Inflammatory Bowel Diseases, Colitis, Ulcerative
Conditions
Keywords
Ulcerative Colitis (UC), Inflammatory Bowel Disease (IBD), a4b7, Moderately to severely active ulcerative colitis, Integrin
Brief summary
This is an open-label, single arm, multicenter, Phase 2a study evaluating the efficacy, safety, and tolerability of MORF-057 in adult patients with Moderately to Severely Active Ulcerative Colitis (UC)
Detailed description
The main part of this Phase 2a study will consist of 3 study periods: a Screening Period, a Treatment Period and a Safety Follow-up Period. All participants who complete the open-label Treatment Period will have the opportunity to continue their treatment in an optional 26-week Long-term Extension study after completing the Week 52 assessments.
Interventions
DRUGMORF-057
MORF-057 is a small molecule that is designed to selectively inhibit integrin α4β7 and is administered orally.
Sponsors
Morphic Therapeutic, Inc. (A Wholly Owned Subsidiary of Eli Lilly and Company)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Has signs/symptoms of moderately to severely active UC for at least 3 months prior to Screening * Has evidence of UC extending at least 15 cm from the anal verge * Is bio-naïve or had an inadequate response, loss of response, or intolerance to other UC drugs * 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 * Primary non-responder to vedolizumab or other 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 |
|---|---|---|
| Main Cohort: Change From Baseline to Week 12 in the Robarts Histopathology Index (RHI) Score | From baseline to 12 weeks | Robarts Histopathology Index (RHI) Score: the total RHI Score ranges from 0 (no disease activity) to 33 (severe disease activity) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Main Cohort: Change From Baseline to Week 12 in the Modified Mayo Clinic Score | From baseline to 12 weeks | The Modified Mayo Clinic Score (mMCS) is a composite of the following Mayo Clinic Score subscores: Endoscopy subscore (range: 0=Normal or inactive disease to 3=Severe disease (spontaneous bleeding, ulceration), Stool Frequency subscore (range: 0=Normal number of stools for this participant to 3=5 or more stools more than normal), and Rectal Bleeding subscore (range: 0=No blood seen to 3=Blood alone passed). The total mMCS ranges from 0 to 9, with higher scores indicating more severe disease. |
| Main Cohort: Maximum Plasma Concentration (Cmax) During Multiple Doses of MORF-057 | 12 weeks | To determine the Maximum Plasma Concentration of MORF-057, blood samples were collected per the study protocol at the following time points: Study Day 1 (first dose), predose and 1, 2, 3, 4, and 6 hours post the AM dose; Week 2, predose and 1, 2, 3, 4, and 6 hours post the AM dose; Week 6, predose and 1 and 3 hours post the AM dose; Week 12, predose and 1, 2, 3, 4, and 6 hours post the AM dose. On Study Day 1, Week 2, and Week 12, blood sampling for pharmacokinetics was optional at 8, 10, and 12 hours post the AM dose. |
| Main Cohort: Time to Reach Cmax (Tmax) During Multiple Doses of MORF-057 | 12 weeks | To determine the Tmax of MORF-057, blood samples were collected per the study protocol at the following time points: Study Day 1 (first dose), predose and 1, 2, 3, 4, and 6 hours post the AM dose; Week 2, predose and 1, 2, 3, 4, and 6 hours post the AM dose; Week 6, predose and 1 and 3 hours post the AM dose; Week 12, predose and 1, 2, 3, 4, and 6 hours post the AM dose. On Study Day 1, Week 2, and Week 12, blood sampling for pharmacokinetics was optional at 8, 10, and 12 hours post the AM dose. |
| Main Cohort: Area Under the Curve (AUC) Following Multiple Doses of MORF-057 | 12 weeks | To determine the area under the concentration-time curve of MORF-057, blood samples were collected per the study protocol at the following time points: Study Day 1 (first dose), predose and 1, 2, 3, 4, and 6 hours post the AM dose; Week 2, predose and 1, 2, 3, 4, and 6 hours post the AM dose; Week 6, predose and 1 and 3 hours post the AM dose; Week 12, predose and 1, 2, 3, 4, and 6 hours post the AM dose. On Study Day 1, Week 2, and Week 12, blood sampling for pharmacokinetics was optional at 8, 10, and 12 hours post the AM dose. |
Countries
Poland, United States
Participant flow
Recruitment details
The study plan included two cohorts. Both cohorts receive the same MORF-057 treatment regimen. * Main cohort for formal assessment of study objectives. Participants in this cohort were biologic-naïve or previously exposed to biologic therapies, with no prior vedolizumab exposure. * Exploratory cohort for exploratory purposes only and not used to assess the study objectives. Participants in this cohort had prior vedolizumab exposure with intolerance or secondary non-response.
Participants by arm
| Arm | Count |
|---|---|
| MORF-057 MORF-057: MORF-057 is a small molecule that is designed to selectively inhibit integrin α4β7 and is administered orally. | 35 |
| Total | 35 |
Baseline characteristics
| Characteristic | MORF-057 | — |
|---|---|---|
| Age, Continuous | 39.2 years STANDARD_DEVIATION 14.1 | 41.3 years STANDARD_DEVIATION 15.27 |
| Age, Customized 18 to 64 years | 34 Participants | 36 Participants |
| Age, Customized 65 to 84 years | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 35 Participants | 39 Participants |
| Region of Enrollment Poland | 28 Participants | 31 Participants |
| Region of Enrollment United States | 7 Participants | 8 Participants |
| Sex: Female, Male Female | 16 Participants | 17 Participants |
| Sex: Female, Male Male | 19 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 35 | 0 / 4 |
| other Total, other adverse events | 19 / 35 | 4 / 4 |
| serious Total, serious adverse events | 0 / 35 | 0 / 4 |
Outcome results
Primary
Change From Baseline to Week 12 in the Robarts Histopathology Index (RHI) Score
Robarts Histopathology Index (RHI) Score: the total RHI Score ranges from 0 (no disease activity) to 33 (severe disease activity)
Time frame: From baseline to 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MORF-057 | Change From Baseline to Week 12 in the Robarts Histopathology Index (RHI) Score | -6.4 score on a scale | Standard Deviation 11.18 |
Secondary
Area Under the Curve (AUC) Following Multiple Doses of MORF-057
To determine the area under the concentration-time curve of MORF-057, blood samples were collected per the study protocol at the following time points: Study Day 1 (first dose), predose and 1, 2, 3, 4, and 6 hours post the AM dose; Week 2, predose and 1, 2, 3, 4, and 6 hours post the AM dose; Week 6, predose and 1 and 3 hours post the AM dose; Week 12, predose and 1, 2, 3, 4, and 6 hours post the AM dose. On Study Day 1, Week 2, and Week 12, blood sampling for pharmacokinetics was optional at 8, 10, and 12 hours post the AM dose.
Time frame: 12 weeks
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MORF-057 | Area Under the Curve (AUC) Following Multiple Doses of MORF-057 | 3070 hours*ng/mL | Geometric Coefficient of Variation 45.7 |
Secondary
Change From Baseline to Week 12 in the Modified Mayo Clinic Score
The Modified Mayo Clinic Score (mMCS) is a composite of the following Mayo Clinic Score subscores: Endoscopy subscore (range: 0=Normal or inactive disease to 3=Severe disease (spontaneous bleeding, ulceration), Stool Frequency subscore (range: 0=Normal number of stools for this participant to 3=5 or more stools more than normal), and Rectal Bleeding subscore (range: 0=No blood seen to 3=Blood alone passed). The total mMCS ranges from 0 to 9, with higher scores indicating more severe disease.
Time frame: From baseline to 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MORF-057 | Change From Baseline to Week 12 in the Modified Mayo Clinic Score | -2.3 score on a scale | Standard Deviation 2.14 |
Secondary
Maximum Plasma Concentration (Cmax) During Multiple Doses of MORF-057
To determine the Maximum Plasma Concentration of MORF-057, blood samples were collected per the study protocol at the following time points: Study Day 1 (first dose), predose and 1, 2, 3, 4, and 6 hours post the AM dose; Week 2, predose and 1, 2, 3, 4, and 6 hours post the AM dose; Week 6, predose and 1 and 3 hours post the AM dose; Week 12, predose and 1, 2, 3, 4, and 6 hours post the AM dose. On Study Day 1, Week 2, and Week 12, blood sampling for pharmacokinetics was optional at 8, 10, and 12 hours post the AM dose.
Time frame: 12 weeks
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MORF-057 | Maximum Plasma Concentration (Cmax) During Multiple Doses of MORF-057 | 766 ng/mL | Geometric Coefficient of Variation 46.4 |
Secondary
Time to Reach Cmax (Tmax) During Multiple Doses of MORF-057
To determine the Tmax of MORF-057, blood samples were collected per the study protocol at the following time points: Study Day 1 (first dose), predose and 1, 2, 3, 4, and 6 hours post the AM dose; Week 2, predose and 1, 2, 3, 4, and 6 hours post the AM dose; Week 6, predose and 1 and 3 hours post the AM dose; Week 12, predose and 1, 2, 3, 4, and 6 hours post the AM dose. On Study Day 1, Week 2, and Week 12, blood sampling for pharmacokinetics was optional at 8, 10, and 12 hours post the AM dose.
Time frame: 12 weeks
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MORF-057 | Time to Reach Cmax (Tmax) During Multiple Doses of MORF-057 | 2.014 hours | Geometric Coefficient of Variation 58.4534 |