Inflammatory Bowel Diseases, Colitis, Ulcerative
Conditions
Keywords
Ulcerative Colitis (UC), Inflammatory Bowel Disease (IBD), a4b7, Moderate-to-severe, Integrin, EMERALD
Brief summary
This is a Phase 2b randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of three active dose regimens of MORF-057 in adult patients with moderately to severely active Ulcerative Colitis (UC).
Detailed description
This is a Phase 2b randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of three active dose regimens of MORF-057 plus a placebo regimen in study participants with moderately to severely active UC. After completion of the 12-week Induction Period, participants may be switched to a different active MORF-057 regimen during the Maintenance Period. Those randomized into the placebo group in the Induction Period will be switched to receive an active MORF-057 regimen during the Maintenance Period.
Interventions
DRUGMORF-057
MORF-057 is a small molecule that is designed to selectively inhibit integrin α4β7 and is administered orally.
DRUGPlacebo
Matching placebo (identical appearance to MORF-057) administered orally.
Sponsors
Morphic Therapeutic, Inc. (A Wholly Owned Subsidiary of Eli Lilly and Company)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Has signs/symptoms of moderate to severe UC for at least 3 months prior to Screening * Has evidence of UC extending at least 15 cm from the anal verge * Demonstrated an inadequate response, loss of response, or intolerance to at least one of the following treatments: Oral aminosalicylates (e.g., mesalamine, sulfasalazine, olsalazine, or balsalazide), corticosteroids, immunosuppressants (e.g., azathioprine, 6-mercaptopurine, or methotrexate), advanced therapies for UC (e.g., biologic agents, Janus kinase \[JAK\] antagonists, or sphingosine-1-phosphate \[S1P\] receptor agonists) * Subject has no prior exposure to approved or investigational anti-integrin therapies * Agrees to abide by the study guidelines and requirements * Capable of giving signed informed consent
Exclusion criteria
* Diagnosed with indeterminate colitis, microscopic colitis, ischemic colitis, radiation colitis, or Crohn's disease or has clinical findings suggestive of Crohn's disease * Has positive findings on a subjective neurological screening questionnaire * Has a concurrent, clinically significant, serious, unstable comorbidity * Previous treatment with vedolizumab or other licensed or investigational integrin inhibitors * Participation in any other interventional study or received any investigational therapy within 30 days * Previous exposure to MORF-057 and/or a known hypersensitivity to drugs with a similar mechanism to MORF-057 * Unable to attend study visits or comply with study procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants in Clinical Remission as Determined Using the Modified Mayo Clinic Score (mMCS) | Week 12 | * The mMCS is a scoring system for assessment of ulcerative colitis activity and is a composite of Endoscopic subscore (range: 0=Normal or inactive disease to 3=Severe disease (spontaneous bleeding, ulceration)), Stool Frequency subscore (range: 0=Normal number of stools to 3=5 or more stools more than normal), and Rectal Bleeding subscore (range: 0=No blood seen to 3=Blood alone passed). The mMCS total score ranges from 0 to 9, with higher scores indicating more severe disease. * Clinical remission per mMCS is defined as rectal bleeding subscore of 0; a stool frequency subscore of \< or =1; and an endoscopy subscore of \< or =1 without friability. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants in Clinical Response as Determined Using the Modified Mayo Clinic Score (mMCS) | Week 12 | * The mMCS is a scoring system for assessment of ulcerative colitis activity and is a composite of Endoscopic subscore (range: 0=Normal or inactive disease to 3=Severe disease (spontaneous bleeding, ulceration)), Stool Frequency subscore (range: 0=Normal number of stools to 3=5 or more stools more than normal), and Rectal Bleeding subscore (range: 0=No blood seen to 3=Blood alone passed). The mMCS total score ranges from 0 to 9, with higher scores indicating more severe disease. * Clinical response per mMCS is defined as decrease from baseline in the mMCS score \> or =2 points and \> or =30% from baseline, plus a decrease in rectal bleeding subscore \> or =1 or an absolute rectal bleeding subscore \< or =1. |
Countries
Australia, Austria, Bulgaria, Czechia, Estonia, France, Georgia, Germany, Hungary, India, Israel, Italy, Latvia, Lithuania, Poland, Romania, Serbia, Slovakia, South Korea, Taiwan, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MORF-057 200 mg BID Participants received a 200 mg oral dose of MORF-057 twice daily for 12 weeks. | 69 |
| MORF-057 100 mg BID Participants received a 100 mg oral dose of MORF-057 twice daily for 12 weeks. | 71 |
| MORF-057 100 mg QD-M Participants received a 100 mg oral dose of MORF-057 once daily in the morning for 12 weeks. | 70 |
| Placebo Participants received an oral dose of matching placebo for 12 weeks. | 70 |
| Total | 280 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 0 | 1 |
| Overall Study | Lack of Efficacy | 1 | 0 | 1 | 2 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 1 | 2 | 1 |
Baseline characteristics
| Characteristic | Total | MORF-057 200 mg BID | MORF-057 100 mg BID | MORF-057 100 mg QD-M | Placebo |
|---|---|---|---|---|---|
| Age, Continuous | 40.2 years STANDARD_DEVIATION 14.57 | 41.0 years STANDARD_DEVIATION 17.14 | 41.8 years STANDARD_DEVIATION 14.35 | 38.9 years STANDARD_DEVIATION 13.57 | 39.1 years STANDARD_DEVIATION 13 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 273 Participants | 66 Participants | 70 Participants | 69 Participants | 68 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 51 Participants | 14 Participants | 11 Participants | 13 Participants | 13 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 | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 227 Participants | 53 Participants | 60 Participants | 57 Participants | 57 Participants |
| Sex: Female, Male Female | 125 Participants | 28 Participants | 32 Participants | 31 Participants | 34 Participants |
| Sex: Female, Male Male | 155 Participants | 41 Participants | 39 Participants | 39 Participants | 36 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 / 70 | 0 / 71 | 0 / 70 | 0 / 69 |
| other Total, other adverse events | 9 / 70 | 8 / 71 | 5 / 70 | 10 / 69 |
| serious Total, serious adverse events | 1 / 70 | 3 / 71 | 0 / 70 | 1 / 69 |
Outcome results
Primary
Percentage of Participants in Clinical Remission as Determined Using the Modified Mayo Clinic Score (mMCS)
* The mMCS is a scoring system for assessment of ulcerative colitis activity and is a composite of Endoscopic subscore (range: 0=Normal or inactive disease to 3=Severe disease (spontaneous bleeding, ulceration)), Stool Frequency subscore (range: 0=Normal number of stools to 3=5 or more stools more than normal), and Rectal Bleeding subscore (range: 0=No blood seen to 3=Blood alone passed). The mMCS total score ranges from 0 to 9, with higher scores indicating more severe disease. * Clinical remission per mMCS is defined as rectal bleeding subscore of 0; a stool frequency subscore of \< or =1; and an endoscopy subscore of \< or =1 without friability.
Time frame: Week 12
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MORF-057 200 mg BID | Percentage of Participants in Clinical Remission as Determined Using the Modified Mayo Clinic Score (mMCS) | 31.9 percentage of participants |
| MORF-057 100 mg BID | Percentage of Participants in Clinical Remission as Determined Using the Modified Mayo Clinic Score (mMCS) | 23.9 percentage of participants |
| MORF-057 100 mg QD-M | Percentage of Participants in Clinical Remission as Determined Using the Modified Mayo Clinic Score (mMCS) | 17.1 percentage of participants |
| Placebo | Percentage of Participants in Clinical Remission as Determined Using the Modified Mayo Clinic Score (mMCS) | 24.3 percentage of participants |
95% CI: [-7.76, 21.18]
95% CI: [-13.99, 13.17]
95% CI: [-19.74, 5.88]
Secondary
Percentage of Participants in Clinical Response as Determined Using the Modified Mayo Clinic Score (mMCS)
* The mMCS is a scoring system for assessment of ulcerative colitis activity and is a composite of Endoscopic subscore (range: 0=Normal or inactive disease to 3=Severe disease (spontaneous bleeding, ulceration)), Stool Frequency subscore (range: 0=Normal number of stools to 3=5 or more stools more than normal), and Rectal Bleeding subscore (range: 0=No blood seen to 3=Blood alone passed). The mMCS total score ranges from 0 to 9, with higher scores indicating more severe disease. * Clinical response per mMCS is defined as decrease from baseline in the mMCS score \> or =2 points and \> or =30% from baseline, plus a decrease in rectal bleeding subscore \> or =1 or an absolute rectal bleeding subscore \< or =1.
Time frame: Week 12
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MORF-057 200 mg BID | Percentage of Participants in Clinical Response as Determined Using the Modified Mayo Clinic Score (mMCS) | 62.3 percentage of participants |
| MORF-057 100 mg BID | Percentage of Participants in Clinical Response as Determined Using the Modified Mayo Clinic Score (mMCS) | 53.5 percentage of participants |
| MORF-057 100 mg QD-M | Percentage of Participants in Clinical Response as Determined Using the Modified Mayo Clinic Score (mMCS) | 57.1 percentage of participants |
| Placebo | Percentage of Participants in Clinical Response as Determined Using the Modified Mayo Clinic Score (mMCS) | 54.3 percentage of participants |
95% CI: [-8.77, 22.86]
95% CI: [-16.74, 14.88]
95% CI: [-12.78, 18.92]