Evaluation of the Safety, Tolerability, and Efficacy of MDGN-002 in Adults With Moderate to Severe Active Crohn's Disease or Ulcerative Colitis

• MDGN-002 (Drug), also known as AVTX-002, AEVI-002: MDGN-002 is a fully human IgG4 monoclonal antibody specific to human LIGHT.

Primary outcomes

• 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 outcomes

• 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 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 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.
• 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.

Sex: All, ages: 18 Years to 75 Years

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.

Participant flow

Outcome results

• Change From Baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) (Primary), Mean, score on a scale: Cohort 1 -4.0 +/- 4.36; Cohort 2 1.3 +/- 7.50
• Change From Baseline in Crohn's Disease Activity Index (CDAI) (Secondary), Mean, score on a scale: Cohort 1 -19.2 +/- 38.34; Cohort 2 -123.6 +/- NA
• Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBD-Q). (Secondary), Mean, score on a scale: Cohort 1 43.5 +/- 29.01; Cohort 2 47.0 +/- 31.59
• Change From Baseline in Total Number of Stools Daily (Secondary), Mean, number of total daily stools: Cohort 1 1.37 +/- 0.286; Cohort 2 -0.99 +/- 4.462
• Change From Baseline in Total Number of Loose/Watery Stools Daily (Secondary), Mean, number of daily loose/watery stools: Cohort 1 0.90 +/- 1.077; Cohort 2 -1.07 +/- 5.758
• Change From Baseline in Abdominal Pain (Secondary), Mean, score on a scale: Cohort 1 -0.75 +/- 0.354; Cohort 2 0.18 +/- 0.455
• Change From Baseline in General Well-Being (Secondary), Mean, score on a scale: Cohort 1 -0.11 +/- 0.859; Cohort 2 -0.27 +/- 0.623

Adverse events

Time frame: All adverse events were collected from the time of the informed consent until the final safety follow-up visit (Day 84 or 28 days after Early Termination). This included events occurring during the screening phase of the study, regardless of whether investigational product was administered. Therefore all serious and non-serious events are included regardless of meeting or not meeting the study definition of treatment emergent.

Serious adverse events by term

Other adverse events by term

Limitations and caveats: This was an open label study, exploratory in nature, without a placebo control group, and as such, limits the interpretation of the study data.

• Study Protocol (PDF, 2021-07-23)
• Statistical Analysis Plan (PDF, 2021-10-05)