (TPN). 3. Positive Clostridium difficile toxin stool assay. 4. Tested positive for active/latent mycobacterium tuberculosis (TB) infection. 5. Pregnant or breast-feeding, or plan to become pregnant during the study. 6. Males who are young and childless or planning to have more children in the future. 7. Known hypersensitivity to bertilimumab or any of the drug excipients. 8. History of infection requiring administration of any IV antibiotic, antiviral or antifungal medication within 30 days of Screening or any oral anti-infective agent within 14 days of Screening. 9. Severe UC evidenced by the following signs of toxicity: heart rate \>100 beats/min at rest, temperature \>37.8°C, hemoglobin \<10.0 g/dL. 10. Ulcerative proctitis, defined as disease limited to less than 15 cm from the anal verge. 11. Received a vaccine or other immunostimulator within 4 weeks prior to screening. 12. Use of \>4.8 g mesalazine or equivalent within 2 weeks prior to the screening visit. Mesalazine ≤4.8 g is allowed if the dose during the 2 weeks prior to the screening visit was stable. 13. Use of systemic corticosteroids exceeding the equivalent of 20 mg/day of prednisone within four weeks prior to the screening visit (see Section 6.9.1). 14. Change in dose of immunosuppressive drugs (e.g., corticosteroids, 6-mercaptopurine \[6-MP\], azathioprine) within four weeks prior to the screening visit. 15. Use of TNF-blockers (e.g., infliximab or adalimumab) within 60 days of the screening visit. 16. Use of chronic non-steroidal anti-inflammatory (NSAID) therapy. Occasional use of NSAIDs or acetaminophen for headache, arthritis, myalgias, menstrual cramps, etc., or daily use of low dose (81-162 mg) aspirin for cardiovascular prophylaxis is allowed. 17. Patients diagnosed with: * Crohn's disease * Diverticulitis or diverticulosis * Indeterminate colitis (inability to distinguish between UC and Crohn's disease \[as assessed by the Investigator\]) * Microscopic colitis (collagenous or lymphocytic colitis) * Ischemic or infectious colitis * Clostridium difficile colitis within 90 days of the screening visit * Parasitic disease within 90 days of the screening visit * Systemic fungal infection within 90 days of the screening visit. 18. History of positive serology of hepatitis B or C, or human immunodeficiency virus (HIV) infection. 19. Congenital or acquired immunodeficiency (e.g., common variable immunodeficiency, organ transplantation). 20. Clinically significant abnormal laboratory test results, unless regarded by the Investigator as related to UC, including but not limited to: * Hemoglobin level \<10.0 g/dL * White blood cell count \< 3 x 103/µL * Lymphocyte count \< 0.5 x 103/µL * Platelet count \<100 x 103/µL or \>1200 x 103/µL * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>3 the upper limit of normal (ULN) * Alkaline phosphatase \>3 ULN * Serum creatinine \>2 ULN. 21. Active abuse of alcohol or drugs. 22. Known malignancy or history of malignancy that could reduce life expectancy. 23. Any condition, which in the opinion of the Investigator, would place the patient at an unacceptable risk if participating in the study protocol. 24. Participation in a clinical trial of an investigational (unapproved) product
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Total Mayo Score at Day 56 | Baseline, Day 56 | The Total Mayo score is an instrument designed to measure disease activity of ulcerative colitis and ranged from 0 (normal or inactive disease) to 12 (severe disease). It is a composite of 4 sub-scores: Stool frequency sub-score, rectal bleeding sub-score, endoscopic finding sub-score, and physician's global assessment sub-score, each of which ranges from 0 (normal) to 3 (severe disease). The sub-scores were summed to give a total score that ranged from 0-12. Change in mayo score was calculated as the sum of scores at Day 56 minus the sum of scores at Baseline divided by 14 for bertilimumab arm and sum of scores at Day 56 minus the sum of scores at Baseline divided by 6 for placebo arm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Ulcerative Colitis Endoscopic Index of Severity (UCEIS) Score at Day 56 | Baseline, Day 56 | The UCEIS is the validated index for the assessment of overall endoscopic activity. The model incorporated the vascular pattern score (0-2), the presence of bleeding score (0-3) and the presence of erosions and ulcers score (0-3). The total score ranged from 0-8. Higher scores indicated more severe disease. Change in mayo score was calculated as the sum of scores at Day 56 minus the sum of scores at Baseline divided by 15 for bertilimumab arm and sum of scores at Day 56 minus the sum of scores at Baseline divided by 6 for placebo arm. |
Countries
Israel
Participant flow
Pre-assignment details
The study was initiated in Jul 2015 and was early terminated due to sponsor decision.
Participants by arm
| Arm | Count |
|---|---|
| Bertilimumab Participants with active moderate to severe ulcerative colitis received bertilimumab 10 mg/kg IV infusion biweekly for 12 weeks. | 20 |
| Placebo Participants with active moderate to severe ulcerative colitis received placebo IV infusion matched to bertilimumab biweekly for 12 weeks. | 12 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Disease progression | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Bertilimumab | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants | 12 Participants | 31 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 20 Participants | 12 Participants | 32 Participants |
| Sex: Female, Male Female | 9 Participants | 7 Participants | 16 Participants |
| Sex: Female, Male Male | 11 Participants | 5 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 12 |
| other Total, other adverse events | 14 / 20 | 5 / 12 |
| serious Total, serious adverse events | 2 / 20 | 1 / 12 |
Outcome results
Primary
Change From Baseline in Total Mayo Score at Day 56
The Total Mayo score is an instrument designed to measure disease activity of ulcerative colitis and ranged from 0 (normal or inactive disease) to 12 (severe disease). It is a composite of 4 sub-scores: Stool frequency sub-score, rectal bleeding sub-score, endoscopic finding sub-score, and physician's global assessment sub-score, each of which ranges from 0 (normal) to 3 (severe disease). The sub-scores were summed to give a total score that ranged from 0-12. Change in mayo score was calculated as the sum of scores at Day 56 minus the sum of scores at Baseline divided by 14 for bertilimumab arm and sum of scores at Day 56 minus the sum of scores at Baseline divided by 6 for placebo arm.
Time frame: Baseline, Day 56
Population: The modified intent to treat (mITT) analysis set included all randomized participants who received at least one dose of study treatment (placebo or bertilimumab) and had at least a full Mayo score at screening and at least one post-baseline partial Mayo score from visit 3 onwards. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Bertilimumab | Change From Baseline in Total Mayo Score at Day 56 | 2.7 scores on a scale |
| Placebo | Change From Baseline in Total Mayo Score at Day 56 | 2.5 scores on a scale |
Secondary
Change From Baseline in Ulcerative Colitis Endoscopic Index of Severity (UCEIS) Score at Day 56
The UCEIS is the validated index for the assessment of overall endoscopic activity. The model incorporated the vascular pattern score (0-2), the presence of bleeding score (0-3) and the presence of erosions and ulcers score (0-3). The total score ranged from 0-8. Higher scores indicated more severe disease. Change in mayo score was calculated as the sum of scores at Day 56 minus the sum of scores at Baseline divided by 15 for bertilimumab arm and sum of scores at Day 56 minus the sum of scores at Baseline divided by 6 for placebo arm.
Time frame: Baseline, Day 56
Population: The mITT analysis set included all randomized participants who received at least one dose of study treatment (placebo or bertilimumab) and had at least a full Mayo score at screening and at least one post-baseline partial Mayo score from visit 3 onwards. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Bertilimumab | Change From Baseline in Ulcerative Colitis Endoscopic Index of Severity (UCEIS) Score at Day 56 | 1.2 score on a scale |
| Placebo | Change From Baseline in Ulcerative Colitis Endoscopic Index of Severity (UCEIS) Score at Day 56 | 0.4 score on a scale |