Crohn Disease
Conditions
Keywords
Crohn Disease, PF-06480605, SES-CD, CDAI,
Brief summary
This Phase 2a, multicenter, randomized, double-blind, placebo-controlled study examines subcutaneous dose of PF-06480605 150 mg administered every 4 weeks in participants with moderate to severe active Crohn's Disease to characterize safety, efficacy, pharmacokinetics, and immunogenicity
Interventions
PF-06480605 150 mg
DRUGPlacebo
Placebo
Sponsors
Pfizer
Telavant, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Participants are assigned to one of two groups in parallel for the duration of the study
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of ileocolonic or colonic CD with at least 3 months or longer prior to the baseline; * Central read total SES-CD score of ≥7. For isolated ileal disease, SES-CD total score should be ≥4; * An average daily liquid/very soft SF ≥4 or daily AP score ≥2.0; * CDAI between 220 and 450 inclusive; * Must have inadequate response to, loss of response to, or intolerance to at least one conventional therapy for CD
Exclusion criteria
* Diagnosis of indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, radiation colitis, diverticular disease, UC, or clinical findings suggestive of UC; * Presence of active (draining) fistulae or intra-abdominal or perineal abscesses; * Strictures or stenosis with obstructive symptoms; * Short bowel syndrome; * History of bowel perforation requiring surgical intervention within the past 12 months prior to baseline; * Previous bowel surgery resulting in an existing stoma. Participants who have a j-pouch are excluded, as a j-pouch can result in a stoma; * History of bowel surgery within 6 months prior to baseline.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants with endoscopic response 50 | Week 14 | Endoscopy response 50 (SES-CD50) is defined as a reduction from baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) at least 50% or more. SES-CD score assesses the presence of ulcers, the percentage of ulcerated surface, the percentage of affected surface, and the presence of narrowing using scales ranging from 0 to 3 in each following bowel segment: Ileum, right colon, transverse colon, left colon, rectum. The score ranges from 0 to 60 with higher score indicating more severe disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants with a Crohn's Disease Activity Index (CDAI) clinical remission | Week 14 | Clinical remission is defined as CDAI \< 150. CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity. |
| Proportion of participants achieving endoscopic remission | Week 14 | Endoscopic remission is defined as SES-CD \< 4 and at least 2-point reduction versus Baseline and no individual subscore \> 1 |
| Proportion of participants achieving endoscopic mucosal healing | Week 14 | Endoscopic mucosal healing defined as complete absence of ulcers in SES-CD |
| The proportion of participants with Inflammatory Bowel Disease Questioners (IBDQ) total score ≥170 | Week 14 | Inflammatory Bowel Disease Questionnaire (IBDQ) score ranges from 32 to 224. A higher score indicates better quality of life. A score of at least 170 corresponds to clinical remission. |
| Proportion of participants achieving endoscopic response | Week 52 | Endoscopic response defined as improvement of SES-CD score at least 50% from baseline |
| Incidence of development of severe and serious infections | Up to week 52 | — |
| Proportion of participants with a CDAI clinical response | Up to week 52 | As defined by a decrease from baseline in CDAI score of at least 100 points or more |
| Proportion of participants achieving Patient Reported Outcome 2 (PRO2) clinical response | Up to week 52 | PRO2 clinical response is define by improvement in number of liquid/soft stool frequency and abdominal pain score at least 30% from baseline |
| Proportion of participants achieving PRO2 clinical remission | Up to week 52 | PRO2 clinical remission is defined as SF≤2.5 and AP≤1 |
| Incidence of AEs or SAEs including events leading to withdrawal due to abnormalities in laboratory, vital signs, and ECG. | up to week 52 | — |
| Proportion of participants with a CDAI clinical remission | Week 52 | Clinical remission is defined as CDAI \< 150. CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity. |
Outcome results
None listed