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Pilot Study of Simtuzumab in the Treatment of Liver Fibrosis

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ClinicalTrials.gov Identifier: NCT01452308
Recruitment Status : Completed
First Posted : October 14, 2011
Last Update Posted : February 3, 2014
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Brief 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.


Condition or disease Intervention/treatment Phase
Liver Fibrosis Biological: Simtuzumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : November 2011
Actual Primary Completion Date : January 2013
Actual Study Completion Date : August 2013

Resource links provided by the National Library of Medicine


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 Name: 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 Name: GS-6624




Primary Outcome Measures :
  1. Incidence of adverse events on multiple, escalating IV doses of simtuzumab [ Time Frame: Through Week 14 ]
    The endpoints to be evaluated will include graded Adverse Events, laboratory abnormalities, and vital sign measurements


Secondary Outcome Measures :
  1. Assessment of serum concentration of simtuzumab [ Time Frame: Through Week 14 ]
    Trough concentrations will be summarized by day, treatment and dose.

  2. Antibody formation to simtuzumab (anti-simtuzumab Abs) [ Time Frame: Through Week 14 ]
    Immunogenicity endpoints will be geometric mean titer (GMT) and geometric mean fold rate (GMFR) for a select set of antibodies.

  3. Measurement of pharmacodynamic (PD) markers after administration of simtuzumab [ Time Frame: Through Week 14 ]
    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.

  4. Assessing the effects of chronic dosing of simtuzumab on liver structure and fibrotic markers [ Time Frame: Up to 24 weeks ]
    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



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01452308


Locations
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United States, New York
Weill Cornell Medical College: NewYork-Presbyterian Hospital
New York, New York, United States, 10065
Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Jeffrey Bornstein, MD Gilead Sciences

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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01452308     History of Changes
Other Study ID Numbers: GS-US-321-0101
First Posted: October 14, 2011    Key Record Dates
Last Update Posted: February 3, 2014
Last Verified: January 2014
Keywords provided by Gilead Sciences:
Gilead
Gilead Sciences
GSI
Liver Fibrosis
Liver
Fibrosis
Additional relevant MeSH terms:
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Liver Cirrhosis
Fibrosis
Pathologic Processes
Liver Diseases
Digestive System Diseases
Liver Extracts
Hematinics