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

Ulcerative Colitis Clinical Trial

Official title:

Phase Ib Escalating Dose, Open-Label, Signal-Finding Study to Evaluate the Safety, Tolerability, and Short-Term Efficacy of the Anti-Light Monoclonal Antibody MDGN-002 in Adults With Moderate to Severe Active Crohn's Disease or Ulcerative Colitis Who Previously Failed Treatment With an Anti-TNFα Agent

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03169894
• Other study ID #: MDGN-002-CD-101
• Status: Terminated
• Phase: Phase 1
• Start date: July 14, 2017
• Est. completion date: October 12, 2021

Study information

• Verified date: July 2023
• Source: Avalo Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 8
• Est. completion date: October 12, 2021
• Est. primary completion date: September 14, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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-TNFa 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.

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Crohn Disease
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• MDGN-002
MDGN-002 is a fully human IgG4 monoclonal antibody specific to human LIGHT.

Locations

Country	Name	City	State
United States	Egleston Hospital	Atlanta	Georgia
United States	Hassman Research Institute	Berlin	New Jersey
United States	University of Cincinnati	Cincinnati	Ohio
United States	Sweet Hope Research Specialty, Inc.	Hialeah	Florida
United States	The University of Texas Health Science Center at Houston	Houston	Texas
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	University of Louisville	Louisville	Kentucky
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Advanced Research Institute, Inc.	New Port Richey	Florida
United States	Penn Presbyterian Medical Center	Philadelphia	Pennsylvania
United States	The Center for Pediatric Inflammatory Bowel Disease, Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Care Access Research	Salt Lake City	Utah
United States	Clinical Associates in Research Therapeutics of America, LLC	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Avalo Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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	Baseline to Visit 10 (Day 56) or early termination
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).	Baseline to Visit 10 (Day 56) or early termination.
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.	Baseline to Visit 10 (Day 56) or Early Termination
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.	Baseline to Visit 10 (Day 56) or Early Termination
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.	Baseline to Visit 10 (Day 56) or Early Termination
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.	Baseline to Visit 10 (Day 56) or Early Termination
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.	Baseline to Visit 10 (Day 56) or Early Termination