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

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

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

Study Overview

• Status: Withdrawn
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Biological: HGS1025; Biological: HGS1025; Drug: Placebo

• Study Type: Interventional
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; 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.
Experimental: HGS1025 2 mg/kg	Biological: HGS1025; 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; Biological: HGS1025; 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
Experimental: HGS1025 10 mg/kg	Biological: HGS1025; 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; Biological: HGS1025; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Human Genome Sciences Inc.

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Anticipated): December 1, 2012

Study Registration Dates

• First Submitted: September 1, 2011
• First Submitted That Met QC Criteria: September 13, 2011
• First Posted (Estimate): September 15, 2011

Study Record Updates

• Last Update Posted (Estimate): August 2, 2013
• Last Update Submitted That Met QC Criteria: August 1, 2013
• Last Verified: August 1, 2013

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; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: HGS1025-C1106