Pilot Study of Simtuzumab in the Treatment of Liver Fibrosis

A Phase 2a, Pilot, Open-Label Trial Evaluating the Safety, Tolerability and Pharmacodynamic Effects of GS-6624 in Subjects With Fibrosis of the Liver

This study will evaluate the safety and tolerability of simtuzumab (GS-6624) in patients with fibrosis of the liver.

Up to 20 participants will be enrolled into two sequential cohorts. Cohort 1 will consist of 10 participants who will receive simtuzumab every other week for a total of 3 infusions. Participants in Cohort 2 (10 subjects) will also receive simtuzumab every other week for a total of 3 infusions; the dose will depend on the safety and tolerability of simtuzumab seen in Cohort 1.

Participants from both cohorts who have completed the main study will be allowed to continue on simtuzumab treatment for an additional extension period, and will receive up to 13 additional infusions of simtuzumab at a fixed dose of 700 mg for an additional 24 weeks.

Study Overview

• Status: Completed
• Conditions: Liver Fibrosis
• Intervention / Treatment: Biological: Simtuzumab

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medical College: NewYork-Presbyterian Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males and females 18 - 65 years of age
• Chronic liver disease of any etiology
• Stage 1-3 fibrosis by Metavir score on a liver biopsy.
• Body mass index <36 kg/m2

Exclusion Criteria:

• Any evidence of hepatic decompensation past or present
• Subjects currently abusing amphetamines, cocaine, opiates, or alcohol
• Clinically significant cardiac disease
• History of cancer, other than non-melanomatous skin cancer, within 5 years prior to Screening
• Systemic fungal, bacterial, viral, or other infection that is not controlled
• Use of systemic immunosuppressants within 28 days of the Pre-treatment Phase
• Use of approved therapy for hepatitis C or hepatitis B virus within 28 days of the Pre-treatment Phase
• Pregnant or lactating
• History of bleeding diathesis within the last 6 months of study Day 1

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Participants will receive simtuzumab at a dose of 10 mg/kg by intravenous (IV) infusion every other week for a total of 3 infusions.	Biological: Simtuzumab; Other Names: GS-6624
Experimental: Cohort 2; Participants will receive simtuzumab IV every other week for a total of 3 infusions. The dose will depend on the safety and tolerability of simtuzumab seen in Cohort 1 but will not exceed 20 mg/kg.	Biological: Simtuzumab; Other Names: GS-6624

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events on multiple, escalating IV doses of simtuzumab	The endpoints to be evaluated will include graded Adverse Events, laboratory abnormalities, and vital sign measurements	Through Week 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of serum concentration of simtuzumab	Trough concentrations will be summarized by day, treatment and dose.	Through Week 14
Antibody formation to simtuzumab (anti-simtuzumab Abs)	Immunogenicity endpoints will be geometric mean titer (GMT) and geometric mean fold rate (GMFR) for a select set of antibodies.	Through Week 14
Measurement of pharmacodynamic (PD) markers after administration of simtuzumab	Pharmacodynamic markers include: Tissue PD markers through mRNA expression, LOXL2, LOX, Other LOXL proteins, αSMA, Collagen 1A1, NFKB1, Caspase 1, SMAD, and NOD; Serum and plasma PD markers include: APRI, LOXL2, Osteopontin, Hyaluronic Acid, CXCL 9, 10 and 11, MMP1, MMP3, MMP9, TIMP1, CD40L, TGF-β1, ET-1, VEGF, GAL3, IL-6 / IL-8 / TNFα / IFNγ, α2-macroglobulin, Apolipoprotein A1.	Through Week 14
Assessing the effects of chronic dosing of simtuzumab on liver structure and fibrotic markers	Measuring the effect of an additional 24 weeks of simtuzumab dosing on liver histology, LOXL2 and mRNA expression in the liver and serum markers of liver fibrosis	Up to 24 weeks

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Jeffrey Bornstein, MD, Gilead Sciences

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: October 11, 2011
• First Submitted That Met QC Criteria: October 11, 2011
• First Posted (Estimate): October 14, 2011

Study Record Updates

• Last Update Posted (Estimate): February 3, 2014
• Last Update Submitted That Met QC Criteria: January 2, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: Fibrosis; Liver; Gilead; Gilead Sciences; GSI; Liver Fibrosis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis
• Other Study ID Numbers: GS-US-321-0101