Ulcerative Colitis
Conditions
Keywords
microbiome
Brief summary
A Randomized, Double-Blind, Placebo-Controlled, Multiple Dose, Multicenter Study to Assess Efficacy and Safety of SER-287 in Adults with Active Mild-to-Moderate Ulcerative Colitis
Detailed description
This is a Phase 2B randomized, double-blind, placebo-controlled, multiple dose, multicenter study designed to evaluate the efficacy, safety and microbiome alterations associated with two dose levels of SER-287, after pre-treatment with vancomycin, in adult subjects, age 18-80, with active mild-to-moderate ulcerative colitis (UC).
Interventions
Four times per day dosing of vancomycin pre-treatment
DRUGPlacebo for Vancomycin Pre-Treatment
Four times per day dosing of placebo pre-treatment
DRUGSER-287
Once-daily dosing of SER-287
DRUGPlacebo for SER-287
Once-daily dosing of Placebo for SER-287
Sponsors
Seres Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Documented diagnosis of UC at least three months prior to screening, and with a minimum disease extent of 15 cm from the anal verge * Active mild-to-moderate UC * Inadequate response to, loss of response to, or intolerance of, at least one of the following conventional therapies: 5-ASA compounds, corticosteroids, 6-mercaptopurine (6-MP) or azathioprine (AZA), anti-TNFα, anti-integrin or tofacitinib
Exclusion criteria
* Known history of Crohn's disease * No previous history of treatment for UC (treatment-naïve) * Subjects on steroid medication who are unable to have steroids tapered and be completely off steroids at least two weeks prior to screening * Unable to stop steroid enemas or suppositories, or 5-ASA enemas or suppositories, at least two weeks prior to screening * Subjects who have received any investigational or approved biologic therapy within eight weeks or five half-lives prior to screening (whichever is longer) * Subjects who have received any investigational or approved non-biologic therapy, except for those specifically listed in the Permitted Concomitant Medications, for the treatment of underlying disease, within 30 days or five half-lives prior to screening (whichever is longer) * Major gastrointestinal surgery (not including appendectomy or cholecystectomy) within two months before screening, or any history of total colectomy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Remission (Count of Participants) | After 10 weeks of induction dosing | Clinical remission for the induction treatment period: * Stool Frequency subscore = 0 or 1, with at least 1-point decrease from baseline * Rectal Bleeding subscore = 0 * Endoscopic subscore = 0 or 1 on modified Mayo Score, with at least 1-point decrease from baseline * No occurrence of UC Flare during the treatment period Clinical remission was measured using 3 components of the modified Mayo Score (stool frequency, rectal bleeding and endoscopic subscore), a measure of UC disease activity. These 3 components are each graded from 0 to 3, and are summed together for a composite score, with a higher overall score indicating more severe disease (0 = no disease; 9 = worst disease). The modified Mayo endoscopic subscore excludes friability from an endoscopic subscore of 1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Endoscopic Improvement (Count of Participants) | After 10 weeks of induction dosing | Endoscopic subscore decrease from baseline of at least 1 point, as assessed by flexible sigmoidoscopy or colonoscopy. Endoscopic improvement was measured using the modified Mayo Score endoscopic subscore, graded from 0 to 3, with higher scores indicating more severe disease. The modified Mayo endoscopic subscore excludes friability from an endoscopic subscore of 1. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo (After Placebo Pre-treatment) Once-daily dosing of Placebo (after placebo pre-treatment)
Placebo for Vancomycin Pre-Treatment: Four times per day dosing of placebo pre-treatment
Placebo for SER-287: Once-daily dosing of Placebo for SER-287 | 69 |
| SER-287 Induction Dosing (After Vancomycin Pre-treatment) Once-daily dosing of SER-287 (Induction Dose, after vancomycin pre-treatment)
Vancomycin Pre-Treatment: Four times per day dosing of vancomycin pre-treatment
SER-287: Once-daily dosing of SER-287 | 68 |
| SER-287 Step-Down Induction Dosing (After Vancomycin Pre-treatment) Once-daily dosing of SER-287 (Step-Down Induction Dose, after vancomycin pre-treatment)
Vancomycin Pre-Treatment: Four times per day dosing of vancomycin pre-treatment
SER-287: Once-daily dosing of SER-287 | 66 |
| Total | 203 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 3 | 4 |
| Overall Study | Lack of Efficacy | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 7 | 2 | 2 |
| Overall Study | Other reason for discontinuation | 0 | 2 | 1 |
| Overall Study | Study Terminated by Sponsor | 15 | 16 | 10 |
| Overall Study | Subjects did not have a discontinuation page completed | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 10 | 10 |
Baseline characteristics
| Characteristic | Placebo (After Placebo Pre-treatment) | Total | SER-287 Step-Down Induction Dosing (After Vancomycin Pre-treatment) | SER-287 Induction Dosing (After Vancomycin Pre-treatment) |
|---|---|---|---|---|
| Age, Continuous | 46.6 years STANDARD_DEVIATION 13.24 | 45.6 years STANDARD_DEVIATION 14.07 | 44.4 years STANDARD_DEVIATION 14.7 | 45.7 years STANDARD_DEVIATION 14.37 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 23 Participants | 6 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 61 Participants | 177 Participants | 59 Participants | 57 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 12 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 18 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | NA Participants | NA Participants | NA Participants | NA Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) White | 56 Participants | 170 Participants | 55 Participants | 59 Participants |
| Region of Enrollment Canada | 8 participants | 27 participants | 7 participants | 12 participants |
| Region of Enrollment United States | 61 participants | 176 participants | 59 participants | 56 participants |
| Sex: Female, Male Female | 28 Participants | 98 Participants | 34 Participants | 36 Participants |
| Sex: Female, Male Male | 41 Participants | 105 Participants | 32 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 69 | 0 / 68 | 0 / 65 |
| other Total, other adverse events | 6 / 69 | 23 / 68 | 12 / 65 |
| serious Total, serious adverse events | 1 / 69 | 3 / 68 | 1 / 65 |
Outcome results
Primary
Clinical Remission (Count of Participants)
Clinical remission for the induction treatment period: * Stool Frequency subscore = 0 or 1, with at least 1-point decrease from baseline * Rectal Bleeding subscore = 0 * Endoscopic subscore = 0 or 1 on modified Mayo Score, with at least 1-point decrease from baseline * No occurrence of UC Flare during the treatment period Clinical remission was measured using 3 components of the modified Mayo Score (stool frequency, rectal bleeding and endoscopic subscore), a measure of UC disease activity. These 3 components are each graded from 0 to 3, and are summed together for a composite score, with a higher overall score indicating more severe disease (0 = no disease; 9 = worst disease). The modified Mayo endoscopic subscore excludes friability from an endoscopic subscore of 1.
Time frame: After 10 weeks of induction dosing
Population: Intent-to-treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (After Placebo Pre-treatment) | Clinical Remission (Count of Participants) | 8 Participants |
| SER-287 Induction Dosing (After Vancomycin Pre-treatment) | Clinical Remission (Count of Participants) | 7 Participants |
| SER-287 Step-Down Induction Dosing (After Vancomycin Pre-treatment) | Clinical Remission (Count of Participants) | 7 Participants |
Secondary
Endoscopic Improvement (Count of Participants)
Endoscopic subscore decrease from baseline of at least 1 point, as assessed by flexible sigmoidoscopy or colonoscopy. Endoscopic improvement was measured using the modified Mayo Score endoscopic subscore, graded from 0 to 3, with higher scores indicating more severe disease. The modified Mayo endoscopic subscore excludes friability from an endoscopic subscore of 1.
Time frame: After 10 weeks of induction dosing
Population: Intent-to-treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (After Placebo Pre-treatment) | Endoscopic Improvement (Count of Participants) | 17 Participants |
| SER-287 Induction Dosing (After Vancomycin Pre-treatment) | Endoscopic Improvement (Count of Participants) | 17 Participants |
| SER-287 Step-Down Induction Dosing (After Vancomycin Pre-treatment) | Endoscopic Improvement (Count of Participants) | 16 Participants |