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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Crohn Disease, Ulcerative Colitis

Intervention / Treatment
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* Drug: MDGN-002


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MDGN-002<br>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<br>* MDGN-002 is a fully human IgG4 monoclonal antibody specific to human LIGHT.<br>* Other names: AVTX-002, AEVI-002;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] |  | Through study completion, up to 12 weeks | 
| Incidence of Vital Signs Findings [Safety and Tolerability] |  | Through study completion, up to 12 weeks | 
| Incidence of Electrocardiogram (ECG) Findings [Safety and Tolerability] |  | Through study completion, up to 12 weeks | 
| Incidence of Clinical Laboratory Tests Findings [Safety and Tolerability] |  | Through study completion, up to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MDGN-002 Plasma Concentration |  | Through study completion, up to 12 weeks | 
| Change from baseline in Simple Endoscopy Score for Crohn's Disease (SES-CD) | 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 8 weeks of treatment | 
| Change from baseline in Crohn's Disease Activity Index (CDAI) | The total CDAI score can range from 0 to approximately 600 with higher scores indicating more active disease. | Baseline to 8 weeeks of treatment | 
| Change from baseline in Inflammatory Bowel Disease Questionnaire (IBD-Q). | The IBD-Q is a 32-item questionnaire scored on a 1 to 7 scale, where higher scores represent a more positive response. | Baseline to 8 weeeks of treatment | 
| Change from baseline in abdominal pain and loose/watery stool frequency | Abdominal pain will be assessed on a scale of 0 to 3 with higher values indicating greater pain severity. The stool frequency including number of loose and/or watery stools per day, equivalent to a score of a 6 or 7 on the Bristol Stool Scale, will be recorded. | Baseline to 8 weeeks of treatment | 
| Change from baseline in Modified Mayo Endoscopic Score | The Modified Mayo Endoscopic Score can range from 0 to 3, with higher scores indicating more severe disease. | Baseline to 8 weeks of treatment |