Ulcerative Colitis
Conditions
Brief summary
The purpose of this study is to evaluate efficacy and safety of PF-06826647 in moderate to severe ulcerative colitis
Interventions
DRUGPF-06826647 100 mg QD
Investigational Product
DRUGPF-06826647 300 mg QD
Investigational Product
DRUGPF-06826647 600 mg QD
Investigational Product
DRUGPlacebo
Matched Placebo
DRUGPF-6826647 400 mg QD
Investigational Product
Sponsors
Pfizer
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 75 Years
Healthy volunteers
No
Inclusion criteria
* Participants with moderate to severe UC as defined by a total Mayo score of ≥6, with a rectal bleeding subscore of ≥1 and an endoscopic subscore of ≥2; * Participants must have inadequate response to, loss of response to, or intolerance to at least one conventional therapy for UC: Oral, intravascular, or intramuscular corticosteroids; Immunosuppressants (azathioprine \[AZA\], 6-MP, or methotrexate \[MTX\]); Anti-tumor necrosis factor (TNF) inhibitors (eg, infliximab, adalimumab, or golimumab); Anti-integrin inhibitors (eg, vedolizumab); JAK inhibitor (eg, tofacitinib); Anti-IL-12/IL-23 inhibitors (eg, ustekinumab).
Exclusion criteria
* Presence of indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, radiation colitis, and diverticular disease associated with colitis, or Crohn's disease * Participants displaying clinical signs of fulminant colitis or toxic megacolon; * Participants with evidence of colonic dysplasia, adenomas or neoplasia.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants achieving endoscopic response | At Week 8 | Endoscopic response is defined by Mayo endoscopic index \< 2 |
| Number of Adverse Events (AEs), Serious Adverse Events (SAEs) based on severity and withdrawals due to adverse events (AEs) | At Week 60 | — |
| Number of Participants With Clinical Laboratory Abnormalities | At Week 60 | Following parameters will be analyzed for laboratory examination: hematology (hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); liver function (aspartate aminotransferase, alanine aminotransferase, total bilirubin, lactate dehydrogenase, alkaline phosphatase, albumin, total protein); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (sodium, potassium, chloride, calcium, phosphate, bicarbonate); clinical chemistry (glucose, creatine kinase); immunology (CRP); urinalysis (dipstick \[urine specific gravity, decimal logarithm of reciprocal of hydrogen ion activity {pH} of urine, glucose, protein, blood, ketones, bilirubin\], microscopy \[urine RBC, WBC, urate crystals, calcium, oxalate, miscellaneous \[urine mucus and leucocytes\]). |
| Percentage of participants with clinically significant changes in Electrocardiogram (ECG) | At Week 60 | Clinical significant changes in ECG |
| Number of Participants With Categorical changes from baseline in Vital Signs Data | At Week 60 | Number of participants with increase from baseline in sitting SBP and DBP of greater than or equal to 30 mmHg at Week 60. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in total Mayo score | At Week 8 and 60 | — |
| Number of Adverse Events (AEs), Serious Adverse Events (SAEs) based on severity and withdrawals due to adverse events (AEs) | At Week 8 | — |
| Percentage of participants achieving clinical remission | At Week 8 and 60 | Clinical remission is defined by total Mayo score of ≤ 2 with no individual subscore of \> 1 |
| Percentage of participants with clinically significant changes in Electrocardiogram (ECG) | At Week 8 | Clinically significant changes from baseline in ECG (heart rate, QT, QTc, PR and QRS intervals) |
| Number of Participants With Categorical Vital Signs Data | At Week 8 | Number of participants with increase from baseline in sitting SBP and DBP of greater than or equal to 30 mmHg at Week 8. |
| Number of Participants With Clinical Laboratory Abnormalities | At Week 8 | Following parameters will be analyzed for laboratory examination: hematology (hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); liver function (aspartate aminotransferase, alanine aminotransferase, total bilirubin, lactate dehydrogenase, alkaline phosphatase, albumin, total protein); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (sodium, potassium, chloride, calcium, phosphate, bicarbonate); clinical chemistry (glucose, creatine kinase); immunology (CRP); urinalysis (dipstick \[urine specific gravity, decimal logarithm of reciprocal of hydrogen ion activity {pH} of urine, glucose, protein, blood, ketones, bilirubin\], microscopy \[urine RBC, WBC, urate crystals, calcium, oxalate, miscellaneous \[urine mucus and leucocytes\]). |
| Percentage of participants achieving endoscopic remission | At Week 8 and 60 | Endoscopic remission is defined as Mayo endoscopic index of 0 |
| Percentage of participants achieving mucosal healing | At Week 8 and 60 | Mucosal healing is defined as both total Mayo score and histologic index of ≤ 1. |
| Percentage of participants achieving clinical response | At Week 8 and 60 | Clinical response is defined as a decrease from baseline of at least 3 points in total Mayo score with at least 30% change, accompanied by at least one point decrease or absolute score of 0 or 1 in rectal bleeding subscore. |
| Mean change from baseline in partial Mayo score over time | Up to 60 weeks | — |
Countries
United States
Outcome results
None listed