Crohn Disease, Ulcerative Colitis
Conditions
Brief summary
This is a Phase 1b, open-label, dose-escalation, signal-finding, multi-center study. The study will evaluate the safety, tolerability, pharmacokinetics and short-term efficacy of MDGN-002 in adults with moderate to severe, active Crohn's disease or Ulcerative Colitis who have previously failed anti-tumor necrosis factor alpha (anti-TNFα) treatment.
Interventions
DRUGMDGN-002
MDGN-002 is a fully human IgG4 monoclonal antibody specific to human LIGHT.
Sponsors
Avalo Therapeutics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Subject is male or female, ≥ 18 to ≤ 75 years of age. 2. Subject has a documented diagnosis of CD via endoscopy/colonoscopy and histological confirmation, or subject has received a diagnosis of UC for 90 days or greater prior to Visit 1, confirmed by endoscopy during the Screening Period, with exclusion of current infection, dysplasia and/or malignancy. 3. Subject has moderate to severe, active CD as evidenced Simple Endoscopy Score for Crohn's Disease (SES-CD) score of ≥7, and histological confirmation, or subject has moderately to severely active UC, as defined by a Modified Mayo Score (excluding the PGA component) of 5 to 9 points at Visit 1. 4. Subject has failed treatment with an approved therapeutic dose of an anti-TNFα monoclonal antibody treatment.
Exclusion criteria
1. Subject has a diagnosis of ulcerative colitis (UC) or indeterminate colitis or subject has a diagnosis of Crohn's disease or indeterminate colitis . 2. Subject with signs or symptoms of bowel obstruction. 3. Subject has short bowel syndrome. 4. Subject has a current functional colostomy or ileostomy. 5. Subject has had a surgical bowel resection within the past 6 months prior to screening or is planning any resection during the study period. 6. Subject is pregnant or a nursing mother. 7. Subject is sexually active and not using effective contraception as defined in the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) | Baseline to Visit 10 (Day 56) or early termination | The SES-CD is assessed through endoscopic review of 5 predefined gastrointestinal (GI) segments (ileum; right colon; transverse colon; left colon; rectum). For each segment, 4 endoscopic variables are assessed (presence of ulcers, ulcerated surface, affected surface, and presence of narrowing). Each variable is scored from 0 to 3 with higher scores indicating more severe symptoms. For each variable, the total score is calculated as the sum across all segments of the GI tract. The SES-CD total score, ranging from 0-60, is calculated as the sum of all variable total scores with a higher score indicating more severe endoscopic activity |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBD-Q). | Baseline to Visit 10 (Day 56) or Early Termination | The IBD-Q is a 32-item questionnaire validated to measure quality of life in Crohn's disease subjects. The IBD-Q assesses the dimensions of bowel function, emotional status, systemic symptoms, and social function. Each of the 32 items is scored on a 1 to 7 scale, where higher scores represent a more positive response, and better outcome. The IBD-Q total score is calculated as the sum of all 32 items in the questionnaire, ranging from 32 to 224. |
| Change From Baseline in Total Number of Stools Daily | Baseline to Visit 10 (Day 56) or Early Termination | Subjects reported their daily stool frequency including loose and/or watery stools via a diary. The stool frequency including the number of loose and/or watery stools per day, equivalent to a score of a 6 or 7 on the Bristol Stool Scale, was recorded. Loose stools were described as fluffy pieces with ragged edges, a mushy stool. Watery stools were described as watery, no solid pieces. |
| Change From Baseline in Crohn's Disease Activity Index (CDAI) | Baseline to Visit 10 (Day 56) or early termination. | The Crohn's Disease Activity Index (CDAI) consists of the following 8 items: abdominal pain, number of liquid stools, general well-being, extraintestinal complication, use of antidiarrheal drugs, abdominal mass, hematocrit, and body weight. Information on abdominal pain, general well-being, and frequency of loose and watery stools was taken from a daily diary completed by the subject. Total CDAI scores can range from 0 to approximately 600 with higher scores indicating more active disease. Disease severity as measured by CDAI is categorized as: Remission (\<150), Mildly active disease (150 - 219); Moderately active disease (220 - 450); Severe disease (\> 450). |
| Change From Baseline in Abdominal Pain | Baseline to Visit 10 (Day 56) or Early Termination | Subjects reported their daily assessment of abdominal pain via a diary. Abdominal pain was assessed on a scale of 0 to 3 with higher values indicating greater pain severity. |
| Change From Baseline in General Well-Being | Baseline to Visit 10 (Day 56) or Early Termination | Subjects reported their daily assessment of well-being via a diary. General well being was assessed on a scale of 0 to 4, with higher values indicating a poorer condition of health. |
| Change From Baseline in Total Number of Loose/Watery Stools Daily | Baseline to Visit 10 (Day 56) or Early Termination | Subjects reported their daily assessment of stool frequency including loose and/or watery stools via a diary. The stool frequency including the number of loose and/or watery stools per day, equivalent to a score of a 6 or 7 on the Bristol Stool Scale, was recorded. Loose stools were described as fluffy pieces with ragged edges, a mushy stool. Watery stools were described as watery, no solid pieces. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 MDGN-002 1.0 mg/kg | 4 |
| Cohort 2 MDGN-002 3.0 mg/kg | 4 |
| Total | 8 |
Baseline characteristics
| Characteristic | Cohort 1 | Total | Cohort 2 |
|---|---|---|---|
| Age, Continuous | 45.3 years STANDARD_DEVIATION 14.66 | 35.9 years STANDARD_DEVIATION 14.27 | 26.5 years STANDARD_DEVIATION 5.07 |
| Body Mass Index (BMI) | 27.37 kg/m2 STANDARD_DEVIATION 10.192 | 22.43 kg/m2 STANDARD_DEVIATION 9.82 | 15.84 kg/m2 STANDARD_DEVIATION 4.428 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 8 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 8 Participants | 4 Participants |
| Region of Enrollment United States | 4 participants | 8 participants | 4 participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 2 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 2 Participants |
| Time Since Diagnosis (Years) | 25.2 years STANDARD_DEVIATION 6.17 | 15.7 years STANDARD_DEVIATION 11 | 6.2 years STANDARD_DEVIATION 2.18 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 4 |
| other Total, other adverse events | 2 / 4 | 3 / 4 |
| serious Total, serious adverse events | 1 / 4 | 1 / 4 |
Outcome results
Primary
Change From Baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD)
The SES-CD is assessed through endoscopic review of 5 predefined gastrointestinal (GI) segments (ileum; right colon; transverse colon; left colon; rectum). For each segment, 4 endoscopic variables are assessed (presence of ulcers, ulcerated surface, affected surface, and presence of narrowing). Each variable is scored from 0 to 3 with higher scores indicating more severe symptoms. For each variable, the total score is calculated as the sum across all segments of the GI tract. The SES-CD total score, ranging from 0-60, is calculated as the sum of all variable total scores with a higher score indicating more severe endoscopic activity
Time frame: Baseline to Visit 10 (Day 56) or early termination
Population: Full Analysis Set, with data analyzed and presented only for subjects with both a Baseline and Visit 10 or Early Termination assessment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Change From Baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) | -4.0 score on a scale | Standard Deviation 4.36 |
| Cohort 2 | Change From Baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) | 1.3 score on a scale | Standard Deviation 7.5 |
Secondary
Change From Baseline in Abdominal Pain
Subjects reported their daily assessment of abdominal pain via a diary. Abdominal pain was assessed on a scale of 0 to 3 with higher values indicating greater pain severity.
Time frame: Baseline to Visit 10 (Day 56) or Early Termination
Population: Full Analysis Set, with data analyzed and presented only for subjects with both a Baseline and Visit 10 or Early Termination assessment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Change From Baseline in Abdominal Pain | -0.75 score on a scale | Standard Deviation 0.354 |
| Cohort 2 | Change From Baseline in Abdominal Pain | 0.18 score on a scale | Standard Deviation 0.455 |
Secondary
Change From Baseline in Crohn's Disease Activity Index (CDAI)
The Crohn's Disease Activity Index (CDAI) consists of the following 8 items: abdominal pain, number of liquid stools, general well-being, extraintestinal complication, use of antidiarrheal drugs, abdominal mass, hematocrit, and body weight. Information on abdominal pain, general well-being, and frequency of loose and watery stools was taken from a daily diary completed by the subject. Total CDAI scores can range from 0 to approximately 600 with higher scores indicating more active disease. Disease severity as measured by CDAI is categorized as: Remission (\<150), Mildly active disease (150 - 219); Moderately active disease (220 - 450); Severe disease (\> 450).
Time frame: Baseline to Visit 10 (Day 56) or early termination.
Population: Full Analysis Set, with data analyzed and presented only for subjects with both a Baseline and Visit 10 or Early Termination assessment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Change From Baseline in Crohn's Disease Activity Index (CDAI) | -19.2 score on a scale | Standard Deviation 38.34 |
| Cohort 2 | Change From Baseline in Crohn's Disease Activity Index (CDAI) | -123.6 score on a scale | — |
Secondary
Change From Baseline in General Well-Being
Subjects reported their daily assessment of well-being via a diary. General well being was assessed on a scale of 0 to 4, with higher values indicating a poorer condition of health.
Time frame: Baseline to Visit 10 (Day 56) or Early Termination
Population: Full Analysis Set, with data analyzed and presented only for subjects with both a Baseline and Visit 10 or Early Termination assessment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Change From Baseline in General Well-Being | -0.11 score on a scale | Standard Deviation 0.859 |
| Cohort 2 | Change From Baseline in General Well-Being | -0.27 score on a scale | Standard Deviation 0.623 |
Secondary
Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBD-Q).
The IBD-Q is a 32-item questionnaire validated to measure quality of life in Crohn's disease subjects. The IBD-Q assesses the dimensions of bowel function, emotional status, systemic symptoms, and social function. Each of the 32 items is scored on a 1 to 7 scale, where higher scores represent a more positive response, and better outcome. The IBD-Q total score is calculated as the sum of all 32 items in the questionnaire, ranging from 32 to 224.
Time frame: Baseline to Visit 10 (Day 56) or Early Termination
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBD-Q). | 43.5 score on a scale | Standard Deviation 29.01 |
| Cohort 2 | Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBD-Q). | 47.0 score on a scale | Standard Deviation 31.59 |
Secondary
Change From Baseline in Total Number of Loose/Watery Stools Daily
Subjects reported their daily assessment of stool frequency including loose and/or watery stools via a diary. The stool frequency including the number of loose and/or watery stools per day, equivalent to a score of a 6 or 7 on the Bristol Stool Scale, was recorded. Loose stools were described as fluffy pieces with ragged edges, a mushy stool. Watery stools were described as watery, no solid pieces.
Time frame: Baseline to Visit 10 (Day 56) or Early Termination
Population: Full Analysis Set with data analyzed and presented only for subjects with both a Baseline and Visit 10 or Early Termination assessment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Change From Baseline in Total Number of Loose/Watery Stools Daily | 0.90 number of daily loose/watery stools | Standard Deviation 1.077 |
| Cohort 2 | Change From Baseline in Total Number of Loose/Watery Stools Daily | -1.07 number of daily loose/watery stools | Standard Deviation 5.758 |
Secondary
Change From Baseline in Total Number of Stools Daily
Subjects reported their daily stool frequency including loose and/or watery stools via a diary. The stool frequency including the number of loose and/or watery stools per day, equivalent to a score of a 6 or 7 on the Bristol Stool Scale, was recorded. Loose stools were described as fluffy pieces with ragged edges, a mushy stool. Watery stools were described as watery, no solid pieces.
Time frame: Baseline to Visit 10 (Day 56) or Early Termination
Population: Full Analysis Set, with data analyzed and presented only for subjects with both a Baseline and Visit 10 or Early Termination assessment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Change From Baseline in Total Number of Stools Daily | 1.37 number of total daily stools | Standard Deviation 0.286 |
| Cohort 2 | Change From Baseline in Total Number of Stools Daily | -0.99 number of total daily stools | Standard Deviation 4.462 |