Pilot Study of Simtuzumab in the Treatment of Liver Fibrosis

Liver Fibrosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01452308
• Other study ID #: GS-US-321-0101
• Status: Completed
• Phase: Phase 2
• First received: October 11, 2011
• Last updated: January 2, 2014
• Start date: November 2011
• Est. completion date: August 2013

Study information

• Verified date: January 2014
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: August 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fibrosis
• Liver Cirrhosis
• Liver Fibrosis

Intervention

Biological:
• Simtuzumab

Locations

Country	Name	City	State
United States	Weill Cornell Medical College: NewYork-Presbyterian Hospital	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	Assessment of serum concentration of simtuzumab	Trough concentrations will be summarized by day, treatment and dose.	Through Week 14	No
Secondary	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	No
Secondary	Measurement of pharmacodynamic (PD) markers after administration of simtuzumab	Pharmacodynamic markers include: Tissue PD markers through mRNA expression, LOXL2, LOX, Other LOXL proteins, aSMA, 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-ß1, ET-1, VEGF, GAL3, IL-6 / IL-8 / TNFa / IFN?, a2-macroglobulin, Apolipoprotein A1.	Through Week 14	No
Secondary	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	No