Study to Evaluate the Pharmacodynamics and Safety of HGS1025 in Patients With Ulcerative Colitis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the pharmacodynamics, safety, and pharmacokinetics of HGS1025 in patients with moderate to severe ulcerative colitis.

Official Title
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A Phase 1b, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Pharmacodynamics and Safety of HGS1025, a Human Monoclonal Anti-CCR5 Antibody, in Subjects With Ulcerative Colitis

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Biological: HGS1025
* Biological: HGS1025
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults at least 18 years of age Active, moderate to severe ulcerative colitis (UC) confirmed by endoscopy Currently on 1 or more of the following UC treatment medications: 5-aminosalicylates (5-ASA), corticosteroids, azathioprine, 6-mercaptopurine (6MP), and/or other immunosuppressive or immunomodulatory agents including cyclosporine, tacrolimus, methotrexate, and mycophenolic acid Not pregnant or nursing Females of non-childbearing potential or females of childbearing potential must be willing to practice abstinence from intercourse from 2 weeks prior to first dose of study agent and for 8 weeks after the last dose of study agent or use effective contraception for 1 month prior to the 1st dose of study agent and through 8 weeks after the last dose of study agent Males must agree to use effective contraception throughout the study and for 8 weeks after the last dose of study agent Have the ability to provide informed consent and comply with study procedures Exclusion Criteria: Received any of the following within 60 days of the first dose of study agent: Anti-TNFα therapy; integrin receptor antagonist; intravenous immunoglobulin; high dose prednisone or prednisone equivalent (greater than 60 mg/day); any investigational agent including immunosuppressive/immunomodulatory or non-biologic agents Have had a change in corticosteroid, 5-ASA, or other immunosuppressive/immunomodulatory agents within 30 days of Day 0 History of liver disease History of a major organ transplant History of prior large bowel resection Current unstable or uncontrolled acute or chronic diseases not due to UC History of malignant neoplasm within the last 5 years, except for some types of adequately treated cancers of the skin or carcinoma in situ of the uterine cervix Current or recent drug or alcohol abuse or dependence History of a positive test for HIV or test positive for Hepatitis B (HBsAg) or Hepatitis C Have a history of severe drug allergies

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HGS1025 2 mg/kg<br> | Biological: HGS1025<br>* 2 mg/kg of HGS1025 administered by IV infusion on Day 0, 14, 28 and 56, and then every 28 days thereafter if patient achieves clinical response<br>|
| Experimental: HGS1025 10 mg/kg<br> | Biological: HGS1025<br>* 10 mg/kg of HGS1025 administered by IV infusion on Day 0, 14, 28 and 56, and then every 28 days thereafter if patient achieves clinical response<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo administered by IV infusion on Day 0, 14, 28 and 56. Subjects receiving placebo during the first 8 weeks of treatment will be given the option to receive HGS1025 10 mg/kg in the continuation phase of the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacodynamics (serum & tissue biological markers; CCR5 receptor occupancy) | Change in CCR5 properties; change in inflammatory markers in blood and colon. | 8 weeks | 
| Clinical Response | Decrease in Mayo Score and rectal bleeding. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Type, frequency, and severity of adverse events |  | Through 8 weeks after the last dose of study agent | 
| Clinical response | Decrease in Mayo Score and rectal bleeding. | 4 weeks | 
| Clinical remission | Decrease in Mayo Score and no rectal bleeding or colon friability. | 4 weeks & 8 weeks | 
| Mucosal healing |  | 4 weeks & 8 weeks |