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

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

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.

Study Overview

• Status: Terminated
• Conditions: Crohn Disease; Ulcerative Colitis
• Intervention / Treatment: Drug: MDGN-002

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Hialeah, Florida, United States, 33016
      • Sweet Hope Research Specialty, Inc.
    • New Port Richey, Florida, United States, 34653
      • Advanced Research Institute, Inc.
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Egleston Hospital
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville
  • New Jersey
    • Berlin, New Jersey, United States, 08900
      • Hassman Research Institute
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Penn Presbyterian Medical Center
    • Philadelphia, Pennsylvania, United States, 19104
      • The Center for Pediatric Inflammatory Bowel Disease, Children's Hospital of Philadelphia
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center at Houston
    • San Antonio, Texas, United States, 78212
      • Clinical Associates in Research Therapeutics of America, LLC
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • Care Access Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: MDGN-002; MDGN-002 is a fully human IgG4 monoclonal antibody specific to human LIGHT.; Other Names: AVTX-002, AEVI-002

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Avalo Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 14, 2017
• Primary Completion (Actual): September 14, 2021
• Study Completion (Actual): October 12, 2021

Study Registration Dates

• First Submitted: May 24, 2017
• First Submitted That Met QC Criteria: May 25, 2017
• First Posted (Actual): May 30, 2017

Study Record Updates

• Last Update Posted (Actual): February 26, 2024
• Last Update Submitted That Met QC Criteria: July 27, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Crohn Disease; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: MDGN-002-CD-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No