Evaluation of the Safety, Tolerability, and Efficacy of MDGN-002 in Adults With Moderate to Severe Active Crohn's Disease or Ulcerative Colitis
- Registration Number
- NCT03169894
- Lead Sponsor
- Avalo Therapeutics, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 8
- Subject is male or female, ≥ 18 to ≤ 75 years of age.
- 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.
- 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.
- Subject has failed treatment with an approved therapeutic dose of an anti-TNFα monoclonal antibody treatment.
- Subject has a diagnosis of ulcerative colitis (UC) or indeterminate colitis or subject has a diagnosis of Crohn's disease or indeterminate colitis .
- Subject with signs or symptoms of bowel obstruction.
- Subject has short bowel syndrome.
- Subject has a current functional colostomy or ileostomy.
- Subject has had a surgical bowel resection within the past 6 months prior to screening or is planning any resection during the study period.
- Subject is pregnant or a nursing mother.
- Subject is sexually active and not using effective contraception as defined in the protocol.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description MDGN-002 MDGN-002 MDGN-002 will be supplied in vials of 150 mg/mL. MDGN-002 will be administered by SQ injection in the abdomen every 14 days at 1 of 2 dose levels: 1.0 mg/kg or 3.0 mg/kg.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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 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 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 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.
Trial Locations
- Locations (13)
Advanced Research Institute, Inc.
🇺🇸New Port Richey, Florida, United States
Sweet Hope Research Specialty, Inc.
🇺🇸Hialeah, Florida, United States
Egleston Hospital
🇺🇸Atlanta, Georgia, United States
The Center for Pediatric Inflammatory Bowel Disease, Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
The University of Texas Health Science Center at Houston
🇺🇸Houston, Texas, United States
Penn Presbyterian Medical Center
🇺🇸Philadelphia, Pennsylvania, United States
Clinical Associates in Research Therapeutics of America, LLC
🇺🇸San Antonio, Texas, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
Hassman Research Institute
🇺🇸Berlin, New Jersey, United States
University of Louisville
🇺🇸Louisville, Kentucky, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Care Access Research
🇺🇸Salt Lake City, Utah, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States